Rebecca S. Graves, MLS

Evidence summary

Most studies of ADHD medication have lasted fewer than 4 months. The National Institute of Mental Health Collaborative Multisite Multimodal Treatment Study of Children with Attention Deficit/Hyperactivity Disorder (known as the MTA study) is the longest treatment study of children to date. This study—a 28-day, double-blind placebo-controlled trial—enrolled children aged 7 to 9 years with ADHD and compared 4 treatment strategies (including medication and behavioral interventions) over 14 months.^1-3

Of particular interest was the dose-titration evaluation at the beginning of the study. Daily dose-switching titration of methylphenidate was used to identify the optimal starting dose for each child assigned to receive medication. In all, 289 children were randomized to receive methylphenidate, and 256 completed the titration (17 children refused to take medication, 1 moved, 4 had side effects, 4 had missing data, and 7 stopped mid-titration because of inability to follow the titration protocol).

Of the 256 children who completed titration, 198 (77%) responded favorably to 1 of the following doses: low (15 mg/day), intermediate (25 mg/day), or high (35 mg/day for children weighing less than 25 kg; or 50 mg/day for children weighing 25 kg or more). Of the remaining 23%, 32 children responded best to placebo and 26 were methylphenidate nonresponders and were subsequently placed on dextroamphetamine.

Children who responded to methylphenidate entered the 13-month maintenance phase on the optimal dose identified in the titration trial. They were monitored by monthly re-examination and review of information from parents and teachers regarding ADHD symptoms and potential drug side effects. The dose was changed if symptoms were not well controlled or if side effects were present. Subsequently, if no effective and well-tolerated dose of methylphenidate could be identified, the drug was deemed ineffective for that child and was replaced by another medication.

Of the children who responded to methylphenidate, 88% were still taking it at the end of the maintenance trial; 29% were still taking the titration-determined dose of methylphenidate, 18% took a lower dose, and 41% took a higher dose as their “optimal” dose, at which there were no clinically significant symptoms, or “no room for improvement.” The mean dose increased from 31 mg/day at the start to 34 mg/day at the end of the study. Of the 430 total changes in dose made during the maintenance period, 62% were dose increases.

While commendable for its design and large study population, the MTA study had several limitations. The titration trial’s complex method of determining each child’s “best dose” may not be feasible in clinical practice. Furthermore, the study enrolled only children aged 7 to 9 years, while ADHD affects a much broader age range. Finally, the chronic nature of ADHD limits the generalizability of this study beyond 14 months. Additional long-term studies are needed.

Recommendations from others

The most common strategy for managing children taking methylphenidate is to start with a low dose and gradually adjust upward, as required by residual symptoms and as allowed by side effects. This escalating-dose titration reflects typical practice in the United States, as described in several clinical guides.^4,5 The Physician’s Desk Reference states that the maximum total daily dose is 60 mg for methylphenidate, and experts often limit the upper range to 25 mg for a single dose.⁶

The American Academy of Child and Adolescent Psychiatry suggests using a consistent titration schedule with weekly increases in increments of 5–10 mg per dose to achieve symptom control. Alternatively, a fixed-dose titration trial similar to that found in the MTA study may be employed, in which a full set of different doses is switched on a weekly basis. If the top recommended dose does not help, a change in drug or psychosocial intervention may be more beneficial than an increase in methylphenidate dose.⁶

Evidence summary

Most studies of ADHD medication have lasted fewer than 4 months. The National Institute of Mental Health Collaborative Multisite Multimodal Treatment Study of Children with Attention Deficit/Hyperactivity Disorder (known as the MTA study) is the longest treatment study of children to date. This study—a 28-day, double-blind placebo-controlled trial—enrolled children aged 7 to 9 years with ADHD and compared 4 treatment strategies (including medication and behavioral interventions) over 14 months.^1-3

Of particular interest was the dose-titration evaluation at the beginning of the study. Daily dose-switching titration of methylphenidate was used to identify the optimal starting dose for each child assigned to receive medication. In all, 289 children were randomized to receive methylphenidate, and 256 completed the titration (17 children refused to take medication, 1 moved, 4 had side effects, 4 had missing data, and 7 stopped mid-titration because of inability to follow the titration protocol).

