Lamotrigine versus inert placebo in the treatment of borderline personality disorder: study protocol for a randomized controlled trial and economic evaluation

Background: People with borderline personality disorder (BPD) experience rapid and distressing changes in mood, poor social functioning and have high rates of suicidal behaviour. Several small scale studies suggest that mood stabilizers may produce short-term reductions in symptoms of BPD, but have not been large enough to fully examine clinical and cost-effectiveness. Methods/Design: A two parallel-arm, placebo controlled randomized trial of usual care plus either lamotrigine or an inert placebo for people aged over 18 who are using mental health services and meet diagnostic criteria for BPD. We will exclude people with comorbid bipolar affective disorder or psychosis, those already taking a mood stabilizer, those who speak insufficient English to complete the baseline assessment and women who are pregnant or contemplating becoming pregnant. Those meeting inclusion criteria and provide written informed consent will be randomized to up to 200mg of lamotrigine per day or an inert placebo (up to 400mg if taking combined oral contraceptives).Participants will be randomized via a remote web-based system using permuted stacked blocks stratified by study centre, severity of personality disorder, and level of bipolarity. Follow-up assessments will be conducted by masked researchers 12, 24 weeks, and 52 weeks after randomization. The primary outcome is the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). The secondary outcomes are depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment, adverse events and withdrawal of trial medication due to adverse effects. The main analyses will use intention to treat without imputation of missing data. The economic evaluation will take an NHS/Personal Social Services perspective. A cost-utility analysis will compare differences in total costs and differences in quality of life using QALYs derived from the EQ-5D. Discussion: The evidence base for the use of pharmacological treatments for people with borderline personality disorder is poor. In this trial we will examine the clinical and cost-effectiveness of lamotrigine to assess what if any impact offering this has on peoples’ mental health, social functioning, and use of other medication and other resources. Trial registration: Current Controlled Trials ISRCTN90916365 (registered 01/08/2012

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

The clinical effectiveness and cost effectiveness of lamotrigine for people with borderline personality disorder: a randomized, placebo-controlled trial

Objectives: To examine whether lamotrigine is a clinically effective and cost-effective treatment for people with borderline personality disorder. Method: Multicentre, double-blind, placebo-controlled randomized trial. Between July 2013 to November 2016, we recruited 276 people aged 18 or over, who met diagnostic criteria for borderline personality disorder. We excluded those with co-existing bipolar affective disorder or psychosis, those already taking a mood stabiliser, and women at risk of pregnancy. We randomly allocated participants on a 1:1 ratio to up to 400mg of lamotrigine per day or an inert placebo using a remote web-based randomization service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. Secondary outcomes included depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Results: 195 (70.6%) participants were followed up at 52 weeks, at which point 49 (36%) of those prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. Mean total ZAN-BPD score was 11.3 (SD = 6.6) among those randomized to lamotrigine and 11.5 (SD = 7.7) among those randomized to placebo (adjusted difference in means = 0.1, 95% C.I = -1.8 to 2.0, p=0.91). There was no evidence of any differences in secondary outcomes. Costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. Conclusions: Treating people with borderline personality disorder with lamotrigine is not a clinically effective or cost-effective use of resources