What are the best pharmaceutical options for patients with Attention Deficit Hyperactivity Disorder (ADHD) who have a history of substance abuse?

Non-Stimulant Medications for ADHD in Patients with Substance Abuse History

Non-stimulant medications, particularly atomoxetine, should be considered first-line pharmacological treatment for patients with ADHD who have a history of substance abuse.

First-Line Treatment Options

Atomoxetine (Strattera)

• Recommended as first-line therapy for ADHD patients with substance use disorders due to its non-controlled status and negligible risk of abuse or diversion 1, 2
• Provides "around-the-clock" effects without the rebound/crash experienced with stimulants 1, 3
• Mechanism: Selective norepinephrine reuptake inhibitor that increases both norepinephrine and dopamine in the prefrontal cortex 1
• Dosing: Start at 40mg daily for adults, titrate to target dose of approximately 80mg daily after minimum 3 days, with maximum dose of 100mg daily 4
• Can be administered as a single daily dose or split into two evenly divided doses to reduce side effects 5, 6
• Takes 6-12 weeks to achieve full therapeutic effect, requiring patience during the transition period 1, 5

Guanfacine Extended-Release

• Alternative first-line option for patients with ADHD and substance use disorders 1
• Alpha-2 adrenergic agonist that enhances noradrenergic neurotransmission 1
• Particularly beneficial for patients with comorbid sleep disturbances 1, 3
• Available in tablet form with doses of 1,2,3, and 4 mg 1
• Dosing should be adjusted to body weight with once-daily administration (0.1 mg/kg as a rule of thumb) 1

Clonidine Extended-Release

• Another alpha-2 adrenergic agonist option for patients with substance use disorders 1
• Available in tablet form with dosages of 0.1 and 0.2 mg 1
• Starting dose is 0.1 mg tablet at bedtime, which can be increased to twice-daily administration 1
• Maximum recommended dose is 0.4 mg/day 1

Second-Line Treatment Option

Bupropion

• Can be considered if first-line options are ineffective 2
• Potential benefits include addressing both ADHD and depression symptoms 2
• Low potential for abuse or diversion 7

Monitoring and Side Effects

Atomoxetine

• Common side effects: decreased appetite, headache, stomach pain, nausea, dry mouth, insomnia 1, 8
• Requires monitoring of vital signs, particularly blood pressure and heart rate 1, 5
• FDA black box warning for increased risk of suicidal ideation in children and adolescents (0.4% risk) 5, 4

Guanfacine/Clonidine

• Common side effects: somnolence, fatigue, hypotension, irritability 1
• Require monitoring of blood pressure and pulse 1
• Administration in the evening is generally preferable due to somnolence/fatigue 1

Important Considerations

• Traditional stimulants should be avoided or used with extreme caution in patients with substance abuse history due to their controlled status and abuse potential 1, 2
• Pharmacological treatment should be part of a multimodal approach including psychoeducation and psychosocial interventions 1
• Regular reassessment of treatment efficacy and continued need for medication is recommended 1, 4
• Treatment decisions should follow a shared decision-making model, involving the patient in the process 1

Clinical Pearls

• Non-stimulants generally have smaller effect sizes compared to stimulants but offer advantages for patients with substance abuse history 1, 5
• Atomoxetine can be administered in the evening if needed, offering flexibility in dosing schedule 5, 6
• The delayed onset of action with non-stimulants (particularly atomoxetine) requires setting appropriate expectations with patients 1, 5
• Atomoxetine is the first ADHD treatment approved specifically for adult use based on well-controlled adult trials 8, 6