Betsy Bates

Major Finding: Risk of breast cancer death was 24%–91% higher when women took paroxetine while on tamoxifen.

Data Source: Retrospective, population-based cohort study of 2,430 women.

Disclosures: Dr. Kelly reported no relevant financial disclosures.

SAN ANTONIO — Breast cancer patients who took the antidepressant paroxetine during their course of tamoxifen therapy were up to 91% more likely to die from their disease than were those who did not take the two drugs together, according to a retrospective, population-based cohort study conducted in the Canadian province of Ontario.

Investigators used health card identification numbers to track women aged 66 years and older who were treated with tamoxifen for breast cancer. Almost a third of patients were taking an antidepressant during their tamoxifen therapy, including 2,430 who were taking a selective serotonin reuptake inhibitor.

As a class, SSRIs are known to inhibit cytochrome P450 2D6 (CYP 2D6), an enzyme critical for the conversion of tamoxifen to endoxifen, its active metabolite. The ability of SSRIs to interfere with the efficacy of tamoxifenwos been theorized, but studies attempting to clarify the issue have reported conflicting results.

In the Canadian study reported at the annual meeting of the San Antonio Breast Cancer Symposium, 1,074 (44.2%) of the women taking an SSRI during tamoxifen therapy had died as of Dec. 31, 2007, when primary data analysis began. After statistical adjustment, investigators found that breast cancer mortality risk increased 24% among women who were coprescribed paroxetine during 25% of their tamoxifen treatment.

If patients took paroxetine for more than half of their tamoxifen course, their breast cancer mortality risk rose to 54%. Patients who took both drugs for 75% of the time they received tamoxifen had a 91% risk of breast cancer mortality.

The results were significant only for paroxetine, and not for other SSRIs—including fluoxetine, sertraline, fluvoxamine, or citalopram—that were taken concurrently with tamoxifen, reported Dr. Catherine M. Kelly at the meeting.

Dr. Kelly hypothesized that the explanation lies in the degree to which various SSRIs inhibit CYP 2D6. “Paroxetine is the only SSRI that is an irreversible—or 'suicide'—inhibitor of CYP 2D6,” she said in an interview.

The dose-response curve of the study, with escalating mortality risk paralleling time on paroxetine, adds significant weight to the findings with regard to paroxetine, marketed as Paxil by GlaxoSmithKline.

The company did not respond to a request for a comment on this study.

Fluoxetine is also a potent inhibitor of CYP 2D6, but was not shown to increase breast cancer mortality in the study, said Dr. Kelly, who was with the University of Toronto Sunnybrook Health Sciences Centre while conducting the study and is currently a breast medical oncology fellow at the University of Texas M.D. Anderson Cancer Center in Houston.

Major Finding: Risk of breast cancer death was 24%–91% higher when women took paroxetine while on tamoxifen.

Data Source: Retrospective, population-based cohort study of 2,430 women.

Disclosures: Dr. Kelly reported no relevant financial disclosures.

SAN ANTONIO — Breast cancer patients who took the antidepressant paroxetine during their course of tamoxifen therapy were up to 91% more likely to die from their disease than were those who did not take the two drugs together, according to a retrospective, population-based cohort study conducted in the Canadian province of Ontario.

Investigators used health card identification numbers to track women aged 66 years and older who were treated with tamoxifen for breast cancer. Almost a third of patients were taking an antidepressant during their tamoxifen therapy, including 2,430 who were taking a selective serotonin reuptake inhibitor.

As a class, SSRIs are known to inhibit cytochrome P450 2D6 (CYP 2D6), an enzyme critical for the conversion of tamoxifen to endoxifen, its active metabolite. The ability of SSRIs to interfere with the efficacy of tamoxifenwos been theorized, but studies attempting to clarify the issue have reported conflicting results.

In the Canadian study reported at the annual meeting of the San Antonio Breast Cancer Symposium, 1,074 (44.2%) of the women taking an SSRI during tamoxifen therapy had died as of Dec. 31, 2007, when primary data analysis began. After statistical adjustment, investigators found that breast cancer mortality risk increased 24% among women who were coprescribed paroxetine during 25% of their tamoxifen treatment.

If patients took paroxetine for more than half of their tamoxifen course, their breast cancer mortality risk rose to 54%. Patients who took both drugs for 75% of the time they received tamoxifen had a 91% risk of breast cancer mortality.

The results were significant only for paroxetine, and not for other SSRIs—including fluoxetine, sertraline, fluvoxamine, or citalopram—that were taken concurrently with tamoxifen, reported Dr. Catherine M. Kelly at the meeting.

Dr. Kelly hypothesized that the explanation lies in the degree to which various SSRIs inhibit CYP 2D6. “Paroxetine is the only SSRI that is an irreversible—or 'suicide'—inhibitor of CYP 2D6,” she said in an interview.

The dose-response curve of the study, with escalating mortality risk paralleling time on paroxetine, adds significant weight to the findings with regard to paroxetine, marketed as Paxil by GlaxoSmithKline.

The company did not respond to a request for a comment on this study.

Fluoxetine is also a potent inhibitor of CYP 2D6, but was not shown to increase breast cancer mortality in the study, said Dr. Kelly, who was with the University of Toronto Sunnybrook Health Sciences Centre while conducting the study and is currently a breast medical oncology fellow at the University of Texas M.D. Anderson Cancer Center in Houston.

Major Finding: Risk of breast cancer death was 24%–91% higher when women took paroxetine while on tamoxifen.

Data Source: Retrospective, population-based cohort study of 2,430 women.

Disclosures: Dr. Kelly reported no relevant financial disclosures.

SAN ANTONIO — Breast cancer patients who took the antidepressant paroxetine during their course of tamoxifen therapy were up to 91% more likely to die from their disease than were those who did not take the two drugs together, according to a retrospective, population-based cohort study conducted in the Canadian province of Ontario.

Investigators used health card identification numbers to track women aged 66 years and older who were treated with tamoxifen for breast cancer. Almost a third of patients were taking an antidepressant during their tamoxifen therapy, including 2,430 who were taking a selective serotonin reuptake inhibitor.

As a class, SSRIs are known to inhibit cytochrome P450 2D6 (CYP 2D6), an enzyme critical for the conversion of tamoxifen to endoxifen, its active metabolite. The ability of SSRIs to interfere with the efficacy of tamoxifenwos been theorized, but studies attempting to clarify the issue have reported conflicting results.

In the Canadian study reported at the annual meeting of the San Antonio Breast Cancer Symposium, 1,074 (44.2%) of the women taking an SSRI during tamoxifen therapy had died as of Dec. 31, 2007, when primary data analysis began. After statistical adjustment, investigators found that breast cancer mortality risk increased 24% among women who were coprescribed paroxetine during 25% of their tamoxifen treatment.

If patients took paroxetine for more than half of their tamoxifen course, their breast cancer mortality risk rose to 54%. Patients who took both drugs for 75% of the time they received tamoxifen had a 91% risk of breast cancer mortality.

The results were significant only for paroxetine, and not for other SSRIs—including fluoxetine, sertraline, fluvoxamine, or citalopram—that were taken concurrently with tamoxifen, reported Dr. Catherine M. Kelly at the meeting.

Dr. Kelly hypothesized that the explanation lies in the degree to which various SSRIs inhibit CYP 2D6. “Paroxetine is the only SSRI that is an irreversible—or 'suicide'—inhibitor of CYP 2D6,” she said in an interview.

The dose-response curve of the study, with escalating mortality risk paralleling time on paroxetine, adds significant weight to the findings with regard to paroxetine, marketed as Paxil by GlaxoSmithKline.

The company did not respond to a request for a comment on this study.

Fluoxetine is also a potent inhibitor of CYP 2D6, but was not shown to increase breast cancer mortality in the study, said Dr. Kelly, who was with the University of Toronto Sunnybrook Health Sciences Centre while conducting the study and is currently a breast medical oncology fellow at the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Richard Gottlieb has experienced the worst of times and the best of times in collaborative practice.

Also known as the “split care model” or, less formally, “doing the meds,” the approach encompasses a range of formal or informal arrangements in which a psychiatrist takes responsibility for the medication management of a patient while another health care professional conducts psychotherapy.

The worst, without question, was when he was moonlighting as a psychiatric resident at a public mental health agency and was handed a stack of pre-written scripts for medications and asked to sign his name.

When he explained that it would be inappropriate for him to order or renew medications for patients he had never evaluated, “it created an uproar,” he recalled in an interview.

“We're just trying to save you time,” he was told.

“I was expected to be a pill dispenser, really, literally signing a stamp of approval on someone else's judgment,” he said in an interview.

Fast forward to 2010.

Dr. Gottlieb is founder, owner, and clinic manager of PsycHealth, a cooperative independent practice association (IPA) in Phoenix, where he conducts diagnostic interviews with patients that draw on his training both as a psychiatrist and a psychoanalysis-trained psychologist.

Although he sees some patients on an ongoing basis for psychoanalysis, he directs most to colleagues with counseling skills best suited for each patient's needs, whether that might be a child psychiatrist, neuropsychologist, or a master's level counselor adept in cognitive-behavioral therapy (CBT).

He maintains responsibility for the patients' medications and overall progress, but otherwise acts as a “casting director,” matching patients to the “right people with the right personalities and the right skill sets”–predominantly within the IPA.

The group shares leased office space and secretarial services, but each professional operates an independent solo practice–with no strings attached.

If he feels that a patient would be best served by a clinician with a psychotherapeutic orientation not found within the IPA, Dr. Gottlieb said he has no qualms about referring outside the group.

The IPA designed by Dr. Gottlieb “tries to pull together the benefits” of other models, bridging a voluntary integration of skills and resources with the autonomy intrinsic to a fulfilling psychiatric practice, he said.

Controversial to its core, collaborative practice between psychiatrists and other mental health professionals appears to be on the rise, driven by economic pressures of managed care.

A recent study tracked psychiatric patient office visits between 1996 and 2005, documenting a 35% reduction in psychotherapy-dominant appointments, from 44.4% to 28.9% (Arch. Gen. Psychiatry 2008;65:952–70).

The number of psychiatrists who said they provided at least 30 minutes of psychotherapy during all patient visits declined to 10.8% in 2004–2005, from 19.1% in 1996.

(Psychotherapeutic visits were statistically more common among self-pay patients, white patients, older patients, and patients in the Northeast region of the United States.)

The numbers represented a sharper decline in psychotherapeutic visits to psychiatrists than was seen during the late 1980s and early 1990s, and likely reflect basic arithmetic in a managed care world, said several clinicians who were interviewed for this story. A 50-minute visit for psychotherapy cannot match the reimbursement for four medication management visits during the same hour.

From their point of view, managed care systems would rather pay the lower reimbursement rates charged by non-MD mental health professionals for ongoing psychotherapy visits, reserving payments to psychiatrists for brief medication management visits that other therapists cannot provide.

In another development, psychiatry's rich history of psychoanalytic therapy seems to be giving way in academic training to “evidence-based” psychopharmacology and CBT, approaches that are easier to assess in randomized trials than the slow unfolding of the unconscious through talk therapy.

Other forms of psychotherapy, including CBT, supportive or solution-focused therapy, or family therapy, are practiced by many mental health professionals, from psychologists and master's-level social workers and marriage and family therapists.

The APA Commission on Psychotherapy by Psychiatrists has voiced concern that in residency programs, fewer senior psychiatrists and mentors model and emphasize psychotherapy, and a newly released study appears to back up that belief.

Among 249 psychiatric residents from 15 training programs in the United States, 28% felt that not enough time and resources were devoted to psychotherapy, and a third did not believe psychotherapy training was fully supported by “key” leaders in their departments (Acad. Psychiatry 2010;34:13–20).

“Changes in practice patterns are affected by socioeconomic forces, the insurance industry, and pharmaceutical companies, all of which conspire to create specialization,” Dr. Gottlieb said.

Although he pursued doctoral-level psychoanalytic training, which he feels helps him understand the epistemology of belief systems that influence his patients' illnesses, “it's very hard to see that level of investment is going to pay off in the long-run in today's climate,” he said.

Fewer and fewer psychiatrists are able to do it all, delving into complexities of their patients' lives and minds during weekly psychotherapy visits, then taking out the prescription pad to manage their meds. It's a reality with which many psychiatrists have made their peace, particularly when the setting is conducive to true collaboration.

One of the study's co-authors, Dr. Ramin Mojtabai, works in a system at Johns Hopkins University that fosters periodic psychopharmacology assessment meetings that include himself, the patient, and the therapist–often a social worker by training–“who spends a longer time with the patient, and brings unique insights about the symptoms and the function of the patient.

“The therapist and the prescribing psychiatrist have the same goals in working with the patient. We are informed of each other's work, and that's a major positive point,” said Dr. Mojtabai of the Johns Hopkins Department of Psychiatry and Bloomberg School of Public Health.

After publication of the paper that he coauthored with Dr. Mark Olfson of Columbia University, New York, Dr. Majtabai said that he was approached by several psychiatrists who relayed to him that “even in a short, 15-minute visit, they feel that a lot of therapy work is accomplished.

“I agree with that,” Dr. Olfson said, particularly when occasional evaluative conferences are held to consider whether the goals of therapy are being met, or adjustments should be made–either in the medication or dose, or in the psychotherapeutic approach being employed. In real life practice, the “teamwork” concept varies widely, from scheduled patient conferences to “no real integration by design,” even when professionals share office space and patients, Dr. Mojtabai said.

The patchwork quilt of current collaborative practice models has never been systematically studied to see whether patients benefit, or even if money is saved in the long run when more than one practitioner provides care.

Well-designed studies could lead to best-practice models, he said.

“We don't know which groups of patients benefit from which settings,” or how often psychiatrists should see a patient receiving psychotherapy elsewhere,” Dr. Mojtabai said, adding that models of collaboration need to be studied as well.

At his Center for Collaborative Psychology & Psychiatry in Kentfield, Calif., Dr. Steven A. Frankel spends a great deal of time interacting with colleagues, a welcome change from the long hours he once spent conducting psychoanalytic therapy.

These days, he's a self-designated Med-Psych Coordinating Physician, doing a careful evaluation of each new patient, ordering psychological and medical testing, deconstructing the problems underlying symptoms, and assigning therapy to carefully selected consulting professionals such as social workers, school counselors, family therapists, psychopharmacologists, or primary care physicians.

“Personally, I enjoy this a lot more,” Dr. Frankel said in an interview. “I like working with other people. I love collaborating. It seems to be more honest to refer to people who are very skilled in what they do–more skilled in parts of this than I am.”

Serving as a coordinator of care requires a deep understanding of the patient, the diagnosis, and the system, Dr. Frankel added. “It's a relationship that has tremendous therapeutic significance.”

Dr. Frankel said that he is implementing the Collaborative Treatment Method into his practice, and intends to soon implement studies of its efficacy and practicality.

His hypothesis? The collaborative model will prove to be more cost effective than slap-dash arrangements implemented by managed care systems today, and more practical than the psychotherapy-driven psychiatric practices of the past.

“I think the patients will fare better, too,” he said.

By Betsy Bates. Share your thoughts and suggestions at cpnews@elsevier.com

Serving as a coordinator of care 'has tremendous therapeutic significance.'

Source DR. FRANKEL

The IPA tries to integrate skills and resources with the autonomy intrinsic to a fulfilling psychiatric practice.

Source DR. GOTTLIEB

Dr. Richard Gottlieb has experienced the worst of times and the best of times in collaborative practice.

