What is the recommended dose of Trazodone (trazodone) when switching from Seroquel (quetiapine) for sleep?

Switching from Seroquel to Trazodone for Sleep: Dosing Recommendation

Do not switch from Seroquel to trazodone for sleep—trazodone is explicitly not recommended for insomnia treatment based on the highest quality evidence, and you should instead transition to low-dose doxepin 3-6 mg or a benzodiazepine receptor agonist like zolpidem. 1

Why Trazodone Should Be Avoided

The 2017 American Academy of Sleep Medicine clinical practice guideline—the most authoritative and recent evidence on insomnia pharmacotherapy—explicitly recommends against using trazodone for either sleep onset or sleep maintenance insomnia. 1 The evidence shows:

• Sleep latency reduction: Only 10 minutes greater than placebo (95% CI: 9-11 minutes) 1
• Wake after sleep onset reduction: Only 8 minutes greater than placebo (95% CI: 7-9 minutes) 1
• Sleep quality: No improvement compared to placebo 1
• Dose studied: 50 mg 1

Additionally, a 2025 retrospective cohort study in older adults found that low-dose quetiapine (which you're currently using) had significantly higher mortality (HR 3.1), dementia risk (HR 8.1), and falls (HR 2.8) compared to trazodone. 2 However, this does not make trazodone a good choice—it simply means both medications are problematic for insomnia.

Recommended Alternative Medications

First-Line Option: Low-Dose Doxepin

Start with doxepin 3-6 mg at bedtime as the preferred alternative to Seroquel for sleep maintenance. 1, 3

• Evidence: Mean total sleep time improvement of 26-32 minutes vs placebo 3
• Wake after sleep onset: Reduction of 22-23 minutes vs placebo 3
• Sleep quality: Small-to-moderate improvement 3
• Safety profile: Comparable to placebo in clinical trials 3
• Key advantage: Minimal anticholinergic effects at low doses, no weight gain 4, 3

Critical dosing note: Use 3-6 mg only—NOT 20 mg or higher antidepressant doses, as higher doses shift from selective H1-receptor antagonism to broader tricyclic effects with increased adverse effects. 3

Second-Line Options: Benzodiazepine Receptor Agonists

If doxepin is contraindicated or ineffective:

• Zolpidem 10 mg: Effective for both sleep onset and maintenance; mean sleep latency reduction of 25 minutes, total sleep time improvement of 29 minutes 1
• Eszopiclone 2-3 mg: Particularly effective for sleep maintenance; total sleep time improvement of 28-57 minutes with moderate-to-large sleep quality improvement 1, 3
• Zaleplon 10 mg: Best for sleep onset only; very short half-life with minimal residual sedation 1

Third-Line Option: Ramelteon

Ramelteon 8 mg is appropriate for sleep onset insomnia, particularly in patients with substance use history, as it has zero addiction potential and is not DEA-scheduled. 1, 4

Transition Strategy from Seroquel

Assuming you're using low-dose Seroquel (12.5-50 mg) for sleep:

1. Abrupt discontinuation of Seroquel is generally safe at low doses used for sleep (unlike antipsychotic doses) 1
2. Start doxepin 3 mg on the same night you discontinue Seroquel 3
3. Titrate to doxepin 6 mg after 3-7 days if 3 mg provides insufficient benefit 3
4. Reassess after 1-2 weeks to evaluate efficacy on sleep latency, maintenance, and daytime functioning 4

Critical Safety Considerations

Why Seroquel Should Be Discontinued

• Not indicated for primary insomnia: The American Academy of Sleep Medicine explicitly warns against off-label use of atypical antipsychotics for chronic primary insomnia 4
• Significant adverse effects: Weight gain, metabolic syndrome, neurological side effects 4
• Increased mortality in older adults: HR 3.1 vs trazodone 2
• Dementia risk: HR 8.1 vs trazodone, HR 7.1 vs mirtazapine 2
• Fall risk: HR 2.8 vs trazodone 2

Drug Interaction Warning

If the patient is on other serotonergic medications (SSRIs, SNRIs), be aware that combining trazodone with quetiapine has precipitated serotonin syndrome in documented case reports. 5, 6 This is another reason to avoid trazodone entirely.

Non-Pharmacologic Treatment

Before or concurrent with any medication change, implement Cognitive Behavioral Therapy for Insomnia (CBT-I), which the American Academy of Sleep Medicine recommends as standard of care before pharmacotherapy. 1, 4 CBT-I demonstrates superior long-term outcomes with sustained benefits after discontinuation. 4

CBT-I components include: 4

• Stimulus control therapy
• Sleep restriction therapy
• Relaxation techniques
• Cognitive restructuring
• Sleep hygiene (avoiding caffeine/alcohol in evening, consistent sleep-wake times, limiting daytime naps to 30 minutes before 2 PM)

Common Pitfalls to Avoid

• Do not use trazodone 50 mg or higher for insomnia—it lacks efficacy evidence and has significant side effects 1
• Do not use doxepin 20 mg or higher for sleep—this shifts to antidepressant dosing with increased adverse effects 3
• Do not use diphenhydramine or other OTC antihistamines—strong anticholinergic effects cause confusion, urinary retention, fall risk 4
• Do not continue Seroquel long-term for primary insomnia given metabolic and mortality risks 4, 2
• Avoid long-acting benzodiazepines (lorazepam, temazepam >15 mg) due to accumulation, fall risk, and cognitive impairment, especially in older adults 1, 4