Happiness during ketamine infusion predicts treatment-resistant depression outcomes

Subjective happiness during ketamine infusion may be linked to a reduction in depressive symptoms during follow-up, according to study results published in Journal of Clinical Psychiatry.

“Several studies have investigated the clinical predictors of treatment response to ketamine infusion in patients with [treatment-resistant depression], suggesting that a family history of an alcohol use disorder in a first-degree relative, non-melancholic and melancholic-anxious features, moderate or severe anhedonia at baseline, and the absence of a prior suicide attempt predicted the likelihood of response,” Mu-Hong Chen, MD, PhD, of the division of psychiatry at National Yang-Ming University in Taiwan, and colleagues wrote. “However, only a few studies have examined the relationship between subjective psychological experience during ketamine infusion and the antidepressant response of ketamine infusion in patients with [treatment-resistant depression.]”

Results of prior studies suggested that ketamine may potentially increase subjective happiness among healthy individuals. In the current study, Chen and colleagues aimed to determine the association between ketamine infusion and subjective happiness among 71 adults with treatment-resistant depression according to DSM-4-TR criteria. Participants were randomly assigned to receive a 40-minute ketamine or normal saline placebo infusion. Prior to infusion, at 40 and 240 minutes post-infusion, as well as sequentially on days 2 to 7 and 14 post-infusion, the investigators used the 17-item Hamilton Depression Rating Scale to measure depressive symptoms. Further, they used the visual analog scale for happiness (VASH) to assess happiness during infusion and the positive symptoms subscale of the Brief Psychiatric Rating Scale (BPRS-P) to measure ketamine’s potential psychotomimetic effects.

Results showed infusion response type, or happiness vs. nonhappiness, significantly predicted the trajectory of post-infusion depressive symptoms for both the two-factor ketamine vs. placebo model and the three factor 0.5 mg/kg vs. 0.2 mg/kg of ketamine vs. placebo model, according to a generalized estimating equation model. The researchers observed no association between changes in VASH and BPRS-P measures.

“Further studies may be required to validate our findings and to investigate the neurobiological mechanism between ketamine-induced happiness and the antidepressant effect of ketamine infusion,” Chen and colleagues wrote.

In a related editorial, George I. Papakostas, MD, of Massachusetts General Hospital, noted several questions that these findings raise, one of which centers around the generalizability of these findings.

“There is a need to replicate these findings, especially in groups of different racial and ethnic backgrounds,” Papakostas wrote. “In turn, this brings up the question of whether the construct of happiness as used in this study is understood similarly or differently among patients of various backgrounds and whether that would result in discrepant findings. A brief review conducted by the authors of the article suggests that their finding may, indeed, be generalizable. Nonetheless, a replication in a variety of groups would only strengthen this finding.”