Sustained Improvement of Negative Self-Schema After a Single Ketamine Infusion: An Open-Label Study

Abstract

Conventional antidepressants have several important limitations, including a lack of direct effects on negative self-schema, which is at the core of Beck's cognitive theory of depression. Based on previous studies showing a positive effect of ketamine on negative cognition, we compared reductions in negative self-schema between responders and non-responders to a single infusion of ketamine. In an open-label study, 26 participants with treatment-resistant depression received 0.5 mg/kg ketamine via infusion. Depression symptoms were assessed at baseline, 24 h, and 7 days after treatment with Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI-II). Nine of the 26 participants fulfilled response criteria after 24 h. Of these, eight still fulfilled response criteria after 7 days. Response was defined as a reduction in MADRS total score of 50% or more. Responders improved significantly more than non-responders both 24 h and 7 days after ketamine treatment on the following BDI-II items: item 1 ("Sadness"), item 7 ("Self-Dislike"), and item 8 ("Self-Criticalness"). These results suggest an important therapeutic effect of ketamine on negative self-schema, which is a fundamental cognitive aspect of depression. This effect is unique and might be associated with ketamine's profound effects on neuroplasticity. Small sample size and lack of a placebo control group are the major limitations of this study.

Analysis of recreational psychedelic substance use experiences classified by substance

“…Though no prior study has compared the present combination of psychedelic substances on psycholinguistic variables like this study did, previous research used similar outcomes or analytic methods. Studies that examined the effects of psychedelic drugs on the psychological states or processes underlying the psycholinguistic outcomes of this study reported emotional effects of psychedelic drugs, such as an emotionally intensifying profile on MDMA (Agurto et al 2020 ; Bedi et al 2014 ), decreased negative emotions like sadness on ketamine (Hasler et al 2020 ), increased 5D-ASC blissful state and increased emotional excitability with a bias toward positive emotion on LSD (Carhart-Harris et al 2016a ; Liechti et al 2017 ; Schmid et al 2015 ), and emotional excitability on psilocybin (Hasler et al 2004 ). Furthermore, some research also observed cognitive disorganization on LSD (Carhart-Harris et al 2016b ).…”

Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial

“…Moreover, ketamine has been shown to have a rapid onset of marked effects on dendritic architecture and spine density and function in prefrontal cortical regions that persist for at least 1 week after a single administration [41] and may be extended with subchronic dosing [42]. Further, there is preliminary evidence that ketamine can improve negative self-schema, which is one of the key psychotherapeutic targets of CBT [43]. Although several important mechanistic details remain to be elucidated, there is increasing evidence from our group and others suggesting overall improvement in gross cognitive function following a series of ketamine treatments [15, 44-46].…”

Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression

“…Interestingly, pharmacological studies on healthy participants have shown that ketamine disturbs the belief-updating process by changing the way participants update their beliefs when faced with new information. [28][29][30] Moreover, another study on MDD has shown that a single ketamine infusion can produce a sustained improvement in depressive beliefs. 30 However, it is unknown how ketamine affects the mechanisms of belief updating in patients with TRD, which are potentially key to understanding its antidepressant effects.…”

“…[28][29][30] Moreover, another study on MDD has shown that a single ketamine infusion can produce a sustained improvement in depressive beliefs. 30 However, it is unknown how ketamine affects the mechanisms of belief updating in patients with TRD, which are potentially key to understanding its antidepressant effects.…”