Also known as the “split care model” or, less formally, “doing the meds,” the approach encompasses a range of formal or informal arrangements in which a psychiatrist takes responsibility for the medication management of a patient while another health care professional conducts psychotherapy.

The worst, without question, was when he was moonlighting as a psychiatric resident at a public mental health agency and was handed a stack of pre-written scripts for medications and asked to sign his name.

When he explained that it would be inappropriate for him to order or renew medications for patients he had never evaluated, “it created an uproar,” he recalled in an interview.

“We're just trying to save you time,” he was told.

“I was expected to be a pill dispenser, really, literally signing a stamp of approval on someone else's judgment,” he said in an interview.

Fast forward to 2010.

Dr. Gottlieb is founder, owner, and clinic manager of PsycHealth, a cooperative independent practice association (IPA) in Phoenix, where he conducts diagnostic interviews with patients that draw on his training both as a psychiatrist and a psychoanalysis-trained psychologist.

Although he sees some patients on an ongoing basis for psychoanalysis, he directs most to colleagues with counseling skills best suited for each patient's needs, whether that might be a child psychiatrist, neuropsychologist, or a master's level counselor adept in cognitive-behavioral therapy (CBT).

He maintains responsibility for the patients' medications and overall progress, but otherwise acts as a “casting director,” matching patients to the “right people with the right personalities and the right skill sets”–predominantly within the IPA.

The group shares leased office space and secretarial services, but each professional operates an independent solo practice–with no strings attached.

If he feels that a patient would be best served by a clinician with a psychotherapeutic orientation not found within the IPA, Dr. Gottlieb said he has no qualms about referring outside the group.

The IPA designed by Dr. Gottlieb “tries to pull together the benefits” of other models, bridging a voluntary integration of skills and resources with the autonomy intrinsic to a fulfilling psychiatric practice, he said.

Controversial to its core, collaborative practice between psychiatrists and other mental health professionals appears to be on the rise, driven by economic pressures of managed care.

A recent study tracked psychiatric patient office visits between 1996 and 2005, documenting a 35% reduction in psychotherapy-dominant appointments, from 44.4% to 28.9% (Arch. Gen. Psychiatry 2008;65:952–70).

The number of psychiatrists who said they provided at least 30 minutes of psychotherapy during all patient visits declined to 10.8% in 2004–2005, from 19.1% in 1996.

(Psychotherapeutic visits were statistically more common among self-pay patients, white patients, older patients, and patients in the Northeast region of the United States.)

The numbers represented a sharper decline in psychotherapeutic visits to psychiatrists than was seen during the late 1980s and early 1990s, and likely reflect basic arithmetic in a managed care world, said several clinicians who were interviewed for this story. A 50-minute visit for psychotherapy cannot match the reimbursement for four medication management visits during the same hour.

From their point of view, managed care systems would rather pay the lower reimbursement rates charged by non-MD mental health professionals for ongoing psychotherapy visits, reserving payments to psychiatrists for brief medication management visits that other therapists cannot provide.

In another development, psychiatry's rich history of psychoanalytic therapy seems to be giving way in academic training to “evidence-based” psychopharmacology and CBT, approaches that are easier to assess in randomized trials than the slow unfolding of the unconscious through talk therapy.

Other forms of psychotherapy, including CBT, supportive or solution-focused therapy, or family therapy, are practiced by many mental health professionals, from psychologists and master's-level social workers and marriage and family therapists.

The APA Commission on Psychotherapy by Psychiatrists has voiced concern that in residency programs, fewer senior psychiatrists and mentors model and emphasize psychotherapy, and a newly released study appears to back up that belief.

Among 249 psychiatric residents from 15 training programs in the United States, 28% felt that not enough time and resources were devoted to psychotherapy, and a third did not believe psychotherapy training was fully supported by “key” leaders in their departments (Acad. Psychiatry 2010;34:13–20).

“Changes in practice patterns are affected by socioeconomic forces, the insurance industry, and pharmaceutical companies, all of which conspire to create specialization,” Dr. Gottlieb said.

Although he pursued doctoral-level psychoanalytic training, which he feels helps him understand the epistemology of belief systems that influence his patients' illnesses, “it's very hard to see that level of investment is going to pay off in the long-run in today's climate,” he said.

Fewer and fewer psychiatrists are able to do it all, delving into complexities of their patients' lives and minds during weekly psychotherapy visits, then taking out the prescription pad to manage their meds. It's a reality with which many psychiatrists have made their peace, particularly when the setting is conducive to true collaboration.

One of the study's co-authors, Dr. Ramin Mojtabai, works in a system at Johns Hopkins University that fosters periodic psychopharmacology assessment meetings that include himself, the patient, and the therapist–often a social worker by training–“who spends a longer time with the patient, and brings unique insights about the symptoms and the function of the patient.

“The therapist and the prescribing psychiatrist have the same goals in working with the patient. We are informed of each other's work, and that's a major positive point,” said Dr. Mojtabai of the Johns Hopkins Department of Psychiatry and Bloomberg School of Public Health.

After publication of the paper that he coauthored with Dr. Mark Olfson of Columbia University, New York, Dr. Majtabai said that he was approached by several psychiatrists who relayed to him that “even in a short, 15-minute visit, they feel that a lot of therapy work is accomplished.

“I agree with that,” Dr. Olfson said, particularly when occasional evaluative conferences are held to consider whether the goals of therapy are being met, or adjustments should be made–either in the medication or dose, or in the psychotherapeutic approach being employed. In real life practice, the “teamwork” concept varies widely, from scheduled patient conferences to “no real integration by design,” even when professionals share office space and patients, Dr. Mojtabai said.

The patchwork quilt of current collaborative practice models has never been systematically studied to see whether patients benefit, or even if money is saved in the long run when more than one practitioner provides care.

Well-designed studies could lead to best-practice models, he said.

“We don't know which groups of patients benefit from which settings,” or how often psychiatrists should see a patient receiving psychotherapy elsewhere,” Dr. Mojtabai said, adding that models of collaboration need to be studied as well.

At his Center for Collaborative Psychology & Psychiatry in Kentfield, Calif., Dr. Steven A. Frankel spends a great deal of time interacting with colleagues, a welcome change from the long hours he once spent conducting psychoanalytic therapy.

These days, he's a self-designated Med-Psych Coordinating Physician, doing a careful evaluation of each new patient, ordering psychological and medical testing, deconstructing the problems underlying symptoms, and assigning therapy to carefully selected consulting professionals such as social workers, school counselors, family therapists, psychopharmacologists, or primary care physicians.

“Personally, I enjoy this a lot more,” Dr. Frankel said in an interview. “I like working with other people. I love collaborating. It seems to be more honest to refer to people who are very skilled in what they do–more skilled in parts of this than I am.”

Serving as a coordinator of care requires a deep understanding of the patient, the diagnosis, and the system, Dr. Frankel added. “It's a relationship that has tremendous therapeutic significance.”

Dr. Frankel said that he is implementing the Collaborative Treatment Method into his practice, and intends to soon implement studies of its efficacy and practicality.

His hypothesis? The collaborative model will prove to be more cost effective than slap-dash arrangements implemented by managed care systems today, and more practical than the psychotherapy-driven psychiatric practices of the past.

“I think the patients will fare better, too,” he said.

By Betsy Bates. Share your thoughts and suggestions at cpnews@elsevier.com

Serving as a coordinator of care 'has tremendous therapeutic significance.'

Source DR. FRANKEL

The IPA tries to integrate skills and resources with the autonomy intrinsic to a fulfilling psychiatric practice.

Source DR. GOTTLIEB

Dr. Richard Gottlieb has experienced the worst of times and the best of times in collaborative practice.

Also known as the “split care model” or, less formally, “doing the meds,” the approach encompasses a range of formal or informal arrangements in which a psychiatrist takes responsibility for the medication management of a patient while another health care professional conducts psychotherapy.

The worst, without question, was when he was moonlighting as a psychiatric resident at a public mental health agency and was handed a stack of pre-written scripts for medications and asked to sign his name.

When he explained that it would be inappropriate for him to order or renew medications for patients he had never evaluated, “it created an uproar,” he recalled in an interview.

“We're just trying to save you time,” he was told.

“I was expected to be a pill dispenser, really, literally signing a stamp of approval on someone else's judgment,” he said in an interview.

Fast forward to 2010.

Dr. Gottlieb is founder, owner, and clinic manager of PsycHealth, a cooperative independent practice association (IPA) in Phoenix, where he conducts diagnostic interviews with patients that draw on his training both as a psychiatrist and a psychoanalysis-trained psychologist.

Although he sees some patients on an ongoing basis for psychoanalysis, he directs most to colleagues with counseling skills best suited for each patient's needs, whether that might be a child psychiatrist, neuropsychologist, or a master's level counselor adept in cognitive-behavioral therapy (CBT).

He maintains responsibility for the patients' medications and overall progress, but otherwise acts as a “casting director,” matching patients to the “right people with the right personalities and the right skill sets”–predominantly within the IPA.

The group shares leased office space and secretarial services, but each professional operates an independent solo practice–with no strings attached.

If he feels that a patient would be best served by a clinician with a psychotherapeutic orientation not found within the IPA, Dr. Gottlieb said he has no qualms about referring outside the group.

The IPA designed by Dr. Gottlieb “tries to pull together the benefits” of other models, bridging a voluntary integration of skills and resources with the autonomy intrinsic to a fulfilling psychiatric practice, he said.

Controversial to its core, collaborative practice between psychiatrists and other mental health professionals appears to be on the rise, driven by economic pressures of managed care.

A recent study tracked psychiatric patient office visits between 1996 and 2005, documenting a 35% reduction in psychotherapy-dominant appointments, from 44.4% to 28.9% (Arch. Gen. Psychiatry 2008;65:952–70).

The number of psychiatrists who said they provided at least 30 minutes of psychotherapy during all patient visits declined to 10.8% in 2004–2005, from 19.1% in 1996.

(Psychotherapeutic visits were statistically more common among self-pay patients, white patients, older patients, and patients in the Northeast region of the United States.)

The numbers represented a sharper decline in psychotherapeutic visits to psychiatrists than was seen during the late 1980s and early 1990s, and likely reflect basic arithmetic in a managed care world, said several clinicians who were interviewed for this story. A 50-minute visit for psychotherapy cannot match the reimbursement for four medication management visits during the same hour.

From their point of view, managed care systems would rather pay the lower reimbursement rates charged by non-MD mental health professionals for ongoing psychotherapy visits, reserving payments to psychiatrists for brief medication management visits that other therapists cannot provide.

In another development, psychiatry's rich history of psychoanalytic therapy seems to be giving way in academic training to “evidence-based” psychopharmacology and CBT, approaches that are easier to assess in randomized trials than the slow unfolding of the unconscious through talk therapy.

Other forms of psychotherapy, including CBT, supportive or solution-focused therapy, or family therapy, are practiced by many mental health professionals, from psychologists and master's-level social workers and marriage and family therapists.

The APA Commission on Psychotherapy by Psychiatrists has voiced concern that in residency programs, fewer senior psychiatrists and mentors model and emphasize psychotherapy, and a newly released study appears to back up that belief.

Among 249 psychiatric residents from 15 training programs in the United States, 28% felt that not enough time and resources were devoted to psychotherapy, and a third did not believe psychotherapy training was fully supported by “key” leaders in their departments (Acad. Psychiatry 2010;34:13–20).

“Changes in practice patterns are affected by socioeconomic forces, the insurance industry, and pharmaceutical companies, all of which conspire to create specialization,” Dr. Gottlieb said.

Although he pursued doctoral-level psychoanalytic training, which he feels helps him understand the epistemology of belief systems that influence his patients' illnesses, “it's very hard to see that level of investment is going to pay off in the long-run in today's climate,” he said.

Fewer and fewer psychiatrists are able to do it all, delving into complexities of their patients' lives and minds during weekly psychotherapy visits, then taking out the prescription pad to manage their meds. It's a reality with which many psychiatrists have made their peace, particularly when the setting is conducive to true collaboration.

One of the study's co-authors, Dr. Ramin Mojtabai, works in a system at Johns Hopkins University that fosters periodic psychopharmacology assessment meetings that include himself, the patient, and the therapist–often a social worker by training–“who spends a longer time with the patient, and brings unique insights about the symptoms and the function of the patient.

“The therapist and the prescribing psychiatrist have the same goals in working with the patient. We are informed of each other's work, and that's a major positive point,” said Dr. Mojtabai of the Johns Hopkins Department of Psychiatry and Bloomberg School of Public Health.

After publication of the paper that he coauthored with Dr. Mark Olfson of Columbia University, New York, Dr. Majtabai said that he was approached by several psychiatrists who relayed to him that “even in a short, 15-minute visit, they feel that a lot of therapy work is accomplished.

“I agree with that,” Dr. Olfson said, particularly when occasional evaluative conferences are held to consider whether the goals of therapy are being met, or adjustments should be made–either in the medication or dose, or in the psychotherapeutic approach being employed. In real life practice, the “teamwork” concept varies widely, from scheduled patient conferences to “no real integration by design,” even when professionals share office space and patients, Dr. Mojtabai said.

The patchwork quilt of current collaborative practice models has never been systematically studied to see whether patients benefit, or even if money is saved in the long run when more than one practitioner provides care.

Well-designed studies could lead to best-practice models, he said.

“We don't know which groups of patients benefit from which settings,” or how often psychiatrists should see a patient receiving psychotherapy elsewhere,” Dr. Mojtabai said, adding that models of collaboration need to be studied as well.

At his Center for Collaborative Psychology & Psychiatry in Kentfield, Calif., Dr. Steven A. Frankel spends a great deal of time interacting with colleagues, a welcome change from the long hours he once spent conducting psychoanalytic therapy.

These days, he's a self-designated Med-Psych Coordinating Physician, doing a careful evaluation of each new patient, ordering psychological and medical testing, deconstructing the problems underlying symptoms, and assigning therapy to carefully selected consulting professionals such as social workers, school counselors, family therapists, psychopharmacologists, or primary care physicians.

“Personally, I enjoy this a lot more,” Dr. Frankel said in an interview. “I like working with other people. I love collaborating. It seems to be more honest to refer to people who are very skilled in what they do–more skilled in parts of this than I am.”

Serving as a coordinator of care requires a deep understanding of the patient, the diagnosis, and the system, Dr. Frankel added. “It's a relationship that has tremendous therapeutic significance.”

Dr. Frankel said that he is implementing the Collaborative Treatment Method into his practice, and intends to soon implement studies of its efficacy and practicality.

His hypothesis? The collaborative model will prove to be more cost effective than slap-dash arrangements implemented by managed care systems today, and more practical than the psychotherapy-driven psychiatric practices of the past.

“I think the patients will fare better, too,” he said.

By Betsy Bates. Share your thoughts and suggestions at cpnews@elsevier.com

Serving as a coordinator of care 'has tremendous therapeutic significance.'

Source DR. FRANKEL

The IPA tries to integrate skills and resources with the autonomy intrinsic to a fulfilling psychiatric practice.

Source DR. GOTTLIEB

LOS ANGELES – Persistent cravings, as opposed to a difficult struggle with withdrawal, are likely responsible for the grip of methamphetamine on addicted individuals who want to quit, according to results of an inpatient study presented at the annual meeting of the American Association of Addiction Psychiatrists.

