Cochrane for Clinicians
Putting Evidence into Practice
Tricyclic Antidepressants for the Treatment of ADHD in Children and Adolescents
Am Fam Physician. 2015 Sep 1;92(5):352-353.
Do tricyclic antidepressants (TCAs) effectively treat attention-deficit/hyperactivity disorder (ADHD) in children and adolescents?
TCAs, specifically desipramine and nortriptyline (Pamelor), are superior to placebo at reducing ADHD symptoms in the short term (two to six weeks); however, the quality of evidence is low. Increased heart rate and diastolic blood pressure may be noted with treatment. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
ADHD is defined as a pattern of behavior with onset before 12 years of age with components of inattention, hyperactivity, and impulsivity that are present in multiple settings and cause impairment.1 Stimulants are first-line treatment for patients with ADHD, but they are associated with decreased appetite, decreased height, and development or worsening of tic disorder.2,3
This review included six double-blind, randomized controlled trials (RCTs) with a total of 216 patients treated for ADHD with desipramine, clomipramine (Anafranil), and nortriptyline. Two of the trials had coexisting tic disorder or Tourette syndrome as inclusion criteria, and in one of these, clonidine was compared with desipramine. Of the 216 participants, 90% were males from urban areas, with a mean age of 9.9 years (range = six to 17 years). More than 50% of participants had been treated with stimulants in the past. Symptoms were assessed during a two- to six-week treatment period. Only studies with low risk of selection, performance, or attrition bias were used in the review.
Primary outcome measures were an improvement in core ADHD symptoms, the proportion of patients achieving a set improvement in those core symptoms (as measured by parents, teachers, or clinicians), and adverse effects of treatment. The scales used included the Conners' Rating Scale,4 which is rated by parents or teachers, the Child Behaviour Checklist,5 which is rated by parents or teachers, and the Clinical Global Impression (CGI),6 a clinician-rated scale.
Because of the range of outcomes and the variety of instruments used to rate those outcomes, making comparisons was challenging. However, three trials compared TCAs with placebo using the same rating scale, the CGI. These three trials included 125 participants and found that desipramine and nortriptyline were more effective than placebo in improving core ADHD symptoms (odds ratio = 18.50; 95% confidence interval [CI], 6.29 to 54.39). The number needed to treat to benefit one additional person was two.
Two additional trials compared desipramine with placebo using teacher rating scales; core ADHD symptoms improved more in patients taking desipramine than in those given placebo (standardized mean difference [SMD] = −0.97; 95% CI, −1.66 to −0.28). Two trials using different parent rating scales also found that desipramine improved ADHD symptoms more than placebo (SMD = −1.42; 95% CI, −1.99 to −0.85).
Although no serious adverse effects were noted, desipramine was associated with mild increases in diastolic blood pressure and heart rate, as well as higher rates of appetite suppression compared with placebo. Other adverse effects included dry mouth, abdominal discomfort, diaphoresis, sedation, fatigue, headache, confusion, blurred vision, constipation, and urinary retention. None of the studies looked at long-term adverse effects of chronic use. Treatment discontinuation was similar for desipramine and placebo.
Current guidelines recommend the use of medications approved by the U.S. Food and Drug Administration (FDA) for patients diagnosed with ADHD.7 TCAs are not FDA-approved for children, and further study is warranted to determine if they are an appropriate treatment for patients with ADHD.
The practice recommendations in this activity are available at http://summaries.cochrane.org/CD006997.
The views expressed in this article are those of the authors and do not reflect the policy or position of the U.S. Army Medical Department, the Department of the Army, the U.S. Air Force, the Department of Defense, or the U.S. government.
Otasowie J, Castells X, Ehimare UP, Smith CH. Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2014;(9):CD0006997.
REFERENCESshow all references
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013....
2. Lerner M, Wigal T. Long-term safety of stimulant medications used to treat children with ADHD. J Psychosoc Nurs Ment Health Serv. 2008;46(8):38–48.
3. Charach A, Figueroa M, Chen S, Ickowicz A, Schachar R. Stimulant treatment over 5 years: effects on growth. J Am Acad Child Adolesc Psychiatry. 2006;45(4):415–421.
4. Conners CK. Conners’ rating scales. In: Maruish ME, ed. The Use of Psychological Testing for Treatment Planning and Outcome Assessment. Hillsdate, N.J.: L. Erlbaum Associates; 1994:550–578.
5. Achenbach TM. Manual for the Child Behavior Checklist/4–18 and 1991 Profile. Burlington, Vt.: University of Vermont Department of Psychiatry; 1991.
6. National Institute of Mental Health. CGI (Clinical Global Impression Scale). Psychopharmacol Bull. 1985;21:839–844.
7. Wolraich M, Brown L, Brown RT, et al.; Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011;128(5):1007–1022.
These are summaries of reviews from the Cochrane Library.
This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.
A collection of Cochrane for Clinicians published in AFP is available at https://www.aafp.org/afp/cochrane.
Copyright © 2015 by the American Academy of Family Physicians.
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