Clinical Question

Do tricyclic antidepressants (TCAs) effectively treat attention-deficit/hyperactivity disorder (ADHD) in children and adolescents?

Evidence-Based Answer

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.)

Practice Pointers

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.