Researchers at the University of California, Los Angeles, admitted 66 non–treatment-seeking methamphetamine-addicted patients and 89 healthy controls to an inpatient clinical research center for up to 5 weeks as part of several imaging studies conducted as those patients addicted to methamphetamine withdrew from the drug.

The addicted patients were active users at admission and were monitored daily via urine screening to ensure that they remained abstinent throughout their hospitalizations.

To study the “pure” effects of methamphetamine withdrawal, those addicted were excluded if they were simultaneously addicted to other substances (except nicotine) or if they had pre-existing psychiatric diagnoses or serious medical conditions, said Dr. Todd Zorick of the Center for Addictive Behaviors at UCLA.

Methamphetamine-dependent subjects were compared with matched healthy control subjects on the Beck Depression Inventory (mood), and Brief Symptom Inventory (general psychiatric symptoms, including hostility, anxiety, depression, and psychosis).

Addicted subjects experienced a variety of prominent withdrawal symptoms on days 1–3, including diarrhea, red/itchy eyes, suicidal thoughts, and mild psychotic symptoms.

Symptoms of psychoticism, obsessional behavior, interpersonal sensitivity, hostility, and paranoia, and somatic symptoms were “quite high” early on, particularly in the first 24–48 hours of abstinence.

On days 4–14, other symptoms came to the fore, including a lack of motivation, increased appetite, sleep difficulties, and fatigue, Dr. Zorick reported.

However, most of these symptoms were mild, manageable, and gradually declined over time.

“Pretty much anything we saw [in these symptom clusters] was gone in 2 weeks,” he said.

Depression symptoms, which have been hypothesized to drive relapse, were elevated over those of healthy controls at study entry but generally declined over 4 weeks. Although a small subset of patients had Beck Depression Inventory scores that persisted at a mean level of about 12 on the 0–63 scale, most had scores at 1 month that were “at least as low or lower” than scores of healthy controls.

What did persist was craving, which began at a mean of 40–50 on a 0–100 visual analog scale and remained in the 20–30 range at the end of week 1.

Over the first 14 days of abstinence, cravings subsided somewhat, but for many users, the desire for methamphetamine did not completely wane even after a month had passed since last use.

“Even at week 5, [craving is] not zero,” Dr. Zorick said. “These are people who haven't touched meth in 5 weeks. [They] are still thinking about meth a lot [in a controlled, hospital environment]… not being exposed to it whatsoever.”

Craving scores were not associated with depression symptoms except during weeks 1 and 2 of abstinence, he noted.

Dr. Zorick said the results might serve to inform clinicians about the clinical course of withdrawal in their patients and the need to continue to address craving over the long term.

“If you get somebody in your office who recently quit methamphetamine or is trying to quit… he's likely to experience a lot of psychiatric symptoms, including hostility, paranoia, interpersonal sensitivity, and high levels of depression,” he said. “These are not happy people.

“However, the good news is that these symptoms decrease to a pretty low baseline on average within the first 2 weeks or so.”

At that time, “they are likely to feel a lot better, not experiencing depression, no psychotic symptoms, sleep normalized, but they may have high levels of craving for methamphetamine.”

No drugs have been approved by the Food and Drug Administration to reduce craving in patients addicted to methamphetamine who are attempting to quit, although this should be a crucial goal for future research, Dr. Zorick said.

Dr. Zorick's research and that of Edythe London, Ph.D., also of UCLA and the principal investigator of the inpatient imaging studies, were sponsored by government grants.

Neither investigator reported any relevant financial disclosures.

LOS ANGELES – Persistent cravings, as opposed to a difficult struggle with withdrawal, are likely responsible for the grip of methamphetamine on addicted individuals who want to quit, according to results of an inpatient study presented at the annual meeting of the American Association of Addiction Psychiatrists.

Researchers at the University of California, Los Angeles, admitted 66 non–treatment-seeking methamphetamine-addicted patients and 89 healthy controls to an inpatient clinical research center for up to 5 weeks as part of several imaging studies conducted as those patients addicted to methamphetamine withdrew from the drug.

The addicted patients were active users at admission and were monitored daily via urine screening to ensure that they remained abstinent throughout their hospitalizations.

To study the “pure” effects of methamphetamine withdrawal, those addicted were excluded if they were simultaneously addicted to other substances (except nicotine) or if they had pre-existing psychiatric diagnoses or serious medical conditions, said Dr. Todd Zorick of the Center for Addictive Behaviors at UCLA.

Methamphetamine-dependent subjects were compared with matched healthy control subjects on the Beck Depression Inventory (mood), and Brief Symptom Inventory (general psychiatric symptoms, including hostility, anxiety, depression, and psychosis).

Addicted subjects experienced a variety of prominent withdrawal symptoms on days 1–3, including diarrhea, red/itchy eyes, suicidal thoughts, and mild psychotic symptoms.

Symptoms of psychoticism, obsessional behavior, interpersonal sensitivity, hostility, and paranoia, and somatic symptoms were “quite high” early on, particularly in the first 24–48 hours of abstinence.

On days 4–14, other symptoms came to the fore, including a lack of motivation, increased appetite, sleep difficulties, and fatigue, Dr. Zorick reported.

However, most of these symptoms were mild, manageable, and gradually declined over time.

“Pretty much anything we saw [in these symptom clusters] was gone in 2 weeks,” he said.

Depression symptoms, which have been hypothesized to drive relapse, were elevated over those of healthy controls at study entry but generally declined over 4 weeks. Although a small subset of patients had Beck Depression Inventory scores that persisted at a mean level of about 12 on the 0–63 scale, most had scores at 1 month that were “at least as low or lower” than scores of healthy controls.

What did persist was craving, which began at a mean of 40–50 on a 0–100 visual analog scale and remained in the 20–30 range at the end of week 1.

Over the first 14 days of abstinence, cravings subsided somewhat, but for many users, the desire for methamphetamine did not completely wane even after a month had passed since last use.

“Even at week 5, [craving is] not zero,” Dr. Zorick said. “These are people who haven't touched meth in 5 weeks. [They] are still thinking about meth a lot [in a controlled, hospital environment]… not being exposed to it whatsoever.”

Craving scores were not associated with depression symptoms except during weeks 1 and 2 of abstinence, he noted.

Dr. Zorick said the results might serve to inform clinicians about the clinical course of withdrawal in their patients and the need to continue to address craving over the long term.

“If you get somebody in your office who recently quit methamphetamine or is trying to quit… he's likely to experience a lot of psychiatric symptoms, including hostility, paranoia, interpersonal sensitivity, and high levels of depression,” he said. “These are not happy people.

“However, the good news is that these symptoms decrease to a pretty low baseline on average within the first 2 weeks or so.”

At that time, “they are likely to feel a lot better, not experiencing depression, no psychotic symptoms, sleep normalized, but they may have high levels of craving for methamphetamine.”

No drugs have been approved by the Food and Drug Administration to reduce craving in patients addicted to methamphetamine who are attempting to quit, although this should be a crucial goal for future research, Dr. Zorick said.

Dr. Zorick's research and that of Edythe London, Ph.D., also of UCLA and the principal investigator of the inpatient imaging studies, were sponsored by government grants.

Neither investigator reported any relevant financial disclosures.

LOS ANGELES – Persistent cravings, as opposed to a difficult struggle with withdrawal, are likely responsible for the grip of methamphetamine on addicted individuals who want to quit, according to results of an inpatient study presented at the annual meeting of the American Association of Addiction Psychiatrists.

Researchers at the University of California, Los Angeles, admitted 66 non–treatment-seeking methamphetamine-addicted patients and 89 healthy controls to an inpatient clinical research center for up to 5 weeks as part of several imaging studies conducted as those patients addicted to methamphetamine withdrew from the drug.

The addicted patients were active users at admission and were monitored daily via urine screening to ensure that they remained abstinent throughout their hospitalizations.

To study the “pure” effects of methamphetamine withdrawal, those addicted were excluded if they were simultaneously addicted to other substances (except nicotine) or if they had pre-existing psychiatric diagnoses or serious medical conditions, said Dr. Todd Zorick of the Center for Addictive Behaviors at UCLA.

Methamphetamine-dependent subjects were compared with matched healthy control subjects on the Beck Depression Inventory (mood), and Brief Symptom Inventory (general psychiatric symptoms, including hostility, anxiety, depression, and psychosis).

Addicted subjects experienced a variety of prominent withdrawal symptoms on days 1–3, including diarrhea, red/itchy eyes, suicidal thoughts, and mild psychotic symptoms.

Symptoms of psychoticism, obsessional behavior, interpersonal sensitivity, hostility, and paranoia, and somatic symptoms were “quite high” early on, particularly in the first 24–48 hours of abstinence.

On days 4–14, other symptoms came to the fore, including a lack of motivation, increased appetite, sleep difficulties, and fatigue, Dr. Zorick reported.

However, most of these symptoms were mild, manageable, and gradually declined over time.

“Pretty much anything we saw [in these symptom clusters] was gone in 2 weeks,” he said.

Depression symptoms, which have been hypothesized to drive relapse, were elevated over those of healthy controls at study entry but generally declined over 4 weeks. Although a small subset of patients had Beck Depression Inventory scores that persisted at a mean level of about 12 on the 0–63 scale, most had scores at 1 month that were “at least as low or lower” than scores of healthy controls.

What did persist was craving, which began at a mean of 40–50 on a 0–100 visual analog scale and remained in the 20–30 range at the end of week 1.

Over the first 14 days of abstinence, cravings subsided somewhat, but for many users, the desire for methamphetamine did not completely wane even after a month had passed since last use.

“Even at week 5, [craving is] not zero,” Dr. Zorick said. “These are people who haven't touched meth in 5 weeks. [They] are still thinking about meth a lot [in a controlled, hospital environment]… not being exposed to it whatsoever.”

Craving scores were not associated with depression symptoms except during weeks 1 and 2 of abstinence, he noted.

Dr. Zorick said the results might serve to inform clinicians about the clinical course of withdrawal in their patients and the need to continue to address craving over the long term.

“If you get somebody in your office who recently quit methamphetamine or is trying to quit… he's likely to experience a lot of psychiatric symptoms, including hostility, paranoia, interpersonal sensitivity, and high levels of depression,” he said. “These are not happy people.

“However, the good news is that these symptoms decrease to a pretty low baseline on average within the first 2 weeks or so.”

At that time, “they are likely to feel a lot better, not experiencing depression, no psychotic symptoms, sleep normalized, but they may have high levels of craving for methamphetamine.”

No drugs have been approved by the Food and Drug Administration to reduce craving in patients addicted to methamphetamine who are attempting to quit, although this should be a crucial goal for future research, Dr. Zorick said.

Dr. Zorick's research and that of Edythe London, Ph.D., also of UCLA and the principal investigator of the inpatient imaging studies, were sponsored by government grants.

Neither investigator reported any relevant financial disclosures.

Major finding: ADHD symptoms improved and substance use declined with CBT, regardless of whether adolescents received OROS-MPH or placebo.

Source of data: A randomized controlled trial with 303 adolescents with ADHD and a substance use disorder.

Disclosures: The trial was sponsored by the National Institute of Drug Abuse. The lead investigator reported no conflicts of interest.

LOS ANGELES – Psychostimulant treatment did not outperform placebo when structured cognitive-behavioral therapy was integrated into the treatment of adolescents with attention-deficit/hyperactivity disorder and substance use disorders.

In a 16-week, randomized, placebo-controlled trial, ADHD symptoms significantly improved and substance use declined regardless of whether adolescents received OROS-MPH (Concerta) or placebo, Dr. Paula Riggs said at the annual meeting of the American Academy of Addiction Psychiatry.

Rather than being seen as a negative trial, the study appears to speak to the usefulness of structured, individualized weekly CBT, said Dr. Riggs, the primary investigator of the 11-center trial sponsored by the National Institute of Drug Abuse and professor of psychiatry at the University of Colorado, Denver.

The trial enrolled 303 adolescents aged 13–18 who met DSM-IV criteria for ADHD and for at least substance use disorder (other than nicotine dependence, and excluding current opiate dependence or methamphetamine abuse or dependence).

The average age of participants was 16.5 years. About 80% of the participants were male, and 20% female. Whites constituted 64% of the medication arm and 55% of the placebo arm. Roughly a fourth of the subjects in each group were African American; 15% were Hispanic .

About one-third of subjects had ADHD-inattentive type; 67% had ADHD-combined type; and less than 2%, ADHD-hyperactive type.

Cannabis and alcohol use/dependence were the most commonly represented substance use disorders, although use and/or abuse of hallucinogens, opioids, cocaine, and amphetamines also were reported.

Adolescents with major depression, anxiety disorders, and/or conduct disorder were included in the trial, resulting in a high baseline level of psychopathology among participants. Almost 75% of the subjects completed the trial.

“We wanted to keep this real and generalizable,” Dr. Riggs said.

In the medication arm, 80% of 151 patients were compliant with doses, which were successfully titrated to 72 mg/daily in 96% and sustained at that dose in 86%.

Participants received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse.

An intent-to-treat analysis was used to calculate results.

“This was the shocker,” Dr. Riggs said. “We saw a clinically and statistically significant reduction in ADHD symptoms in both groups.”

Symptoms declined 46% in the medication group and 45% in the placebo group.

Parents reported symptom reductions of 26% and 30% in adolescents receiving active medication or placebo on a DSM-IV symptom checklist at 8 weeks, and 24% and 30.9% reductions at 16 weeks.

Past 28-day substance use reports declined by 6.1 days (43%) in the medication arm and 4.9 days (33%) in the placebo arm–a statistically insignificant between-group difference.

Slightly more negative drug screens–3.8 compared with 2.8–were found in adolescents assigned to receive active medication, and this group also showed greater improvements in problem-solving skills and focused-coping skills that had been addressed in CBT, Dr. Riggs reported.

Subjects deemed by investigators to be “medication responders” had twice as many negative drug screens as nonresponders or those receiving placebo.

Titrated OROS-MPH was “stunningly safe and well-tolerated” in the trial, with 11 serious adverse events, 7 of which occurred in the placebo group. The only event seen more frequently in the medication arm was limb injury, an event not considered to be related to the medication.

The trial results were inconsistent with the results of trials pitting psychostimulants against placebo in non–substance-abusing youth.

However, they were consistent with three previous controlled psychostimulant trials in non–substance-abusing adolescents when concurrent CBT was included for subjects in both the medication and placebo arms.

As in this trial, significant reductions were seen in ADHD in both groups, but with no significant advantage to medication over placebo.

Major finding: ADHD symptoms improved and substance use declined with CBT, regardless of whether adolescents received OROS-MPH or placebo.

Source of data: A randomized controlled trial with 303 adolescents with ADHD and a substance use disorder.

Disclosures: The trial was sponsored by the National Institute of Drug Abuse. The lead investigator reported no conflicts of interest.

LOS ANGELES – Psychostimulant treatment did not outperform placebo when structured cognitive-behavioral therapy was integrated into the treatment of adolescents with attention-deficit/hyperactivity disorder and substance use disorders.

In a 16-week, randomized, placebo-controlled trial, ADHD symptoms significantly improved and substance use declined regardless of whether adolescents received OROS-MPH (Concerta) or placebo, Dr. Paula Riggs said at the annual meeting of the American Academy of Addiction Psychiatry.

Rather than being seen as a negative trial, the study appears to speak to the usefulness of structured, individualized weekly CBT, said Dr. Riggs, the primary investigator of the 11-center trial sponsored by the National Institute of Drug Abuse and professor of psychiatry at the University of Colorado, Denver.

