What medications are suitable for a patient with primary Attention Deficit Hyperactivity Disorder (ADHD) and comorbid depression?

Treatment Approach for ADHD with Comorbid Depression

Start with a stimulant medication (methylphenidate or amphetamine) as first-line treatment for the ADHD, then add an SSRI if depressive symptoms persist after ADHD symptoms improve. 1

Primary Treatment Algorithm

Step 1: Initiate Stimulant Therapy

• Begin with a stimulant medication trial for patients with primary ADHD and milder mood symptoms, as stimulants are highly effective for ADHD (70-80% response rate) and may indirectly improve mood symptoms by reducing ADHD-related functional impairment. 1
• Stimulants work rapidly, allowing quick assessment of ADHD symptom response within days. 1
• Long-acting formulations provide "around-the-clock" effects and reduce rebound symptoms. 1
• Typical dosing for adults:
  • Methylphenidate: 5-20 mg three times daily 1
  • Dextroamphetamine: 5 mg three times daily to 20 mg twice daily 1

Step 2: Reassess and Add SSRI if Needed

• If ADHD symptoms improve but depressive symptoms persist, add an SSRI to the stimulant regimen. 2, 1
• There are no significant drug-drug interactions between stimulants and SSRIs, as SSRIs are metabolized in the liver while 80% of methylphenidate metabolism is extrahepatic. 2
• SSRIs remain the treatment of choice for depression and are weight-neutral with long-term use. 1

Important Exception: Severe Depression First

• If major depressive disorder presents with severe symptoms (psychosis, suicidality, or severe neurovegetative signs), treat the mood disorder first before addressing ADHD. 1, 3
• Once mood is stabilized, reassess ADHD symptoms and then initiate stimulant therapy. 3

Alternative Medication Options

Bupropion as Second-Line

• Bupropion is a second-line agent for ADHD compared to stimulants and should not be used alone to treat both ADHD and depression, as no single antidepressant is proven for this dual purpose. 1
• Consider bupropion if the patient has failed or cannot tolerate stimulants, or if there are comorbid concerns like smoking cessation or weight gain from other antidepressants. 1
• Bupropion may be added to stimulant medication to enhance effect on ADHD symptoms, particularly when stimulants alone are not providing adequate symptom control. 1
• Dosing: Start bupropion SR at 100-150 mg daily or XL at 150 mg daily, titrating to maintenance doses of 100-150 mg twice daily (SR) or 150-300 mg daily (XL), with a maximum of 450 mg per day. 1

Atomoxetine for Special Populations

• For patients with substance abuse history, consider atomoxetine (60-100 mg daily) as first-line instead of stimulants due to its lower abuse potential as an uncontrolled substance. 1, 3
• Atomoxetine requires 4-6 weeks at therapeutic dose for full effect and should be assessed after 6-8 weeks. 3
• Monitor for suicidality and clinical worsening, particularly important in patients already on antidepressants. 1

Critical Safety Considerations

Absolute Contraindications

• Never use MAO inhibitors concurrently with stimulants or bupropion due to risk of hypertensive crisis. 2, 1, 4
• At least 14 days should elapse between discontinuation of an MAOI and initiation of bupropion or stimulants. 4

Drug Interactions to Monitor

• Bupropion inhibits CYP2D6 and can increase exposures of drugs metabolized by this enzyme, including certain antidepressants (venlafaxine, SSRIs, TCAs). 4
• When combining bupropion with SSRIs or other antidepressants, monitor closely but no dose adjustment is typically required. 4
• Be cautious when combining stimulants with tricyclic antidepressants, though recent studies show no significant pharmacokinetic interactions. 2

Monitoring Parameters

• Monitor blood pressure and pulse at baseline and regularly during stimulant treatment. 1
• Monitor for worsening hyperactivity, insomnia, anxiety, and agitation during the first 2-4 weeks when using bupropion. 1
• Monitor height, weight, sleep disturbances, and appetite changes as common adverse effects of stimulants. 1

Common Pitfalls to Avoid

• Do not assume a single antidepressant will effectively treat both ADHD and depression—evidence specifically states no single antidepressant is proven for this dual purpose. 1
• Do not use bupropion as first-line for patients with prominent hyperactivity or anxiety, as it is inherently activating and can exacerbate these symptoms. 1
• Avoid stimulants in patients with uncontrolled hypertension, symptomatic cardiovascular disease, or active substance abuse. 1
• Do not expect immediate results with atomoxetine—allow full 6-8 weeks at therapeutic dose before declaring treatment failure. 3