Is mirtazapine (Remeron) 15mg effective for treating Post-Traumatic Stress Disorder (PTSD)?

Mirtazapine 15 mg for PTSD

Mirtazapine at 15 mg daily is an effective treatment option for PTSD, with evidence showing significant symptom reduction, though it is not considered first-line therapy compared to SSRIs.

Evidence for Efficacy

Mirtazapine demonstrates clear benefit in treating PTSD symptoms based on controlled trial data. A placebo-controlled trial showed that 65% of patients on mirtazapine achieved treatment response compared to only 22% on placebo (RR 0.45,95% CI 0.22 to 0.94), though this is based on low-certainty evidence 1. An open-label study of combat veterans found significant reductions in PTSD symptoms, with CAPS scores decreasing from 87.5 to 64.4 (p = 0.01), and 4 of 13 patients achieving full remission 2.

Dosing Strategy

• Start at 15 mg at bedtime, which is the recommended initial dose 2, 3
• Titrate based on response to 15-45 mg daily over several weeks 2, 3
• The 15 mg dose may provide benefit within the first week for sleep disturbances and anxiety symptoms, though full antidepressant effect requires 2-4 weeks 3
• In the combat veteran study, doses ranged from 15-45 mg with good tolerability 2

Position in Treatment Algorithm

SSRIs remain the first-line pharmacotherapy for PTSD based on moderate-certainty evidence, with 58% response rates compared to 35% for placebo 1. However, mirtazapine serves as a valuable alternative, particularly when:

• SSRIs have failed or are not tolerated 1
• Prominent sleep disturbances and anxiety require early intervention 2, 3
• Weight loss or poor appetite are concerns (mirtazapine increases appetite) 2, 3

Mechanism Supporting PTSD Treatment

Mirtazapine's unique mechanism makes it theoretically suited for PTSD 4:

• Blocks presynaptic α2-adrenergic receptors, increasing noradrenergic activity 3, 5
• Enhances specific serotonergic neurotransmission at 5-HT1A receptors while blocking 5-HT2 and 5-HT3 receptors 3, 5
• This dual noradrenergic and serotonergic enhancement addresses the neurobiological dysfunction in PTSD 4

Tolerability Profile

Mirtazapine is generally well-tolerated with a favorable safety profile 2, 4:

• Common side effects: Sedation (beneficial for PTSD-related insomnia), increased appetite, and weight gain 2, 3
• Minimal adverse effects: Low anticholinergic effects, no cardiovascular concerns, and essentially no sexual dysfunction 3, 5
• Weight gain is expected: All subjects in the combat veteran study experienced weight increases, with one gaining 8.75 kg (8.4%) 2
• Metabolic monitoring needed: One patient developed diabetes mellitus (fasting glucose increased from 83 to 155 mg/dL) 2

Critical Monitoring Points

• Monitor fasting blood glucose, lipids, and weight at baseline and during treatment 2
• Assess for excessive sedation, particularly in the first weeks 3
• The once-daily bedtime dosing (elimination half-life 20-40 hours) optimizes tolerability 3
• Safe in overdose with minimal cardiovascular or respiratory effects 3

Comparative Effectiveness

While mirtazapine shows benefit, the evidence base is less robust than for SSRIs. The Cochrane review classified mirtazapine evidence as "low-certainty" compared to "moderate-certainty" for SSRIs 1. The single controlled trial included only 26 participants 1, though results were supported by the larger open-label study 2.

Clinical Caveats

• Sedation can be dose-dependent: Lower doses (15 mg) may cause more sedation than higher doses due to antihistamine effects 3
• Not mentioned in nightmare-specific guidelines: The American Academy of Sleep Medicine guidelines for PTSD-associated nightmares do not include mirtazapine in their recommendations, focusing instead on prazosin (Level A) and other agents 6
• Limited data on specific PTSD symptom clusters: Most evidence addresses global PTSD symptoms rather than specific domains like nightmares or hyperarousal 2, 4