User login
While family physicians play a leading role in caring for patients with major depression, the quality of that care that could be greatly improved. A 1997 to 1998 survey of a national sample of adults with depressive or anxiety disorders revealed that 83% of these patients visited a health care provider.1 Of this total, 84% were treated by primary care clinicians, compared with 16% who were treated by mental health professionals. However, about 90% of those cared for by mental health professionals received treatment that met criteria for adequacy outlined in treatment guidelines, compared with 19% of those cared for by primary care professionals.
A critical role for family physicians is to integrate treatment of depression with that of other conditions, especially in light of the association of depression with a variety of chronic diseases. The Institute of Medicine has concluded that depression is strongly associated with the occurrence of, and death following, myocardial infarctions.2 In diabetes, depression is associated with a 2% increase in glycosylated hemoglobin levels3 and can predict occurrence of diabetic complications. Additionally, chronic illnesses may, in themselves, exacerbate depression several fold.
Primary care clinicians are ideally positioned to serve as the central health care providers for patients with major depression. These physicians have many attributes that support this role, including their longitudinal relationship with patients, response to undifferentiated problems, frequent use of the biopsychosocial model, and ability to integrate care of mental and medical conditions. However, challenges in fulfilling this role also exist, including difficulties in recognizing patients with major depression, developing an adequate diagnostic initial assessment, implementing effective short- and long-term treatment and management strategies, and integrating care of depression with that of other conditions affecting patients.4 This article will review each of these challenges.
Recognition of major depression
DeGruy has eloquently described the barriers to recognition and management of mental disorders in primary care, including infrequent use of diagnostic criteria, concern regarding treatment effectiveness, availability of time and resources, the presence of other pressing clinical problems, and issues of third-party reimbursement and other organizational concerns.4
Family physicians and their patients often do not recognize somatic symptoms as originating from depression. In one study, primary care physicians correctly identified 94% of depressed patients presenting with psychological complaints, but they failed to recognize the psychiatric nature of somatic complaints in about half of the patients. This finding is of concern because 83% of depressed patients presented with somatic complaints.5
The attribution patients assign to their problems can also contribute to lack of recognition. In one general practice study, patients’ attributions were classified as somatizing (5%), psychologizing (23%), normalizing (48%), or no predominate attribution (24%).6 For example, patients in this study might attribute fatigue to anemia (somatizing), emotional exhaustion (psychologizing), or being over-extended (normalizing). The likelihood of a missed diagnosis in patients who met criteria for depression or anxiety was strongly associated with attribution: Physicians diagnosed 72% of psychologizing patients accurately, but they reported a correct diagnosis in only 17% of somatizing patients, 15% of normalizing patients, and 31% of patients with no predominate attribution.
Initial diagnostic assessment
The United States Preventive Services Task Force suggests that primary care physicians screen for major depression. The Task Force recommends using 2 simple questions about mood and anhedonia (Table 1) that are generally as effective as longer instruments.7 The Patient Health Questionnaire-9 (PHQ-9) or the longer Prime-MD can be used for further evaluation of patients who respond positively to either question, thus helping to both confirm the diagnosis of depression and measure severity.8,9 Other instruments include the Beck Depression Inventory,10 the Zung scale,11 and the General Health Questionnaire.12 These tools take longer to administer, are not specific in measuring the criteria for major depression, and do not measure severity well.
In family practices, pregnant and postpartum women represent a special population at increased risk for depression.13 About 5% of middle class women and up to one quarter of low income women experience postpartum depression.14 In about half, onset of the depressive disorder occurs before delivery.15 Women who have previously suffered postpartum depression are at high risk, as are those with histories of depression or premenstrual dysphoric disorder. The Edinburgh Postnatal Depression Scale is a useful 10-item self-report instrument available in Spanish and English (Table 1).16,17 Similar instruments have not been developed for pregnant women.
A patient who responds positively to the 2 screening questions in Table 1 or to another screening approach should be further evaluated to confirm the diagnosis of major depression. Many primary care clinicians do this through unstructured history taking. Others use an instrument such as the previously discussed PHQ-9. This tool offers an advantage because it provides a reliable symptom assessment, measures severity, and can be repeated over time to evaluate therapeutic response.8
The physician should consider bereavement and substance abuse as possible causes of depression; bereaved patients who continue to meet criteria for major depression at 2 months often benefit from treatment. By that time, the sadness, poor concentration, and other symptoms associated with normal grief are no longer constant and occur in waves brought on by memories. Conversely, persons also suffering from depression report these symptoms as enduring and autonomous.18
The primary care physician also should inquire about agitation and symptoms of anxiety disorders. These are experienced by 85% of depressed patients; 50% have comorbid anxiety disorders.19-21 Identification of such comorbidity is helpful in determining treatment, evaluating response, and managing patients over the long term. The Prime-MD, available in multiple languages, is also useful for screening for both anxiety and substance abuse, which can complicate both the recognition and treatment of comorbid depression.9
Sexual function is often affected by depression. The physician should inquire about sexual arousal, erection or lubrication, and orgasm during the initial assessment.22 Approximately 50% of women and 40% of men with major depression report sexual-arousal problems, and 15% to 20% report orgasm problems during the month prior to diagnosis.23 Further questioning can assess whether this dysfunction is caused by another disorder (eg, diabetes) or whether it is part of the depressive syndrome. This provides a baseline for later assessment of side effects and treatment effectiveness, and it communicates to the patient that the physician will be attentive to this area. In discussing sexual function with depressed patients, it may be helpful to tell patients that a study of the effectiveness of treatment of depression with selective serotonin reuptake inhibitors (SSRIs) found that patients reported modestly improved sexual function with treatment.24
TABLE 1
Screening for depression
| Outpatient adults | |
| |
| Postpartum women (Edinburgh Postnatal Depression Scale) | |
1. I have been able to laugh and see the funny side of things
| 6. Things have been getting on top of me
|
2. I have looked forward with enjoyment to things
| 7. I have been so unhappy that I have had difficulty sleeping
|
3. I have blamed myself unnecessarily when things went wrong
| 8. I have felt sad or miserable
|
4. I have been anxious or worried for no good reason
| 9. I have been so unhappy that I have been crying
|
5. I have felt scared or panicky for no very good reason
| 10. The thought of harming myself has occurred to me
|
| Reprinted with permission, from Cox JL et al. British Journal of Psychiatry. 1987; 150:782-786. | |
Management of major depression
The acute management of the patient with major depression includes patient education, shared decision-making regarding a treatment modality, supportive counseling, and treatment-specific counseling.25 Education and counseling should extend over the initial weeks of treatment and be combined with monitoring response, identifying and managing any treatment-emergent side effects, and adjusting medications. Long-term management goals include attaining full remission of symptoms, assisting the patient to return to full functional status, integrating depression care with the treatment of other chronic illnesses, maintaining or tapering pharmacologic treatment, and monitoring for and preventing relapse or recurrence.
Education
Education should help patients understand and accept the diagnosis, reduce any stigma they or their families might attach to major depression, and build increased adherence to subsequent treatment.26 It might be helpful to provide a brief explanation of the biologic basis of depression (including biochemical changes in brain function and “chemical imbalances” of serotonin and other neurotransmitters). Explaining pharmacotherapeutic effects (if medication is desired) as mechanisms to help rebalance brain chemistry further emphasizes the biologic basis of depression and decreases any perceptions that depression is a result of moral or character weakness. This educational message should also stress that antidepressants are not habit-forming or addictive, are not “uppers” or “downers,” and are not tranquilizers. The physician also should convey a positive prognosis but note that several weeks and, possibly, adjustments in treatments, may be required. For patients choosing antidepressants, the McArthur Foundation Initiative has identified 7 key educational messages (Table 2).27
TABLE 2
Key messages for patient education about depression
|
Counseling
Patients often benefit from counseling regarding sleep, exercise, and substance use. Many patients with depression experience early morning awakening. Those with agitated depression also often experience delayed sleep onset associated with worry. Providing the patient with information on basic sleep hygiene, exercise, and encouraging abstinence from or moderation in consumption of alcohol might all help.28-30 Additionally, sleep disturbances can indicate the possibility of comorbid disorders. A report that a patient fears going to sleep because of nightmares suggests posttraumatic stress disorder.
For some patients, counseling by the family physician or through referral may be a helpful treatment adjunct. Often depressed patients have deficient coping mechanisms and need assistance in developing strategies to resolve issues in their life. Principles used in cognitive behavioral therapy might be helpful in patient education and counseling.31 These include problem-solving strategies to resolve stressful concerns and cognitive techniques to identify and correct distorted or maladaptive thought patterns.29
As patients respond to depression treatment, an additional component of primary-care-based counseling should target reinvolvement with pleasurable social and physical activities. This may simply involve identifying activities the patient enjoyed prior to the onset of depression but has since stopped, and focusing on the steps required to reactivate these interests.
Shared decision-making with regard to treatment will improve subsequent patient adherence.27 Treatment options include psychotherapy, particularly cognitive behavioral therapy, pharmacotherapy, and electroconvulsive therapy. The latter should be considered for severely depressed patients, particularly persons with few social supports who are at significant risk of suicide.25
Cognitive behavioral therapy and other psychotherapies can show effectiveness equal to that of pharmacotherapy, although response usually lags by a month to 6 weeks compared with that attained by pharmacotherapy.32 For moderately to severely depressed patients, pharmacotherapy is the treatment of choice in part because of its more rapid onset of action.25
Pharmacotherapy
Pharmacotherapy, most often in the form of an SSRI, is the treatment of choice for depression as a result of patient preference, insurance coverage limitations, or time constraints. In choosing an anti-depressant, the family physician should be guided by effectiveness and potential for drug–drug interactions and for both short-and long-term side effects.33
Tricyclics, the SSRIs, and other newer antidepressants offer similar efficacy.34 While efficacy assesses outcome under ideal treatment conditions, the primary care physician is more concerned with effectiveness, defined as the proportion of patients started on an antidepressant during routine clinical practice who attain lasting benefit. Effectiveness includes consideration of patients who discontinue treatment because of side effects or drug–drug interactions, as well as those who do not obtain adequate therapeutic response. Since about 25% of patients discontinue SSRIs because of side effects, this is an important concern.24 Few studies have been conducted comparing the effectiveness of antidepressants.
