Taking Bupropion at Night Increases—Rather Than Decreases—the Risk of Insomnia
Bupropion should be dosed in the morning and early afternoon (before 3 PM for the second dose of SR formulations) to minimize insomnia risk, not at night. 1
Why Morning Dosing Is Recommended
Bupropion has activating properties that can improve energy levels and reduce apathy, making morning administration ideal for leveraging these therapeutic effects while avoiding sleep disruption. 1 The drug's noradrenergic and dopaminergic activity stimulates alertness, which is beneficial during waking hours but counterproductive at bedtime. 1
Formulation-Specific Timing Guidelines
Bupropion SR (sustained-release): The first dose should be taken in the morning and the second dose must be administered before 3 PM to prevent insomnia. 1 This twice-daily regimen (typically 150 mg twice daily) provides steady drug levels throughout the day while allowing plasma concentrations to decline before sleep. 1
Bupropion XL (extended-release): Administer 300 mg once daily in the morning only. 1 The extended-release formulation is designed for single daily dosing and should never be taken at night. 1
For older adults: Start with 37.5 mg every morning, increase by 37.5 mg every 3 days as tolerated, and ensure the second dose (if using SR) is given before 3 PM. 1
Evidence on Insomnia as a Side Effect
Insomnia is one of the most common adverse effects of bupropion, occurring significantly more frequently than with placebo in clinical trials. 2, 3 In smoking-cessation studies using bupropion SR 300 mg/day, insomnia was the predominant side effect compared to nicotine patches (where dream abnormalities were more common). 2
The incidence of insomnia is dose-related and timing-dependent—late-day dosing exacerbates this effect by maintaining stimulating plasma levels during hours when sleep consolidation should occur. 1, 2
Common Side Effects Beyond Insomnia
Other frequent neurological effects include headache, dizziness, tremor, nervousness, and anxiety. 4, 3, 5 Gastrointestinal effects such as dry mouth, nausea, and constipation are also common. 4, 2, 3 Importantly, only insomnia and dry mouth occurred significantly more often with bupropion SR than placebo in controlled trials. 2
Baseline Insomnia Does Not Predict Response
Pretreatment insomnia levels do not predict whether a patient will respond to bupropion, nor do they contraindicate its use. 6 In a study of 797 patients with major depression treated with bupropion SR 300 mg/day, 67% achieved response regardless of baseline insomnia severity. 6 However, higher baseline insomnia was associated with earlier onset of antidepressant response (approximately one week sooner). 6
This finding suggests that patients with existing sleep disturbance can still benefit from bupropion, but proper timing of doses becomes even more critical to avoid worsening insomnia. 1, 6
Management of Bupropion-Induced Insomnia
If insomnia develops despite proper morning/early-afternoon dosing:
First-line approach: Reduce the bupropion dose temporarily. Most insomnia is transient and resolves within days to weeks without intervention. 2
Adjunctive sleep aid: Trazodone 100 mg at bedtime has been reported as safe when combined with bupropion and other antidepressants for sleep management. 1
Do not shift doses to nighttime—this will worsen rather than improve insomnia due to bupropion's stimulating pharmacology. 1
Critical Safety Monitoring
Beyond insomnia, monitor for:
Blood pressure and heart rate elevation, especially in the first 12 weeks, as bupropion can cause hypertension and tachycardia. 1, 4
Seizure risk factors: Maximum dose must not exceed 450 mg/day (or 300 mg/day for smoking cessation) to maintain seizure risk at 0.1%. 1, 4 Screen for history of seizures, eating disorders, abrupt alcohol/benzodiazepine discontinuation, or structural brain lesions. 4
Suicidal ideation, particularly in patients under 24 years, during the first 1–2 weeks of treatment. 1
Common Pitfall to Avoid
The most critical error is dosing bupropion in the evening or at bedtime, which directly contradicts the drug's pharmacodynamic profile and will predictably worsen insomnia, jitteriness, and anxiety rather than mitigate these effects. 1, 2, 3 The activating properties that make bupropion useful for depression with low energy become liabilities when the drug is present at high concentrations during sleep hours. 1, 5