Ketamine Treatment
Embarking on your Journey: Discovering the possibility of Ketamine Therapy
Spectrum Psychiatry
- Why Ketamine?
- Ketamine is one of the most effective ways to treat TRD (treatment-resistant depression). Ketamine treatment also promotes the growth of synaptic connections and brain plasticity.
- Why Ketamine?
- Ketamine can also help with the activation of AMPA receptors which helps increase the synaptic activity.
Spectrum Psychiatry
Benefits of Ketamine
Ketamine is not limited to individuals living with depression but the possibilities reach beyond.
- Ketamine is effective, safe, and acceptable treatments for individuals living with depression.
- Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. In a meta-analysis(reference #1) where authors used pooled data from 36 studies (2903 participants, 57% female, 45.1 +/- 7.0 years), nine trials used esketamine, while the rest used racemic ketamine. The overall study quality was high. Treatment with any form of ketamine was associated with improved response (RR=2.14; 95% CI, 1.72-2.66; I2=65%), remission (RR=1.64; 95% CI, 1.33-2.02; I2=39%), and depression severity (d=-0.63; 95% CI, -0.80 to -0.45; I2=78%) against placebo. Overall, there was no association between treatment with any form of ketamine and retention in treatment (RR=1.00; 95% CI, 0.99-1.01; I2<1%).
- Racemic ketamine appears to be more efficacious than esketamine for the treatment of depression
- In a systematic review and meta-analysis(reference #2) study which aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar depression, authors compared response and remission from depression, change in depression severity, suicidality, retention in treatment. 24 trials representing 1877 participants were pooled. Racemic ketamine relative to esketamine demonstrated greater overall response (RR = 3.01 vs. RR = 1.38) and remission rates (RR = 3.70 vs. RR = 1.47), as well as lower dropouts (RR = 0.76 vs. RR = 1.37).
- Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation.
- Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. Individual participant data were obtained from 10 of 11 identified comparison intervention studies that used either saline or midazolam as a control treatment. The analysis included only participants who had suicidal ideation at baseline (N=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (the Montgomery-Åsberg Depression Rating Scale [MADRS] or the Hamilton Depression Rating Scale [HAM-D]) and self-report scales (the Quick Inventory of Depressive Symptomatology-Self Report [QIDS-SR] or the Beck Depression Inventory [BDI]), obtained for up to 1 week after ketamine administration. Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen's d=0.48-0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. Ketamine's effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms. Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation. Ketamine's effects on suicidal ideation were partially independent of its effects on mood, although subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation.
- Ketamine is effective in treatment-resistant Bipolar Disorder
- Authors studied(reference #4) the real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression. This study was conducted in a community clinic in Mississauga, Ontario (Canadian Rapid Treatment Centre of Excellence; Braxia Health). In this observational study (NCT04209296), patients with treatment-resistant bipolar I/II depression (n = 66) received four sub-anesthetic doses of IV ketamine (0.5-0.75 mg/kg) over a two-week period. Symptoms of depression, suicidality, anxiety, and functioning were assessed with validated self-report measures. Statistically and clinically significant antidepressant effects were observed in the overall sample, as measured by the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR16 ) with further reductions in depressive symptoms observed after each subsequent infusion (n = 66; mean QIDS-SR16 reduction of 6.08+/-1.39; p < 0.0001). Significant reductions of suicidal thoughts (QIDS-SR16 -Suicide Item) and anxiety (Generalized Anxiety Disorder-7) were also observed with functional improvements on the Sheehan Disability Scale (p < 0.0001 on all measures). Moreover, the response rate (QIDS-SR16 total score decrease ≥50% from baseline) was 35% and remission rate (QIDS-SR16 total score ≤5) was 20% after four infusions. Infusions were generally well tolerated with treatment-emergent hypomania observed in only three patients (4.5%) with zero cases of mania or psychosis. Real-world effectiveness of ketamine for bipolar depression was observed. Repeated doses were associated with greater symptom reduction and adequate tolerability.
- Ketamine is effective for PTSD
- Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. In a randomized controlled trial(Reference #6), researchers tested the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD. Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures. The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events. This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD.
References
Our Sources
- Bahji A, Zarate CA, Vazquez GH. Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis. Expert Opin Drug Saf. 2022 Jun;21(6):853-866. doi: 10.1080/14740338.2022.2047928. Epub 2022 Mar 9. PMID: 35231204; PMCID: PMC9949988. https://pubmed.ncbi.nlm.nih.gov/35231204/
- Bahji A, Vazquez GH, Zarate CA Jr. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. J Affect Disord. 2021 Jan 1;278:542-555. doi: 10.1016/j.jad.2020.09.071. Epub 2020 Sep 23. Erratum in: J Affect Disord. 2020 Nov 20;: PMID: 33022440; PMCID: PMC7704936. https://pubmed.ncbi.nlm.nih.gov/33022440/
- Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, Sos P, Wang G, Zarate CA Jr, Sanacora G. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry. 2018 Feb 1;175(2):150-158. doi: 10.1176/appi.ajp.2017.17040472. Epub 2017 Oct 3. PMID: 28969441; PMCID: PMC5794524. https://pubmed.ncbi.nlm.nih.gov/28969441/
- Fancy F, Rodrigues NB, Di Vincenzo JD, Chau EH, Sethi R, Husain MI, Gill H, Tabassum A, Mckenzie A, Phan L, McIntyre RS, Rosenblat JD. Real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression. Bipolar Disord. 2023 Mar;25(2):99-109. doi: 10.1111/bdi.13284. Epub 2022 Dec 26. PMID: 36516343. https://pubmed.ncbi.nlm.nih.gov/36516343/
- Lu YY, Lin CH, Lane HY. Mania following ketamine abuse. Neuropsychiatr Dis Treat. 2016 Jan 27;12:237-9. doi: 10.2147/NDT.S97696. PMID: 26869791; PMCID: PMC4737325. https://pubmed.ncbi.nlm.nih.gov/26869791/
- Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, Jha MK, Horn SR, Kautz M, Corniquel M, Collins KA, Bevilacqua L, Glasgow AM, Brallier J, Pietrzak RH, Murrough JW, Charney DS. A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Am J Psychiatry. 2021 Feb 1;178(2):193-202. doi: 10.1176/appi.ajp.2020.20050596. Epub 2021 Jan 5. PMID: 33397139. https://pubmed.ncbi.nlm.nih.gov/33397139/