Drug–drug interactions are mediated predominately by the cytochrome P450 isoenzymes responsible for drug metabolism in the liver.35-37 The 2D6 isoenzyme is responsible for 50% of drug metabolism in the liver; the 3A4 isoenzyme is responsible for another 30%.38 As a clinical example of the importance of such inhibition, codeine requires 2D6-mediated metabolism to become morphine and is ineffective for pain in many patients who are prescribed a 2D6 inhibitor. Patients receiving such agents also can have a 300% to 400% increase in blood levels of previously stable ß-blockers. Paroxetine and fluoxetine, the two SSRIs that strongly inhibit the 2D6 isoenzyme, cause clinically significant interactions; fluoxetine is also a moderate inhibitor of the 3A4 isoenzyme.35 Because of the number of potential drug–drug interactions through these isoenzymes, physicians must check for interactions before prescribing these medications or adding other new medications in patients already receiving these agents. This also is a consideration for patients who might require additional medications acutely, for instance in response to a cardiac or other emergency.
Side effects of concern include gastrointestinal effects, particularly nausea, and central nervous system (CNS) effects, including anxiety and agitation, sleep disturbance, and tremor. When these occur, they often decrease rapidly over the first 1 to 3 weeks. If severe, they can be managed by a temporary dosage decrease. For patients with significant CNS side effects, altering the timing of the daily dose might provide relief from daytime somnolence or agitation or from nighttime insomnia.
Long-term side effects of concern include weight gain and sexual dysfunction. While other SSRIs have low rates for weight gain, paroxetine causes a weight gain of more than 7% (about 10 lbs for a patient of average weight) in 20% to 25% of patients.39 Some element of sexual dysfunction, most often delayed orgasm, is estimated to occur in 30% to 40% of individuals receiving SSRIs.40,41 Management options include delaying dosage of agents with a half-life of about 24 hours (escitalopram, citalopram, sertraline).42 For instance, an individual who usually takes one of these agents in the morning may delay a day’s dose until after engaging in sexual intercourse in the evening. While open-label studies support augmentation, particularly with bupropion or buspirone, the few small randomized double-blind trials available suggest that positive results should be interpreted with caution.43 Alternatively, patients may benefit from sildenafil44 or a switch to a non-SSRI antidepressant.
While management of side effects presents one option, the best clinical approach may be to select an agent with minimal side-effect potential. In double-blind randomized trials, escitalopram, a new SSRI treatment option, was demonstrated to require treatment termination in less than 5% of recipients at its usual dose of 10 mg, a rate no different from that of placebo.45 In contrast, rates of 15% to 30% have been reported for other SSRIs and newer antidepressants at the time of their initial release.
Adjusting treatment
One recent primary care trial examined the effectiveness of 3 SSRIs: fluoxetine, sertraline, and paroxetine. At the time this study was designed, citalopram was not in common use. While about 75% of patients attained remission, only 40% to 50% of patients were maintained on the first prescribed agent.24 Additionally, about 20% of depression “treatment resistance” resulted because patients did not fill their prescriptions or adhere to treatment.46 For patients who do not respond within the first month, increasing the dosage is appropriate.47 About 25% of patients respond to this adjustment.48 For patients who do not respond, reassessment of the diagnosis, as well as assessment of potential psychiatric comorbidities and suicidal ideation, is indicated. For nonresponders, and for those with intolerable side effects, switching to a second SSRI is a reasonable next step.49 About 50% of patients switched to a second agent respond.50 For those who do not respond, the primary care physician might consider a second medication switch or psychiatric consultation.
Further treatment adjustment is indicated for patients who experience partial response. This might take the form of augmentation with psychotherapy51 or with another agent.52 Lithium and thyroid hormone (often as 25 to 50 mg T3 daily) are the most frequently used options, although stimulants, other antidepressants, and atypical antipsychotics are all of value in some patients.48,49,53
When indicated, treatment should be discontinued by tapering the dose over several weeks to months, depending on the duration and severity of past episodes. Patients should be educated to be alert for recurrence. They should also be monitored for recurrence and restarted on full-dose therapy if this occurs. If patients stop therapy abruptly, the likelihood of withdrawal symptoms (agitation, irritability, dizziness, ataxia, nausea, paresthesias, sleep disturbances) is highly related to the half-life of the SSRI.39 For paroxetine, which has the shortest half-life, withdrawal is frequent; the extended release preparation does not decrease the likelihood of withdrawal. Withdrawal symptoms are infrequent (< 2%) for sertraline, citalopram, and escitalopram, and they do not occur with fluoxetine.
Duration of treatment
A major challenge in family practice is maintaining patient adherence to treatment for the recommended interval to prevent relapse and to avoid recurrence in those with a history of prior episodes. In one study, 25% to 33% of primary care patients stopped depression therapy within 1 month and over 40% within 3 months. Additionally, 62% failed to inform their physicians.54 Depression also adversely affects compliance with treatment of comorbid medical conditions; in one meta-analysis, depression increased noncompliance 3-fold.54
For the first lifetime episode, the recommended duration of treatment is 6 to 9 months (4 to 6 months after recovery).55 Longer therapy is appropriate for those with comorbid anxiety disorders, severe initial symptoms, difficulty in attaining therapeutic response, deficient social support, or a history of substance abuse, as well as for older adults. For patients with 3 or more previous episodes, long-term maintenance therapy is recommended.55 For those with even one past episode, extended maintenance therapy might be beneficial. Maintenance therapy should be at the full dose required to attain initial response. In one study, only about 20% to 30% (depending on the treatment) experienced recurrence over 3 years if maintained at full dose, compared with 70% maintained at half the initial treatment dose, and 78% of those receiving placebo.56 For women who have previously suffered from postpartum depression, postpartum prophylaxis can be very effective. In one randomized trial, 62.5% of women on place-bo experienced recurrence compared with only 6.7% of those receiving prophylaxis.57
Practice strategies to improve care
A number of primary care investigators have demonstrated the value of practice management and quality improvement techniques to increase the portion of patients who achieve and maintain response to depression therapy. These studies share an approach of “active management” to promote adherence to treatment guidelines.58-63 For instance, Simon and colleagues demonstrated the value of initial and monthly phone contact.64
Active management techniques include the following:
- Initial and ongoing patient education and counseling, as discussed above
- Patient involvement and agreement in treatment choice
- Initial phone contact to assure the prescription has been filled and initial dose taken
- Periodic contact to inquire about adherence, treatment response, side effects, and to answer patient questions
- Adjustment of therapy for those not responding adequately by 4 to 6 weeks
- Establishment of a collaborative relationship with a psychiatrist for consultation and telephone advice
Additionally, primary care clinicians may find it helpful to add depression to their medical record preventive health maintenance flow chart, especially for patients with any past history of depression. Using the PHQ-9 can be beneficial in providing both the patient and physician with an objective measure of monitoring response and remission.
Conclusions
Effective and available treatments can have a major beneficial impact on patients with depression. To be maximally effective, primary care clinicians must actively manage the care of their depressed patients, using screening strategies to recognize depression in addition to targeted educational messages and active follow-up to improve treatment adherence. Long-term maintenance treatment prevents further recurrences in those who have already experienced multiple episodes. Choice of treatment should be guided by patient preference. For pharmacologic agents, selection should be based on effectiveness, likelihood of side effects and resultant premature discontinuation, and potential for drug–drug interaction. The majority of individuals with depression are managed solely in primary-care settings. With adequate treatment, remission of symptoms, significant improvement in quality of life, and return to full function at home and at work can be attained.
1. Young AS, Klap R, Sherbourne CD, Wells KB. The quality of care for depressive and anxiety disorders in the United States. Arch Gen Psychiatry. 2001;58:55-61.
2. Institute of Medicine (U.S.). Committee on Health and Behavior: Research Practice and Policy. Health and Behavior: The Interplay of Biological, Behavioral, and Societal Influences. Washington, DC: National Academy Press. 2001.
3. Lustman PJ, Griffith LS, Freedland KE, Clouse RE. The course of major depression in diabetes. Gen Hosp Psychiatry. 1997;19:138-143.
4. deGruy F, III. Mental health care in the primary care setting. In: Donaldson MS, ed. Primary Care: America’s Health in a New Era. Washington, DC: National Academy Press; 1996;285-311.
5. Bridges KW, Goldberg DP. Somatic presentation of DSM III psychiatric disorders in primary care. J Psychosom Res. 1985;29:563-569.
6. Kessler D, Lloyd K, Lewis G, Gray DP. Cross sectional study of symptom attribution and recognition of depression and anxiety in primary care. BMJ. 1999;318:436-439.
7. Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression: two questions are as good as many. J Gen Intern Med. 1997;12:439-445.
8. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606-613.
9. Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999;282:1737-1744.
10. Steer RA, Cavalieri TA, Leonard DM, Beck AT. Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders. Gen Hosp Psychiatry. 1999;21:106-111.
11. Biggs JT, Wylie LT, Ziegler VE. Validity of the Zung Self-rating Depression Scale. Br J Psychiatry. 1978;132:381-385.
12. Goldberg DP, Gater R, Sartorius N, et al. The validity of two versions of the GHQ in the WHO study of mental illness in general health care. Psychol Med. 1997;27:191-197.
13. Susman JL. Postpartum depressive disorders. J Fam Pract. 1996;43(6 suppl):S17-24.
14. O’Hara MW, Schlechte JA, Lewis DA, Varner MW. Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables. J Abnorm Psychol. 1991;100:63-73.
15. Yonkers KA, Ramin SM, Rush AJ, et al. Onset and persistence of postpartum depression in an inner-city maternal health clinic system. Am J Psychiatry. 2001;158:1856-1863.
16. Georgiopoulos AM, Bryan TL, Wollan P, Yawn BP. Routine screening for postpartum depression. J Fam Pract. 2001;50:117-122.
17. Eberhard-Gran M, Eskild A, Tambs K, Opjordsmoen S, Samuelsen SO. Review of validation studies of the Edinburgh Postnatal Depression Scale. Acta Psychiatr Scand. 2001;104:243-249.
18. Osterweis M, Solomon F, Green M. Institute of Medicine (U.S.). Committee for the Study of Health Consequences of the Stress of Bereavement. Bereavement: Reactions, Consequences, and Care. Washington, DC: National Academy Press; 1984.
19. Keller MB, Hanks DL. The natural history and heterogeneity of depressive disorders: implications for rational antidepressant therapy. J Clin Psychiatry. 1994;55 (suppl A):25-31;discussion32-23,98-100.
