The effects of ketamine on typical and atypical depressive symptoms

Abstract

Objective Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery–Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5), and atypical symptoms (measured using the Scale for Atypical Symptoms (SAS)). Methods Data from 68 participants with treatment‐resistant major depressive disorder (MDD) or bipolar depression were pooled from three separate, double‐blind, placebo‐controlled, crossover studies investigating ketamine's efficacy in depression. MDD participants were unmedicated; bipolar participants received therapeutic‐dose lithium or valproate. Clinical symptoms were collected preinfusion and up to 14 days postinfusion. Effect sizes were calculated for days 1 and 3 postinfusion. The primary measures of interest for this exploratory analysis were total MADRS, MADRS5, and SAS scores. Individual symptoms were also analyzed in an exploratory manner. Results Scores improved significantly at Day 1 postinfusion (MADRS: Cohen's d = 0.64; MADRS5: Cohen's d = 0.61; SAS: Cohen's d = 0.41) and continued to be significantly improved over placebo at Day 3 (MADRS: Cohen's d = 0.49; MADRS5: Cohen's d = 0.43; SAS: Cohen's d = 0.39). Effect sizes were greater for typical/melancholic than atypical symptoms at Day 1 postinfusion. Conclusion Ketamine appears to effectively treat both the typical/melancholic and atypical symptoms of depression, but may have early preferential effects for the former.

Ketamine treatment for depression: a review

“…Preliminary evidence suggests that anxious depression may respond better to ketamine treatment than non-anxious depression [ 49 , 50 ]. In addition, both typical (melancholic) and atypical depressive symptoms appear to respond to ketamine, though typical symptoms demonstrate greater effect sizes at earlier time points (i.e., 24 h) [ 51 ]. However, additional prospective controlled studies are needed to systematically confirm these results.…”

Low‐dose ketamine infusion in treatment‐resistant double depression: Revisiting the adjunctive ketamine study of Taiwanese patients with treatment‐resistant depression

“…The question regarding the symptom domains, such as melancholic, anxious distress, or atypical symptom domains, that are most alleviated by a low-dose ketamine infusion remains controversial Lucchese et al, 2021;Park et al, 2020;Wang et al, 2019). Wang et al reported that patients with melancholic or melancholic-anxious features were less likely to respond or remit and took longer to achieve response or remission with a treatment of six ketamine infusions than did those with anxious or no subtype In conclusion, only a 0.5 mg/kg ketamine infusion, but not a lower dose (0.2 mg/kg) of ketamine infusion, exerted rapid and sustained antidepressant and antisuicidal effects in patients with treatment-resistant double depression.…”

“…HDRS, 17-item Hamilton Rating Scale for Depression; MADRS, Montgomery-Åsberg Depression Rating Scale features(Wang et al, 2019). Park et al demonstrated that the effect sizes of a low-dose ketamine infusion against depression were greater for melancholic than atypical symptoms at Day 1 postinfusion(Park et al, 2020). Lucchese et al discovered that depression comorbid with anxiety disorder had a better response to a course of six subcutaneous esketamine infusions than it did to other treatments(Lucchese et al, 2021).…”

Ketamine in COVID‐19 patients: Thinking out of the box

“…[5][6][7] Recent data have come to show that, it effectively treats both typical/melancholic and atypical depressive symptoms, even though, the exact mechanism underlying its efficacy remains unclear. 5 Previous animal studies have unveiled that, ketamine generates an anti-inflammatory effect that could contribute to its antidepressant action. 8 After all, lowgrade inflammation, characterized by an increase in serum proinflammatory cytokines, including IL-6, IL-1β, CRP, and so forth, may play a role in depression pathogenesis and represents a good predictor of clinical response.…”

“…Ketamine, on the other hand, has been long used in the management of treatment-resistant-depression, as a nonselective NMDA receptor antagonist, utilising both its intranasal and intravenous form, even though the latter showing better efficacy. [5][6][7] Recent data have come to show that, it effectively treats both typical/melancholic and atypical depressive symptoms, even though, the exact mechanism underlying its efficacy remains unclear. 5 Previous animal studies have unveiled that, ketamine generates an anti-inflammatory effect that could contribute to its antidepressant action.…”