Of the 256 children who completed titration, 198 (77%) responded favorably to 1 of the following doses: low (15 mg/day), intermediate (25 mg/day), or high (35 mg/day for children weighing less than 25 kg; or 50 mg/day for children weighing 25 kg or more). Of the remaining 23%, 32 children responded best to placebo and 26 were methylphenidate nonresponders and were subsequently placed on dextroamphetamine.

Children who responded to methylphenidate entered the 13-month maintenance phase on the optimal dose identified in the titration trial. They were monitored by monthly re-examination and review of information from parents and teachers regarding ADHD symptoms and potential drug side effects. The dose was changed if symptoms were not well controlled or if side effects were present. Subsequently, if no effective and well-tolerated dose of methylphenidate could be identified, the drug was deemed ineffective for that child and was replaced by another medication.

Of the children who responded to methylphenidate, 88% were still taking it at the end of the maintenance trial; 29% were still taking the titration-determined dose of methylphenidate, 18% took a lower dose, and 41% took a higher dose as their “optimal” dose, at which there were no clinically significant symptoms, or “no room for improvement.” The mean dose increased from 31 mg/day at the start to 34 mg/day at the end of the study. Of the 430 total changes in dose made during the maintenance period, 62% were dose increases.

While commendable for its design and large study population, the MTA study had several limitations. The titration trial’s complex method of determining each child’s “best dose” may not be feasible in clinical practice. Furthermore, the study enrolled only children aged 7 to 9 years, while ADHD affects a much broader age range. Finally, the chronic nature of ADHD limits the generalizability of this study beyond 14 months. Additional long-term studies are needed.

Recommendations from others

The most common strategy for managing children taking methylphenidate is to start with a low dose and gradually adjust upward, as required by residual symptoms and as allowed by side effects. This escalating-dose titration reflects typical practice in the United States, as described in several clinical guides.^4,5 The Physician’s Desk Reference states that the maximum total daily dose is 60 mg for methylphenidate, and experts often limit the upper range to 25 mg for a single dose.⁶

The American Academy of Child and Adolescent Psychiatry suggests using a consistent titration schedule with weekly increases in increments of 5–10 mg per dose to achieve symptom control. Alternatively, a fixed-dose titration trial similar to that found in the MTA study may be employed, in which a full set of different doses is switched on a weekly basis. If the top recommended dose does not help, a change in drug or psychosocial intervention may be more beneficial than an increase in methylphenidate dose.⁶

Evidence summary

Most studies of ADHD medication have lasted fewer than 4 months. The National Institute of Mental Health Collaborative Multisite Multimodal Treatment Study of Children with Attention Deficit/Hyperactivity Disorder (known as the MTA study) is the longest treatment study of children to date. This study—a 28-day, double-blind placebo-controlled trial—enrolled children aged 7 to 9 years with ADHD and compared 4 treatment strategies (including medication and behavioral interventions) over 14 months.^1-3

Of particular interest was the dose-titration evaluation at the beginning of the study. Daily dose-switching titration of methylphenidate was used to identify the optimal starting dose for each child assigned to receive medication. In all, 289 children were randomized to receive methylphenidate, and 256 completed the titration (17 children refused to take medication, 1 moved, 4 had side effects, 4 had missing data, and 7 stopped mid-titration because of inability to follow the titration protocol).

Of the 256 children who completed titration, 198 (77%) responded favorably to 1 of the following doses: low (15 mg/day), intermediate (25 mg/day), or high (35 mg/day for children weighing less than 25 kg; or 50 mg/day for children weighing 25 kg or more). Of the remaining 23%, 32 children responded best to placebo and 26 were methylphenidate nonresponders and were subsequently placed on dextroamphetamine.

Children who responded to methylphenidate entered the 13-month maintenance phase on the optimal dose identified in the titration trial. They were monitored by monthly re-examination and review of information from parents and teachers regarding ADHD symptoms and potential drug side effects. The dose was changed if symptoms were not well controlled or if side effects were present. Subsequently, if no effective and well-tolerated dose of methylphenidate could be identified, the drug was deemed ineffective for that child and was replaced by another medication.

Of the children who responded to methylphenidate, 88% were still taking it at the end of the maintenance trial; 29% were still taking the titration-determined dose of methylphenidate, 18% took a lower dose, and 41% took a higher dose as their “optimal” dose, at which there were no clinically significant symptoms, or “no room for improvement.” The mean dose increased from 31 mg/day at the start to 34 mg/day at the end of the study. Of the 430 total changes in dose made during the maintenance period, 62% were dose increases.