20. Keller MB, Hanks DL. Anxiety symptom relief in depression treatment outcomes. J Clin Psychiatry. 1995;56(suppl 6):22-29.
21. Kravitz HM, Fogg L, Fawcett J, Edwards J. Antidepressant or antianxiety? A study of the efficacy of antidepressant medication. Psychiatry Res. 1990;32:141-149.
22. Clayton AH. Recognition and assessment of sexual dysfunction associated with depression. J Clin Psychiatry. 2001;62(suppl 3):5-9.
23. Kennedy SH, Dickens SE, Eisfeld BS, et al. Sexual dysfunction before antidepressant therapy in major depression. J Affect Disord. 1999;201-208.
24. Kroenke K, West SL, Swindle R, et al. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA. 2001;286:2947-2955.
25. Depression Guideline Panel. Depression in Primary Care: Volume 2. Treatment of Major Depression. Clinical Practice Guideline, Number 5. Rockville, MD: U.S. Dept. of Health and Human Services, Agency for Health Care Policy and Research; April 1993. AHCPR publication 93-0551.
26. Hegner RE. Dispelling the myths and stigma of mental illness: the Surgeon General’s report on mental health. Issue Brief Natl Health Policy Forum. 2000;(754):1-7.
27. Lin EH, Von Korff M, Katon W, et al. The role of the primary care physician in patients’ adherence to antidepressant therapy. Med Care. 1995;33:67-74.
28. Bootzin RR, Epstein D, Wood JM. Stimulus control instructions. In: Hauri P, ed. Case Studies in Insomnia. New York: Plenum Medical Book; 1991:xiv, 254.
29. Culpepper L. Worries and anxiety. In: Staton EW, ed. 20 Common Problems in Behavioral Health. New York: McGraw-Hill; 2002;385-404.
30. Miser WF. Exercise as an effective treatment option for major depression in older adults. J Fam Pract. 2000;49:109-110.
31. Robinson P, Bush T, Von Korff M, et al. Primary care physician use of cognitive behavioral techniques with depressed patients. J Fam Pract. 1995;40:352-357.
32. Rush AJ, Thase ME. Psychotherapies for depressive disorders: a review. In: Sartorius N, ed. Depressive Disorders. New York: John Wiley and Sons; 1999.
33. Preskorn SH. Selection of an antidepressant: mirtazapine. J Clin Psychiatry. 1997;58(suppl 6):3-8.
34. Geddes JR, Freemantle N, Mason J, Eccles MP, Boynton J. SSRIs versus other antidepressants for depressive disorder. Cochrane Database Syst Rev. 2000;CD001851.-
35. Preskorn SH. Debate resolved: there are differential effects of serotonin selective reuptake inhibitors on cytochrome P450 enzymes. J Psychopharmacol. 1998;12(3 suppl B):S89-97.
36. Preskorn SH. Antidepressant options in primary care. Clin Cornerstone. 1999;1:31-55.
37. Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI. Drug interactions with newer antidepressants: role of human cytochromes P450. J Clin Psychiatry. 1998;59 (suppl. 15):19-27.
38. Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet. 1997;32(suppl 1):1-21.
39. Fava M, Judge R, Hoog SL, Nilsson ME, Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry. 2000;61:863-867.
40. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, et al. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997;23:176-194.
41. Fava M, Rankin M. Sexual functioning and SSRIs. J Clin Psychiatry. 2002;63(suppl 5):13-16;discussion 23-15.
42. Zajecka J. Strategies for the treatment of antidepressant-related sexual dysfunction. J Clin Psychiatry. 2001;62 (suppl 3):35-43.
43. Sturpe DA, Mertens MK, Scoville C. What are the treatment options for SSRI-related sexual dysfunction? J Fam Practice. 2002;51:681.-
44. Nurnberg HG, Hensley PL, Lauriello J, Parker LM, Keith SJ. Sildenafil for women patients with antidepressant-induced sexual dysfunction. Psychiatr Serv. 1999;50:1076-1078.
45. Wade A, Michael Lemming O, Bang Hedegaard K. Escitalopram 10mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2002;95-102.
46. Souery D, Mendlewicz J. Compliance and therapeutic issues in resistant depression. Int Clin Psychopharmacol. 1998;13 (suppl 2):S13-18.
47. Thase ME, Rush AJ. Treatment-resistant depression. In: Kupfer DJ, ed. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press; 1995;1081-1097.
48. Thase ME. What role do atypical antipsychotic drugs have in treatment-resistant depression. J Clin Psychiatry. 2002;63:95-103.
49. Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association. Am J Psychiatry. 2000;157(4 suppl):1-45.
50. Howland RH, Thase ME. What to do with SSRI non-responders? J Pract Psychiatry Behav Health. 1999;5:216-233.
51. Thase ME, Friedman ES, Howland RH. Management of treatment-resistant depression: psychotherapeutic perspectives. J Clin Psychiatry. 2001;62(suppl 18):18-24.
52. Fava M. Augmentation and combination strategies in treatment-resistant depression. J Clin Psychiatry. 2001;62 (suppl 18):4-11.
53. Thase ME, Howland RH, Friedman ES. Treating antidepressant nonresponders with augmentation strategies: an overview. J Clin Psychiatry. 1998;59(suppl 5):5-12;discussion 13-15.
54. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101-2107.
55. Keller MB. The long-term treatment of depression. J Clin Psychiatry. 1999;60(suppl 17):41-45;discussion 46-48.
56. Shea MT, Elkin I, Imber SD, et al. Course of depressive symptoms over follow-up. Findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Arch Gen Psychiatry. 1992;49:782-787.
57. Wisner KL, Wheeler SB. Prevention of recurrent postpartum major depression. Hosp Community Psychiatry. 1994;45:1191-1196.
58. Schulberg HC, Katon W, Simon GE, Rush AJ. Treating major depression in primary care practice: an update of the Agency for Health Care Policy and Research Practice Guidelines. Arch Gen Psychiatry. 1998;55:1121-1127.
59. Schulberg HC. Treating depression in primary care practice: applications of research findings. J Fam Pract. 2001;50:535-537.
60. Katon W, Von Korff M, Lin E, et al. Collaborative management to achieve treatment guidelines. Impact on depression in primary care. JAMA. 1995;273:1026-1031.
61. Katon W, Robinson P, Von Korff M, et al. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry. 1996;53:924-932.
62. Katon W, Von Korff M, Lin E, et al. Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial. Arch Gen Psychiatry. 1999;56:1109-1115.
63. Von Korff M, Katon W, Unutzer J, Wells K, Wagner EH. Improving depression care: barriers, solutions, and research needs. J Fam Pract. 2001;50:E1.-
64. Simon GE, VonKorff M, Rutter C, Wagner E. Randomised trial of monitoring, feedback, and management of care by telephone to improve treatment of depression in primary care. BMJ. 2000;320:550-554.
While family physicians play a leading role in caring for patients with major depression, the quality of that care that could be greatly improved. A 1997 to 1998 survey of a national sample of adults with depressive or anxiety disorders revealed that 83% of these patients visited a health care provider.1 Of this total, 84% were treated by primary care clinicians, compared with 16% who were treated by mental health professionals. However, about 90% of those cared for by mental health professionals received treatment that met criteria for adequacy outlined in treatment guidelines, compared with 19% of those cared for by primary care professionals.
A critical role for family physicians is to integrate treatment of depression with that of other conditions, especially in light of the association of depression with a variety of chronic diseases. The Institute of Medicine has concluded that depression is strongly associated with the occurrence of, and death following, myocardial infarctions.2 In diabetes, depression is associated with a 2% increase in glycosylated hemoglobin levels3 and can predict occurrence of diabetic complications. Additionally, chronic illnesses may, in themselves, exacerbate depression several fold.
Primary care clinicians are ideally positioned to serve as the central health care providers for patients with major depression. These physicians have many attributes that support this role, including their longitudinal relationship with patients, response to undifferentiated problems, frequent use of the biopsychosocial model, and ability to integrate care of mental and medical conditions. However, challenges in fulfilling this role also exist, including difficulties in recognizing patients with major depression, developing an adequate diagnostic initial assessment, implementing effective short- and long-term treatment and management strategies, and integrating care of depression with that of other conditions affecting patients.4 This article will review each of these challenges.
Recognition of major depression
DeGruy has eloquently described the barriers to recognition and management of mental disorders in primary care, including infrequent use of diagnostic criteria, concern regarding treatment effectiveness, availability of time and resources, the presence of other pressing clinical problems, and issues of third-party reimbursement and other organizational concerns.4
Family physicians and their patients often do not recognize somatic symptoms as originating from depression. In one study, primary care physicians correctly identified 94% of depressed patients presenting with psychological complaints, but they failed to recognize the psychiatric nature of somatic complaints in about half of the patients. This finding is of concern because 83% of depressed patients presented with somatic complaints.5
The attribution patients assign to their problems can also contribute to lack of recognition. In one general practice study, patients’ attributions were classified as somatizing (5%), psychologizing (23%), normalizing (48%), or no predominate attribution (24%).6 For example, patients in this study might attribute fatigue to anemia (somatizing), emotional exhaustion (psychologizing), or being over-extended (normalizing). The likelihood of a missed diagnosis in patients who met criteria for depression or anxiety was strongly associated with attribution: Physicians diagnosed 72% of psychologizing patients accurately, but they reported a correct diagnosis in only 17% of somatizing patients, 15% of normalizing patients, and 31% of patients with no predominate attribution.
Initial diagnostic assessment
The United States Preventive Services Task Force suggests that primary care physicians screen for major depression. The Task Force recommends using 2 simple questions about mood and anhedonia (Table 1) that are generally as effective as longer instruments.7 The Patient Health Questionnaire-9 (PHQ-9) or the longer Prime-MD can be used for further evaluation of patients who respond positively to either question, thus helping to both confirm the diagnosis of depression and measure severity.8,9 Other instruments include the Beck Depression Inventory,10 the Zung scale,11 and the General Health Questionnaire.12 These tools take longer to administer, are not specific in measuring the criteria for major depression, and do not measure severity well.
