The Paradoxical Importance of Side Effects: Ketamine's Effect on Heart Rate Variability mediated by Drug High

This study investigated whether ketamine’s side effects can exert antidepressant effects. Eventually, this could be helpful for people with treatment resistant depression (TRD), namely individuals for whom at least two different types of antidepressants proved ineffective. Recently, psychedelic-assisted psychotherapy (PAP) has been introduced as an innovative treatment for TRD. Although PAP is very promising, it is not yet widely implemented, due to lack of adequate knowledge about the underlying working mechanism. Ketamine as an indicative tool, shows rapid antidepressant and psychedelic effects that are considered to be side effects. Heart rate variability (HRV) as a putative mechanism of the antidepressant effects of ketamine, is thought to act via cognitive symptoms of depression, such as rumination, since higher HRV indicates lower rumination. This study experimentally investigated the effects of ketamine infusion in healthy participants, to get a better understanding of the...Show moreThis study investigated whether ketamine’s side effects can exert antidepressant effects. Eventually, this could be helpful for people with treatment resistant depression (TRD), namely individuals for whom at least two different types of antidepressants proved ineffective. Recently, psychedelic-assisted psychotherapy (PAP) has been introduced as an innovative treatment for TRD. Although PAP is very promising, it is not yet widely implemented, due to lack of adequate knowledge about the underlying working mechanism. Ketamine as an indicative tool, shows rapid antidepressant and psychedelic effects that are considered to be side effects. Heart rate variability (HRV) as a putative mechanism of the antidepressant effects of ketamine, is thought to act via cognitive symptoms of depression, such as rumination, since higher HRV indicates lower rumination. This study experimentally investigated the effects of ketamine infusion in healthy participants, to get a better understanding of the working mechanisms. The ultimate goal of this research is to clarify the PAP working mechanism, which we hypothesize to be: ketamine increases HRV via its (psychedelic) side effects, which in turn decreases rumination, which increases PAP treatment success. This translated into the following research questions: ‘What are the effects of ketamine on the HRV’ and, ‘Are these effects possibly mediated by the side effects?’. The participants (N=15) received ketamine and placebo on different occasions in a crossover design. The HRV and the experienced side effects were measured on both occasions. The results showed that ketamine infusion significantly decreased HRV, an effect which was not significantly mediated by the side effects. In contrast to the hypothesis that ketamine would increase HRV through the side effects, the findings indicate that ketamine leads to an acute reduction in HRV. In conclusion, the findings reveal that the side effects did not mediate the relationship between ketamine and HRV, which does not provide support for the psychedelic assisted therapy's beneficial impact on individuals with MDD. Keywords: Major Depressive Disorder, ketamine, rumination, Heart Rate Variability, side EffectsShow less

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The Paradoxical Importance of Side Effects: Ketamine's Effect on Heart Rate Variability mediated by Drug High