PTSD 101: Nine Off-Label Meds | The Carlat Psychiatry Podcast

Should psychiatrists stick with FDA-approved SSRIs like sertraline and paroxetine for PTSD, or consider off-label options like prazosin? This episode dives into the evidence, exploring prazosin’s benefits for PTSD nightmares and hyperarousal, alongside tips for titration and alternative treatments like fluoxetine, trazodone, and topiramate.
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00:00 Intro
00:04 Podcast

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When it comes to PTSD treatment, the debate between sticking to FDA-approved medications or exploring off-label options is ongoing. SSRIs like sertraline and paroxetine are FDA-approved but have limitations, including inconsistent efficacy in military trauma and significant side effects like sexual dysfunction, withdrawal symptoms, and weight gain. This episode of the Carlat Psychiatry Podcast delves into why some experts, including Dr. Chris Aiken and Kellie Newsome, recommend fluoxetine over FDA-approved SSRIs and why prazosin might be a first-line choice for PTSD patients with nightmares and nocturnal hyperarousal.

Prazosin, an alpha-1 antagonist, has shown significant benefits in reducing PTSD nightmares and hyperarousal, with additional benefits for daytime symptoms like hypervigilance, difficulty concentrating, and anhedonia. Despite a large 2018 trial casting doubt on its efficacy, meta-analyses continue to support prazosin for sleep and daytime PTSD symptoms. This episode provides practical guidance on starting and titrating prazosin, including dosage recommendations (starting at 1 mg QHS and titrating up to 12–16 mg/day) and monitoring for risks like orthostatic hypotension and falls. Learn why prazosin’s safety profile and tolerability make it a compelling choice, particularly for patients struggling with SSRI-induced apathy, sleep disruption, or sexual dysfunction.

For patients with alcohol use disorder, the combination of prazosin and cyproheptadine has shown promise in reducing alcohol consumption. The episode also explores other off-label options like clonidine, trazodone, mirtazapine, and topiramate, each with unique benefits and considerations for PTSD comorbidities. While SSRIs remain a standard recommendation, this podcast emphasizes patient-centered care, highlighting the importance of tailoring treatment to individual needs and symptoms.

Additionally, we tackle common misconceptions about medications like mirtazapine’s role in sleep apnea and clarify recent research errors, ensuring listeners stay informed with accurate and practical insights. Whether you’re considering prazosin, fluoxetine, or other pharmacological strategies for PTSD, this episode equips you with evidence-based recommendations and thoughtful commentary on managing this complex condition. Stay tuned for next week’s episode, where we’ll explore topiramate and additional off-label options for PTSD.