Management of Treatment-Resistant Posttraumatic Stress Disorder

Purpose of review The management of treatment-resistant posttraumatic stress disorder (TRPTSD) is a complex clinical challenge, and many patients may continue to endure a heavy symptom burden, even despite the best available treatments. We review the recent literature to provide an update on the evidence base and offer guidance to clinicians on available approaches, including a number of novel and emerging options. Recent findings If adequate trials of treatment with first-line antidepressants (SSRIs or venlafaxine) or trauma-focused psychotherapy have failed, dosage increase, switching to an alternative first-line option, or combining medication and psychotherapy are reasonable initial approaches. If these remain insufficient, augmentation strategies should be offered, including addition of second-generation antipsychotics (such as risperidone) or the adrenergic antagonist prazosin (especially if sleep disturbance or nightmares are problematic). Further options include the use of other antidepressants (most notably mirtazapine, duloxetine, and trazodone), and the anticonvulsants topiramate or lamotrigine, though the evidence for these is relatively weak. Having tried all these possibilities, the clinician may wish to suggest complementary approaches such as yoga, mindfulness meditation, or acupuncture for symptom reduction and overall well-being. Emerging alternatives, if available, could also be considered, such as augmentation of exposure therapy with d-cycloserine or MDMA, or the use of device-based brain stimulation (such as transcranial magnetic stimulation), though the evidence for these is still preliminary. Summary Comprehensive assessment of TRPTSD, including a thorough evaluation of associated comorbidity, should inform individualized care, incorporating a process of shared decision-making. Despite the complex clinical challenge of TRPTSD, clinicians should remain hopeful however, that translational neuroscience and clinical trials of emerging approaches will allow progressively better treatment alternatives to be established.