A single dose of lamotrigine induces a positive memory bias in healthy volunteers

Background: Lamotrigine has been shown to be effective in the long-term treatment and relapse prevention of depression in bipolar disorder. However, the neuropsychological mechanisms underlying these effects are unclear. We investigated the effects of lamotrigine on a battery of emotional processing tasks, previously shown to be sensitive to antidepressant drug action in healthy volunteers. Methods: Healthy volunteers (n=36) were randomised in a double blind design to receive a single dose of placebo or 300mg lamotrigine. Mood and subjective effects were monitored throughout the study period and emotional processing was assessed using the Oxford Emotional Test Battery (ETB) 3 hours post administration. Results: Participants receiving lamotrigine showed increased accuracy for the recall of positive vs. negative self-descriptors, compared to those in the placebo group. There were no other signficant effects on emotional processing in the ETB, and lamotrigine did not affect ratings of mood or subjective experience. Conclusions: Lamotrigine induced a positive bias in emotional memory, similar to the effects of other antidepressants as reported in previous studies. Further work is needed to assess whether similar effects are seen in the clinical treatment of patients with bipolar disorder and the extent to which this is associated with its clinical action in relapse prevention. ### Competing Interest Statement CJH has received consultancy fees from P1vital Ltd., Janssen Pharmaceuticals, Sage Therapeutics, Pfizer, Zogenix, Compass Pathways, and Lundbeck. CJH holds grant income from Zogenix, UCB Pharma, Pfizer, Janssen Pharmaceuticals. GMG is Chief Medical Officer at Compass pathways, holds shares and share options in Compass pathways PLC and has served as consultant, advisor or CME speaker in the last 3 years for Beckley Psytech, Boehringer Ingelheim, Clerkenwell Health, Compass pathways, Evapharma, Janssen, Lundbeck, Medscape, Novartis, Ocean Neuroscience, P1Vital, Servier, Takeda. ### Clinical Trial NCT04396938 ### Funding Statement This research study was supported by the NIHR Oxford Health Biomedical Research Centre (OH BRC). The views expressed here are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the Central University Research Ethics Committee (CUREC), from the University of Oxford (UK). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.