In a 40-year-old man taking bupropion (Wellbutrin) 450 mg daily and trazodone 100 mg at night for depression and insomnia, should the bupropion be reduced to 300 mg and the trazodone increased?

Should Bupropion Be Reduced and Trazodone Increased?

Do not reduce bupropion to 300 mg or increase trazodone—this patient is already on the maximum FDA-approved dose of bupropion (450 mg) for depression, and trazodone is explicitly not recommended for insomnia treatment by current guidelines.

Critical Safety Issue: Bupropion 450 mg Daily

Your patient is already at the maximum FDA-approved dose of bupropion for depression treatment. 1 Reducing to 300 mg without clear evidence of treatment failure or intolerable side effects would potentially compromise depression control. The FDA labeling confirms 450 mg daily as the upper limit, with seizure risk being dose-dependent—but at 450 mg or less in divided doses, the seizure rate is comparable to other antidepressants. 2

Key consideration: If insomnia is the primary concern driving this question, reducing an effective antidepressant dose is not the solution—addressing the insomnia directly with evidence-based treatments is the correct approach.

Why NOT Increase Trazodone

The American Academy of Sleep Medicine explicitly recommends against using trazodone for insomnia treatment. 3, 4 Here's why this recommendation is so strong:

Evidence Against Trazodone for Insomnia

• Clinical trials of trazodone 50 mg showed no significant improvement in objective sleep parameters (sleep efficiency, sleep-onset latency, total sleep time, or wake after sleep onset) compared to placebo. 4
• While modest subjective sleep quality improvements were noted, the harms outweigh benefits according to guideline panels. 3, 4
• Trazodone causes dose-dependent cognitive and psychomotor impairments including deficits in short-term memory, verbal learning, equilibrium, and muscle endurance—effects that persist into the next day. 5
• The most common side effect is drowsiness (which may seem desirable for sleep but creates daytime dysfunction), followed by dizziness, dry mouth, and nervousness. 6

The Evidence Quality Problem

The trials supporting trazodone were extremely short (mean 1.7 weeks) with follow-up of only 1-4 weeks, providing low-quality evidence that cannot justify long-term use. 4 Your patient is already on 100 mg nightly—increasing this dose would amplify side effects without reliable evidence of improved sleep outcomes.

What You SHOULD Do Instead

First-Line: Cognitive Behavioral Therapy for Insomnia (CBT-I)

Initiate CBT-I immediately—this is the gold standard and must be offered before or alongside any medication changes. 3 CBT-I provides superior long-term efficacy compared to medications, with sustained benefits after treatment ends. 3

Core components include:

• Stimulus control: Use bed only for sleep; leave bed if unable to sleep within 20 minutes
• Sleep restriction: Limit time in bed to actual sleep time plus 30 minutes
• Relaxation techniques: Progressive muscle relaxation, guided imagery, breathing exercises
• Cognitive restructuring: Address negative beliefs about sleep
• Sleep hygiene: Consistent wake time, avoid caffeine 6+ hours before bed, limit screens 1+ hour before bed 3

CBT-I can be delivered via individual therapy, group sessions, telephone, web-based modules, or self-help books—all formats show effectiveness. 3

Second-Line: Switch to Evidence-Based Sleep Medication

If CBT-I alone is insufficient after 4-8 weeks, replace trazodone with a first-line pharmacologic agent:

For Sleep Maintenance Insomnia (if that's the primary complaint):

• Low-dose doxepin 3-6 mg is the preferred option—reduces wake after sleep onset by 22-23 minutes, has minimal anticholinergic effects at hypnotic doses, and carries no abuse potential. 3
• Suvorexant 10 mg (orexin receptor antagonist) reduces wake after sleep onset by 16-28 minutes with lower cognitive/psychomotor impairment risk than benzodiazepine-type agents. 3

For Combined Sleep Onset + Maintenance:

• Eszopiclone 2-3 mg increases total sleep time by 28-57 minutes with moderate-to-large improvements in sleep quality. 3
• Zolpidem 10 mg (5 mg if age ≥65) shortens sleep-onset latency by ~25 minutes and adds ~29 minutes to total sleep time. 3

For Sleep Onset Only:

• Zaleplon 10 mg has a very short half-life (~1 hour) with minimal next-day sedation. 3
• Ramelteon 8 mg is a melatonin-receptor agonist with no abuse potential and no DEA scheduling—ideal if substance use history is a concern. 3

Treatment Algorithm

1. Keep bupropion at 450 mg unless there's evidence of treatment failure or intolerable side effects (agitation, insomnia directly caused by bupropion timing). 1, 2

2. Start CBT-I immediately for all patients with chronic insomnia. 3

3. Taper and discontinue trazodone over 1-2 weeks while initiating CBT-I. 3

4. If CBT-I alone insufficient after 4-8 weeks, add low-dose doxepin 3 mg at bedtime (can increase to 6 mg after 1-2 weeks if needed). 3

5. Reassess after 1-2 weeks of any new sleep medication for efficacy (sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning) and adverse effects (morning sedation, cognitive impairment, complex sleep behaviors). 3

6. Use lowest effective dose for shortest duration—FDA labeling recommends hypnotics for ≤4 weeks for acute insomnia; long-term use requires periodic reassessment. 3

Common Pitfalls to Avoid

• Do not reduce an effective antidepressant dose to treat insomnia—this risks depression relapse without addressing the root sleep problem. 1
• Do not increase trazodone beyond 100 mg for insomnia—the evidence does not support efficacy, and side effects worsen with higher doses. 3, 4, 5
• Do not start sleep medication without CBT-I—behavioral therapy provides more durable benefits than medication alone. 3
• Do not combine multiple sedating agents (e.g., trazodone + benzodiazepine + Z-drug)—this markedly increases risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors. 3
• Do not use over-the-counter antihistamines (diphenhydramine, doxylamine)—they lack efficacy data, cause anticholinergic effects (confusion, falls, urinary retention), and develop tolerance within 3-4 days. 3

Special Considerations for Bupropion Timing

If insomnia is caused or worsened by bupropion, consider adjusting the timing rather than the dose:

• Give the second dose of bupropion before 3 PM to minimize insomnia risk. 7
• Bupropion is "activating" and can cause insomnia if taken too late in the day. 7
• This timing adjustment preserves the full antidepressant dose while reducing sleep interference.

Bottom Line

Keep bupropion at 450 mg (unless specific reasons to reduce), discontinue trazodone, initiate CBT-I immediately, and if pharmacotherapy is still needed after 4-8 weeks, switch to low-dose doxepin 3-6 mg as the evidence-based first-line option for sleep maintenance. 3, 4, 1