Lamotrigine for people with borderline personality disorder: a RCT

Abstract

BackgroundNo 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.ObjectiveTo examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD.DesignA 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.SettingSecondary care NHS mental health services in six centres in England.ParticipantsPotential 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.InterventionsUp 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 measuresOutcomes 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.ResultsBetween 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.LimitationsLevels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health.ConclusionsThe 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 workFuture 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 registrationCurrent Controlled Trials ISRCTN90916365.FundingFunding 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 inHealth 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.

Current Clinical Psychopharmacology in Borderline Personality Disorder

“…However, a more recent 52-week, two-arm, double-blind, large-scale multicenter RCT comparison of lamotrigine versus placebo in BPD patients failed to show significant superiority of lamotrigine [ 94 ]. This evidence underlines that lamotrigine is not clinically or more costly effective than the usual care in BPD subjects [ 94 , 95 ]. In brief, although several studies showed that lamotrigine had shown evidence of efficacy in reducing aggressive symptoms, affective lability, and impulsivity in BPD, the most extensive study failed to find any effect at all.…”

Pharmacotherapy of Personality Disorders

“…However, most reports are based on studies with patients presenting not only borderline PD but also, for example, bipolar II disorder. Therefore, a special consideration merits the recent study of Crawford et al (2018a), which was based on a well-elaborated methodology (Crawford et al 2015(Crawford et al , 2018b. They described the effect of lamotrigine in a group of borderline PD patients, from which bipolar patients were excluded: They concluded that this anticonvulsant and mood-stabilizing drug is not a clinically effective or costeffective treatment.…”

No Effect of Lamotrigine in Subgroups of Patients With Borderline Personality Disorder: Response to Smith

“…As requested, we have examined mean scores on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 12 weeks in subsamples of people who were adherent with medication during this period, those without coexisting substance misuse, and those who had a recent history of deliberate self-harm. While conducting this analysis, we identified a typographical error that appeared in our article (1) but not in the monograph that has subsequently been published that provides additional information about the trial (2). The number of participants in the placebo arm of the trial who reported deliberate self-harm in the 6 months prior to randomization was 87 (63%), not 51 (37%) as erroneously stated in our article.…”

“…The second measured but unaccounted for confounding effect stemmed from the inclusion of subjects with schizoaffective disorder. Compared with schizophrenia, schizoaffective disorder may have better outcomes (2). The authors could have mentioned and compared the number and distribution of subjects with schizoaffective disorder among the users and discontinuers to examine the effect of this potential confounder.…”