The trial enrolled 303 adolescents aged 13–18 who met DSM-IV criteria for ADHD and for at least substance use disorder (other than nicotine dependence, and excluding current opiate dependence or methamphetamine abuse or dependence).

The average age of participants was 16.5 years. About 80% of the participants were male, and 20% female. Whites constituted 64% of the medication arm and 55% of the placebo arm. Roughly a fourth of the subjects in each group were African American; 15% were Hispanic .

About one-third of subjects had ADHD-inattentive type; 67% had ADHD-combined type; and less than 2%, ADHD-hyperactive type.

Cannabis and alcohol use/dependence were the most commonly represented substance use disorders, although use and/or abuse of hallucinogens, opioids, cocaine, and amphetamines also were reported.

Adolescents with major depression, anxiety disorders, and/or conduct disorder were included in the trial, resulting in a high baseline level of psychopathology among participants. Almost 75% of the subjects completed the trial.

“We wanted to keep this real and generalizable,” Dr. Riggs said.

In the medication arm, 80% of 151 patients were compliant with doses, which were successfully titrated to 72 mg/daily in 96% and sustained at that dose in 86%.

Participants received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse.

An intent-to-treat analysis was used to calculate results.

“This was the shocker,” Dr. Riggs said. “We saw a clinically and statistically significant reduction in ADHD symptoms in both groups.”

Symptoms declined 46% in the medication group and 45% in the placebo group.

Parents reported symptom reductions of 26% and 30% in adolescents receiving active medication or placebo on a DSM-IV symptom checklist at 8 weeks, and 24% and 30.9% reductions at 16 weeks.

Past 28-day substance use reports declined by 6.1 days (43%) in the medication arm and 4.9 days (33%) in the placebo arm–a statistically insignificant between-group difference.

Slightly more negative drug screens–3.8 compared with 2.8–were found in adolescents assigned to receive active medication, and this group also showed greater improvements in problem-solving skills and focused-coping skills that had been addressed in CBT, Dr. Riggs reported.

Subjects deemed by investigators to be “medication responders” had twice as many negative drug screens as nonresponders or those receiving placebo.

Titrated OROS-MPH was “stunningly safe and well-tolerated” in the trial, with 11 serious adverse events, 7 of which occurred in the placebo group. The only event seen more frequently in the medication arm was limb injury, an event not considered to be related to the medication.

The trial results were inconsistent with the results of trials pitting psychostimulants against placebo in non–substance-abusing youth.

However, they were consistent with three previous controlled psychostimulant trials in non–substance-abusing adolescents when concurrent CBT was included for subjects in both the medication and placebo arms.

As in this trial, significant reductions were seen in ADHD in both groups, but with no significant advantage to medication over placebo.

Major finding: ADHD symptoms improved and substance use declined with CBT, regardless of whether adolescents received OROS-MPH or placebo.

Source of data: A randomized controlled trial with 303 adolescents with ADHD and a substance use disorder.

Disclosures: The trial was sponsored by the National Institute of Drug Abuse. The lead investigator reported no conflicts of interest.

LOS ANGELES – Psychostimulant treatment did not outperform placebo when structured cognitive-behavioral therapy was integrated into the treatment of adolescents with attention-deficit/hyperactivity disorder and substance use disorders.

In a 16-week, randomized, placebo-controlled trial, ADHD symptoms significantly improved and substance use declined regardless of whether adolescents received OROS-MPH (Concerta) or placebo, Dr. Paula Riggs said at the annual meeting of the American Academy of Addiction Psychiatry.

Rather than being seen as a negative trial, the study appears to speak to the usefulness of structured, individualized weekly CBT, said Dr. Riggs, the primary investigator of the 11-center trial sponsored by the National Institute of Drug Abuse and professor of psychiatry at the University of Colorado, Denver.

The trial enrolled 303 adolescents aged 13–18 who met DSM-IV criteria for ADHD and for at least substance use disorder (other than nicotine dependence, and excluding current opiate dependence or methamphetamine abuse or dependence).

The average age of participants was 16.5 years. About 80% of the participants were male, and 20% female. Whites constituted 64% of the medication arm and 55% of the placebo arm. Roughly a fourth of the subjects in each group were African American; 15% were Hispanic .

About one-third of subjects had ADHD-inattentive type; 67% had ADHD-combined type; and less than 2%, ADHD-hyperactive type.

Cannabis and alcohol use/dependence were the most commonly represented substance use disorders, although use and/or abuse of hallucinogens, opioids, cocaine, and amphetamines also were reported.

Adolescents with major depression, anxiety disorders, and/or conduct disorder were included in the trial, resulting in a high baseline level of psychopathology among participants. Almost 75% of the subjects completed the trial.

“We wanted to keep this real and generalizable,” Dr. Riggs said.

In the medication arm, 80% of 151 patients were compliant with doses, which were successfully titrated to 72 mg/daily in 96% and sustained at that dose in 86%.

Participants received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse.

An intent-to-treat analysis was used to calculate results.

“This was the shocker,” Dr. Riggs said. “We saw a clinically and statistically significant reduction in ADHD symptoms in both groups.”

Symptoms declined 46% in the medication group and 45% in the placebo group.

Parents reported symptom reductions of 26% and 30% in adolescents receiving active medication or placebo on a DSM-IV symptom checklist at 8 weeks, and 24% and 30.9% reductions at 16 weeks.

Past 28-day substance use reports declined by 6.1 days (43%) in the medication arm and 4.9 days (33%) in the placebo arm–a statistically insignificant between-group difference.

Slightly more negative drug screens–3.8 compared with 2.8–were found in adolescents assigned to receive active medication, and this group also showed greater improvements in problem-solving skills and focused-coping skills that had been addressed in CBT, Dr. Riggs reported.

Subjects deemed by investigators to be “medication responders” had twice as many negative drug screens as nonresponders or those receiving placebo.

Titrated OROS-MPH was “stunningly safe and well-tolerated” in the trial, with 11 serious adverse events, 7 of which occurred in the placebo group. The only event seen more frequently in the medication arm was limb injury, an event not considered to be related to the medication.

The trial results were inconsistent with the results of trials pitting psychostimulants against placebo in non–substance-abusing youth.

However, they were consistent with three previous controlled psychostimulant trials in non–substance-abusing adolescents when concurrent CBT was included for subjects in both the medication and placebo arms.

As in this trial, significant reductions were seen in ADHD in both groups, but with no significant advantage to medication over placebo.

Major Finding: Women who had a BMI higher than 25 were more likely than normal-weight women to die of breast cancer 10 or more years after diagnosis.

Data Source: Analysis of a registry of nearly 19,000 breast cancer patients.

Disclosures: The investigator received a grant from Novartis Pharmaceuticals, and GlaxoSmithKline sponsored her trip to the meeting. The study was conducted without support from pharmaceutical companies.

SAN ANTONIO — Obese women are substantially more likely than women of normal weight to die of breast cancer, a large Danish registry study concluded.

Researchers from the Danish Breast Cancer Cooperative Group examined extensive health information from nearly 19,000 women with breast cancer, with follow-up data available for up to 30 years post diagnosis.

Breast cancer patients who had body mass indexes greater than 25 kg/m

The disparity showed up early in the course of their disease, Dr. Marianne Ewertz reported at the annual San Antonio Breast Cancer Symposium.

“For distant metastasis, the curves begin to separate after 3 years,” said Dr. Ewertz, professor of oncology at Odense (Denmark) University Hospital.

By 5 years, women who had a BMI of 25-30 had an increased adjusted hazard ratio of developing distant metastasis of 1.42. For those who had a BMI greater than 30, the adjusted hazard ratio of distant metastasis beginning at 5 years was 1.46.

Women with a BMI of 25-30 were 26% more likely and those with a BMI greater than 30 were 38% more likely than normal-weight women to die of their disease 10 or more years after diagnosis, and more likely to die of other causes as well.

Heavier women in the study were older, were more likely to be postmenopausal, had larger tumors, had more positive lymph nodes, and had more tumor invasion into deep fascia than did those with a BMI less than 25. They also had more grade 3 tumors.

However, all of these factors were statistically accounted for in the multivariate analyses of distant metastasis and overall survival.

Poorer outcomes over time may indicate that adjuvant therapy is less effective in obese women than in normal-weight women, Dr. Ewertz suggested.

Inadequate dosing or biologic factors could account for the study's findings, said Dr. Michelle D. Holmes of the Dana-Farber/Harvard Cancer Center in Boston, who was the formal discussant of the presentation.

The impact of lifestyle factors on cancer risk can be “confounding” because they cannot be studied in prospective, randomized trials. Therefore, prospective observational evidence is gathered from huge, well-controlled population databases such as the Danish health registries.

“This is kind of as good as it gets, and it's pretty good,” Dr. Holmes said.

The findings add weight to previous smaller studies, most of which have also found associations between mortality and BMI.

The “vast amount of data” in the Danish registries “allows for a very detailed look at subgroups,” she said.

Dr. Holmes specifically highlighted findings that point to heightened risks of distant metastasis despite equivalent locoregional control, and “a loss of treatment benefit over time in the obese.”

The findings dovetail nicely with recent clinical literature on obese patients with breast cancer that documents profoundly reduced complete responses to neoadjuvant therapy and a two- to four fold-increased likelihood of receiving substandard doses of initial chemotherapy (J. Clin. Oncol. 2008;26:4072-7; J. Clin. Oncol. 2008;26:4060-2).

Social bias, a reluctance on the part of medical oncologists to prescribe full weight-based dosages of medications, and as-yet unidentified biologic differences each may play a role in the poorer outcomes of obese women, Dr. Holmes said.

Major Finding: Women who had a BMI higher than 25 were more likely than normal-weight women to die of breast cancer 10 or more years after diagnosis.

Data Source: Analysis of a registry of nearly 19,000 breast cancer patients.

Disclosures: The investigator received a grant from Novartis Pharmaceuticals, and GlaxoSmithKline sponsored her trip to the meeting. The study was conducted without support from pharmaceutical companies.

SAN ANTONIO — Obese women are substantially more likely than women of normal weight to die of breast cancer, a large Danish registry study concluded.

Researchers from the Danish Breast Cancer Cooperative Group examined extensive health information from nearly 19,000 women with breast cancer, with follow-up data available for up to 30 years post diagnosis.

Breast cancer patients who had body mass indexes greater than 25 kg/m

The disparity showed up early in the course of their disease, Dr. Marianne Ewertz reported at the annual San Antonio Breast Cancer Symposium.

“For distant metastasis, the curves begin to separate after 3 years,” said Dr. Ewertz, professor of oncology at Odense (Denmark) University Hospital.

By 5 years, women who had a BMI of 25-30 had an increased adjusted hazard ratio of developing distant metastasis of 1.42. For those who had a BMI greater than 30, the adjusted hazard ratio of distant metastasis beginning at 5 years was 1.46.

Women with a BMI of 25-30 were 26% more likely and those with a BMI greater than 30 were 38% more likely than normal-weight women to die of their disease 10 or more years after diagnosis, and more likely to die of other causes as well.

Heavier women in the study were older, were more likely to be postmenopausal, had larger tumors, had more positive lymph nodes, and had more tumor invasion into deep fascia than did those with a BMI less than 25. They also had more grade 3 tumors.

However, all of these factors were statistically accounted for in the multivariate analyses of distant metastasis and overall survival.

Poorer outcomes over time may indicate that adjuvant therapy is less effective in obese women than in normal-weight women, Dr. Ewertz suggested.

Inadequate dosing or biologic factors could account for the study's findings, said Dr. Michelle D. Holmes of the Dana-Farber/Harvard Cancer Center in Boston, who was the formal discussant of the presentation.

The impact of lifestyle factors on cancer risk can be “confounding” because they cannot be studied in prospective, randomized trials. Therefore, prospective observational evidence is gathered from huge, well-controlled population databases such as the Danish health registries.

“This is kind of as good as it gets, and it's pretty good,” Dr. Holmes said.

The findings add weight to previous smaller studies, most of which have also found associations between mortality and BMI.

The “vast amount of data” in the Danish registries “allows for a very detailed look at subgroups,” she said.

Dr. Holmes specifically highlighted findings that point to heightened risks of distant metastasis despite equivalent locoregional control, and “a loss of treatment benefit over time in the obese.”

The findings dovetail nicely with recent clinical literature on obese patients with breast cancer that documents profoundly reduced complete responses to neoadjuvant therapy and a two- to four fold-increased likelihood of receiving substandard doses of initial chemotherapy (J. Clin. Oncol. 2008;26:4072-7; J. Clin. Oncol. 2008;26:4060-2).

Social bias, a reluctance on the part of medical oncologists to prescribe full weight-based dosages of medications, and as-yet unidentified biologic differences each may play a role in the poorer outcomes of obese women, Dr. Holmes said.

Major Finding: Women who had a BMI higher than 25 were more likely than normal-weight women to die of breast cancer 10 or more years after diagnosis.

Data Source: Analysis of a registry of nearly 19,000 breast cancer patients.

Disclosures: The investigator received a grant from Novartis Pharmaceuticals, and GlaxoSmithKline sponsored her trip to the meeting. The study was conducted without support from pharmaceutical companies.

SAN ANTONIO — Obese women are substantially more likely than women of normal weight to die of breast cancer, a large Danish registry study concluded.

Researchers from the Danish Breast Cancer Cooperative Group examined extensive health information from nearly 19,000 women with breast cancer, with follow-up data available for up to 30 years post diagnosis.

Breast cancer patients who had body mass indexes greater than 25 kg/m

The disparity showed up early in the course of their disease, Dr. Marianne Ewertz reported at the annual San Antonio Breast Cancer Symposium.

“For distant metastasis, the curves begin to separate after 3 years,” said Dr. Ewertz, professor of oncology at Odense (Denmark) University Hospital.

By 5 years, women who had a BMI of 25-30 had an increased adjusted hazard ratio of developing distant metastasis of 1.42. For those who had a BMI greater than 30, the adjusted hazard ratio of distant metastasis beginning at 5 years was 1.46.

Women with a BMI of 25-30 were 26% more likely and those with a BMI greater than 30 were 38% more likely than normal-weight women to die of their disease 10 or more years after diagnosis, and more likely to die of other causes as well.

Heavier women in the study were older, were more likely to be postmenopausal, had larger tumors, had more positive lymph nodes, and had more tumor invasion into deep fascia than did those with a BMI less than 25. They also had more grade 3 tumors.

However, all of these factors were statistically accounted for in the multivariate analyses of distant metastasis and overall survival.

Poorer outcomes over time may indicate that adjuvant therapy is less effective in obese women than in normal-weight women, Dr. Ewertz suggested.

Inadequate dosing or biologic factors could account for the study's findings, said Dr. Michelle D. Holmes of the Dana-Farber/Harvard Cancer Center in Boston, who was the formal discussant of the presentation.

The impact of lifestyle factors on cancer risk can be “confounding” because they cannot be studied in prospective, randomized trials. Therefore, prospective observational evidence is gathered from huge, well-controlled population databases such as the Danish health registries.

“This is kind of as good as it gets, and it's pretty good,” Dr. Holmes said.

The findings add weight to previous smaller studies, most of which have also found associations between mortality and BMI.

The “vast amount of data” in the Danish registries “allows for a very detailed look at subgroups,” she said.

Dr. Holmes specifically highlighted findings that point to heightened risks of distant metastasis despite equivalent locoregional control, and “a loss of treatment benefit over time in the obese.”

