Vintage Treatments for PTSD: A Reconsideration of Tricyclic Drugs

Serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors (SSRI) are the first-line recommended drug treatments for post-traumatic stress disorder (PTSD); but despite their benefits, much residual pathology remains and no new drugs have yet emerged with a clearly demonstrated benefit for treating the disorder. A case is made that tricyclic drugs deserve a closer look, based on their ability to affect several of the main neurotransmitters that are relevant to PTSD. Their promising efficacy, which was shown 30 years ago, had not been followed up, until a recent trial of desipramine found advantages over a SSRI in PTSD with comorbid alcohol dependence. Opportunities exist for studying newer and purportedly safer tricyclic formulations, as well as further the work with older, established compounds. A reappraisal of their risk:benefit ratio seems in order, when treating PTSD.