The assessment of cardiac risk in patients taking lamotrigine; a systematic review.

OBJECTIVE: The Food and Drug Administration (FDA) warned about lamotrigine's arrhythmogenicity based on in vitro data. This systematic review investigates lamotrigine's effect on cardiac conduction and risk of sudden cardiac death (SCD) in individuals with and without cardiovascular disease. METHODS: We searched Web of Science and PubMed from inception through August 2021. We included studies measuring electrocardiogram (ECG) changes, laboratory abnormalities, or SCD among patients taking lamotrigine. Studies examining sudden unexpected death in epilepsy were excluded for scope. Two reviewers assessed articles and extracted data. We used the Effective Public Healthcare Panacea Project tool to evaluate confidence in evidence. RESULTS: Eight randomized controlled trials, 9 nonrandomized observational studies, and 24 case reports were identified, with >3054 total participants, >1606 of whom used lamotrigine. One randomized trial of older patients found an average QRS increase of 3.5 +/- 13.1 ms. Fifteen studies reported no changes in ECG parameters. Case reports documented QRS widening (13), Brugada syndrome (6), QTc prolongation (1) and SCD (2), though many ingested toxic quantities of lamotrigine and/or other medications. CONCLUSIONS: Evidence is insufficient to support the breadth of the FDA warning concerning lamotrigine's cardiac risk. Lamotrigine at therapeutic doses may be associated with modest, non-dangerous QRS widening.

Lamotrigine for people with borderline personality disorder: a RCT.

BACKGROUND: No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD. OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD. DESIGN: A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms. SETTING: Secondary care NHS mental health services in six centres in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant. INTERVENTIONS: Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day. MAIN OUTCOME MEASURES: Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes. RESULTS: Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0; p = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. LIMITATIONS: Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health. CONCLUSIONS: The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources. FUTURE WORK: Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90916365. FUNDING: Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in Health Technology Assessment; Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morriss' salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands.

Risks associated with lamotrigine prescription: a review and personal observations.

OBJECTIVES:: To detail some serious lamotrigine side effects and their management, and raise awareness about the possible lack of quality control of some brands of lamotrigine. METHODS:: A literature review is provided and some personal observations added. RESULTS:: While most psychiatrists are aware of the risks of Stevens-Johnson syndrome (SJS), awareness of two other serious side effects - toxic epidermal necrosis (TEN) and drug-related eosinophilia and systemic symptoms (DRESS) - is seemingly lower. Awareness that failure to respond to lamotrigine and that the prevalence of serious side effects may reflect poor quality control of some preparations is also less well recognized. CONCLUSIONS:: While lamotrigine may be retrialled at a lower dose escalation rate following some skin reactions, it should not be recommenced following a SJS, TEN or DRESS reaction. Prescribers should be aware of quality control concerns about some available brands of lamotrigine.

Assessment of atherosclerotic risk among patients with epilepsy on valproic acid, lamotrigine, and carbamazepine treatment.

OBJECTIVE: To compare the long-term effects of carbamazepine (CBZ), valproic acid (VPA), and lamotrigine (LTG) as monotherapy on the markers of vascular risk. METHODS: The present cross-sectional study was carried out at the Department of Neurology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, from 2012 to 2013. We selected 120 adult patients with epilepsy and 40 control subjects. The patients with epilepsy were divided into 3 groups according to the use of antiepileptic drugs (AEDs) (CBZ, n = 40; VPA, n = 40; and LTG, n = 40). All participants` total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), high-density lipoprotein cholesterol (HDL-c), ratio of TC/HDL-c, ratio of LDL-c/HDL-c, body mass index (BMI), and blood pressure was determined. RESULTS: In patients with epilepsy, CBZ and VPA treatment caused a noteworthy increase in the concentrations of TG, TC, and LDL-c compared with LTG treatment and the control group (p<0.001). The HDL-c significantly decreased in CBZ, VPA, and LTG-treated patients as compared with controls (p<0.001). The ratio of LDL-c/HDL-c and TC/HDL-c significantly increased in VPA- and CBZ-treated groups compared with the LTG-treated, and control group, while the ratio was also considerably elevated in patients treated with CBZ as compared with the patients treated with VPA. The weight and BMI of the patients treated with AEDs were higher (p<0.01). CONCLUSION: Patients with epilepsy on CBZ or VPA have changed vascular risk markers that may lead to atherosclerosis, while LTG-treated patients have less alteration in lipid profile.