In family practices, pregnant and postpartum women represent a special population at increased risk for depression.13 About 5% of middle class women and up to one quarter of low income women experience postpartum depression.14 In about half, onset of the depressive disorder occurs before delivery.15 Women who have previously suffered postpartum depression are at high risk, as are those with histories of depression or premenstrual dysphoric disorder. The Edinburgh Postnatal Depression Scale is a useful 10-item self-report instrument available in Spanish and English (Table 1).16,17 Similar instruments have not been developed for pregnant women.
A patient who responds positively to the 2 screening questions in Table 1 or to another screening approach should be further evaluated to confirm the diagnosis of major depression. Many primary care clinicians do this through unstructured history taking. Others use an instrument such as the previously discussed PHQ-9. This tool offers an advantage because it provides a reliable symptom assessment, measures severity, and can be repeated over time to evaluate therapeutic response.8
The physician should consider bereavement and substance abuse as possible causes of depression; bereaved patients who continue to meet criteria for major depression at 2 months often benefit from treatment. By that time, the sadness, poor concentration, and other symptoms associated with normal grief are no longer constant and occur in waves brought on by memories. Conversely, persons also suffering from depression report these symptoms as enduring and autonomous.18
The primary care physician also should inquire about agitation and symptoms of anxiety disorders. These are experienced by 85% of depressed patients; 50% have comorbid anxiety disorders.19-21 Identification of such comorbidity is helpful in determining treatment, evaluating response, and managing patients over the long term. The Prime-MD, available in multiple languages, is also useful for screening for both anxiety and substance abuse, which can complicate both the recognition and treatment of comorbid depression.9
Sexual function is often affected by depression. The physician should inquire about sexual arousal, erection or lubrication, and orgasm during the initial assessment.22 Approximately 50% of women and 40% of men with major depression report sexual-arousal problems, and 15% to 20% report orgasm problems during the month prior to diagnosis.23 Further questioning can assess whether this dysfunction is caused by another disorder (eg, diabetes) or whether it is part of the depressive syndrome. This provides a baseline for later assessment of side effects and treatment effectiveness, and it communicates to the patient that the physician will be attentive to this area. In discussing sexual function with depressed patients, it may be helpful to tell patients that a study of the effectiveness of treatment of depression with selective serotonin reuptake inhibitors (SSRIs) found that patients reported modestly improved sexual function with treatment.24
TABLE 1
Screening for depression
| Outpatient adults | |
| |
| Postpartum women (Edinburgh Postnatal Depression Scale) | |
1. I have been able to laugh and see the funny side of things
| 6. Things have been getting on top of me
|
2. I have looked forward with enjoyment to things
| 7. I have been so unhappy that I have had difficulty sleeping
|
3. I have blamed myself unnecessarily when things went wrong
| 8. I have felt sad or miserable
|
4. I have been anxious or worried for no good reason
| 9. I have been so unhappy that I have been crying
|
5. I have felt scared or panicky for no very good reason
| 10. The thought of harming myself has occurred to me
|
| Reprinted with permission, from Cox JL et al. British Journal of Psychiatry. 1987; 150:782-786. | |
Management of major depression
The acute management of the patient with major depression includes patient education, shared decision-making regarding a treatment modality, supportive counseling, and treatment-specific counseling.25 Education and counseling should extend over the initial weeks of treatment and be combined with monitoring response, identifying and managing any treatment-emergent side effects, and adjusting medications. Long-term management goals include attaining full remission of symptoms, assisting the patient to return to full functional status, integrating depression care with the treatment of other chronic illnesses, maintaining or tapering pharmacologic treatment, and monitoring for and preventing relapse or recurrence.
Education
Education should help patients understand and accept the diagnosis, reduce any stigma they or their families might attach to major depression, and build increased adherence to subsequent treatment.26 It might be helpful to provide a brief explanation of the biologic basis of depression (including biochemical changes in brain function and “chemical imbalances” of serotonin and other neurotransmitters). Explaining pharmacotherapeutic effects (if medication is desired) as mechanisms to help rebalance brain chemistry further emphasizes the biologic basis of depression and decreases any perceptions that depression is a result of moral or character weakness. This educational message should also stress that antidepressants are not habit-forming or addictive, are not “uppers” or “downers,” and are not tranquilizers. The physician also should convey a positive prognosis but note that several weeks and, possibly, adjustments in treatments, may be required. For patients choosing antidepressants, the McArthur Foundation Initiative has identified 7 key educational messages (Table 2).27
TABLE 2
Key messages for patient education about depression
|
Counseling
Patients often benefit from counseling regarding sleep, exercise, and substance use. Many patients with depression experience early morning awakening. Those with agitated depression also often experience delayed sleep onset associated with worry. Providing the patient with information on basic sleep hygiene, exercise, and encouraging abstinence from or moderation in consumption of alcohol might all help.28-30 Additionally, sleep disturbances can indicate the possibility of comorbid disorders. A report that a patient fears going to sleep because of nightmares suggests posttraumatic stress disorder.
For some patients, counseling by the family physician or through referral may be a helpful treatment adjunct. Often depressed patients have deficient coping mechanisms and need assistance in developing strategies to resolve issues in their life. Principles used in cognitive behavioral therapy might be helpful in patient education and counseling.31 These include problem-solving strategies to resolve stressful concerns and cognitive techniques to identify and correct distorted or maladaptive thought patterns.29
As patients respond to depression treatment, an additional component of primary-care-based counseling should target reinvolvement with pleasurable social and physical activities. This may simply involve identifying activities the patient enjoyed prior to the onset of depression but has since stopped, and focusing on the steps required to reactivate these interests.
Shared decision-making with regard to treatment will improve subsequent patient adherence.27 Treatment options include psychotherapy, particularly cognitive behavioral therapy, pharmacotherapy, and electroconvulsive therapy. The latter should be considered for severely depressed patients, particularly persons with few social supports who are at significant risk of suicide.25
Cognitive behavioral therapy and other psychotherapies can show effectiveness equal to that of pharmacotherapy, although response usually lags by a month to 6 weeks compared with that attained by pharmacotherapy.32 For moderately to severely depressed patients, pharmacotherapy is the treatment of choice in part because of its more rapid onset of action.25
Pharmacotherapy
Pharmacotherapy, most often in the form of an SSRI, is the treatment of choice for depression as a result of patient preference, insurance coverage limitations, or time constraints. In choosing an anti-depressant, the family physician should be guided by effectiveness and potential for drug–drug interactions and for both short-and long-term side effects.33
Tricyclics, the SSRIs, and other newer antidepressants offer similar efficacy.34 While efficacy assesses outcome under ideal treatment conditions, the primary care physician is more concerned with effectiveness, defined as the proportion of patients started on an antidepressant during routine clinical practice who attain lasting benefit. Effectiveness includes consideration of patients who discontinue treatment because of side effects or drug–drug interactions, as well as those who do not obtain adequate therapeutic response. Since about 25% of patients discontinue SSRIs because of side effects, this is an important concern.24 Few studies have been conducted comparing the effectiveness of antidepressants.
Drug–drug interactions are mediated predominately by the cytochrome P450 isoenzymes responsible for drug metabolism in the liver.35-37 The 2D6 isoenzyme is responsible for 50% of drug metabolism in the liver; the 3A4 isoenzyme is responsible for another 30%.38 As a clinical example of the importance of such inhibition, codeine requires 2D6-mediated metabolism to become morphine and is ineffective for pain in many patients who are prescribed a 2D6 inhibitor. Patients receiving such agents also can have a 300% to 400% increase in blood levels of previously stable ß-blockers. Paroxetine and fluoxetine, the two SSRIs that strongly inhibit the 2D6 isoenzyme, cause clinically significant interactions; fluoxetine is also a moderate inhibitor of the 3A4 isoenzyme.35 Because of the number of potential drug–drug interactions through these isoenzymes, physicians must check for interactions before prescribing these medications or adding other new medications in patients already receiving these agents. This also is a consideration for patients who might require additional medications acutely, for instance in response to a cardiac or other emergency.
Side effects of concern include gastrointestinal effects, particularly nausea, and central nervous system (CNS) effects, including anxiety and agitation, sleep disturbance, and tremor. When these occur, they often decrease rapidly over the first 1 to 3 weeks. If severe, they can be managed by a temporary dosage decrease. For patients with significant CNS side effects, altering the timing of the daily dose might provide relief from daytime somnolence or agitation or from nighttime insomnia.
Long-term side effects of concern include weight gain and sexual dysfunction. While other SSRIs have low rates for weight gain, paroxetine causes a weight gain of more than 7% (about 10 lbs for a patient of average weight) in 20% to 25% of patients.39 Some element of sexual dysfunction, most often delayed orgasm, is estimated to occur in 30% to 40% of individuals receiving SSRIs.40,41 Management options include delaying dosage of agents with a half-life of about 24 hours (escitalopram, citalopram, sertraline).42 For instance, an individual who usually takes one of these agents in the morning may delay a day’s dose until after engaging in sexual intercourse in the evening. While open-label studies support augmentation, particularly with bupropion or buspirone, the few small randomized double-blind trials available suggest that positive results should be interpreted with caution.43 Alternatively, patients may benefit from sildenafil44 or a switch to a non-SSRI antidepressant.
While management of side effects presents one option, the best clinical approach may be to select an agent with minimal side-effect potential. In double-blind randomized trials, escitalopram, a new SSRI treatment option, was demonstrated to require treatment termination in less than 5% of recipients at its usual dose of 10 mg, a rate no different from that of placebo.45 In contrast, rates of 15% to 30% have been reported for other SSRIs and newer antidepressants at the time of their initial release.
Adjusting treatment
One recent primary care trial examined the effectiveness of 3 SSRIs: fluoxetine, sertraline, and paroxetine. At the time this study was designed, citalopram was not in common use. While about 75% of patients attained remission, only 40% to 50% of patients were maintained on the first prescribed agent.24 Additionally, about 20% of depression “treatment resistance” resulted because patients did not fill their prescriptions or adhere to treatment.46 For patients who do not respond within the first month, increasing the dosage is appropriate.47 About 25% of patients respond to this adjustment.48 For patients who do not respond, reassessment of the diagnosis, as well as assessment of potential psychiatric comorbidities and suicidal ideation, is indicated. For nonresponders, and for those with intolerable side effects, switching to a second SSRI is a reasonable next step.49 About 50% of patients switched to a second agent respond.50 For those who do not respond, the primary care physician might consider a second medication switch or psychiatric consultation.