The findings dovetail nicely with recent clinical literature on obese patients with breast cancer that documents profoundly reduced complete responses to neoadjuvant therapy and a two- to four fold-increased likelihood of receiving substandard doses of initial chemotherapy (J. Clin. Oncol. 2008;26:4072-7; J. Clin. Oncol. 2008;26:4060-2).

Social bias, a reluctance on the part of medical oncologists to prescribe full weight-based dosages of medications, and as-yet unidentified biologic differences each may play a role in the poorer outcomes of obese women, Dr. Holmes said.

SAN ANTONIO — Women who were moderate to heavy drinkers had a 1.3-fold increase in breast cancer recurrence, compared with those who abstained or drank only minimally, according to a study presented at the San Antonio Breast Cancer Symposium.

The highest risk was seen among the heaviest drinkers and overweight and/or post-menopausal survivors.

Researchers from Kaiser Permanente in Oakland, Calif. prospectively followed 1,897 women for 8 years following their diagnoses with early-stage breast cancer, studying lifestyle factors that might be associated with recurrence or death, either from cancer or other causes.

About half the cohort reported drinking alcohol. Ninety percent drank wine, 43% drank liquor, and 36% drank beer, said Marilyn L. Kwan, Ph.D., a research scientist with the large Northern California HMO.

In all, 18% of the cohort experienced a recurrence, and 17% of the cohort died, reported Dr. Kwan. Slightly more than half of the women who died succumbed to breast cancer, while 43% died from other causes.

Women who drank alcohol tended to be younger, thinner, better educated, and white, but statisticians accounted for these factors in their analysis.

After adjustment, survivors who drank at least the equivalent of 3–4 drinks per week (about a half drink per day) were 1.3 times more likely to have a recurrence of their cancer, compared with those who either did not drink or drank less than an average of 0.5 grams of alcohol per day. The results followed a positive dose-response curve, indicating that the more women drank, the more likely they were to experience a recurrence.

Women who drank less than 6 grams of alcohol per day (about a half-glass) had no increased recurrence risk.

When researchers examined subgroups of survivors, they found a 1.5-fold elevated risk among post-menopausal women, but no elevated risk among pre-menopausal women and a 1.58-fold increase in risk among overweight and obese women but no increase among normal-weight women.

Whether a survivor's breast cancer was estrogen-receptor positive or negative had no influence on her risk for recurrence if she drank alcohol.

The risk of death from breast cancer was elevated 1.5-fold among survivors who drank a mean of a half-glass of alcohol per day or more.

There was no association with death from all causes, and even a suggestion of survival protection among moderate to heavy drinkers, likely capturing the well-known cardiovascular benefits of modest alcohol consumption. Thus, the results leave unanswered the question of whether some women with breast cancer might ultimately benefit in terms of survival from modest alcohol consumption, particularly now that many women live for decades following a diagnosis.

“Our message to women with breast cancer may need to be as nuanced as our message to women without breast cancer,” said Dr. Michelle D. Holmes of the Dana-Farber/Harvard Cancer Center in Boston.

“Our results are consistent with alcohol's effect on increasing the risk of primary breast cancer,” Dr. Kwan said. “We do need the confirmation of a large, prospective study in breast cancer survivors before we can make any [definitive] lifestyle recommendations.”

Based on the signals offered in the study, however, women “should possibly consider limiting” their use of alcohol after a breast cancer diagnosis, realizing that the highest risk appears to be conferred on post-menopausal women and those who are overweight or obese, she said.

SAN ANTONIO — Women who were moderate to heavy drinkers had a 1.3-fold increase in breast cancer recurrence, compared with those who abstained or drank only minimally, according to a study presented at the San Antonio Breast Cancer Symposium.

The highest risk was seen among the heaviest drinkers and overweight and/or post-menopausal survivors.

Researchers from Kaiser Permanente in Oakland, Calif. prospectively followed 1,897 women for 8 years following their diagnoses with early-stage breast cancer, studying lifestyle factors that might be associated with recurrence or death, either from cancer or other causes.

About half the cohort reported drinking alcohol. Ninety percent drank wine, 43% drank liquor, and 36% drank beer, said Marilyn L. Kwan, Ph.D., a research scientist with the large Northern California HMO.

In all, 18% of the cohort experienced a recurrence, and 17% of the cohort died, reported Dr. Kwan. Slightly more than half of the women who died succumbed to breast cancer, while 43% died from other causes.

Women who drank alcohol tended to be younger, thinner, better educated, and white, but statisticians accounted for these factors in their analysis.

After adjustment, survivors who drank at least the equivalent of 3–4 drinks per week (about a half drink per day) were 1.3 times more likely to have a recurrence of their cancer, compared with those who either did not drink or drank less than an average of 0.5 grams of alcohol per day. The results followed a positive dose-response curve, indicating that the more women drank, the more likely they were to experience a recurrence.

Women who drank less than 6 grams of alcohol per day (about a half-glass) had no increased recurrence risk.

When researchers examined subgroups of survivors, they found a 1.5-fold elevated risk among post-menopausal women, but no elevated risk among pre-menopausal women and a 1.58-fold increase in risk among overweight and obese women but no increase among normal-weight women.

Whether a survivor's breast cancer was estrogen-receptor positive or negative had no influence on her risk for recurrence if she drank alcohol.

The risk of death from breast cancer was elevated 1.5-fold among survivors who drank a mean of a half-glass of alcohol per day or more.

There was no association with death from all causes, and even a suggestion of survival protection among moderate to heavy drinkers, likely capturing the well-known cardiovascular benefits of modest alcohol consumption. Thus, the results leave unanswered the question of whether some women with breast cancer might ultimately benefit in terms of survival from modest alcohol consumption, particularly now that many women live for decades following a diagnosis.

“Our message to women with breast cancer may need to be as nuanced as our message to women without breast cancer,” said Dr. Michelle D. Holmes of the Dana-Farber/Harvard Cancer Center in Boston.

“Our results are consistent with alcohol's effect on increasing the risk of primary breast cancer,” Dr. Kwan said. “We do need the confirmation of a large, prospective study in breast cancer survivors before we can make any [definitive] lifestyle recommendations.”

Based on the signals offered in the study, however, women “should possibly consider limiting” their use of alcohol after a breast cancer diagnosis, realizing that the highest risk appears to be conferred on post-menopausal women and those who are overweight or obese, she said.

SAN ANTONIO — Women who were moderate to heavy drinkers had a 1.3-fold increase in breast cancer recurrence, compared with those who abstained or drank only minimally, according to a study presented at the San Antonio Breast Cancer Symposium.

The highest risk was seen among the heaviest drinkers and overweight and/or post-menopausal survivors.

Researchers from Kaiser Permanente in Oakland, Calif. prospectively followed 1,897 women for 8 years following their diagnoses with early-stage breast cancer, studying lifestyle factors that might be associated with recurrence or death, either from cancer or other causes.

About half the cohort reported drinking alcohol. Ninety percent drank wine, 43% drank liquor, and 36% drank beer, said Marilyn L. Kwan, Ph.D., a research scientist with the large Northern California HMO.

In all, 18% of the cohort experienced a recurrence, and 17% of the cohort died, reported Dr. Kwan. Slightly more than half of the women who died succumbed to breast cancer, while 43% died from other causes.

Women who drank alcohol tended to be younger, thinner, better educated, and white, but statisticians accounted for these factors in their analysis.

After adjustment, survivors who drank at least the equivalent of 3–4 drinks per week (about a half drink per day) were 1.3 times more likely to have a recurrence of their cancer, compared with those who either did not drink or drank less than an average of 0.5 grams of alcohol per day. The results followed a positive dose-response curve, indicating that the more women drank, the more likely they were to experience a recurrence.

Women who drank less than 6 grams of alcohol per day (about a half-glass) had no increased recurrence risk.

When researchers examined subgroups of survivors, they found a 1.5-fold elevated risk among post-menopausal women, but no elevated risk among pre-menopausal women and a 1.58-fold increase in risk among overweight and obese women but no increase among normal-weight women.

Whether a survivor's breast cancer was estrogen-receptor positive or negative had no influence on her risk for recurrence if she drank alcohol.

The risk of death from breast cancer was elevated 1.5-fold among survivors who drank a mean of a half-glass of alcohol per day or more.

There was no association with death from all causes, and even a suggestion of survival protection among moderate to heavy drinkers, likely capturing the well-known cardiovascular benefits of modest alcohol consumption. Thus, the results leave unanswered the question of whether some women with breast cancer might ultimately benefit in terms of survival from modest alcohol consumption, particularly now that many women live for decades following a diagnosis.

“Our message to women with breast cancer may need to be as nuanced as our message to women without breast cancer,” said Dr. Michelle D. Holmes of the Dana-Farber/Harvard Cancer Center in Boston.

“Our results are consistent with alcohol's effect on increasing the risk of primary breast cancer,” Dr. Kwan said. “We do need the confirmation of a large, prospective study in breast cancer survivors before we can make any [definitive] lifestyle recommendations.”

Based on the signals offered in the study, however, women “should possibly consider limiting” their use of alcohol after a breast cancer diagnosis, realizing that the highest risk appears to be conferred on post-menopausal women and those who are overweight or obese, she said.

LOS ANGELES — A new nationwide study has begun to shed light on the complex relationship between personality disorders, and substance use onset and dependence.

The odds of alcohol dependence, drug abuse/dependence, and nicotine dependence were elevated for people with any personality disorder in the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a longitudinal study of more than 43,000 Americans, reported Deborah S. Hasin, Ph.D., professor of clinical public health at Columbia University New York.

Dr. Hasin unveiled results of a selective analysis of substance use prevalence and persistence data from NESARC Waves 1 (2001–2002) and 2 (2004–2005) during a symposium at the annual meeting of the American Academy of Addiction Psychiatrists.

For example, she found that having any personality disorder based on DSM-IV diagnostic criteria increased the odds of meeting criteria for alcohol dependence more than sevenfold at an initial interview during Wave 1 of the study.

The highest baseline rates of alcohol dependence were among individuals with schizotypal personality disorder, dependent personality disorder, or borderline personality disorder, Dr. Hasin said at the annual meeting of the American Academy of Addiction Psychiatrists.

The odds of drug abuse or dependence were elevated more than 13-fold for people with any personality disorder, 13.2, with the highest odds for current use seen among people with schizotypal (odds ratio, 13.2) or borderline personality disorders (see chart).

Nicotine dependence was nine times higher among people with personality disorders as other respondents.

People with schizotypal, borderline, or antisocial personality disorders who initially were identified as dependent on alcohol were at least twice as likely as others in the study to be persistently dependent 3 years later, even after adjusting for demographic factors and comorbid Axis I diagnoses.

The odds of chronic drug abuse also were elevated more than twofold for those with schizotypal or antisocial personality after adjustment.

The persistence of nicotine dependence was even more striking among people with personality disorders, with the odds among those with antisocial, borderline, obsessive/compulsive, and schizoid personality disorders elevated by 3.0, 2.0, 1.5, and 1.4, respectively, over other smokers interviewed in the study.

The study results might have implications for research, particularly with an eye toward substance abuse treatment modalities that might not be ideal for people with personality disorders, Dr. Hasin said.

Dr. Hasin's research and NESARC were government-funded studies. She reported no financial disclosures.

VITALS

Source Elsevier Global Medical News

LOS ANGELES — A new nationwide study has begun to shed light on the complex relationship between personality disorders, and substance use onset and dependence.

The odds of alcohol dependence, drug abuse/dependence, and nicotine dependence were elevated for people with any personality disorder in the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a longitudinal study of more than 43,000 Americans, reported Deborah S. Hasin, Ph.D., professor of clinical public health at Columbia University New York.

Dr. Hasin unveiled results of a selective analysis of substance use prevalence and persistence data from NESARC Waves 1 (2001–2002) and 2 (2004–2005) during a symposium at the annual meeting of the American Academy of Addiction Psychiatrists.

For example, she found that having any personality disorder based on DSM-IV diagnostic criteria increased the odds of meeting criteria for alcohol dependence more than sevenfold at an initial interview during Wave 1 of the study.

The highest baseline rates of alcohol dependence were among individuals with schizotypal personality disorder, dependent personality disorder, or borderline personality disorder, Dr. Hasin said at the annual meeting of the American Academy of Addiction Psychiatrists.

The odds of drug abuse or dependence were elevated more than 13-fold for people with any personality disorder, 13.2, with the highest odds for current use seen among people with schizotypal (odds ratio, 13.2) or borderline personality disorders (see chart).

Nicotine dependence was nine times higher among people with personality disorders as other respondents.

People with schizotypal, borderline, or antisocial personality disorders who initially were identified as dependent on alcohol were at least twice as likely as others in the study to be persistently dependent 3 years later, even after adjusting for demographic factors and comorbid Axis I diagnoses.

The odds of chronic drug abuse also were elevated more than twofold for those with schizotypal or antisocial personality after adjustment.

The persistence of nicotine dependence was even more striking among people with personality disorders, with the odds among those with antisocial, borderline, obsessive/compulsive, and schizoid personality disorders elevated by 3.0, 2.0, 1.5, and 1.4, respectively, over other smokers interviewed in the study.

The study results might have implications for research, particularly with an eye toward substance abuse treatment modalities that might not be ideal for people with personality disorders, Dr. Hasin said.

Dr. Hasin's research and NESARC were government-funded studies. She reported no financial disclosures.

VITALS

Source Elsevier Global Medical News

LOS ANGELES — A new nationwide study has begun to shed light on the complex relationship between personality disorders, and substance use onset and dependence.

The odds of alcohol dependence, drug abuse/dependence, and nicotine dependence were elevated for people with any personality disorder in the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a longitudinal study of more than 43,000 Americans, reported Deborah S. Hasin, Ph.D., professor of clinical public health at Columbia University New York.

Dr. Hasin unveiled results of a selective analysis of substance use prevalence and persistence data from NESARC Waves 1 (2001–2002) and 2 (2004–2005) during a symposium at the annual meeting of the American Academy of Addiction Psychiatrists.

For example, she found that having any personality disorder based on DSM-IV diagnostic criteria increased the odds of meeting criteria for alcohol dependence more than sevenfold at an initial interview during Wave 1 of the study.

The highest baseline rates of alcohol dependence were among individuals with schizotypal personality disorder, dependent personality disorder, or borderline personality disorder, Dr. Hasin said at the annual meeting of the American Academy of Addiction Psychiatrists.

The odds of drug abuse or dependence were elevated more than 13-fold for people with any personality disorder, 13.2, with the highest odds for current use seen among people with schizotypal (odds ratio, 13.2) or borderline personality disorders (see chart).

Nicotine dependence was nine times higher among people with personality disorders as other respondents.

People with schizotypal, borderline, or antisocial personality disorders who initially were identified as dependent on alcohol were at least twice as likely as others in the study to be persistently dependent 3 years later, even after adjusting for demographic factors and comorbid Axis I diagnoses.

The odds of chronic drug abuse also were elevated more than twofold for those with schizotypal or antisocial personality after adjustment.

The persistence of nicotine dependence was even more striking among people with personality disorders, with the odds among those with antisocial, borderline, obsessive/compulsive, and schizoid personality disorders elevated by 3.0, 2.0, 1.5, and 1.4, respectively, over other smokers interviewed in the study.

The study results might have implications for research, particularly with an eye toward substance abuse treatment modalities that might not be ideal for people with personality disorders, Dr. Hasin said.

