Should a patient taking sertraline (selective serotonin reuptake inhibitor) 150mg and prazosin (alpha-adrenergic blocker) for nightmares and anxiety, who is having trouble sleeping, start trazodone or have their prazosin dose increased?

Medication Management for Sleep Disturbance in Patient on Sertraline and Prazosin

Direct Recommendation

Increase prazosin dose first before adding trazodone, as prazosin remains the first-line pharmacologic agent for nightmares and can improve sleep quality when optimally dosed, with trazodone reserved as adjunctive therapy if prazosin optimization fails to adequately address insomnia. 1

Rationale for Prazosin Optimization

Prazosin should be titrated upward as the initial intervention because:

• The American Academy of Sleep Medicine identifies prazosin as the primary pharmacologic treatment for PTSD-associated nightmares, with effective doses ranging from 3-15 mg at bedtime 1
• The average effective dose is approximately 3 mg, though chronic PTSD often requires higher doses with mean effective doses of 9.5-15.6 mg 1
• Prazosin demonstrated superiority over placebo in reducing nightmare frequency and improving sleep quality (PSQI scores) in multiple randomized controlled trials 1
• The current prazosin dose may be subtherapeutic if nightmares and sleep disturbance persist 1

Titration protocol:

• Start increases of 1-2 mg every few days until nightmares improve or side effects emerge 1
• Monitor for orthostatic hypotension during titration, though this is generally well-tolerated 1
• Target dose range of 3-15 mg at bedtime based on response 1

Important Caveat Regarding Prazosin and SSRIs

There is a critical interaction to consider: Prazosin efficacy may be reduced in patients taking selective serotonin reuptake inhibitors like sertraline 1. One study showed decreased prazosin response in participants receiving SSRIs, with total CAPS scores decreasing by 30.1 ± 3.8 in those not taking SSRIs versus only 9.6 ± 6.8 in those taking SSRIs 1. However, prazosin still demonstrated benefit even in SSRI-treated patients, just with attenuated response 1.

When to Consider Adding Trazodone

Trazodone should be considered as adjunctive therapy if:

• Prazosin optimization (doses of 10-15 mg) fails to adequately control nightmares or improve sleep 1, 2
• Insomnia persists despite nightmare reduction with prazosin 1, 2
• The patient requires additional sleep maintenance support 2, 3

Trazodone dosing for nightmares and insomnia:

• Effective dose range for PTSD-associated nightmares is 50-200 mg nightly, with mean effective dose of 212 mg/day 1, 2
• 72% of patients experienced decreased nightmare frequency from 3.3 to 1.3 nights per week 1, 2
• 92% reported improvement in sleep onset and 78% in sleep maintenance 2
• Start at 25-50 mg and titrate upward based on response 4, 2

Critical Safety Considerations for Trazodone

Significant side effects require careful monitoring:

• Priapism occurs in approximately 12% of patients - clinicians must directly ask about this side effect 2
• 60% of patients experience side effects, particularly daytime sedation and dizziness 1, 2
• 19% discontinued trazodone due to intolerable side effects including priapism (5 subjects), daytime sedation (5 subjects), and other adverse effects 1, 2
• Use caution in patients with cardiovascular disease due to potential for orthostatic hypotension and cardiac effects 4, 5

Algorithmic Approach

Step 1: Increase prazosin by 1-2 mg every few days, targeting 10-15 mg at bedtime 1

Step 2: Assess response after 2-3 weeks of optimized prazosin dosing 1

Step 3: If nightmares improve but insomnia persists, or if nightmares remain problematic despite prazosin doses of 10-15 mg, add trazodone 50 mg at bedtime 1, 4, 2

Step 4: Titrate trazodone to 100-200 mg as needed for effect, monitoring for priapism and daytime sedation 1, 2

Common Pitfalls to Avoid

• Do not add trazodone without first optimizing prazosin dose, as many patients respond to higher prazosin doses alone 1
• Do not forget to directly ask about priapism when prescribing trazodone, as this serious side effect occurs more frequently than expected 2
• Do not ignore the potential SSRI-prazosin interaction - patients on sertraline may require higher prazosin doses or may have attenuated response 1
• Do not use trazodone as monotherapy for nightmares when prazosin has not been adequately trialed, as prazosin has stronger evidence as first-line therapy 1