Further treatment adjustment is indicated for patients who experience partial response. This might take the form of augmentation with psychotherapy51 or with another agent.52 Lithium and thyroid hormone (often as 25 to 50 mg T3 daily) are the most frequently used options, although stimulants, other antidepressants, and atypical antipsychotics are all of value in some patients.48,49,53
When indicated, treatment should be discontinued by tapering the dose over several weeks to months, depending on the duration and severity of past episodes. Patients should be educated to be alert for recurrence. They should also be monitored for recurrence and restarted on full-dose therapy if this occurs. If patients stop therapy abruptly, the likelihood of withdrawal symptoms (agitation, irritability, dizziness, ataxia, nausea, paresthesias, sleep disturbances) is highly related to the half-life of the SSRI.39 For paroxetine, which has the shortest half-life, withdrawal is frequent; the extended release preparation does not decrease the likelihood of withdrawal. Withdrawal symptoms are infrequent (< 2%) for sertraline, citalopram, and escitalopram, and they do not occur with fluoxetine.
Duration of treatment
A major challenge in family practice is maintaining patient adherence to treatment for the recommended interval to prevent relapse and to avoid recurrence in those with a history of prior episodes. In one study, 25% to 33% of primary care patients stopped depression therapy within 1 month and over 40% within 3 months. Additionally, 62% failed to inform their physicians.54 Depression also adversely affects compliance with treatment of comorbid medical conditions; in one meta-analysis, depression increased noncompliance 3-fold.54
For the first lifetime episode, the recommended duration of treatment is 6 to 9 months (4 to 6 months after recovery).55 Longer therapy is appropriate for those with comorbid anxiety disorders, severe initial symptoms, difficulty in attaining therapeutic response, deficient social support, or a history of substance abuse, as well as for older adults. For patients with 3 or more previous episodes, long-term maintenance therapy is recommended.55 For those with even one past episode, extended maintenance therapy might be beneficial. Maintenance therapy should be at the full dose required to attain initial response. In one study, only about 20% to 30% (depending on the treatment) experienced recurrence over 3 years if maintained at full dose, compared with 70% maintained at half the initial treatment dose, and 78% of those receiving placebo.56 For women who have previously suffered from postpartum depression, postpartum prophylaxis can be very effective. In one randomized trial, 62.5% of women on place-bo experienced recurrence compared with only 6.7% of those receiving prophylaxis.57
Practice strategies to improve care
A number of primary care investigators have demonstrated the value of practice management and quality improvement techniques to increase the portion of patients who achieve and maintain response to depression therapy. These studies share an approach of “active management” to promote adherence to treatment guidelines.58-63 For instance, Simon and colleagues demonstrated the value of initial and monthly phone contact.64
Active management techniques include the following:
- Initial and ongoing patient education and counseling, as discussed above
- Patient involvement and agreement in treatment choice
- Initial phone contact to assure the prescription has been filled and initial dose taken
- Periodic contact to inquire about adherence, treatment response, side effects, and to answer patient questions
- Adjustment of therapy for those not responding adequately by 4 to 6 weeks
- Establishment of a collaborative relationship with a psychiatrist for consultation and telephone advice
Additionally, primary care clinicians may find it helpful to add depression to their medical record preventive health maintenance flow chart, especially for patients with any past history of depression. Using the PHQ-9 can be beneficial in providing both the patient and physician with an objective measure of monitoring response and remission.
Conclusions
Effective and available treatments can have a major beneficial impact on patients with depression. To be maximally effective, primary care clinicians must actively manage the care of their depressed patients, using screening strategies to recognize depression in addition to targeted educational messages and active follow-up to improve treatment adherence. Long-term maintenance treatment prevents further recurrences in those who have already experienced multiple episodes. Choice of treatment should be guided by patient preference. For pharmacologic agents, selection should be based on effectiveness, likelihood of side effects and resultant premature discontinuation, and potential for drug–drug interaction. The majority of individuals with depression are managed solely in primary-care settings. With adequate treatment, remission of symptoms, significant improvement in quality of life, and return to full function at home and at work can be attained.
While family physicians play a leading role in caring for patients with major depression, the quality of that care that could be greatly improved. A 1997 to 1998 survey of a national sample of adults with depressive or anxiety disorders revealed that 83% of these patients visited a health care provider.1 Of this total, 84% were treated by primary care clinicians, compared with 16% who were treated by mental health professionals. However, about 90% of those cared for by mental health professionals received treatment that met criteria for adequacy outlined in treatment guidelines, compared with 19% of those cared for by primary care professionals.
A critical role for family physicians is to integrate treatment of depression with that of other conditions, especially in light of the association of depression with a variety of chronic diseases. The Institute of Medicine has concluded that depression is strongly associated with the occurrence of, and death following, myocardial infarctions.2 In diabetes, depression is associated with a 2% increase in glycosylated hemoglobin levels3 and can predict occurrence of diabetic complications. Additionally, chronic illnesses may, in themselves, exacerbate depression several fold.
Primary care clinicians are ideally positioned to serve as the central health care providers for patients with major depression. These physicians have many attributes that support this role, including their longitudinal relationship with patients, response to undifferentiated problems, frequent use of the biopsychosocial model, and ability to integrate care of mental and medical conditions. However, challenges in fulfilling this role also exist, including difficulties in recognizing patients with major depression, developing an adequate diagnostic initial assessment, implementing effective short- and long-term treatment and management strategies, and integrating care of depression with that of other conditions affecting patients.4 This article will review each of these challenges.
Recognition of major depression
DeGruy has eloquently described the barriers to recognition and management of mental disorders in primary care, including infrequent use of diagnostic criteria, concern regarding treatment effectiveness, availability of time and resources, the presence of other pressing clinical problems, and issues of third-party reimbursement and other organizational concerns.4
Family physicians and their patients often do not recognize somatic symptoms as originating from depression. In one study, primary care physicians correctly identified 94% of depressed patients presenting with psychological complaints, but they failed to recognize the psychiatric nature of somatic complaints in about half of the patients. This finding is of concern because 83% of depressed patients presented with somatic complaints.5
The attribution patients assign to their problems can also contribute to lack of recognition. In one general practice study, patients’ attributions were classified as somatizing (5%), psychologizing (23%), normalizing (48%), or no predominate attribution (24%).6 For example, patients in this study might attribute fatigue to anemia (somatizing), emotional exhaustion (psychologizing), or being over-extended (normalizing). The likelihood of a missed diagnosis in patients who met criteria for depression or anxiety was strongly associated with attribution: Physicians diagnosed 72% of psychologizing patients accurately, but they reported a correct diagnosis in only 17% of somatizing patients, 15% of normalizing patients, and 31% of patients with no predominate attribution.
Initial diagnostic assessment
The United States Preventive Services Task Force suggests that primary care physicians screen for major depression. The Task Force recommends using 2 simple questions about mood and anhedonia (Table 1) that are generally as effective as longer instruments.7 The Patient Health Questionnaire-9 (PHQ-9) or the longer Prime-MD can be used for further evaluation of patients who respond positively to either question, thus helping to both confirm the diagnosis of depression and measure severity.8,9 Other instruments include the Beck Depression Inventory,10 the Zung scale,11 and the General Health Questionnaire.12 These tools take longer to administer, are not specific in measuring the criteria for major depression, and do not measure severity well.
In family practices, pregnant and postpartum women represent a special population at increased risk for depression.13 About 5% of middle class women and up to one quarter of low income women experience postpartum depression.14 In about half, onset of the depressive disorder occurs before delivery.15 Women who have previously suffered postpartum depression are at high risk, as are those with histories of depression or premenstrual dysphoric disorder. The Edinburgh Postnatal Depression Scale is a useful 10-item self-report instrument available in Spanish and English (Table 1).16,17 Similar instruments have not been developed for pregnant women.
A patient who responds positively to the 2 screening questions in Table 1 or to another screening approach should be further evaluated to confirm the diagnosis of major depression. Many primary care clinicians do this through unstructured history taking. Others use an instrument such as the previously discussed PHQ-9. This tool offers an advantage because it provides a reliable symptom assessment, measures severity, and can be repeated over time to evaluate therapeutic response.8
The physician should consider bereavement and substance abuse as possible causes of depression; bereaved patients who continue to meet criteria for major depression at 2 months often benefit from treatment. By that time, the sadness, poor concentration, and other symptoms associated with normal grief are no longer constant and occur in waves brought on by memories. Conversely, persons also suffering from depression report these symptoms as enduring and autonomous.18
The primary care physician also should inquire about agitation and symptoms of anxiety disorders. These are experienced by 85% of depressed patients; 50% have comorbid anxiety disorders.19-21 Identification of such comorbidity is helpful in determining treatment, evaluating response, and managing patients over the long term. The Prime-MD, available in multiple languages, is also useful for screening for both anxiety and substance abuse, which can complicate both the recognition and treatment of comorbid depression.9
Sexual function is often affected by depression. The physician should inquire about sexual arousal, erection or lubrication, and orgasm during the initial assessment.22 Approximately 50% of women and 40% of men with major depression report sexual-arousal problems, and 15% to 20% report orgasm problems during the month prior to diagnosis.23 Further questioning can assess whether this dysfunction is caused by another disorder (eg, diabetes) or whether it is part of the depressive syndrome. This provides a baseline for later assessment of side effects and treatment effectiveness, and it communicates to the patient that the physician will be attentive to this area. In discussing sexual function with depressed patients, it may be helpful to tell patients that a study of the effectiveness of treatment of depression with selective serotonin reuptake inhibitors (SSRIs) found that patients reported modestly improved sexual function with treatment.24
TABLE 1
Screening for depression
| Outpatient adults | |
| |
| Postpartum women (Edinburgh Postnatal Depression Scale) | |
1. I have been able to laugh and see the funny side of things
| 6. Things have been getting on top of me
|
2. I have looked forward with enjoyment to things
| 7. I have been so unhappy that I have had difficulty sleeping
|
3. I have blamed myself unnecessarily when things went wrong
| 8. I have felt sad or miserable
|
4. I have been anxious or worried for no good reason
| 9. I have been so unhappy that I have been crying
|
5. I have felt scared or panicky for no very good reason
| 10. The thought of harming myself has occurred to me
|
| Reprinted with permission, from Cox JL et al. British Journal of Psychiatry. 1987; 150:782-786. | |
Management of major depression
The acute management of the patient with major depression includes patient education, shared decision-making regarding a treatment modality, supportive counseling, and treatment-specific counseling.25 Education and counseling should extend over the initial weeks of treatment and be combined with monitoring response, identifying and managing any treatment-emergent side effects, and adjusting medications. Long-term management goals include attaining full remission of symptoms, assisting the patient to return to full functional status, integrating depression care with the treatment of other chronic illnesses, maintaining or tapering pharmacologic treatment, and monitoring for and preventing relapse or recurrence.
