What is the role of Tricyclic Antidepressants (TCAs) in treating Attention Deficit Hyperactivity Disorder (ADHD)?

Role of Tricyclic Antidepressants (TCAs) in Treating ADHD

Tricyclic antidepressants are not first-line treatments for ADHD and should only be considered as alternative options when FDA-approved medications (stimulants, atomoxetine, extended-release guanfacine, and extended-release clonidine) have failed or are contraindicated. 1, 2

Treatment Algorithm for ADHD

First-Line Treatment Options (In Order of Evidence Strength)

1. Stimulant medications (methylphenidate, amphetamine-based)

   • Highest efficacy with effect size of approximately 1.0 1, 2
   • Response rate of 70-80% 2

2. Non-stimulant FDA-approved medications (in order of evidence strength)

   • Atomoxetine (effect size ~0.7) 1, 2
   • Extended-release guanfacine (effect size ~0.7) 1
   • Extended-release clonidine (effect size ~0.7) 1

3. Behavioral therapy (particularly important for younger children) 1, 2

When to Consider TCAs

TCAs should only be considered when:

• Patient has failed trials of stimulants AND FDA-approved non-stimulants 2, 3
• Patient has specific contraindications to first-line treatments 3
• Patient has comorbidities that might benefit from TCA treatment 3, 4

Evidence for TCAs in ADHD

The evidence for TCAs in ADHD is limited and of lower quality compared to first-line treatments:

• A Cochrane review found that desipramine improved core ADHD symptoms as assessed by parents (SMD -1.42), teachers (SMD -0.97), and clinicians (OR 26.41), but the quality of evidence was low 5
• Nortriptyline has shown some efficacy in improving core ADHD symptoms (OR 7.88) 5
• TCAs are more effective for behavioral symptoms (hyperactivity, impulsivity) than for attentional and cognitive symptoms 4

Safety Concerns with TCAs

TCAs have significant safety concerns that limit their use:

• Cardiovascular effects: increased diastolic blood pressure, increased pulse rates 5
• Desipramine should be avoided, especially in youth and adolescents, due to safety concerns 4
• Other adverse effects include appetite suppression (desipramine), weight gain (nortriptyline), headache, confusion, sedation, tiredness, blurred vision, diaphoresis, dry mouth, abdominal discomfort, constipation, and urinary retention 5

Specific Clinical Scenarios

1. ADHD with comorbid tic disorders or Tourette syndrome:

   • Desipramine has shown efficacy in reducing ADHD symptoms in patients with comorbid tics (SMD -0.90 compared to clonidine) 5
   • However, atomoxetine would be a safer alternative for these patients 2

2. ADHD with comorbid anxiety or depression:

   • While TCAs have antidepressant properties, atomoxetine is preferred for patients with comorbid anxiety or depression 2

3. ADHD with substance abuse concerns:

   • Non-stimulant options are preferred, with atomoxetine being the recommended choice 2

Important Caveats and Pitfalls

• Never use TCAs as first-line treatment for ADHD when FDA-approved medications are available 1, 2
• Always monitor cardiovascular parameters when using TCAs due to potential cardiac effects 5
• Avoid desipramine in children and adolescents when safer alternatives are available 4
• Do not expect TCAs to improve attentional and cognitive symptoms to the same degree as stimulants 4
• Regular monitoring of side effects is essential if TCAs are used 5

In conclusion, while TCAs (particularly desipramine and nortriptyline) have demonstrated some efficacy in treating ADHD symptoms, their use should be limited to cases where first-line treatments have failed or are contraindicated, and they should be used with careful monitoring due to their side effect profile.