Ketamine Can Reduce Harmful Drinking by Pharmacologically Rewriting Drinking Memories

Das, Ravi; Gale, Grace; Walsh, Katie; Hennessy, Vanessa; Iskandar, Georges; Mordecai, Luke; Brandner, Brigitta; Kindt, Merel; Curran, Valerie H.; Kamboj, Sunjeev K.

doi:10.1016/j.biopsych.2020.02.498

Cited by 10 publications

(14 citation statements)

References 23 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One of the studies we report on this month in the What's New in Research section takes up the challenge. Das and colleagues 1 hypothesized that disrupting positive memories of consuming alcohol could decrease subsequent alcohol use. To test this, they randomized volunteers with problem drinking to three groups.…”

mentioning

confidence: 99%

“…But localized infusion of toxic drugs into the brains of human volunteers is obviously not an option. So, Das et al 1 disrupted protein synthesis via a different route — antagonism of the N‐methyl‐D‐aspartate (NMDA) receptor, using that increasingly popular NMDA antagonist, ketamine (yes, I'm aware that three of the studies we cover in this month's Update involve ketamine/esketamine). However, recognizing the pharmacological and clinical diversity of ketamine's effects, the authors carefully devised their two control groups: ketamine without memory retrieval, to control for other effects that ketamine might have on alcohol consumption unrelated to memory reconsolidation, and placebo saline with memory retrieval, to control for the possibility that the memory retrieval procedure alone might be having an impact.…”

mentioning

confidence: 99%

“…And that's why we decided to give full coverage to the Das et al 1 paper in this month's issue. For lots of those methodological reasons that I didn't get into, it is more a proof‐of‐concept study than a clinical trial with immediate relevance (consistent with its publication in Nature Communications , not exactly a prominent clinical psychiatry venue, unlike the American Journal of Psychiatry , where the Dakwar et al 3 paper appeared).…”

mentioning

confidence: 99%

“…If you are young enough, I expect that at some point in your career a clinical intervention will become available that will let you do what Das et al 1 have demonstrated to be conceptually feasible here — and not just for addiction. Interestingly, they seem to be a bit unsure what to call it — they use the terms “reconsolidation interference,” “reconsolidation blockade,” and “memory rewriting” at various points in their paper.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Memory as a therapeutic target for psychopharmacology

Price¹

2020

Psychopharmacology Update

View full text Add to dashboard Cite

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Memory as a therapeutic target for psychopharmacology

Price¹

2020

Psychopharmacology Update

View full text Add to dashboard Cite

“…Das and colleagues tested the impact of targeted-alcohol maladaptive reward memory interference via ketamine, a high-affinity non-competitive NMDA antagonist. 5 A total of 90 beer-preferring participants with hazardous or harmful drinking patterns were recruited and split into three groups: retrieval of alcohol memories followed by ketamine or placebo (RET + KET and RET + PBO, respectively), and no retrieval followed by ketamine (NoRET + KET). Baseline measures were taken using a cue reactivity task and self-report scales on the hedonic and motivational aspects of alcohol.…”

mentioning

confidence: 99%

Kaleidoscope

Tracy¹,

Joyce²,

Albertson³

et al. 2020

Br J Psychiatry

View full text Add to dashboard Cite

Preventing recurrence after recovery from a major depressive episode is a key clinical goal: but what are the best strategies? During an acute episode, antidepressants and cognitive-behavioural therapy (CBT) are equally efficacious and their combination is typically shown to be superior to either alone. However, there are surprisingly few randomised controlled trials (RCTs) on the longer-term impact of CBT on major depressive episode recurrence, particularly when combined with medication. DeRubeis et al report on 292 individuals who had recovered from a chronic or recurrent major depressive episode through the use of antidepressant medication either with or without CBT. 1 The participants in remission were randomised to either stay on their medication or have it gradually withdrawn, and followed up over 3 years. Those kept on antidepressants did substantially better than those taken off them, regardless of how they had initially attained remission. Interestingly, previous treatment with CBT did not have an impact on the likelihood of recurrence; this is all the more surprising given that those who received both interventions showed superior outcomes in the acute recovery phase. The authors raise an intriguing possibility that medication might interfere with the impact of CBT in the acute phase, and note that a CBT-only arm is needed in future studies.Antidepressant harms are almost as frequently debated as data on their effectiveness. Studies have been somewhat inconsistent, so Dragioti et al report on what they label a 'systematic umbrella review' of 45 meta-analyses of observational studies on the topic. 2 Crucially this graded the available evidencerather than 'just' report it as often occurs in meta-analysesto better understand any drug harms. Observational studies are usually considered better than RCTs when it comes to monitoring harms, as they have more 'real-world' representation and longer follow-up. Overall, the data were mixed: of the 120 affirmative correlations, 74 were nominally statistically significant, 52 had large heterogeneity, small-study effects were found in 17 and an excess significant bias was found for 9. Convincing data were found for an association with suicide attempts and completion in children and adolescents, and exposure in pregnancy and preterm births, low Apgar scores and subsequent autism spectrum disorders. However, critically, these did not reflect causality, and none of these associations remained supported after sensitivity analysis adjusted for confounding by indication. The take-home message is that these medications have no absolute contraindications and the data on harms are actually not that well supported.In both papers there are dangers of misinterpretation of the data: the first study does not downplay the utility of CBT in acute treatment of a major depressive episode, but shows limitations at preventing future recurrence, possibly because of medication interference; 1 in the second, it is critical to note confounding by indication when considering the associations ...

show abstract