Dr. Hasin's research and NESARC were government-funded studies. She reported no financial disclosures.

VITALS

Source Elsevier Global Medical News

Major finding: Significant improvement in ADHD symptoms and a sharp reduction in substance use were observed, regardless of whether adolescents received OROS-MPH (Concerta) or placebo.

Source of data: In a randomized controlled trial, 303 adolescents with ADHD and at least one substance use disorder, received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse. An intent to treat analysis was conducted to determine the results.

Disclosures: The 11-center trial was sponsored by the National Institute of Drug Abuse. The lead investigator reported no conflicts of interest.

LOS ANGELES — Psychostimulant treatment failed to outperform placebo in treating adolescents with comorbid attention-deficit/hyperactivity disorder and substance use disorders when structured cognitive-behavioral therapy was integrated into a randomized, placebo-controlled trial.

However, highly significant improvement in ADHD symptoms and a sharp reduction in substance use were observed, regardless of whether adolescents received OROS-MPH (Concerta) or placebo in the 16-week trial, reported Dr. Paula Riggs at the annual meeting of the American Academy of Addiction Psychiatry.

Rather than being seen as a negative trial, the study appears to speak to the usefulness of structured, individualized weekly CBT, said Dr. Riggs, primary investigator of the 11-center trial sponsored by the National Institute of Drug Abuse and professor of psychiatry at the University of Colorado, Denver.

The trial enrolled 303 adolescents aged 13–18 who met DSM-IV criteria for ADHD and for at least one substance use disorder (other than nicotine dependence, and excluding current opiate dependence or methamphetamine abuse or dependence).

The average age of participants was 16.5 years. About 80% were male and 20% female. Whites constituted 64% of the medication arm and 55% of the placebo arm. Roughly a fourth of the subjects in each group were African American; 15% were Hispanic.

About one-third of subjects had ADHD-inattentive type; 67% had ADHD-combined type; and less than 2%, ADHD-hyperactive type.

Cannabis and alcohol use/dependence were the most commonly represented substance use disorders, although use and/or abuse of hallucinogens, opioids, cocaine, and amphetamines also were reported.

Adolescents with major depression, anxiety disorders, and/or conduct disorder were included in the trial, resulting in a high baseline level of psychopathology among participants.

Despite this severity, almost 75% of adolescents completed the trial.

In the medication arm, 80% of 151 patients were compliant with doses, which were successfully titrated to 72 mg/daily in 96% and sustained at that dose in 86%.

Participants received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse.

In an intent-to-treat analysis, symptoms of ADHD declined 46% in the medication group and 45% in the placebo group.

Parents reported symptom reductions of 26% and 30% in adolescents receiving active medication or placebo on a DSM-IV symptom checklist at 8 weeks, and 24% and 30.9% reductions at 16 weeks.

Past 28-day substance use reports declined by 6.1 days (43%) in the medication arm and 4.9 days (33%) in the placebo arm—a statistically insignificant between-group difference.

Slightly more negative drug screens—3.8 compared with 2.8—were found in adolescents assigned to receive active medication, and this group also showed greater improvements in problem-solving skills and focused-coping skills that had been addressed in CBT, Dr. Riggs reported.

Subjects deemed by investigators to be “medication responders” had twice as many negative drug screens as nonresponders or those receiving placebo.

Titrated OROS-MPH was “stunningly safe and well-tolerated” in the trial, with 11 serious adverse events, 7 of which occurred in the placebo group. The only event seen more frequently in the medication arm was limb injury, an event not considered to be related to the medication.

The results were inconsistent with trials pitting psychostimulants against placebo in non–substance-abusing youth. However, they were consistent with three controlled psychostimulant trials in the non–substance-abusing adolescents when concurrent CBT was included for subjects in both the medication and placebo arms.

As in this trial, significant reductions were seen in ADHD in both groups, but with no significant advantage to medication over placebo.

Trials of psychostimulants show that 20%-50% of adolescents continue to have functionally impairing symptoms despite medication.

Dr. Riggs reported no relevant financial conflicts of interest.

Major finding: Significant improvement in ADHD symptoms and a sharp reduction in substance use were observed, regardless of whether adolescents received OROS-MPH (Concerta) or placebo.

Source of data: In a randomized controlled trial, 303 adolescents with ADHD and at least one substance use disorder, received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse. An intent to treat analysis was conducted to determine the results.

Disclosures: The 11-center trial was sponsored by the National Institute of Drug Abuse. The lead investigator reported no conflicts of interest.

LOS ANGELES — Psychostimulant treatment failed to outperform placebo in treating adolescents with comorbid attention-deficit/hyperactivity disorder and substance use disorders when structured cognitive-behavioral therapy was integrated into a randomized, placebo-controlled trial.

However, highly significant improvement in ADHD symptoms and a sharp reduction in substance use were observed, regardless of whether adolescents received OROS-MPH (Concerta) or placebo in the 16-week trial, reported Dr. Paula Riggs at the annual meeting of the American Academy of Addiction Psychiatry.

Rather than being seen as a negative trial, the study appears to speak to the usefulness of structured, individualized weekly CBT, said Dr. Riggs, primary investigator of the 11-center trial sponsored by the National Institute of Drug Abuse and professor of psychiatry at the University of Colorado, Denver.

The trial enrolled 303 adolescents aged 13–18 who met DSM-IV criteria for ADHD and for at least one substance use disorder (other than nicotine dependence, and excluding current opiate dependence or methamphetamine abuse or dependence).

The average age of participants was 16.5 years. About 80% were male and 20% female. Whites constituted 64% of the medication arm and 55% of the placebo arm. Roughly a fourth of the subjects in each group were African American; 15% were Hispanic.

About one-third of subjects had ADHD-inattentive type; 67% had ADHD-combined type; and less than 2%, ADHD-hyperactive type.

Cannabis and alcohol use/dependence were the most commonly represented substance use disorders, although use and/or abuse of hallucinogens, opioids, cocaine, and amphetamines also were reported.

Adolescents with major depression, anxiety disorders, and/or conduct disorder were included in the trial, resulting in a high baseline level of psychopathology among participants.

Despite this severity, almost 75% of adolescents completed the trial.

In the medication arm, 80% of 151 patients were compliant with doses, which were successfully titrated to 72 mg/daily in 96% and sustained at that dose in 86%.

Participants received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse.

In an intent-to-treat analysis, symptoms of ADHD declined 46% in the medication group and 45% in the placebo group.

Parents reported symptom reductions of 26% and 30% in adolescents receiving active medication or placebo on a DSM-IV symptom checklist at 8 weeks, and 24% and 30.9% reductions at 16 weeks.

Past 28-day substance use reports declined by 6.1 days (43%) in the medication arm and 4.9 days (33%) in the placebo arm—a statistically insignificant between-group difference.

Slightly more negative drug screens—3.8 compared with 2.8—were found in adolescents assigned to receive active medication, and this group also showed greater improvements in problem-solving skills and focused-coping skills that had been addressed in CBT, Dr. Riggs reported.

Subjects deemed by investigators to be “medication responders” had twice as many negative drug screens as nonresponders or those receiving placebo.

Titrated OROS-MPH was “stunningly safe and well-tolerated” in the trial, with 11 serious adverse events, 7 of which occurred in the placebo group. The only event seen more frequently in the medication arm was limb injury, an event not considered to be related to the medication.

The results were inconsistent with trials pitting psychostimulants against placebo in non–substance-abusing youth. However, they were consistent with three controlled psychostimulant trials in the non–substance-abusing adolescents when concurrent CBT was included for subjects in both the medication and placebo arms.

As in this trial, significant reductions were seen in ADHD in both groups, but with no significant advantage to medication over placebo.

Trials of psychostimulants show that 20%-50% of adolescents continue to have functionally impairing symptoms despite medication.

Dr. Riggs reported no relevant financial conflicts of interest.

Major finding: Significant improvement in ADHD symptoms and a sharp reduction in substance use were observed, regardless of whether adolescents received OROS-MPH (Concerta) or placebo.

Source of data: In a randomized controlled trial, 303 adolescents with ADHD and at least one substance use disorder, received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse. An intent to treat analysis was conducted to determine the results.

Disclosures: The 11-center trial was sponsored by the National Institute of Drug Abuse. The lead investigator reported no conflicts of interest.

LOS ANGELES — Psychostimulant treatment failed to outperform placebo in treating adolescents with comorbid attention-deficit/hyperactivity disorder and substance use disorders when structured cognitive-behavioral therapy was integrated into a randomized, placebo-controlled trial.

However, highly significant improvement in ADHD symptoms and a sharp reduction in substance use were observed, regardless of whether adolescents received OROS-MPH (Concerta) or placebo in the 16-week trial, reported Dr. Paula Riggs at the annual meeting of the American Academy of Addiction Psychiatry.

Rather than being seen as a negative trial, the study appears to speak to the usefulness of structured, individualized weekly CBT, said Dr. Riggs, primary investigator of the 11-center trial sponsored by the National Institute of Drug Abuse and professor of psychiatry at the University of Colorado, Denver.

The trial enrolled 303 adolescents aged 13–18 who met DSM-IV criteria for ADHD and for at least one substance use disorder (other than nicotine dependence, and excluding current opiate dependence or methamphetamine abuse or dependence).

The average age of participants was 16.5 years. About 80% were male and 20% female. Whites constituted 64% of the medication arm and 55% of the placebo arm. Roughly a fourth of the subjects in each group were African American; 15% were Hispanic.

About one-third of subjects had ADHD-inattentive type; 67% had ADHD-combined type; and less than 2%, ADHD-hyperactive type.

Cannabis and alcohol use/dependence were the most commonly represented substance use disorders, although use and/or abuse of hallucinogens, opioids, cocaine, and amphetamines also were reported.

Adolescents with major depression, anxiety disorders, and/or conduct disorder were included in the trial, resulting in a high baseline level of psychopathology among participants.

Despite this severity, almost 75% of adolescents completed the trial.

In the medication arm, 80% of 151 patients were compliant with doses, which were successfully titrated to 72 mg/daily in 96% and sustained at that dose in 86%.

Participants received either the active (titrated) drug or placebo along with weekly, individual CBT using a standardized manual targeting drug abuse.

In an intent-to-treat analysis, symptoms of ADHD declined 46% in the medication group and 45% in the placebo group.

Parents reported symptom reductions of 26% and 30% in adolescents receiving active medication or placebo on a DSM-IV symptom checklist at 8 weeks, and 24% and 30.9% reductions at 16 weeks.

Past 28-day substance use reports declined by 6.1 days (43%) in the medication arm and 4.9 days (33%) in the placebo arm—a statistically insignificant between-group difference.

Slightly more negative drug screens—3.8 compared with 2.8—were found in adolescents assigned to receive active medication, and this group also showed greater improvements in problem-solving skills and focused-coping skills that had been addressed in CBT, Dr. Riggs reported.

Subjects deemed by investigators to be “medication responders” had twice as many negative drug screens as nonresponders or those receiving placebo.

Titrated OROS-MPH was “stunningly safe and well-tolerated” in the trial, with 11 serious adverse events, 7 of which occurred in the placebo group. The only event seen more frequently in the medication arm was limb injury, an event not considered to be related to the medication.

The results were inconsistent with trials pitting psychostimulants against placebo in non–substance-abusing youth. However, they were consistent with three controlled psychostimulant trials in the non–substance-abusing adolescents when concurrent CBT was included for subjects in both the medication and placebo arms.

As in this trial, significant reductions were seen in ADHD in both groups, but with no significant advantage to medication over placebo.

Trials of psychostimulants show that 20%-50% of adolescents continue to have functionally impairing symptoms despite medication.

Dr. Riggs reported no relevant financial conflicts of interest.

Even the experts say it's a tough call to diagnose a child–particularly a young child–with bipolar disorder, making for enigmatic medication decisions in the pediatric population.

“It's always difficult, and the diagnosis is the most important thing before beginning treatment,” said Dr. Kiki Chang, founder and director of the Pediatric Bipolar Disorders Program at Stanford (Calif.) University.

“It's a diagnosis I've been looking at for the better part of 35 years, and I still find it very hard,” agreed Dr. Gabrielle Carlson, professor of psychiatry and behavioral science at the State University of New York at Stony Brook. When it comes to very young children–under the age of 10–“you get into really dicey territory.”

The problem is that diagnostic criteria for bipolar I, bipolar II, and bipolar disorder not otherwise specified in the DSM-IV were developed based on research in adults and may be exceedingly difficult to apply to children.

It's been said that all normal 4-year-olds look a bit bipolar, with wild mood swings, euphoria, racing thoughts, grandiosity, periods of extreme creative and physical energy, reports of monsters under their beds, and a seemingly reduced need for sleep (by parental report).

Clinical experience and many longitudinal studies do point to profoundly troubled behavior in some children that does have a flavor of bipolar disorder, and many of these children do go on to have unequivocal bipolar disorder in adulthood.

In the most recently published report from Dr. Barbara Geller's group at Washington University, St. Louis, 44% of young adults identified in childhood with bipolar I disorder symptoms had a manic episode after the age of 18, a rate 13–44 times higher than in the general population (Arch. Gen. Psychiatry 2008;65:1125–33).

However, community diagnoses are notoriously fallible, illustrated by the fact that half of the children referred to the Pediatric Bipolar Disorders Program at Stanford do not have the disease. Often, they prove to have unipolar depression marked by irritability. Or pervasive developmental disorder. Or autism, Dr. Chang said.

Significant language impairment and developmental delays complicated the diagnosis of one of Dr. Carlson's patients who, at age 5, nearly got killed running alongside cars because he thought he could run faster than anyone else. He jumped out of a tree, and displayed other examples of “clearly grandiose” behavior. When he was 7, she asked him about chasing traffic and he said, “I was little at the time.” The tree? “I never did that again,” he said. Later, he boasted he could swim across Long Island Sound–a claim he later traced to his grandfather's musing that he could “swim like a fish.”

By age 10, it was clear that child's diagnosis was autism. “He always had interesting ways of putting the world together. But he wasn't delusional when pressed,” said Dr. Carlson.

Being precise about a diagnosis in children with unusual, shocking, and/or harmful behaviors would make little difference if medication management was the same whether a child has bipolar disorder or one of the many differential diagnoses masquerading as bipolar disorder, such as depression, attention-deficit/hyperactivity disorder (ADHD), pervasive developmental disorder, anxiety disorders, Tourette syndrome, or the autism spectrum disorders. But it's not.

“The question of diagnosis makes a big difference,” Dr. Carlson said. In the case of “diagnostic ambiguity” between severe ADHD and bipolar disorder, she chooses to treat the ADHD first, unless there are clear signs of mania.

One advantage of treating ADHD with stimulants is their quick action, sometimes providing rapid evidence of improvement. Plus, their use over many years in multiple clinical trials in children provides reassurance of their safety and guidance about dosing.

It can be difficult to start on a conservative course of action in the face of extreme behavior and symptoms, but Dr. Carlson remembers the lesson she learned from an adolescent who had been unsuccessfully treated with anticonvulsants and atypical antipsychotics for 5 years.

So frightening were the child's early meltdowns that the mother and a community psychiatrist feared that stimulant medication would be contraindicated, with the potential of making a “nightmare” situation worse. But after years of treatment, the youth's symptoms worsened and he was hospitalized. She decided to taper his medications and try traditional stimulants for ADHD, along with time-outs and consistent behavior-modification strategies. “He responded very nicely,” she said. “What was heartwarming was how proud he was that he had control of himself. The mother told me, 'I was able to be a regular mom.'”

