According to the National Institute of Health: Natural Library of Medicine, 40-60 out of 100 people who took an antidepressant (a Serotonin Reuptake Inhibitor or SSRI) noticed an improvement in their symptoms within 6-8 weeks. About 80% of people stop antidepressants within a month. Treating those with major depression is often a trial-and-error process. Less conventional or novel approaches in managing depression is called for when drug therapies or drug combinations are not effective or result in adverse effects.
Ketamine can have antidepressant effects as well as sedative, analgesic and anesthetic effects. It however, can also cause dissociative reactions and hallucinations. In a multi-center trial, 365 people with treatment resistant depression received either a 3 week course of intravenous Ketamine or electroconvulsive therapy (ECT). At 3 weeks 55% of the Ketamine recipients vs 41% of ECT recipients noted positive effects. At 6 months, a substantial proportion of patients in both groups had relapsed.
Esketamine is an isomer of Ketamine. A study of 676 patients with drug resistant antidepressant used Esketamine given as a nasal spray or oral quetiapine (Seorquel) commonly used as an augmenter along with an oral antidepressant. Remission rates were greater with Esketamine than with Quetiapine at 8 weeks (27% vs 18%) and at 32 weeks (49% vs 33%).
Changes in the gut microbiome play an integral role in depressive symptoms through bi-directional interactions with the brain. A meta analysis has suggested that probiotics alongside standard antidepressants can improve depressive symptoms. A randomized trail in the UK looked at 49 patients with moderately severe depression and incomplete response to an SSRI. Half had comorbid anxiety. After adding a multi strain probiotic (Bio-Kult Advanced;ADM Protein) or placebo for 8 weeks, improvement was greater in the probiotic than in placebo group at 4 and 8 weeks by using 2 depression scales and 2 anxiety scales. We need to take into account that this study was funded by the probiotic manufacturer.
Lastly, there is psilocybin. A single dose was compared with placebo in 104 patients with major depression. At 6 weeks, psilocybin recipients were 42% more likely than placebo (11%) recipients to have sustained response and remission (25% vs 9%).
Let us not forget the importance of psychotherapy which can enhance the effectiveness of drug therapies. The bottom line is that there are many more options than there used to be to help those with drug resistant depression.
References: N England J Med June 22, NEJM JW Gen Med July 1; 388:2315.
N England J Med Oct 5, NEJM JW Gen Med Nov 1; 389:1298.
NEJM JW Gen Med Aug 1, JAMA Psychiatry Aug 80:842
NEJM JW Gen Med Oct 1, JAMA Sept 5; 330:843.
Nikolova VL et al. Acceptability, tolerability, and estimates of putative treatment effects of probiotics as adjunctive treatment patients with depression: A randomized clinical trial. JAMA Psychiatry 2023 June 14 [e-pub]. (https://doi.org/10.1001/jamapsychiatry.2023.1817)