Citalopram for treatment of cocaine use disorder: A Bayesian drop-the-loser randomized clinical trial

Suchting, Robert; Green, Charles E.; Dios, Constanza de; Vincent, Jessica; Moeller, F. Gerard; Lane, Scott D.; Schmitz, Joy M.

doi:10.1016/j.drugalcdep.2021.109054

Cited by 9 publications

(6 citation statements)

References 38 publications

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“…Further, we implemented and assessed intervention enhancements in the same trial, providing evidence that a positive treatment effect was still present after changes. To our knowledge, this is the first RCT to optimise an intervention for the treatment of IMs after traumatic events, and one of the first in mental health to use an adaptive Bayesian approach [42][43][44][45]. At trial entry, participants reported a very high number of work-related traumatic events during the pandemic (on average more than 35 traumas, Supplementary Table 1), most of which had taken place over three months ago.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention

Ramineni¹,

Millroth

Iyadurai

et al. 2022

Preprint

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Intensive care unit (ICU) staff continue to face recurrent work-related traumatic events throughout the COVID-19 pandemic. Intrusive memories (IMs) of such traumatic events comprise sensory image-based memories. Harnessing research on preventing IMs with a novel behavioural intervention on the day of trauma, here we take critical next steps in developing this approach as a treatment for ICU staff who are already experiencing IMs days, weeks, or months post-trauma. To address the urgent need to develop novel mental health interventions, we used Bayesian statistical approaches to optimise a brief imagery-competing task intervention to reduce the number of IMs. We evaluated a digitised version of the intervention for remote, scalable delivery. We conducted a two-arm, parallel-group, randomised, adaptive Bayesian optimisation trial. Eligible participants worked clinically in a UK NHS ICU during the pandemic, experienced at least one work-related traumatic event, and at least three IMs in the week prior to recruitment. Participants were randomised to receive immediate or delayed (after four weeks) access to the intervention. Primary outcome was the number of IMs of trauma during week 4, controlling for baseline week. Analyses were conducted on an intention-to-treat basis as a between-group comparison. Prior to final analysis, sequential Bayesian analyses were conducted (n=20,23,29,37,41,45) to inform early stopping of the trial prior to the planned maximum recruitment (n=150). Final analysis (n=75) showed strong evidence for a positive treatment effect (Bayes factor, BF=1.25 × 106): the immediate arm reported fewer IMs (median=1, IQR=0-3) than the delayed arm (median=10, IQR=6-16.5). With further digital enhancements, the intervention (n=28) also showed a positive treatment effect (BF=7.31). Sequential Bayesian analyses provided evidence for reducing IMs of work-related trauma for healthcare workers. This methodology also allowed us to rule out negative effects early, reduced the planned maximum sample size, and allowed evaluation of enhancements. Trial Registration NCT02044809 (www.clinicaltrials.gov).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention

Ramineni¹,

Millroth

Iyadurai

et al. 2022

Preprint

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“…Serotonin reuptake inhibitors citalopram and escitalopram induced the internalization and decrease in cellular serotonin transporters (SERTs; Figure 1) [67], and decreased compulsive cocaine seeking in mice [65,68]. A double-blind clinical trial compared a placebo with citalopram treatments on the duration of cocaine withdrawal, and provided some evidence for positive effects on the longest duration of withdrawal and negative urine cocaine screens [69].…”

Section: Drugs For Serotoninergic Neuronsmentioning

confidence: 99%

Substance Addiction Rehabilitation Drugs

Yuan,

Jiang,

Zhang

et al. 2024

Pharmaceuticals

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The relapse rate of substance abusers is high, and addiction rehabilitation adjunct drugs need to be developed urgently. There have been numerous reports on blocking the formation of substance addiction, but studies on drugs that can alleviate withdrawal symptoms are very limited. Both the dopamine transporter (DAT) hypothesis and D3 dopamine receptor (D3R) hypothesis are proposed. DAT activators reduce the extracellular dopamine level, and D3R antagonists reduce the neuron’s sensitivity to dopamine, both of which may exacerbate the withdrawal symptoms subsequently. The D3R partial agonist SK608 has biased signaling properties via the G-protein-dependent pathway but did not induce D3R desensitization and, thus, may be a promising drug for the withdrawal symptoms. Drugs for serotoninergic neurons or GABAergic neurons and anti-inflammatory drugs may have auxiliary effects to addiction treatments. Drugs that promote structural synaptic plasticity are also discussed.

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“…Case Study: Cocaine use disorder (CUD) is a difficult condition to treat, and research has not found an effective treatment for the condition. Suchting et al designed a drop-the-loser (DTL) Bayesian adaptive trial to determine the most effective dose of citalopram, a selective serotonin reuptake inhibitor that can treat CUD, to evaluate in a larger confirmatory trial (ClinicalTrials.gov number: NCT01535573) [63]. Using Bayesian posterior probabilities, the researchers decided at the interim analysis which doses would be dropped from the trial (20 mg/day; 40 mg/day).…”

Section: Treatment Arm Selectionmentioning

confidence: 99%

“…In the implementation of the trial, the 20 mg/day dose was dropped after 50% of recruitment given that the 40 mg/day dose had a higher chance of success. Ultimately, the 40 mg/day dose provided “moderate-to-strong evidence” of positive effects at study conclusion [ 63 ].…”

Section: Fda Adaptive Trial Elementsmentioning

confidence: 99%

Recent innovations in adaptive trial designs: A review of design opportunities in translational research

Kaizer

Belli

et al. 2023

J. Clin. Trans. Sci.

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Clinical trials are constantly evolving in the context of increasingly complex research questions and potentially limited resources. In this review article, we discuss the emergence of "adaptive" clinical trials that allow for the preplanned modification of an ongoing clinical trial based on the accumulating evidence with application across translational research. These modifications may include terminating a trial before completion due to futility or efficacy, re-estimating the needed sample size to ensure adequate power, enriching the target population enrolled in the study, selecting across multiple treatment arms, revising allocation ratios used for randomization, or selecting the most appropriate endpoint. Emerging topics related to borrowing information from historic or supplemental data sources, sequential multiple assignment randomized trials (SMART), master protocol and seamless designs, and phase I dose-finding studies are also presented. Each design element includes a brief overview with an accompanying case study to illustrate the design method in practice. We close with brief discussions relating to the statistical considerations for these contemporary designs.

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Citalopram for treatment of cocaine use disorder: A Bayesian drop-the-loser randomized clinical trial

Cited by 9 publications

References 38 publications

Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention

Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention

Substance Addiction Rehabilitation Drugs

Recent innovations in adaptive trial designs: A review of design opportunities in translational research

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