Dr. Chang also favors treating ADHD when the diagnosis tends to lean that way (and doesn't include frank mania). He starts with standard doses of short-acting methylphenidate, even when one or more parents has a history of bipolar disorder.

Whereas experts once believed that stimulants would “tip” most children with undiagnosed bipolar disorder into manic episodes, the consensus now is that this is a rare occurrence and fairly easily managed, he said. “Just stop the stimulants.”

An alternative therapy for ADHD symptoms might be atomoxetine (Strattera), a hydrochloride salt, which Dr. Chang considers if stimulants aggravate hyperactive behavior.

If a traditional therapy for ADHD reduces symptoms, both specialists said they feel comfortable in closely monitoring a child through adolescence, when more typical symptoms of bipolar disorder may emerge.

In looking at studies of patients under the age of 10, Dr. Carlson today sees few data to support the use of “powerful, fat-making antipsychotics” for the rest of the child's life (assuming the child proves to have bipolar disorder). She believes there is support in the literature for the short-term use of atypical antipsychotics for management of aggression associated with many diagnoses, however.

Of note, an international review of five longitudinal studies of the children of parents with bipolar disorder found little evidence of classically defined mania in prepubertal children (J. Can. Acad. Child Adoles. Psychiatry 2009;18:200–5).

In the study by Dr. Anne Duffy of Dalhousie University in Halifax, Nova Scotia, children who went on to develop mood disorders seemed to follow a fairly predictable course leading to a first activated episode in adolescence or early adulthood–nonspecific anxiety and sleep problems in childhood, then mood swings in adolescence, with depressive episodes predating mania by several years.

Dr. Chang said while prepubertal mania has been described, it is likely less common than postpubertal mania, “and harder to diagnose given the natural neurodevelopmental propensity of young children to rapidly cycle with their moods.”

Many experts have called for an evaluation of what symptoms constitute a diagnosis of bipolar disorder in children, rather than trying to shade adult-oriented symptoms to fit children. A precise definition would tailor subjects enrolled in clinical trials so that findings would be meaningful and applicable to the children seen in clinical practice, hopefully pointing the way to an evidence-based approach to pharmacotherapy.

In the meantime, treatment guidelines developed by an expert consensus panel that included Dr. Carlson and Dr. Chang offer diagnostic support and provide algorithms for treatment of bipolar I disorder with or without psychosis in children and adolescents (J. Amer. Acad. Child Adolesc. Psychiatry 2005;44:213–35).

A practice parameter with 11 specific recommendations also offers comprehensive guidance to clinicians (J. Am. Acad. Child Adolesc. Psychiatry 2007; 46:107–25).

Dr. Carlson and Dr. Chang describe personal prescribing patterns that conform to these guidelines, most often selecting lithium or another mood stabilizer or an atypical antipsychotic as first line monotherapy, but sometimes recommending combination therapy.

Lithium, valproate, aripiprazole, and quetiapine all figure prominently in his initial treatment strategies, with quetiapine edging out the others if sleep regulation is a particular problem.

A child presenting with rather classic euphoric mania might make Dr. Chang prescribe lithium first, whereas a more chronic picture of predominantly irritable mania or a mixed state would make him lean toward an atypical antipsychotic.

Depression remains a challenge in youthful populations as well as in adults, and Dr. Chang is generally reluctant to prescribe selective serotonin reuptake inhibitors if there is a reasonable suspicion that the child has bipolar disorder.

“We stay away from them if at all possible,” concerned that they may precipitate a manic episode.

He might consider lamotrigine for a child who is already overweight, dosing it very cautiously at first, especially in smaller children, and being cognizant of the risk of a severe rash. He also now considers adding metformin to the regimen of any child or adolescent who gains considerable weight on the atypicals.

Dr. Carlson cited the same sorts of considerations. Atypical antipsychotics, for example, might be her treatment of choice for a child whose most concerning symptoms are aggression and emotional lability, because these drugs tend to ameliorate these symptoms regardless of whether the ultimate diagnosis is bipolar disorder.

Most children with bipolar disorder end up requiring combination therapy for their symptoms, plus occasional agents to manage side effects.

As the regimens grow more complex, the already limited evidence base shrinks to nearly nil, Dr. Chang said. Side effect patterns in children are also poorly understood. “Cognitive side effects have not really been studied at all. We don't have much evidence to guide us, and compared with adults, the cognitive piece is really important,” he said.

When the adult literature suggests a problematic cognitive picture, as in the case of topiramate, Dr. Chang tends to avoid prescribing that drug.

Both clinicians emphasized the need to address the child's environment within the context of his or her symptoms, incorporating psychotherapeutic and educational interventions in any treatment strategy. “Medication in the absence of the others [interventions] is rarely successful,” Dr. Chang said.

Dr. Carlson reported that she is a consultant for many of the pharmaceutical companies conducting research into bipolar disorder and ADHD and is currently participating in a study of lamotrigine (GlaxoSmithKline). Dr. Chang said he has received research or grant support from, or served on the speakers bureau for, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly & Co., Otsuka America Pharmaceutical Inc., and GlaxoSmithKline.

By Betsy Bates. Share your thoughts and suggestions at cpnews@elsevier.com

Few data support the use of 'powerful, fat-making antipsychotics' for the rest of the child's life.

Source DR. CARLSON

Even the experts say it's a tough call to diagnose a child–particularly a young child–with bipolar disorder, making for enigmatic medication decisions in the pediatric population.

“It's always difficult, and the diagnosis is the most important thing before beginning treatment,” said Dr. Kiki Chang, founder and director of the Pediatric Bipolar Disorders Program at Stanford (Calif.) University.

“It's a diagnosis I've been looking at for the better part of 35 years, and I still find it very hard,” agreed Dr. Gabrielle Carlson, professor of psychiatry and behavioral science at the State University of New York at Stony Brook. When it comes to very young children–under the age of 10–“you get into really dicey territory.”

The problem is that diagnostic criteria for bipolar I, bipolar II, and bipolar disorder not otherwise specified in the DSM-IV were developed based on research in adults and may be exceedingly difficult to apply to children.

It's been said that all normal 4-year-olds look a bit bipolar, with wild mood swings, euphoria, racing thoughts, grandiosity, periods of extreme creative and physical energy, reports of monsters under their beds, and a seemingly reduced need for sleep (by parental report).

Clinical experience and many longitudinal studies do point to profoundly troubled behavior in some children that does have a flavor of bipolar disorder, and many of these children do go on to have unequivocal bipolar disorder in adulthood.

In the most recently published report from Dr. Barbara Geller's group at Washington University, St. Louis, 44% of young adults identified in childhood with bipolar I disorder symptoms had a manic episode after the age of 18, a rate 13–44 times higher than in the general population (Arch. Gen. Psychiatry 2008;65:1125–33).

However, community diagnoses are notoriously fallible, illustrated by the fact that half of the children referred to the Pediatric Bipolar Disorders Program at Stanford do not have the disease. Often, they prove to have unipolar depression marked by irritability. Or pervasive developmental disorder. Or autism, Dr. Chang said.

Significant language impairment and developmental delays complicated the diagnosis of one of Dr. Carlson's patients who, at age 5, nearly got killed running alongside cars because he thought he could run faster than anyone else. He jumped out of a tree, and displayed other examples of “clearly grandiose” behavior. When he was 7, she asked him about chasing traffic and he said, “I was little at the time.” The tree? “I never did that again,” he said. Later, he boasted he could swim across Long Island Sound–a claim he later traced to his grandfather's musing that he could “swim like a fish.”

By age 10, it was clear that child's diagnosis was autism. “He always had interesting ways of putting the world together. But he wasn't delusional when pressed,” said Dr. Carlson.

Being precise about a diagnosis in children with unusual, shocking, and/or harmful behaviors would make little difference if medication management was the same whether a child has bipolar disorder or one of the many differential diagnoses masquerading as bipolar disorder, such as depression, attention-deficit/hyperactivity disorder (ADHD), pervasive developmental disorder, anxiety disorders, Tourette syndrome, or the autism spectrum disorders. But it's not.

“The question of diagnosis makes a big difference,” Dr. Carlson said. In the case of “diagnostic ambiguity” between severe ADHD and bipolar disorder, she chooses to treat the ADHD first, unless there are clear signs of mania.

One advantage of treating ADHD with stimulants is their quick action, sometimes providing rapid evidence of improvement. Plus, their use over many years in multiple clinical trials in children provides reassurance of their safety and guidance about dosing.

It can be difficult to start on a conservative course of action in the face of extreme behavior and symptoms, but Dr. Carlson remembers the lesson she learned from an adolescent who had been unsuccessfully treated with anticonvulsants and atypical antipsychotics for 5 years.

So frightening were the child's early meltdowns that the mother and a community psychiatrist feared that stimulant medication would be contraindicated, with the potential of making a “nightmare” situation worse. But after years of treatment, the youth's symptoms worsened and he was hospitalized. She decided to taper his medications and try traditional stimulants for ADHD, along with time-outs and consistent behavior-modification strategies. “He responded very nicely,” she said. “What was heartwarming was how proud he was that he had control of himself. The mother told me, 'I was able to be a regular mom.'”

Dr. Chang also favors treating ADHD when the diagnosis tends to lean that way (and doesn't include frank mania). He starts with standard doses of short-acting methylphenidate, even when one or more parents has a history of bipolar disorder.

Whereas experts once believed that stimulants would “tip” most children with undiagnosed bipolar disorder into manic episodes, the consensus now is that this is a rare occurrence and fairly easily managed, he said. “Just stop the stimulants.”

An alternative therapy for ADHD symptoms might be atomoxetine (Strattera), a hydrochloride salt, which Dr. Chang considers if stimulants aggravate hyperactive behavior.

If a traditional therapy for ADHD reduces symptoms, both specialists said they feel comfortable in closely monitoring a child through adolescence, when more typical symptoms of bipolar disorder may emerge.

In looking at studies of patients under the age of 10, Dr. Carlson today sees few data to support the use of “powerful, fat-making antipsychotics” for the rest of the child's life (assuming the child proves to have bipolar disorder). She believes there is support in the literature for the short-term use of atypical antipsychotics for management of aggression associated with many diagnoses, however.

Of note, an international review of five longitudinal studies of the children of parents with bipolar disorder found little evidence of classically defined mania in prepubertal children (J. Can. Acad. Child Adoles. Psychiatry 2009;18:200–5).

In the study by Dr. Anne Duffy of Dalhousie University in Halifax, Nova Scotia, children who went on to develop mood disorders seemed to follow a fairly predictable course leading to a first activated episode in adolescence or early adulthood–nonspecific anxiety and sleep problems in childhood, then mood swings in adolescence, with depressive episodes predating mania by several years.

Dr. Chang said while prepubertal mania has been described, it is likely less common than postpubertal mania, “and harder to diagnose given the natural neurodevelopmental propensity of young children to rapidly cycle with their moods.”

Many experts have called for an evaluation of what symptoms constitute a diagnosis of bipolar disorder in children, rather than trying to shade adult-oriented symptoms to fit children. A precise definition would tailor subjects enrolled in clinical trials so that findings would be meaningful and applicable to the children seen in clinical practice, hopefully pointing the way to an evidence-based approach to pharmacotherapy.

In the meantime, treatment guidelines developed by an expert consensus panel that included Dr. Carlson and Dr. Chang offer diagnostic support and provide algorithms for treatment of bipolar I disorder with or without psychosis in children and adolescents (J. Amer. Acad. Child Adolesc. Psychiatry 2005;44:213–35).

A practice parameter with 11 specific recommendations also offers comprehensive guidance to clinicians (J. Am. Acad. Child Adolesc. Psychiatry 2007; 46:107–25).

Dr. Carlson and Dr. Chang describe personal prescribing patterns that conform to these guidelines, most often selecting lithium or another mood stabilizer or an atypical antipsychotic as first line monotherapy, but sometimes recommending combination therapy.

Lithium, valproate, aripiprazole, and quetiapine all figure prominently in his initial treatment strategies, with quetiapine edging out the others if sleep regulation is a particular problem.

A child presenting with rather classic euphoric mania might make Dr. Chang prescribe lithium first, whereas a more chronic picture of predominantly irritable mania or a mixed state would make him lean toward an atypical antipsychotic.

Depression remains a challenge in youthful populations as well as in adults, and Dr. Chang is generally reluctant to prescribe selective serotonin reuptake inhibitors if there is a reasonable suspicion that the child has bipolar disorder.

“We stay away from them if at all possible,” concerned that they may precipitate a manic episode.

He might consider lamotrigine for a child who is already overweight, dosing it very cautiously at first, especially in smaller children, and being cognizant of the risk of a severe rash. He also now considers adding metformin to the regimen of any child or adolescent who gains considerable weight on the atypicals.

Dr. Carlson cited the same sorts of considerations. Atypical antipsychotics, for example, might be her treatment of choice for a child whose most concerning symptoms are aggression and emotional lability, because these drugs tend to ameliorate these symptoms regardless of whether the ultimate diagnosis is bipolar disorder.

Most children with bipolar disorder end up requiring combination therapy for their symptoms, plus occasional agents to manage side effects.

As the regimens grow more complex, the already limited evidence base shrinks to nearly nil, Dr. Chang said. Side effect patterns in children are also poorly understood. “Cognitive side effects have not really been studied at all. We don't have much evidence to guide us, and compared with adults, the cognitive piece is really important,” he said.

When the adult literature suggests a problematic cognitive picture, as in the case of topiramate, Dr. Chang tends to avoid prescribing that drug.

Both clinicians emphasized the need to address the child's environment within the context of his or her symptoms, incorporating psychotherapeutic and educational interventions in any treatment strategy. “Medication in the absence of the others [interventions] is rarely successful,” Dr. Chang said.

Dr. Carlson reported that she is a consultant for many of the pharmaceutical companies conducting research into bipolar disorder and ADHD and is currently participating in a study of lamotrigine (GlaxoSmithKline). Dr. Chang said he has received research or grant support from, or served on the speakers bureau for, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly & Co., Otsuka America Pharmaceutical Inc., and GlaxoSmithKline.

By Betsy Bates. Share your thoughts and suggestions at cpnews@elsevier.com

Few data support the use of 'powerful, fat-making antipsychotics' for the rest of the child's life.

Source DR. CARLSON

Even the experts say it's a tough call to diagnose a child–particularly a young child–with bipolar disorder, making for enigmatic medication decisions in the pediatric population.

“It's always difficult, and the diagnosis is the most important thing before beginning treatment,” said Dr. Kiki Chang, founder and director of the Pediatric Bipolar Disorders Program at Stanford (Calif.) University.

“It's a diagnosis I've been looking at for the better part of 35 years, and I still find it very hard,” agreed Dr. Gabrielle Carlson, professor of psychiatry and behavioral science at the State University of New York at Stony Brook. When it comes to very young children–under the age of 10–“you get into really dicey territory.”

The problem is that diagnostic criteria for bipolar I, bipolar II, and bipolar disorder not otherwise specified in the DSM-IV were developed based on research in adults and may be exceedingly difficult to apply to children.

It's been said that all normal 4-year-olds look a bit bipolar, with wild mood swings, euphoria, racing thoughts, grandiosity, periods of extreme creative and physical energy, reports of monsters under their beds, and a seemingly reduced need for sleep (by parental report).

