Association between depression subtypes and response to repeated‐dose intravenous ketamine

Abstract

Association between depression subtypes and response to repeated-dose intravenous ketamine.Objective: About half or more of treatment-resistant depressed patients do not respond to ketamine, and few clinical predictors to gauge the most likely antidepressant response have been proposed. We explored whether depression subtypes are associated with response to ketamine. Method: Ninety-seven participants with depression were administered six repeated-dose intravenous ketamine and assessed for depression (Montgomery-Asberg Depression Rating Scale, MADRS), anxiety (Hamilton Anxiety Rating Scale, HAMA), and suicidal ideation (Beck Scale for Suicidal Ideation, SSI) at baseline, 24 h after each infusion, and 2 weeks after the whole treatment. Participants were classified by melancholic/ anxious subtype. Individuals who met criteria for neither or both subtypes were classified separately, resulting in four mutually exclusive groups. Results: Patients with melancholic or melancholic-anxious features were less likely to respond (e.g., day 13, melancholic-anxious vs. anxious, OR 0.138, 95% CI 0.032-0.584, P = 0.007) or remit (e.g., day 26, melancholic vs. no subtype, OR 0.182, 95% CI 0.035-0.960, P = 0.045) and took longer to achieve response/remission than those with anxious or no subtype features. Faster HAMA score reductions were observed in patients with anxious or melancholic-anxious features, and faster SSI score reductions were observed among those with melancholic-anxious features. Conclusion: Our study shows promising results for ketamine as a novel antidepressant preferentially for the treatment of non-melancholic or anxious depression. Significant outcomes• Compared to those with pure anxious or no subtype features, patients with pure melancholic or melancholic-anxious features were less likely to respond or remit.• Patients with melancholic or melancholic-anxious depression took longer to achieve response or remission and generally improved less in depression, anxiety, and suicidal ideation than those with pure anxious features or no subtype features.• All subtype groups exhibited significant symptom reductions throughout the treatment, while faster score reductions on HAMA were observed in patients with anxious or melancholic-anxious features, and faster score reductions on SSI-I and SSI-total were shown in patients with melancholic-anxious features. Limitations• Only two depression subtypes (i.e., melancholic and anxious) were classified in the present study drawing into question the confounding effect of other subtypes.• All patients included were treatment-resistant or with suicidality, which limits the generalizability of our results to patients with depression as a whole.• Although patients continued medications that they were receiving at screening at the same stable dosages throughout the study, we cannot rule out the influence of these medications on depressive symptoms.

The effectiveness of intravenous ketamine in adults with treatment-resistant major depressive disorder and bipolar disorder presenting with prominent anxiety: Results from the Canadian Rapid Treatment Center of Excellence

“…Significant reductions in overall depressive symptom severity, as measured by QIDS-SR 16 scores, were seen in both the anxious-distress and low–anxious distress groups with greater reductions observed in the anxious-distress group.We also observed a significant and sustained reduction in SI with IV ketamine treatment in both the anxious-distress and low–anxious distress groups. Anxiety symptoms also significantly reduced in patients with anxious depression, a finding that aligns with extant studies (Ionescu et al, 2015; Salloum et al, 2019; Wang et al, 2019).…”

“…Available studies indicate that IV ketamine may preferentially reduce depression symptoms in patients presenting with anxious depression compared with non–anxious depression. For example, it has been reported that individuals meeting the criteria for anxious depression ( n = 84) exhibited significantly higher response and remission rates with six repeated doses of IV ketamine (Wang et al, 2019). It has also been reported that IV ketamine and its enantiomer esketamine are able to significantly reduce severe anxiety symptoms after a single infusion (Falk et al, 2020; Ionescu et al, 2015; Salloum et al, 2019).…”

The effects of ketamine on typical and atypical depressive symptoms

“…Given the differences in biological substrates elaborated above, it is therefore possible that individuals with atypical depression might also exhibit a differential response to ketamine. In a recent analysis, Wang and colleagues (20) – while not specifically examining atypical depression – demonstrated relatively greater (or more rapid) response to intravenous ketamine in individuals with non‐melancholic or anxious depression.…”

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.…”

“…Trajectory of depressive symptoms. 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).…”