Education
Education should help patients understand and accept the diagnosis, reduce any stigma they or their families might attach to major depression, and build increased adherence to subsequent treatment.26 It might be helpful to provide a brief explanation of the biologic basis of depression (including biochemical changes in brain function and “chemical imbalances” of serotonin and other neurotransmitters). Explaining pharmacotherapeutic effects (if medication is desired) as mechanisms to help rebalance brain chemistry further emphasizes the biologic basis of depression and decreases any perceptions that depression is a result of moral or character weakness. This educational message should also stress that antidepressants are not habit-forming or addictive, are not “uppers” or “downers,” and are not tranquilizers. The physician also should convey a positive prognosis but note that several weeks and, possibly, adjustments in treatments, may be required. For patients choosing antidepressants, the McArthur Foundation Initiative has identified 7 key educational messages (Table 2).27
TABLE 2
Key messages for patient education about depression
|
Counseling
Patients often benefit from counseling regarding sleep, exercise, and substance use. Many patients with depression experience early morning awakening. Those with agitated depression also often experience delayed sleep onset associated with worry. Providing the patient with information on basic sleep hygiene, exercise, and encouraging abstinence from or moderation in consumption of alcohol might all help.28-30 Additionally, sleep disturbances can indicate the possibility of comorbid disorders. A report that a patient fears going to sleep because of nightmares suggests posttraumatic stress disorder.
For some patients, counseling by the family physician or through referral may be a helpful treatment adjunct. Often depressed patients have deficient coping mechanisms and need assistance in developing strategies to resolve issues in their life. Principles used in cognitive behavioral therapy might be helpful in patient education and counseling.31 These include problem-solving strategies to resolve stressful concerns and cognitive techniques to identify and correct distorted or maladaptive thought patterns.29
As patients respond to depression treatment, an additional component of primary-care-based counseling should target reinvolvement with pleasurable social and physical activities. This may simply involve identifying activities the patient enjoyed prior to the onset of depression but has since stopped, and focusing on the steps required to reactivate these interests.
Shared decision-making with regard to treatment will improve subsequent patient adherence.27 Treatment options include psychotherapy, particularly cognitive behavioral therapy, pharmacotherapy, and electroconvulsive therapy. The latter should be considered for severely depressed patients, particularly persons with few social supports who are at significant risk of suicide.25
Cognitive behavioral therapy and other psychotherapies can show effectiveness equal to that of pharmacotherapy, although response usually lags by a month to 6 weeks compared with that attained by pharmacotherapy.32 For moderately to severely depressed patients, pharmacotherapy is the treatment of choice in part because of its more rapid onset of action.25
Pharmacotherapy
Pharmacotherapy, most often in the form of an SSRI, is the treatment of choice for depression as a result of patient preference, insurance coverage limitations, or time constraints. In choosing an anti-depressant, the family physician should be guided by effectiveness and potential for drug–drug interactions and for both short-and long-term side effects.33
Tricyclics, the SSRIs, and other newer antidepressants offer similar efficacy.34 While efficacy assesses outcome under ideal treatment conditions, the primary care physician is more concerned with effectiveness, defined as the proportion of patients started on an antidepressant during routine clinical practice who attain lasting benefit. Effectiveness includes consideration of patients who discontinue treatment because of side effects or drug–drug interactions, as well as those who do not obtain adequate therapeutic response. Since about 25% of patients discontinue SSRIs because of side effects, this is an important concern.24 Few studies have been conducted comparing the effectiveness of antidepressants.
Drug–drug interactions are mediated predominately by the cytochrome P450 isoenzymes responsible for drug metabolism in the liver.35-37 The 2D6 isoenzyme is responsible for 50% of drug metabolism in the liver; the 3A4 isoenzyme is responsible for another 30%.38 As a clinical example of the importance of such inhibition, codeine requires 2D6-mediated metabolism to become morphine and is ineffective for pain in many patients who are prescribed a 2D6 inhibitor. Patients receiving such agents also can have a 300% to 400% increase in blood levels of previously stable ß-blockers. Paroxetine and fluoxetine, the two SSRIs that strongly inhibit the 2D6 isoenzyme, cause clinically significant interactions; fluoxetine is also a moderate inhibitor of the 3A4 isoenzyme.35 Because of the number of potential drug–drug interactions through these isoenzymes, physicians must check for interactions before prescribing these medications or adding other new medications in patients already receiving these agents. This also is a consideration for patients who might require additional medications acutely, for instance in response to a cardiac or other emergency.
Side effects of concern include gastrointestinal effects, particularly nausea, and central nervous system (CNS) effects, including anxiety and agitation, sleep disturbance, and tremor. When these occur, they often decrease rapidly over the first 1 to 3 weeks. If severe, they can be managed by a temporary dosage decrease. For patients with significant CNS side effects, altering the timing of the daily dose might provide relief from daytime somnolence or agitation or from nighttime insomnia.
Long-term side effects of concern include weight gain and sexual dysfunction. While other SSRIs have low rates for weight gain, paroxetine causes a weight gain of more than 7% (about 10 lbs for a patient of average weight) in 20% to 25% of patients.39 Some element of sexual dysfunction, most often delayed orgasm, is estimated to occur in 30% to 40% of individuals receiving SSRIs.40,41 Management options include delaying dosage of agents with a half-life of about 24 hours (escitalopram, citalopram, sertraline).42 For instance, an individual who usually takes one of these agents in the morning may delay a day’s dose until after engaging in sexual intercourse in the evening. While open-label studies support augmentation, particularly with bupropion or buspirone, the few small randomized double-blind trials available suggest that positive results should be interpreted with caution.43 Alternatively, patients may benefit from sildenafil44 or a switch to a non-SSRI antidepressant.
While management of side effects presents one option, the best clinical approach may be to select an agent with minimal side-effect potential. In double-blind randomized trials, escitalopram, a new SSRI treatment option, was demonstrated to require treatment termination in less than 5% of recipients at its usual dose of 10 mg, a rate no different from that of placebo.45 In contrast, rates of 15% to 30% have been reported for other SSRIs and newer antidepressants at the time of their initial release.
Adjusting treatment
One recent primary care trial examined the effectiveness of 3 SSRIs: fluoxetine, sertraline, and paroxetine. At the time this study was designed, citalopram was not in common use. While about 75% of patients attained remission, only 40% to 50% of patients were maintained on the first prescribed agent.24 Additionally, about 20% of depression “treatment resistance” resulted because patients did not fill their prescriptions or adhere to treatment.46 For patients who do not respond within the first month, increasing the dosage is appropriate.47 About 25% of patients respond to this adjustment.48 For patients who do not respond, reassessment of the diagnosis, as well as assessment of potential psychiatric comorbidities and suicidal ideation, is indicated. For nonresponders, and for those with intolerable side effects, switching to a second SSRI is a reasonable next step.49 About 50% of patients switched to a second agent respond.50 For those who do not respond, the primary care physician might consider a second medication switch or psychiatric consultation.
Further treatment adjustment is indicated for patients who experience partial response. This might take the form of augmentation with psychotherapy51 or with another agent.52 Lithium and thyroid hormone (often as 25 to 50 mg T3 daily) are the most frequently used options, although stimulants, other antidepressants, and atypical antipsychotics are all of value in some patients.48,49,53
When indicated, treatment should be discontinued by tapering the dose over several weeks to months, depending on the duration and severity of past episodes. Patients should be educated to be alert for recurrence. They should also be monitored for recurrence and restarted on full-dose therapy if this occurs. If patients stop therapy abruptly, the likelihood of withdrawal symptoms (agitation, irritability, dizziness, ataxia, nausea, paresthesias, sleep disturbances) is highly related to the half-life of the SSRI.39 For paroxetine, which has the shortest half-life, withdrawal is frequent; the extended release preparation does not decrease the likelihood of withdrawal. Withdrawal symptoms are infrequent (< 2%) for sertraline, citalopram, and escitalopram, and they do not occur with fluoxetine.
Duration of treatment
A major challenge in family practice is maintaining patient adherence to treatment for the recommended interval to prevent relapse and to avoid recurrence in those with a history of prior episodes. In one study, 25% to 33% of primary care patients stopped depression therapy within 1 month and over 40% within 3 months. Additionally, 62% failed to inform their physicians.54 Depression also adversely affects compliance with treatment of comorbid medical conditions; in one meta-analysis, depression increased noncompliance 3-fold.54
For the first lifetime episode, the recommended duration of treatment is 6 to 9 months (4 to 6 months after recovery).55 Longer therapy is appropriate for those with comorbid anxiety disorders, severe initial symptoms, difficulty in attaining therapeutic response, deficient social support, or a history of substance abuse, as well as for older adults. For patients with 3 or more previous episodes, long-term maintenance therapy is recommended.55 For those with even one past episode, extended maintenance therapy might be beneficial. Maintenance therapy should be at the full dose required to attain initial response. In one study, only about 20% to 30% (depending on the treatment) experienced recurrence over 3 years if maintained at full dose, compared with 70% maintained at half the initial treatment dose, and 78% of those receiving placebo.56 For women who have previously suffered from postpartum depression, postpartum prophylaxis can be very effective. In one randomized trial, 62.5% of women on place-bo experienced recurrence compared with only 6.7% of those receiving prophylaxis.57
Practice strategies to improve care
A number of primary care investigators have demonstrated the value of practice management and quality improvement techniques to increase the portion of patients who achieve and maintain response to depression therapy. These studies share an approach of “active management” to promote adherence to treatment guidelines.58-63 For instance, Simon and colleagues demonstrated the value of initial and monthly phone contact.64
Active management techniques include the following:
- Initial and ongoing patient education and counseling, as discussed above
- Patient involvement and agreement in treatment choice
- Initial phone contact to assure the prescription has been filled and initial dose taken
- Periodic contact to inquire about adherence, treatment response, side effects, and to answer patient questions
- Adjustment of therapy for those not responding adequately by 4 to 6 weeks
- Establishment of a collaborative relationship with a psychiatrist for consultation and telephone advice
Additionally, primary care clinicians may find it helpful to add depression to their medical record preventive health maintenance flow chart, especially for patients with any past history of depression. Using the PHQ-9 can be beneficial in providing both the patient and physician with an objective measure of monitoring response and remission.