While commendable for its design and large study population, the MTA study had several limitations. The titration trial’s complex method of determining each child’s “best dose” may not be feasible in clinical practice. Furthermore, the study enrolled only children aged 7 to 9 years, while ADHD affects a much broader age range. Finally, the chronic nature of ADHD limits the generalizability of this study beyond 14 months. Additional long-term studies are needed.

Recommendations from others

The most common strategy for managing children taking methylphenidate is to start with a low dose and gradually adjust upward, as required by residual symptoms and as allowed by side effects. This escalating-dose titration reflects typical practice in the United States, as described in several clinical guides.^4,5 The Physician’s Desk Reference states that the maximum total daily dose is 60 mg for methylphenidate, and experts often limit the upper range to 25 mg for a single dose.⁶

The American Academy of Child and Adolescent Psychiatry suggests using a consistent titration schedule with weekly increases in increments of 5–10 mg per dose to achieve symptom control. Alternatively, a fixed-dose titration trial similar to that found in the MTA study may be employed, in which a full set of different doses is switched on a weekly basis. If the top recommended dose does not help, a change in drug or psychosocial intervention may be more beneficial than an increase in methylphenidate dose.⁶

EVIDENCE-BASED ANSWER

Healthy women who urinate within 15 minutes of sexual intercourse may be slightly less likely to develop a urinary tract infection (UTI) than women who do not urinate afterward (grade of recommendation: D, extrapolation of single case-control study with nonsignificant findings).

Evidence summary

A literature review revealed only 1 small case-control study. The goal of this study was to identify possible risk factors for developing UTIs among young, healthy women who presented to the University of California at Los Angeles student health center.¹ A total of 225 women were enrolled in the study. Exclusion criteria included pregnancy, diabetes, vaginitis, can-didiasis, a history of more than 1 prior UTI, hospitalization, or catheterization 4 weeks before study enrollment. The women were surveyed regarding their dietary habits, clothing, sexual and urinary habits, and birth control methods used. From mid-stream urine samples, the authors identified 44 cases of UTI and 181 controls presenting to the health center without urinary symptoms or a history of UTI. A UTI was defined as the presence of more than 50,000 colony forming units of a single species of bacteria per milliliter of urine and the report of 1 or more of the following symptoms: painful urination, frequent urination, urination at night, and urgent need to urinate, or blood in the urine. A primary UTI case was further defined as a not having had a prior history of UTI; a secondary UTI case was defined as a patient who reported 1 prior UTI.

Women who urinated < 15 minutes after intercourse had an estimated relative risk (RR) of 0.40 (95% confidence interval [CI], 0.09–2.17) for developing a primary case of UTI, and an estimated RR of 0.92 (95% CI, 0.18–4.88) for developing a secondary UTI. These findings were not statistically significant, but the power was too low to rule out a potential effect.

This single small case-control study had several limitations. It was not a randomized controlled trial, which would be required to prove that post-coital voiding is an effective intervention. The study included only young, healthy women and excluded women with recurrent UTIs, a subpopulation of sexually active patients who may particularly benefit from the intervention. Finally, the study lacked adequate sample size to detect a small-to-moderate effect of postcoital voiding.

Recommendations from others

A major urology text does not specifically address the prevention strategy of postcoital voiding.² However, Griffith’s 5 Minute Clinical Consult recommends that women with frequent or intercourse related UTIs should “empty [their] bladder immediately before and following intercourse and consider post-coital antibiotic treatment.”³ Furthermore, the American College of Obstetricians and Gynecologists District II NYS recommends urinating after sexual intercourse to prevent recurrent cystitis.⁴

Read a Clinical Commentary by Jay Moreland, MD, online at http://www.FPIN.org.

EVIDENCE-BASED ANSWER

Healthy women who urinate within 15 minutes of sexual intercourse may be slightly less likely to develop a urinary tract infection (UTI) than women who do not urinate afterward (grade of recommendation: D, extrapolation of single case-control study with nonsignificant findings).

