Buddhist-like opposite diminishing and non-judging during ketamine infusion are associated with antidepressant response: an open-label personalized-dosing study

Abstract

Background: Cognition that is not dominated by thinking in terms of opposites (opposite diminishing) or by making judgments (non-judging) can be found both in Buddhist/mindfulness contexts and in mental states that are fostered by dissociative psychedelics (N-methyl-D-aspartate antagonists) such as ketamine. Especially for the Buddhist/mindfulness case, both opposite diminishing and non-judging have been proposed to relate to mental well-being. Whether ketamine-occasioned opposite diminishing and/or non-judging relate to increased mental well-being in the form of antidepressant response is unknown, and was investigated in the present study.Methods: In this open-label outpatient study, the dose level and frequency for the ketamine infusions were adjusted individually in close consultation with the patients suffering from depression with the overall goal to maximize antidepressant benefits—a novel dose regimen that we term personalized antidepressant dosing. In general, treatment started with an initial series of ketamine infusions with a dosage of 0.5 mg/kg body weight and was then adjusted (usually increased). A possible relationship between ketamine-induced antidepressant benefits and retrospectively reported peri-infusion experiences of opposite diminishing and non-judging was assessed based on a total of 45 ketamine-infusion treatment sessions from 11 different patients suffering from depression. Opposite diminishing and non-judging were measured with the two items from the Altered States of Consciousness Inventory (ASCI) that measure these concepts. Depression was measured with the Beck Depression Inventory (BDI-II).Results: Peri-infusion experiences of both opposite diminishing and non-judging were associated with antidepressant responses confirming our hypothesis. Furthermore, opposite diminishing and non-judging were closely related to one another while relating to antidepressant response in distinguishable ways.Conclusion: Future controlled randomized trials with dissociative and other psychedelics and with a larger number of participants are needed to establish the possible link of psychedelically induced opposite diminishing and non-judging with an antidepressant response more firmly.

Case report: Maintaining altered states of consciousness over repeated ketamine infusions may be key to facilitate long-lasting antidepressant effects: some initial lessons from a personalized-dosing single-case study

“…After these three initial infusions, the patient's individual response (tolerability, dissociation, and change in depressive symptomatology) determined the frequency of the subsequent infusion schedule and possible dose adaptions, to facilitate consciousness-altering effects and maximize the treatment outcome (cf. personalized antidepressant dose regimen (27)). Therefore, the treatment intervals were adjusted by the treating physician in close consultation with the patient.…”

“…However, the personalized antidepressant dosing regimen that we used in this study still differs significantly from the widely used medical model of ketamine therapy where ASCs are not specifically sought after (9,11). In this dose regimen, any ASCs that feel pleasant -e.g., bodily lightness, opposite diminishing and non-judging - (27,32) are welcome ASCs. During ketamine infusions, the patient's vital signs were monitored by continuous electrocardiogram (ECG) monitoring, pulse oximetry, and blood pressure measurement as well as regular controls by the clinic's physicians or medical staff.…”

“…Additionally, if still more details had been collected about this patient's diagnostic condition and his own perspective on the therapeutic process, then we could have provided a still more differentiated overall picture of this particular case. Finally, we used the personalized dosing regimen already explained in Stocker and colleagues (27) in which the main criterion for determining the optimal personalized dose is the subjective feedback of the patient on whether she or he feels that the effect of the infusion is sufficiently strong to have an antidepressant effect. In addition to this process, no other methods were used to calibrate an optimal dosage, such as utilizing EEG measurement (cf.…”

“…Depression was measured with the Beck Depression Inventory (BDI-II) (26). Furthermore, the personalized antidepressant ketamine-infusion dose regimen described in (27) was applied. In essence, in this regimen the dose level and frequency for the ketamine infusions are adjusted individually in close consultation with the patients suffering from depression with the overall goal to maximize antidepressant benefits.…”