The Impact of Ketamine for Treatment of Post-Traumatic Stress Disorder: A Systematic Review With Meta-Analyses.

BACKGROUND: Ketamine has been used in anesthesia, pain management, and major depressive disorder. It has recently been studied in patients with post-traumatic stress disorder (PTSD). OBJECTIVE: To determine the impact of ketamine on PTSD symptomatology and depression scores. METHODS: We conducted a literature search of Medline 1960 to May 20, 2023, and found 6 randomized controlled trials that met our inclusion criteria. We extracted data on the Clinician-Administered PTSD (CAPS), PTSD Checklist (PCL), or Montgomery-Asberg Depression Rating (MADRS) scales. RESULTS: The use of ketamine significantly reduced CAPS scores (n = 5, MD: -10.63 [95% CI -14.95 to -6.32]), PCL scores (n = 3, MD: -6.13 [95% CI -8.61 to -3.64]), and MADRS scores (n = 3, MD: -6.33 [95% CI -8.97 to -3.69]) at the maximal follow-up times versus control. Significant benefits were found at day 1 and weeks 1, 2, and 4 for CAPS and PCL scores as well as MADRS scores at day 1, week 1, and week 4 for ketamine versus control. The time to PTSD relapse was prolonged in the patients receiving ketamine versus control (n = 2, 15.74 days [95% CI 3.57 to 29.91 days]). More dry mouth (n = 2, OR 5.85 [95% CI 1.32 to 25.95]), dizziness (n = 2, OR 3.83 [95% CI 1.28 to 11.41]), and blurred vision (n = 2, OR 7.57 [1.00 to 57.10]) occurred with ketamine than control therapy. CONCLUSIONS AND RELEVANCE: Ketamine modestly reduced PTSD and depression scores as early as 1 day of therapy, but the longevity of effect needs to be determined. Given similar magnitude of benefit with SSRIs and venlafaxine, ketamine would not supplant these traditional options for chronic use.

MDMA-Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta-Analysis.

This article discusses current literature on the use of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in the treatment of posttraumatic stress disorder (PTSD). MDMA, the intended active ingredient in illicit Ecstasy or Molly products, is a psychedelic that causes an elevated mood, feeling of bonding, and increased energy. In MDMA-assisted psychotherapy, patients are subjected to 2 or 3 multihour sessions of therapy with a team of psychiatrists. The dosing of MDMA is used to allow the therapist to probe the underlying trauma without causing emotional distress. The use of MDMA-assisted psychotherapy treatment reduced patient's Clinician-Administered PTSD Scale (CAPS) scores from baseline more than control psychotherapy (-22.03; 95%CI, -38.53 to -5.52) but with high statistical heterogeneity. MDMA-assisted psychotherapy enhanced the achievement of clinically significant reductions in CAPS scores (relative risk, 3.65; 95%CI, 2.39-5.57) and CAPS score reductions sufficient to no longer meet the definition of PTSD (relative risk, 2.10; 95%CI, 1.37-3.21) with no detected statistical heterogeneity. While therapy was generally safe and well tolerated, bruxism, anxiety, jitteriness, headache, and nausea are commonly reported. While MDMA-assisted psychotherapy has been shown to be an effective therapy for patients with PTSD with a reasonable safety profile, use of unregulated MDMA or use in the absence of a strongly controlled psychotherapeutic environment has considerable risks.

Impact of Interferons and Biological Drug Inhibitors of IL-2 and IL-6 on Small-Molecule Drug Metabolism Through the Cytochrome P450 System.

OBJECTIVE: Assess the impact of interferons and interleukin (IL)-2 and IL-6 inhibitors on cytochrome P450 (CYP) drug metabolism in human subjects. DATA SOURCES: PubMed search from 1980 to March 31, 2021, limited to human subjects and English language via search strategy: (biological drug names) [AND] (cytochrome [OR] CYP metabolism). STUDY SELECTION AND DATA EXTRACTION: Narrative review of human studies assessing biological drugs in select classes that affect CYP drug metabolism. DATA SYNTHESIS: Exogenous interferons suppress CYP1A2 (theophylline, caffeine, antipyrone) clearance by 20% to 49% in patients; have minimal impact on CYP3A4 (midazolam and dapsone), CYP2C9 (tolbutamide), or CYP2C19 (mephenytoin) metabolism; and increase CYP2D6 (debrisoquine, dextromethorphan) metabolism. Biological IL-2 inhibitors (basiliximab, daclizumab) have no effect on metabolism via CYP1A2 (caffeine), CYP2C9 (s-warfarin), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam, tacrolimus) but may enhance CYP3A4 (cyclosporin) metabolism over time. IL-6 inhibitors (sirukumab, tocilizumab, sarilumab) significantly enhance metabolism via CYP2C9 (s-warfarin), CYP2C19 (omeprazole), and CYP3A4 (simvastatin, midazolam) and reduce metabolism via CYP1A2 (caffeine). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Patients using interferons, IL-2, or IL-6 blocking drugs at steady state with CYP substrates could have altered drug metabolism and experience adverse events. With interferons and biological anti-inflammatory drugs, some isoenzymes will be inhibited, whereas others will be enhanced, and the magnitude of the effect can sometimes be significant. In clinical practice, clinicians may consider these metabolic changes as an additive effect to a patient's entire disease and medication profile when determining risk/benefit of treatment. CONCLUSIONS: Interferon therapy or inflammatory suppression via IL-2 or IL-6 can alter steady-state concentrations of CYP-metabolized small-molecule drugs.