Evidence summary

A literature review revealed only 1 small case-control study. The goal of this study was to identify possible risk factors for developing UTIs among young, healthy women who presented to the University of California at Los Angeles student health center.¹ A total of 225 women were enrolled in the study. Exclusion criteria included pregnancy, diabetes, vaginitis, can-didiasis, a history of more than 1 prior UTI, hospitalization, or catheterization 4 weeks before study enrollment. The women were surveyed regarding their dietary habits, clothing, sexual and urinary habits, and birth control methods used. From mid-stream urine samples, the authors identified 44 cases of UTI and 181 controls presenting to the health center without urinary symptoms or a history of UTI. A UTI was defined as the presence of more than 50,000 colony forming units of a single species of bacteria per milliliter of urine and the report of 1 or more of the following symptoms: painful urination, frequent urination, urination at night, and urgent need to urinate, or blood in the urine. A primary UTI case was further defined as a not having had a prior history of UTI; a secondary UTI case was defined as a patient who reported 1 prior UTI.

Women who urinated < 15 minutes after intercourse had an estimated relative risk (RR) of 0.40 (95% confidence interval [CI], 0.09–2.17) for developing a primary case of UTI, and an estimated RR of 0.92 (95% CI, 0.18–4.88) for developing a secondary UTI. These findings were not statistically significant, but the power was too low to rule out a potential effect.

This single small case-control study had several limitations. It was not a randomized controlled trial, which would be required to prove that post-coital voiding is an effective intervention. The study included only young, healthy women and excluded women with recurrent UTIs, a subpopulation of sexually active patients who may particularly benefit from the intervention. Finally, the study lacked adequate sample size to detect a small-to-moderate effect of postcoital voiding.

Recommendations from others

A major urology text does not specifically address the prevention strategy of postcoital voiding.² However, Griffith’s 5 Minute Clinical Consult recommends that women with frequent or intercourse related UTIs should “empty [their] bladder immediately before and following intercourse and consider post-coital antibiotic treatment.”³ Furthermore, the American College of Obstetricians and Gynecologists District II NYS recommends urinating after sexual intercourse to prevent recurrent cystitis.⁴

Read a Clinical Commentary by Jay Moreland, MD, online at http://www.FPIN.org.

EVIDENCE-BASED ANSWER

Healthy women who urinate within 15 minutes of sexual intercourse may be slightly less likely to develop a urinary tract infection (UTI) than women who do not urinate afterward (grade of recommendation: D, extrapolation of single case-control study with nonsignificant findings).

Evidence summary

A literature review revealed only 1 small case-control study. The goal of this study was to identify possible risk factors for developing UTIs among young, healthy women who presented to the University of California at Los Angeles student health center.¹ A total of 225 women were enrolled in the study. Exclusion criteria included pregnancy, diabetes, vaginitis, can-didiasis, a history of more than 1 prior UTI, hospitalization, or catheterization 4 weeks before study enrollment. The women were surveyed regarding their dietary habits, clothing, sexual and urinary habits, and birth control methods used. From mid-stream urine samples, the authors identified 44 cases of UTI and 181 controls presenting to the health center without urinary symptoms or a history of UTI. A UTI was defined as the presence of more than 50,000 colony forming units of a single species of bacteria per milliliter of urine and the report of 1 or more of the following symptoms: painful urination, frequent urination, urination at night, and urgent need to urinate, or blood in the urine. A primary UTI case was further defined as a not having had a prior history of UTI; a secondary UTI case was defined as a patient who reported 1 prior UTI.

Women who urinated < 15 minutes after intercourse had an estimated relative risk (RR) of 0.40 (95% confidence interval [CI], 0.09–2.17) for developing a primary case of UTI, and an estimated RR of 0.92 (95% CI, 0.18–4.88) for developing a secondary UTI. These findings were not statistically significant, but the power was too low to rule out a potential effect.

This single small case-control study had several limitations. It was not a randomized controlled trial, which would be required to prove that post-coital voiding is an effective intervention. The study included only young, healthy women and excluded women with recurrent UTIs, a subpopulation of sexually active patients who may particularly benefit from the intervention. Finally, the study lacked adequate sample size to detect a small-to-moderate effect of postcoital voiding.

Recommendations from others

A major urology text does not specifically address the prevention strategy of postcoital voiding.² However, Griffith’s 5 Minute Clinical Consult recommends that women with frequent or intercourse related UTIs should “empty [their] bladder immediately before and following intercourse and consider post-coital antibiotic treatment.”³ Furthermore, the American College of Obstetricians and Gynecologists District II NYS recommends urinating after sexual intercourse to prevent recurrent cystitis.⁴

Read a Clinical Commentary by Jay Moreland, MD, online at http://www.FPIN.org.