Posttraumatic Stress Disorder Psychopharmacology Algorithm Update—2024-2025

Since the last publication of the Psychopharmacology Algorithm Project at the Harvard South Shore Program Posttraumatic Stress Disorder (PTSD) algorithm in 2022, additional evidence has reinforced key treatment recommendations. Prazosin remains the first-line treatment for PTSD-related sleep impairment, including nightmares and disturbed awakenings, and it may be useful for individuals with comorbid alcohol use disorder and comorbid headaches. After treating PTSD insomnia, if significant daytime symptoms remain, a selective serotonin reuptake inhibitor (SSRI, sertraline or paroxetine are suggested), and this may be augmented by an antipsychotic (consider aripiprazole first) if psychotic symptoms, if any, do not respond to the SSRI. If results are still unsatisfactory, a second SSRI or a selective norepinephrine reuptake inhibitor (SNRI) could be considered, though they offer no benefit for hyperarousal symptoms, and prazosin may also be tried for residual daytime symptoms. This update also evaluates emerging treatments, including transcranial magnetic stimulation, direct current stimulation, stellate ganglion block, and pimavanserin, though concluding that current evidence does not yet warrant their inclusion in the core algorithm. This update provides clinicians with an evidence-informed approach to pharmacological PTSD management based on the latest available data.