Evidence-Based Reviews

Treating PTSD: A review of 8 studies

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Conclusions/limitations

  • HCORT does not improve PTSD symptoms as assessed with the CAPS and PDS, or depression as assessed with the BDI.
  • The main limitation of this study is generalizability.
  • Further studies are needed to determine whether PE with HCORT could benefit veterans with indicators of enhanced glucocorticoid sensitivity, mild TBI, or postconcussive syndrome.

4. Inslicht SS, Niles AN, Metzler TJ, et al. Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD. Neuropsychopharmacology. 2022;47(11):1945-1952

PE, one of the most well-researched therapies for PTSD, is based on fear extinction. Exploring pharmacotherapies that improve fear extinction learning and their potential as supplements to PE is gaining increased attention. Such pharmacotherapies aim to improve the clinical impact of PE on the extent and persistence of symptom reduction. This study evaluated the effects of HCORT and D-cycloserine (DCS), a partial agonist of the N-methyl-D-aspartate (NMDA) receptor, on the learning and consolidation of fear extinction in patients with PTSD.10

Study design

  • This double-blind, placebo-controlled, 3-group experimental design evaluated 90 individuals with PTSD who underwent fear conditioning with stimuli that was paired (CS+) or unpaired (CS−) with shock.
  • Participants were veterans and civilians age 18 to 65 recruited from VA outpatient and community clinics and internet advertisements who met the criteria for PTSD or subsyndromal PTSD (according to DSM-IV criteria) for at least 3 months.
  • Exclusion criteria included schizophrenia, bipolar disorder, substance abuse or dependence, alcohol dependence, previous moderate or severe head injury, seizure or neurological disorder, current infectious illness, systemic illness affecting CNS function, or other conditions known to affect psychophysiological responses. Excluded medications were antipsychotics, mood stabilizers, alpha- and beta-adrenergics, benzodiazepines, anticonvulsants, antihypertensives, sympathomimetics, anticholinergics, and steroids.
  • Extinction learning took place 72 hours after extinction, and extinction retention was evaluated 1 week later. Placebo, HCORT 25 mg, or DCS 50 mg was given 1 hour before extinction learning.
  • Clinical measures included PTSD diagnosis and symptom levels as determined by interview using CAPS and skin conduction response.

Outcomes

  • The mean shock level, mean pre-stimulus skin conductance level (SCL) during habituation, and mean SC orienting response during the habituation phase did not differ between groups and were not associated with differential fear conditioning. Therefore, variations in shock level preference, resting SCL, or SC orienting response magnitude are unlikely to account for differences between groups during extinction learning and retention.
  • During extinction learning, the DCS and HCORT groups showed a reduced differential CS+/CS− skin conductance response (SCR) compared to placebo.
  • One week later, during the retention testing, there was a nonsignificant trend toward a smaller differential CS+/CS− SCR in the DCS group compared to placebo. HCORT and DCS administered as a single dosage facilitated fear extinction learning in individuals with PTSD symptoms.

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