Can dexamphetamine be started for ADHD in a patient already taking an SSRI, and what are the appropriate starting dose, titration schedule, contraindications, and monitoring requirements?

Dexamphetamine and SSRI Combination for ADHD

Yes, dexamphetamine can be safely started for ADHD in patients already taking an SSRI—there are no significant drug-drug interactions between stimulants and SSRIs, and this combination is well-established in clinical practice. 1, 2

Safety Profile of the Combination

• SSRIs do not interact pharmacokinetically with dexamphetamine or other stimulants, making this a safe and commonly used combination when ADHD and mood/anxiety symptoms coexist 1, 2
• The only absolute contraindication is concurrent MAO inhibitor use—at least 14 days must elapse between discontinuing an MAOI and starting dexamphetamine 1, 2
• Stimulants should not be administered to patients with active psychotic disorders 1

Starting Dose and Titration Schedule

For adults and children ≥6 years:

• Start with 2.5 mg dexamphetamine once or twice daily (morning after breakfast, and optionally around noon after lunch) 1, 3
• Titrate by 2.5-5 mg weekly until optimal response is achieved 1, 3
• Give first dose on awakening; additional doses (1 or 2) at intervals of 4-6 hours 1, 3

For children ages 3-5 years:

• Start with 2.5 mg daily, increasing by 2.5 mg weekly until optimal response 3

Maximum doses:

• Rarely necessary to exceed 40 mg total daily dose in children and adolescents 1, 3
• Adults typically require 10-50 mg daily, with some requiring up to 60 mg/day for narcolepsy 1, 2, 3

Absolute Contraindications

Do not prescribe dexamphetamine if:

• Previous sensitivity to stimulant medications 1
• Glaucoma 1
• Symptomatic cardiovascular disease 1
• Hyperthyroidism 1
• Uncontrolled hypertension 1
• Concomitant MAO inhibitor use (or within 14 days of discontinuation) 1, 2
• Active psychotic disorder 1
• History of illicit stimulant abuse unless in controlled/supervised setting 1

Relative Contraindications Requiring Caution

• History of drug abuse—use with great care, consider long-acting formulations with lower abuse potential 1
• Seizure disorder—stabilize on anticonvulsants before initiating stimulants 1
• Unstable mood disorder—stabilize mood first, though some ADHD patients with secondary depression improve when ADHD is treated 1
• Marked anxiety—though recent literature shows stimulants may not worsen anxiety and can actually improve comorbid anxiety in ADHD patients 1

Required Baseline Monitoring

Before initiating dexamphetamine:

• Physical examination including vital signs (blood pressure, pulse, height, weight) 1, 4
• Detailed cardiac history (syncope, chest pain, palpitations, exercise intolerance) and family history (sudden death <50 years, early cardiovascular disease, arrhythmias, long QT syndrome, hypertrophic cardiomyopathy) 1, 4
• Document prior treatments (medications, dosages, duration, response, side effects, compliance) 1, 4
• Screen for substance abuse risk in adolescents and adults 1, 4
• No routine laboratory tests or EKG required unless clinically indicated by history or physical examination 4

Ongoing Monitoring Requirements

During titration:

• Weekly symptom ratings to assess ADHD symptom control and side effects 2
• Blood pressure and pulse at each dose adjustment 2, 4

During maintenance:

• Quarterly blood pressure and pulse checks in adults 1, 4
• Annual vital signs during routine physical examination in children/adolescents 1
• Height and weight monitoring at each visit to assess for growth effects 1, 4
• Sleep quality and appetite changes 4

Clinical Pearls and Common Pitfalls

Advantages of dexamphetamine:

• Onset of action averages 36 minutes with duration of approximately 6.5 hours for immediate-release formulations 5
• 70-80% response rate when properly titrated 2
• Works within days, allowing rapid assessment of efficacy 2

Common pitfalls to avoid:

• Avoid late evening doses due to resulting insomnia 3
• Do not use weight-adjusted dosing exclusively—systematic titration to optimal clinical effect is more important than strict mg/kg calculations 1
• Greater problematic effects on appetite and sleep compared to methylphenidate due to longer excretion half-life 1
• Small but significant increases in blood pressure (1-4 mmHg systolic/diastolic) and heart rate (1-2 bpm) are expected 5
• If top recommended dose doesn't help, more is not necessarily better—consider changing medication or adding psychosocial interventions rather than exceeding maximum doses 2

Treatment Algorithm When Combining with SSRI

If ADHD is the primary concern:

• Start dexamphetamine as outlined above while continuing SSRI 2
• Assess ADHD response within days to weeks 2

If mood/anxiety symptoms persist after ADHD treatment:

• Continue both medications—the combination is safe and effective 1, 2
• Consider increasing SSRI dose if mood symptoms remain inadequately controlled 2

If starting both simultaneously:

• Begin with stimulant therapy first to quickly assess ADHD symptom response 2
• Add or optimize SSRI if depressive/anxiety symptoms persist after ADHD control is achieved 2