Conclusions
Effective and available treatments can have a major beneficial impact on patients with depression. To be maximally effective, primary care clinicians must actively manage the care of their depressed patients, using screening strategies to recognize depression in addition to targeted educational messages and active follow-up to improve treatment adherence. Long-term maintenance treatment prevents further recurrences in those who have already experienced multiple episodes. Choice of treatment should be guided by patient preference. For pharmacologic agents, selection should be based on effectiveness, likelihood of side effects and resultant premature discontinuation, and potential for drug–drug interaction. The majority of individuals with depression are managed solely in primary-care settings. With adequate treatment, remission of symptoms, significant improvement in quality of life, and return to full function at home and at work can be attained.
1. Young AS, Klap R, Sherbourne CD, Wells KB. The quality of care for depressive and anxiety disorders in the United States. Arch Gen Psychiatry. 2001;58:55-61.
2. Institute of Medicine (U.S.). Committee on Health and Behavior: Research Practice and Policy. Health and Behavior: The Interplay of Biological, Behavioral, and Societal Influences. Washington, DC: National Academy Press. 2001.
3. Lustman PJ, Griffith LS, Freedland KE, Clouse RE. The course of major depression in diabetes. Gen Hosp Psychiatry. 1997;19:138-143.
4. deGruy F, III. Mental health care in the primary care setting. In: Donaldson MS, ed. Primary Care: America’s Health in a New Era. Washington, DC: National Academy Press; 1996;285-311.
5. Bridges KW, Goldberg DP. Somatic presentation of DSM III psychiatric disorders in primary care. J Psychosom Res. 1985;29:563-569.
6. Kessler D, Lloyd K, Lewis G, Gray DP. Cross sectional study of symptom attribution and recognition of depression and anxiety in primary care. BMJ. 1999;318:436-439.
7. Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression: two questions are as good as many. J Gen Intern Med. 1997;12:439-445.
8. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606-613.
9. Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999;282:1737-1744.
10. Steer RA, Cavalieri TA, Leonard DM, Beck AT. Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders. Gen Hosp Psychiatry. 1999;21:106-111.
11. Biggs JT, Wylie LT, Ziegler VE. Validity of the Zung Self-rating Depression Scale. Br J Psychiatry. 1978;132:381-385.
12. Goldberg DP, Gater R, Sartorius N, et al. The validity of two versions of the GHQ in the WHO study of mental illness in general health care. Psychol Med. 1997;27:191-197.
13. Susman JL. Postpartum depressive disorders. J Fam Pract. 1996;43(6 suppl):S17-24.
14. O’Hara MW, Schlechte JA, Lewis DA, Varner MW. Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables. J Abnorm Psychol. 1991;100:63-73.
15. Yonkers KA, Ramin SM, Rush AJ, et al. Onset and persistence of postpartum depression in an inner-city maternal health clinic system. Am J Psychiatry. 2001;158:1856-1863.
16. Georgiopoulos AM, Bryan TL, Wollan P, Yawn BP. Routine screening for postpartum depression. J Fam Pract. 2001;50:117-122.
17. Eberhard-Gran M, Eskild A, Tambs K, Opjordsmoen S, Samuelsen SO. Review of validation studies of the Edinburgh Postnatal Depression Scale. Acta Psychiatr Scand. 2001;104:243-249.
18. Osterweis M, Solomon F, Green M. Institute of Medicine (U.S.). Committee for the Study of Health Consequences of the Stress of Bereavement. Bereavement: Reactions, Consequences, and Care. Washington, DC: National Academy Press; 1984.
19. Keller MB, Hanks DL. The natural history and heterogeneity of depressive disorders: implications for rational antidepressant therapy. J Clin Psychiatry. 1994;55 (suppl A):25-31;discussion32-23,98-100.
20. Keller MB, Hanks DL. Anxiety symptom relief in depression treatment outcomes. J Clin Psychiatry. 1995;56(suppl 6):22-29.
21. Kravitz HM, Fogg L, Fawcett J, Edwards J. Antidepressant or antianxiety? A study of the efficacy of antidepressant medication. Psychiatry Res. 1990;32:141-149.
22. Clayton AH. Recognition and assessment of sexual dysfunction associated with depression. J Clin Psychiatry. 2001;62(suppl 3):5-9.
23. Kennedy SH, Dickens SE, Eisfeld BS, et al. Sexual dysfunction before antidepressant therapy in major depression. J Affect Disord. 1999;201-208.
24. Kroenke K, West SL, Swindle R, et al. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA. 2001;286:2947-2955.
25. Depression Guideline Panel. Depression in Primary Care: Volume 2. Treatment of Major Depression. Clinical Practice Guideline, Number 5. Rockville, MD: U.S. Dept. of Health and Human Services, Agency for Health Care Policy and Research; April 1993. AHCPR publication 93-0551.
26. Hegner RE. Dispelling the myths and stigma of mental illness: the Surgeon General’s report on mental health. Issue Brief Natl Health Policy Forum. 2000;(754):1-7.
27. Lin EH, Von Korff M, Katon W, et al. The role of the primary care physician in patients’ adherence to antidepressant therapy. Med Care. 1995;33:67-74.
28. Bootzin RR, Epstein D, Wood JM. Stimulus control instructions. In: Hauri P, ed. Case Studies in Insomnia. New York: Plenum Medical Book; 1991:xiv, 254.
29. Culpepper L. Worries and anxiety. In: Staton EW, ed. 20 Common Problems in Behavioral Health. New York: McGraw-Hill; 2002;385-404.
30. Miser WF. Exercise as an effective treatment option for major depression in older adults. J Fam Pract. 2000;49:109-110.
31. Robinson P, Bush T, Von Korff M, et al. Primary care physician use of cognitive behavioral techniques with depressed patients. J Fam Pract. 1995;40:352-357.
32. Rush AJ, Thase ME. Psychotherapies for depressive disorders: a review. In: Sartorius N, ed. Depressive Disorders. New York: John Wiley and Sons; 1999.
33. Preskorn SH. Selection of an antidepressant: mirtazapine. J Clin Psychiatry. 1997;58(suppl 6):3-8.
34. Geddes JR, Freemantle N, Mason J, Eccles MP, Boynton J. SSRIs versus other antidepressants for depressive disorder. Cochrane Database Syst Rev. 2000;CD001851.-
35. Preskorn SH. Debate resolved: there are differential effects of serotonin selective reuptake inhibitors on cytochrome P450 enzymes. J Psychopharmacol. 1998;12(3 suppl B):S89-97.
36. Preskorn SH. Antidepressant options in primary care. Clin Cornerstone. 1999;1:31-55.
37. Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI. Drug interactions with newer antidepressants: role of human cytochromes P450. J Clin Psychiatry. 1998;59 (suppl. 15):19-27.
38. Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet. 1997;32(suppl 1):1-21.
39. Fava M, Judge R, Hoog SL, Nilsson ME, Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry. 2000;61:863-867.
40. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, et al. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997;23:176-194.
41. Fava M, Rankin M. Sexual functioning and SSRIs. J Clin Psychiatry. 2002;63(suppl 5):13-16;discussion 23-15.
42. Zajecka J. Strategies for the treatment of antidepressant-related sexual dysfunction. J Clin Psychiatry. 2001;62 (suppl 3):35-43.
43. Sturpe DA, Mertens MK, Scoville C. What are the treatment options for SSRI-related sexual dysfunction? J Fam Practice. 2002;51:681.-
44. Nurnberg HG, Hensley PL, Lauriello J, Parker LM, Keith SJ. Sildenafil for women patients with antidepressant-induced sexual dysfunction. Psychiatr Serv. 1999;50:1076-1078.
45. Wade A, Michael Lemming O, Bang Hedegaard K. Escitalopram 10mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2002;95-102.
46. Souery D, Mendlewicz J. Compliance and therapeutic issues in resistant depression. Int Clin Psychopharmacol. 1998;13 (suppl 2):S13-18.
47. Thase ME, Rush AJ. Treatment-resistant depression. In: Kupfer DJ, ed. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press; 1995;1081-1097.
48. Thase ME. What role do atypical antipsychotic drugs have in treatment-resistant depression. J Clin Psychiatry. 2002;63:95-103.
49. Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association. Am J Psychiatry. 2000;157(4 suppl):1-45.
50. Howland RH, Thase ME. What to do with SSRI non-responders? J Pract Psychiatry Behav Health. 1999;5:216-233.
51. Thase ME, Friedman ES, Howland RH. Management of treatment-resistant depression: psychotherapeutic perspectives. J Clin Psychiatry. 2001;62(suppl 18):18-24.
52. Fava M. Augmentation and combination strategies in treatment-resistant depression. J Clin Psychiatry. 2001;62 (suppl 18):4-11.
53. Thase ME, Howland RH, Friedman ES. Treating antidepressant nonresponders with augmentation strategies: an overview. J Clin Psychiatry. 1998;59(suppl 5):5-12;discussion 13-15.
54. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101-2107.
55. Keller MB. The long-term treatment of depression. J Clin Psychiatry. 1999;60(suppl 17):41-45;discussion 46-48.
56. Shea MT, Elkin I, Imber SD, et al. Course of depressive symptoms over follow-up. Findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Arch Gen Psychiatry. 1992;49:782-787.
57. Wisner KL, Wheeler SB. Prevention of recurrent postpartum major depression. Hosp Community Psychiatry. 1994;45:1191-1196.
58. Schulberg HC, Katon W, Simon GE, Rush AJ. Treating major depression in primary care practice: an update of the Agency for Health Care Policy and Research Practice Guidelines. Arch Gen Psychiatry. 1998;55:1121-1127.
59. Schulberg HC. Treating depression in primary care practice: applications of research findings. J Fam Pract. 2001;50:535-537.
60. Katon W, Von Korff M, Lin E, et al. Collaborative management to achieve treatment guidelines. Impact on depression in primary care. JAMA. 1995;273:1026-1031.
61. Katon W, Robinson P, Von Korff M, et al. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry. 1996;53:924-932.
62. Katon W, Von Korff M, Lin E, et al. Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial. Arch Gen Psychiatry. 1999;56:1109-1115.
