Frontiers | Intranasal Ketamine for Depression in Adults: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials | Psychology

Background: There is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aimed to assess the efficacy and safety of intranasal ketamine in the treatment of major depressive disorder, especially treatment-resistance depression. Method: We searched Medline, EMBASE, and the Cochrane Library until 1 April 2020 to identify double-blind, randomized controlled trials with allocation concealment evaluating intranasal ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The outcome measures were MADRS score improved from baseline, clinical response and remission, dissociative symptoms, and Common adverse events. The Analyses employed a random-effects model. Results: Data were synthesized from five RCTs employing an intranasal esketamine and one RCT employing intranasal ketamine, representing 840 subjects in parallel arms and 18 subjects in cross-over designs [n=858 with major depressive disorder (MDD), n=792 with treatment resistant depression (TRD)]. WMD of MADRS score decreased was observed 6.16 (95% CI 4.44–7.88) in 2-4 hours, 9.96 (95% CI 8.97–10.95) in 24 hours, 4.09 (95% CI 2.18–6.00) in 28 days. The pooled RR was 3.55 (95% CI 1.5–8.38, z=2.89, p<0.001) for clinical remission and 3.22 (95% CI 1.85–5.61, z=4.14, p<0.001) for clinical response at 24 hours, while the pooled RR was 1.7 (95% CI 1.28–2.24 z=3.72, p<0.001) for clinical remission and 1.48 (95% CI 1.17–1.86, z=3.28, p<0.001) for clinical response at 28 days. Intranasal ketamine was associated with transient dissociative symptoms and common adverse events occurring, but no persistent psychosis or affective switches. Conclusion: Our meta-analysis suggests that repeatedly intranasal ketamine conducted a fast-onset antidepression effect in unipolar depression, while the mild and transient adverse effects were acceptable.
— Read on www.frontiersin.org/articles/10.3389/fpsyg.2021.648691/full

‘The ketamine blew my mind’: can psychedelics cure addiction and depression? | Health & wellbeing | The Guardian

This week sees the opening of the first UK high-street clinic offering psychedelic-assisted therapy. Could popping psilocybin be the future of mental healthcare?
— Read on amp.theguardian.com/lifeandstyle/2021/mar/13/it-blew-my-mind-can-psychedelic-drugs-cure-addiction-depression

Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study | Translational Psychiatry

Recently, low-dose ketamine has been proposed as a rapid-acting treatment option for suicidality. The majority of studies to date have utilised intravenous (IV) ketamine, however, this route of administration has limitations. On the other hand, oral ketamine can be administered in a range of settings, which is important in treating suicidality, although studies as to safety and feasibility are lacking. n = 32 adults (aged 22–72 years; 53% female) with chronic suicidal thoughts participated in the Oral Ketamine Trial on Suicidality (OKTOS), an open-label trial of sub-anaesthetic doses of oral ketamine over 6 weeks. Participants commenced with 0.5 mg/kg of ketamine, which was titrated to a maximum 3.0 mg/kg. Follow-up assessments occurred at 4 weeks after the final dose. The primary outcome measure was the Beck Scale for Suicide Ideation (BSS) and secondary measures included scales for suicidality and depressive symptoms, and measures of functioning and well-being. Mean BSS scores significantly reduced from a high level of suicidal ideation at the pre-ketamine (week 0) timepoint to below the clinical threshold at the post-ketamine (week 6) timepoint. The proportion of participants that achieved clinical improvement within the first 6 weeks was 69%, whereas 50% achieved a significant improvement by the follow-up (week 10) timepoint. Six weeks of oral ketamine treatment in participants with chronic suicidality led to significant reduction in suicidal ideation. The response observed in this study is consistent with IV ketamine trials, suggesting that oral administration is a feasible and tolerable alternative treatment for chronic suicidality.
— Read on www.nature.com/articles/s41398-021-01230-z