Clinical experience and many longitudinal studies do point to profoundly troubled behavior in some children that does have a flavor of bipolar disorder, and many of these children do go on to have unequivocal bipolar disorder in adulthood.

In the most recently published report from Dr. Barbara Geller's group at Washington University, St. Louis, 44% of young adults identified in childhood with bipolar I disorder symptoms had a manic episode after the age of 18, a rate 13–44 times higher than in the general population (Arch. Gen. Psychiatry 2008;65:1125–33).

However, community diagnoses are notoriously fallible, illustrated by the fact that half of the children referred to the Pediatric Bipolar Disorders Program at Stanford do not have the disease. Often, they prove to have unipolar depression marked by irritability. Or pervasive developmental disorder. Or autism, Dr. Chang said.

Significant language impairment and developmental delays complicated the diagnosis of one of Dr. Carlson's patients who, at age 5, nearly got killed running alongside cars because he thought he could run faster than anyone else. He jumped out of a tree, and displayed other examples of “clearly grandiose” behavior. When he was 7, she asked him about chasing traffic and he said, “I was little at the time.” The tree? “I never did that again,” he said. Later, he boasted he could swim across Long Island Sound–a claim he later traced to his grandfather's musing that he could “swim like a fish.”

By age 10, it was clear that child's diagnosis was autism. “He always had interesting ways of putting the world together. But he wasn't delusional when pressed,” said Dr. Carlson.

Being precise about a diagnosis in children with unusual, shocking, and/or harmful behaviors would make little difference if medication management was the same whether a child has bipolar disorder or one of the many differential diagnoses masquerading as bipolar disorder, such as depression, attention-deficit/hyperactivity disorder (ADHD), pervasive developmental disorder, anxiety disorders, Tourette syndrome, or the autism spectrum disorders. But it's not.

“The question of diagnosis makes a big difference,” Dr. Carlson said. In the case of “diagnostic ambiguity” between severe ADHD and bipolar disorder, she chooses to treat the ADHD first, unless there are clear signs of mania.

One advantage of treating ADHD with stimulants is their quick action, sometimes providing rapid evidence of improvement. Plus, their use over many years in multiple clinical trials in children provides reassurance of their safety and guidance about dosing.

It can be difficult to start on a conservative course of action in the face of extreme behavior and symptoms, but Dr. Carlson remembers the lesson she learned from an adolescent who had been unsuccessfully treated with anticonvulsants and atypical antipsychotics for 5 years.

So frightening were the child's early meltdowns that the mother and a community psychiatrist feared that stimulant medication would be contraindicated, with the potential of making a “nightmare” situation worse. But after years of treatment, the youth's symptoms worsened and he was hospitalized. She decided to taper his medications and try traditional stimulants for ADHD, along with time-outs and consistent behavior-modification strategies. “He responded very nicely,” she said. “What was heartwarming was how proud he was that he had control of himself. The mother told me, 'I was able to be a regular mom.'”

Dr. Chang also favors treating ADHD when the diagnosis tends to lean that way (and doesn't include frank mania). He starts with standard doses of short-acting methylphenidate, even when one or more parents has a history of bipolar disorder.

Whereas experts once believed that stimulants would “tip” most children with undiagnosed bipolar disorder into manic episodes, the consensus now is that this is a rare occurrence and fairly easily managed, he said. “Just stop the stimulants.”

An alternative therapy for ADHD symptoms might be atomoxetine (Strattera), a hydrochloride salt, which Dr. Chang considers if stimulants aggravate hyperactive behavior.

If a traditional therapy for ADHD reduces symptoms, both specialists said they feel comfortable in closely monitoring a child through adolescence, when more typical symptoms of bipolar disorder may emerge.

In looking at studies of patients under the age of 10, Dr. Carlson today sees few data to support the use of “powerful, fat-making antipsychotics” for the rest of the child's life (assuming the child proves to have bipolar disorder). She believes there is support in the literature for the short-term use of atypical antipsychotics for management of aggression associated with many diagnoses, however.

Of note, an international review of five longitudinal studies of the children of parents with bipolar disorder found little evidence of classically defined mania in prepubertal children (J. Can. Acad. Child Adoles. Psychiatry 2009;18:200–5).

In the study by Dr. Anne Duffy of Dalhousie University in Halifax, Nova Scotia, children who went on to develop mood disorders seemed to follow a fairly predictable course leading to a first activated episode in adolescence or early adulthood–nonspecific anxiety and sleep problems in childhood, then mood swings in adolescence, with depressive episodes predating mania by several years.

Dr. Chang said while prepubertal mania has been described, it is likely less common than postpubertal mania, “and harder to diagnose given the natural neurodevelopmental propensity of young children to rapidly cycle with their moods.”

Many experts have called for an evaluation of what symptoms constitute a diagnosis of bipolar disorder in children, rather than trying to shade adult-oriented symptoms to fit children. A precise definition would tailor subjects enrolled in clinical trials so that findings would be meaningful and applicable to the children seen in clinical practice, hopefully pointing the way to an evidence-based approach to pharmacotherapy.

In the meantime, treatment guidelines developed by an expert consensus panel that included Dr. Carlson and Dr. Chang offer diagnostic support and provide algorithms for treatment of bipolar I disorder with or without psychosis in children and adolescents (J. Amer. Acad. Child Adolesc. Psychiatry 2005;44:213–35).

A practice parameter with 11 specific recommendations also offers comprehensive guidance to clinicians (J. Am. Acad. Child Adolesc. Psychiatry 2007; 46:107–25).

Dr. Carlson and Dr. Chang describe personal prescribing patterns that conform to these guidelines, most often selecting lithium or another mood stabilizer or an atypical antipsychotic as first line monotherapy, but sometimes recommending combination therapy.

Lithium, valproate, aripiprazole, and quetiapine all figure prominently in his initial treatment strategies, with quetiapine edging out the others if sleep regulation is a particular problem.

A child presenting with rather classic euphoric mania might make Dr. Chang prescribe lithium first, whereas a more chronic picture of predominantly irritable mania or a mixed state would make him lean toward an atypical antipsychotic.

Depression remains a challenge in youthful populations as well as in adults, and Dr. Chang is generally reluctant to prescribe selective serotonin reuptake inhibitors if there is a reasonable suspicion that the child has bipolar disorder.

“We stay away from them if at all possible,” concerned that they may precipitate a manic episode.

He might consider lamotrigine for a child who is already overweight, dosing it very cautiously at first, especially in smaller children, and being cognizant of the risk of a severe rash. He also now considers adding metformin to the regimen of any child or adolescent who gains considerable weight on the atypicals.

Dr. Carlson cited the same sorts of considerations. Atypical antipsychotics, for example, might be her treatment of choice for a child whose most concerning symptoms are aggression and emotional lability, because these drugs tend to ameliorate these symptoms regardless of whether the ultimate diagnosis is bipolar disorder.

Most children with bipolar disorder end up requiring combination therapy for their symptoms, plus occasional agents to manage side effects.

As the regimens grow more complex, the already limited evidence base shrinks to nearly nil, Dr. Chang said. Side effect patterns in children are also poorly understood. “Cognitive side effects have not really been studied at all. We don't have much evidence to guide us, and compared with adults, the cognitive piece is really important,” he said.

When the adult literature suggests a problematic cognitive picture, as in the case of topiramate, Dr. Chang tends to avoid prescribing that drug.

Both clinicians emphasized the need to address the child's environment within the context of his or her symptoms, incorporating psychotherapeutic and educational interventions in any treatment strategy. “Medication in the absence of the others [interventions] is rarely successful,” Dr. Chang said.

Dr. Carlson reported that she is a consultant for many of the pharmaceutical companies conducting research into bipolar disorder and ADHD and is currently participating in a study of lamotrigine (GlaxoSmithKline). Dr. Chang said he has received research or grant support from, or served on the speakers bureau for, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly & Co., Otsuka America Pharmaceutical Inc., and GlaxoSmithKline.

By Betsy Bates. Share your thoughts and suggestions at cpnews@elsevier.com

Few data support the use of 'powerful, fat-making antipsychotics' for the rest of the child's life.

Source DR. CARLSON

Fears and misconceptions about influenza vaccination became apparent in a survey of health care workers conducted at a large tertiary children's hospital in the Midwestern United States.

Researchers in Kansas City, Mo., administered a 44-question survey to 63 physicians, 135 nurses, and 376 allied health care workers at a 317-bed children's hospital where seasonal influenza immunization rates are high, Dr. Mary Anne Jackson said at a press briefing during the annual meeting of the Infectious Diseases Society of America (IDSA).

The survey revealed “significant gaps in knowledge” about influenza transmission, nosocomial spread, and vaccine efficacy and safety among all levels of health care professionals.

The results were “somewhat surprising” for a highly educated, highly immunized group of health care workers who are known to be at high risk of acquiring seasonal influenza and passing it on to vulnerable patients, said Dr. Jackson, chief of infectious diseases at Children's Mercy Hospital in Kansas City.

Physicians were significantly more likely than nurses or other health care workers to know that they are at high risk of influenza, that the vaccine prevents spread of the disease, and that it is a safe vaccine for adults and children.

Compared with physicians, other health care workers were significantly more likely to erroneously believe that the vaccine can cause influenza.

Further, many allied health care workers and nurses also believed, incorrectly, that an individual must be symptomatic to transmit the influenza virus.

About 75% of physicians advocated policies mandating influenza immunization among health care workers, compared with fewer than half of nurses or allied health care professionals surveyed.

Mandating influenza immunization for health care workers, a highly controversial proposition briefly enacted in New York State in response to the H1N1 influenza pandemic this year, was rescinded by New York Gov. David A. Paterson on Oct. 22. The governor's office stated that the mandatory vaccination policy for health care workers was dropped due to shortages of vaccine for high-risk populations. Widespread protests, however, were speculated to have played a role in the decision as well.

Based on her study findings and recent public responses to H1N1 vaccine mandates for health care workers, Dr. Jackson concluded that “mandates are going to be difficult.”

On the other hand, educational efforts and campaigns aimed at getting health care workers immunized “have failed dismally in most institutions.” At Children's Mercy Hospital, a vigorous campaign conducted over several years finally achieved an 85% influenza vaccine rate among employees, compared with an average 40% rate among health care workers across the country.

The rising immunization rate in her institution proved to have a ripple effect, she said. When health care workers were vaccinated against the seasonal influenza virus, their children also were more likely to receive the vaccine.

Dr. Jackson reported no relevant financial disclosures.

Educational campaigns aimed at getting health care workers immunized 'have failed dismally in most institutions.'

Source DR. JACKSON

Fears and misconceptions about influenza vaccination became apparent in a survey of health care workers conducted at a large tertiary children's hospital in the Midwestern United States.

Researchers in Kansas City, Mo., administered a 44-question survey to 63 physicians, 135 nurses, and 376 allied health care workers at a 317-bed children's hospital where seasonal influenza immunization rates are high, Dr. Mary Anne Jackson said at a press briefing during the annual meeting of the Infectious Diseases Society of America (IDSA).

The survey revealed “significant gaps in knowledge” about influenza transmission, nosocomial spread, and vaccine efficacy and safety among all levels of health care professionals.

The results were “somewhat surprising” for a highly educated, highly immunized group of health care workers who are known to be at high risk of acquiring seasonal influenza and passing it on to vulnerable patients, said Dr. Jackson, chief of infectious diseases at Children's Mercy Hospital in Kansas City.

Physicians were significantly more likely than nurses or other health care workers to know that they are at high risk of influenza, that the vaccine prevents spread of the disease, and that it is a safe vaccine for adults and children.

Compared with physicians, other health care workers were significantly more likely to erroneously believe that the vaccine can cause influenza.

Further, many allied health care workers and nurses also believed, incorrectly, that an individual must be symptomatic to transmit the influenza virus.

About 75% of physicians advocated policies mandating influenza immunization among health care workers, compared with fewer than half of nurses or allied health care professionals surveyed.

Mandating influenza immunization for health care workers, a highly controversial proposition briefly enacted in New York State in response to the H1N1 influenza pandemic this year, was rescinded by New York Gov. David A. Paterson on Oct. 22. The governor's office stated that the mandatory vaccination policy for health care workers was dropped due to shortages of vaccine for high-risk populations. Widespread protests, however, were speculated to have played a role in the decision as well.

Based on her study findings and recent public responses to H1N1 vaccine mandates for health care workers, Dr. Jackson concluded that “mandates are going to be difficult.”

On the other hand, educational efforts and campaigns aimed at getting health care workers immunized “have failed dismally in most institutions.” At Children's Mercy Hospital, a vigorous campaign conducted over several years finally achieved an 85% influenza vaccine rate among employees, compared with an average 40% rate among health care workers across the country.

The rising immunization rate in her institution proved to have a ripple effect, she said. When health care workers were vaccinated against the seasonal influenza virus, their children also were more likely to receive the vaccine.

Dr. Jackson reported no relevant financial disclosures.

Educational campaigns aimed at getting health care workers immunized 'have failed dismally in most institutions.'

Source DR. JACKSON

Fears and misconceptions about influenza vaccination became apparent in a survey of health care workers conducted at a large tertiary children's hospital in the Midwestern United States.

Researchers in Kansas City, Mo., administered a 44-question survey to 63 physicians, 135 nurses, and 376 allied health care workers at a 317-bed children's hospital where seasonal influenza immunization rates are high, Dr. Mary Anne Jackson said at a press briefing during the annual meeting of the Infectious Diseases Society of America (IDSA).

The survey revealed “significant gaps in knowledge” about influenza transmission, nosocomial spread, and vaccine efficacy and safety among all levels of health care professionals.

The results were “somewhat surprising” for a highly educated, highly immunized group of health care workers who are known to be at high risk of acquiring seasonal influenza and passing it on to vulnerable patients, said Dr. Jackson, chief of infectious diseases at Children's Mercy Hospital in Kansas City.

Physicians were significantly more likely than nurses or other health care workers to know that they are at high risk of influenza, that the vaccine prevents spread of the disease, and that it is a safe vaccine for adults and children.

Compared with physicians, other health care workers were significantly more likely to erroneously believe that the vaccine can cause influenza.

Further, many allied health care workers and nurses also believed, incorrectly, that an individual must be symptomatic to transmit the influenza virus.

About 75% of physicians advocated policies mandating influenza immunization among health care workers, compared with fewer than half of nurses or allied health care professionals surveyed.

Mandating influenza immunization for health care workers, a highly controversial proposition briefly enacted in New York State in response to the H1N1 influenza pandemic this year, was rescinded by New York Gov. David A. Paterson on Oct. 22. The governor's office stated that the mandatory vaccination policy for health care workers was dropped due to shortages of vaccine for high-risk populations. Widespread protests, however, were speculated to have played a role in the decision as well.

Based on her study findings and recent public responses to H1N1 vaccine mandates for health care workers, Dr. Jackson concluded that “mandates are going to be difficult.”

On the other hand, educational efforts and campaigns aimed at getting health care workers immunized “have failed dismally in most institutions.” At Children's Mercy Hospital, a vigorous campaign conducted over several years finally achieved an 85% influenza vaccine rate among employees, compared with an average 40% rate among health care workers across the country.

The rising immunization rate in her institution proved to have a ripple effect, she said. When health care workers were vaccinated against the seasonal influenza virus, their children also were more likely to receive the vaccine.

Dr. Jackson reported no relevant financial disclosures.

Educational campaigns aimed at getting health care workers immunized 'have failed dismally in most institutions.'

Source DR. JACKSON