63. Von Korff M, Katon W, Unutzer J, Wells K, Wagner EH. Improving depression care: barriers, solutions, and research needs. J Fam Pract. 2001;50:E1.-
64. Simon GE, VonKorff M, Rutter C, Wagner E. Randomised trial of monitoring, feedback, and management of care by telephone to improve treatment of depression in primary care. BMJ. 2000;320:550-554.
1. Young AS, Klap R, Sherbourne CD, Wells KB. The quality of care for depressive and anxiety disorders in the United States. Arch Gen Psychiatry. 2001;58:55-61.
2. Institute of Medicine (U.S.). Committee on Health and Behavior: Research Practice and Policy. Health and Behavior: The Interplay of Biological, Behavioral, and Societal Influences. Washington, DC: National Academy Press. 2001.
3. Lustman PJ, Griffith LS, Freedland KE, Clouse RE. The course of major depression in diabetes. Gen Hosp Psychiatry. 1997;19:138-143.
4. deGruy F, III. Mental health care in the primary care setting. In: Donaldson MS, ed. Primary Care: America’s Health in a New Era. Washington, DC: National Academy Press; 1996;285-311.
5. Bridges KW, Goldberg DP. Somatic presentation of DSM III psychiatric disorders in primary care. J Psychosom Res. 1985;29:563-569.
6. Kessler D, Lloyd K, Lewis G, Gray DP. Cross sectional study of symptom attribution and recognition of depression and anxiety in primary care. BMJ. 1999;318:436-439.
7. Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression: two questions are as good as many. J Gen Intern Med. 1997;12:439-445.
8. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606-613.
9. Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999;282:1737-1744.
10. Steer RA, Cavalieri TA, Leonard DM, Beck AT. Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders. Gen Hosp Psychiatry. 1999;21:106-111.
11. Biggs JT, Wylie LT, Ziegler VE. Validity of the Zung Self-rating Depression Scale. Br J Psychiatry. 1978;132:381-385.
12. Goldberg DP, Gater R, Sartorius N, et al. The validity of two versions of the GHQ in the WHO study of mental illness in general health care. Psychol Med. 1997;27:191-197.
13. Susman JL. Postpartum depressive disorders. J Fam Pract. 1996;43(6 suppl):S17-24.
14. O’Hara MW, Schlechte JA, Lewis DA, Varner MW. Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables. J Abnorm Psychol. 1991;100:63-73.
15. Yonkers KA, Ramin SM, Rush AJ, et al. Onset and persistence of postpartum depression in an inner-city maternal health clinic system. Am J Psychiatry. 2001;158:1856-1863.
16. Georgiopoulos AM, Bryan TL, Wollan P, Yawn BP. Routine screening for postpartum depression. J Fam Pract. 2001;50:117-122.
17. Eberhard-Gran M, Eskild A, Tambs K, Opjordsmoen S, Samuelsen SO. Review of validation studies of the Edinburgh Postnatal Depression Scale. Acta Psychiatr Scand. 2001;104:243-249.
18. Osterweis M, Solomon F, Green M. Institute of Medicine (U.S.). Committee for the Study of Health Consequences of the Stress of Bereavement. Bereavement: Reactions, Consequences, and Care. Washington, DC: National Academy Press; 1984.
19. Keller MB, Hanks DL. The natural history and heterogeneity of depressive disorders: implications for rational antidepressant therapy. J Clin Psychiatry. 1994;55 (suppl A):25-31;discussion32-23,98-100.
20. Keller MB, Hanks DL. Anxiety symptom relief in depression treatment outcomes. J Clin Psychiatry. 1995;56(suppl 6):22-29.
21. Kravitz HM, Fogg L, Fawcett J, Edwards J. Antidepressant or antianxiety? A study of the efficacy of antidepressant medication. Psychiatry Res. 1990;32:141-149.
22. Clayton AH. Recognition and assessment of sexual dysfunction associated with depression. J Clin Psychiatry. 2001;62(suppl 3):5-9.
23. Kennedy SH, Dickens SE, Eisfeld BS, et al. Sexual dysfunction before antidepressant therapy in major depression. J Affect Disord. 1999;201-208.
24. Kroenke K, West SL, Swindle R, et al. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA. 2001;286:2947-2955.
25. Depression Guideline Panel. Depression in Primary Care: Volume 2. Treatment of Major Depression. Clinical Practice Guideline, Number 5. Rockville, MD: U.S. Dept. of Health and Human Services, Agency for Health Care Policy and Research; April 1993. AHCPR publication 93-0551.
26. Hegner RE. Dispelling the myths and stigma of mental illness: the Surgeon General’s report on mental health. Issue Brief Natl Health Policy Forum. 2000;(754):1-7.
27. Lin EH, Von Korff M, Katon W, et al. The role of the primary care physician in patients’ adherence to antidepressant therapy. Med Care. 1995;33:67-74.
28. Bootzin RR, Epstein D, Wood JM. Stimulus control instructions. In: Hauri P, ed. Case Studies in Insomnia. New York: Plenum Medical Book; 1991:xiv, 254.
29. Culpepper L. Worries and anxiety. In: Staton EW, ed. 20 Common Problems in Behavioral Health. New York: McGraw-Hill; 2002;385-404.
30. Miser WF. Exercise as an effective treatment option for major depression in older adults. J Fam Pract. 2000;49:109-110.
31. Robinson P, Bush T, Von Korff M, et al. Primary care physician use of cognitive behavioral techniques with depressed patients. J Fam Pract. 1995;40:352-357.
32. Rush AJ, Thase ME. Psychotherapies for depressive disorders: a review. In: Sartorius N, ed. Depressive Disorders. New York: John Wiley and Sons; 1999.
33. Preskorn SH. Selection of an antidepressant: mirtazapine. J Clin Psychiatry. 1997;58(suppl 6):3-8.
34. Geddes JR, Freemantle N, Mason J, Eccles MP, Boynton J. SSRIs versus other antidepressants for depressive disorder. Cochrane Database Syst Rev. 2000;CD001851.-
35. Preskorn SH. Debate resolved: there are differential effects of serotonin selective reuptake inhibitors on cytochrome P450 enzymes. J Psychopharmacol. 1998;12(3 suppl B):S89-97.
36. Preskorn SH. Antidepressant options in primary care. Clin Cornerstone. 1999;1:31-55.
37. Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI. Drug interactions with newer antidepressants: role of human cytochromes P450. J Clin Psychiatry. 1998;59 (suppl. 15):19-27.
38. Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet. 1997;32(suppl 1):1-21.
39. Fava M, Judge R, Hoog SL, Nilsson ME, Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry. 2000;61:863-867.
40. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, et al. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997;23:176-194.
41. Fava M, Rankin M. Sexual functioning and SSRIs. J Clin Psychiatry. 2002;63(suppl 5):13-16;discussion 23-15.
42. Zajecka J. Strategies for the treatment of antidepressant-related sexual dysfunction. J Clin Psychiatry. 2001;62 (suppl 3):35-43.
43. Sturpe DA, Mertens MK, Scoville C. What are the treatment options for SSRI-related sexual dysfunction? J Fam Practice. 2002;51:681.-
44. Nurnberg HG, Hensley PL, Lauriello J, Parker LM, Keith SJ. Sildenafil for women patients with antidepressant-induced sexual dysfunction. Psychiatr Serv. 1999;50:1076-1078.
45. Wade A, Michael Lemming O, Bang Hedegaard K. Escitalopram 10mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2002;95-102.
46. Souery D, Mendlewicz J. Compliance and therapeutic issues in resistant depression. Int Clin Psychopharmacol. 1998;13 (suppl 2):S13-18.
47. Thase ME, Rush AJ. Treatment-resistant depression. In: Kupfer DJ, ed. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press; 1995;1081-1097.
48. Thase ME. What role do atypical antipsychotic drugs have in treatment-resistant depression. J Clin Psychiatry. 2002;63:95-103.
49. Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association. Am J Psychiatry. 2000;157(4 suppl):1-45.
50. Howland RH, Thase ME. What to do with SSRI non-responders? J Pract Psychiatry Behav Health. 1999;5:216-233.
51. Thase ME, Friedman ES, Howland RH. Management of treatment-resistant depression: psychotherapeutic perspectives. J Clin Psychiatry. 2001;62(suppl 18):18-24.
52. Fava M. Augmentation and combination strategies in treatment-resistant depression. J Clin Psychiatry. 2001;62 (suppl 18):4-11.
53. Thase ME, Howland RH, Friedman ES. Treating antidepressant nonresponders with augmentation strategies: an overview. J Clin Psychiatry. 1998;59(suppl 5):5-12;discussion 13-15.
54. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101-2107.
55. Keller MB. The long-term treatment of depression. J Clin Psychiatry. 1999;60(suppl 17):41-45;discussion 46-48.
56. Shea MT, Elkin I, Imber SD, et al. Course of depressive symptoms over follow-up. Findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Arch Gen Psychiatry. 1992;49:782-787.
57. Wisner KL, Wheeler SB. Prevention of recurrent postpartum major depression. Hosp Community Psychiatry. 1994;45:1191-1196.
58. Schulberg HC, Katon W, Simon GE, Rush AJ. Treating major depression in primary care practice: an update of the Agency for Health Care Policy and Research Practice Guidelines. Arch Gen Psychiatry. 1998;55:1121-1127.
59. Schulberg HC. Treating depression in primary care practice: applications of research findings. J Fam Pract. 2001;50:535-537.
60. Katon W, Von Korff M, Lin E, et al. Collaborative management to achieve treatment guidelines. Impact on depression in primary care. JAMA. 1995;273:1026-1031.
61. Katon W, Robinson P, Von Korff M, et al. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry. 1996;53:924-932.
62. Katon W, Von Korff M, Lin E, et al. Stepped collaborative care for primary care patients with persistent symptoms of depression: a randomized trial. Arch Gen Psychiatry. 1999;56:1109-1115.
63. Von Korff M, Katon W, Unutzer J, Wells K, Wagner EH. Improving depression care: barriers, solutions, and research needs. J Fam Pract. 2001;50:E1.-
64. Simon GE, VonKorff M, Rutter C, Wagner E. Randomised trial of monitoring, feedback, and management of care by telephone to improve treatment of depression in primary care. BMJ. 2000;320:550-554.