Can bupropion (Wellbutrin) be taken at night?

Bupropion (Wellbutrin) Should Be Taken in the Morning, Not at Night

Bupropion should be administered in the morning due to its activating properties and significant risk of causing insomnia when taken at night. 1

FDA-Approved Dosing Schedule

• The FDA label explicitly states that bupropion extended-release tablets should be administered in the morning and may be taken with or without food 1
• The recommended starting dose is 150 mg once daily in the morning, with potential increase to 300 mg once daily in the morning after 4 days 1
• This morning-only dosing applies to both major depressive disorder and seasonal affective disorder indications 1

Why Morning Dosing Is Critical

Insomnia Risk

• Insomnia is one of the most common adverse effects of bupropion, occurring significantly more frequently than with placebo 2
• Nervousness and insomnia are the predominant side effects reported in clinical trials 3
• The activating properties of bupropion make nighttime administration inappropriate for most patients 4

Mechanism of Action

• Bupropion functions as a dopamine-norepinephrine reuptake inhibitor, which produces stimulating effects incompatible with nighttime dosing 3, 5
• This mechanism is fundamentally different from sedating antidepressants and explains its wake-promoting properties 5

The Rare Exception: Severe Morning Sleep Inertia

There is one highly specialized scenario where bedtime bupropion may be considered: severe, treatment-refractory morning sleep inertia in patients with hypersomnia disorders 6

• A case series demonstrated that bedtime long-acting bupropion (150 mg) successfully treated severe morning sleep inertia in 3 of 4 patients with idiopathic hypersomnia 6
• This represents an off-label use requiring specialist evaluation and should only be attempted under close supervision 6
• One patient in the series was immediately intolerant to bedtime dosing, highlighting individual variability 6

Clinical Pitfalls to Avoid

• Do not recommend nighttime dosing to patients who report daytime sedation from bupropion - this suggests an atypical response requiring medication reassessment rather than timing adjustment 4
• Do not confuse bupropion with sedating antidepressants like mirtazapine or trazodone, which are appropriately dosed at bedtime 4
• If a patient experiences insomnia on morning bupropion, consider dose reduction or switching medications rather than evening administration 2