Lamotrigine, a mood-stabilising drug, is not clinically effective for the treatment of borderline personality disorder. Over one year follow up, this NIHR-funded trial did not find a difference between lamotrigine and placebo for borderline personality disorder-related symptoms and behavioural problems, depressive symptoms, self-harm, social functioning or quality of life outcomes.
Borderline personality disorder is a severe mental health disorder characterised by rapid and distressing fluctuations in mood, impaired social functioning and increased suicidal behaviour. Since emotional instability is a key clinical feature, it was thought treatments that help to stabilise mood might help in treating the condition.
This was a placebo-controlled, double-blind, randomised trial of lamotrigine in 276 people with borderline personality disorder, the largest trial to date. In contrast to the results of earlier smaller trials, this larger trial did not support the use of lamotrigine in the management of borderline personality disorder.
Why was this study needed?
Borderline personality disorder (BPD) affects around 0.7% of people, and one-fifth of all patients admitted to inpatient mental health units in the UK have this condition. People with BPD experience high levels of unemployment and the rate of completed suicide is 50-times higher than in the general population.
There is little evidence for pharmacological treatments in BPD. However, mood-stabilising drugs can be useful treatments in other mental-health conditions characterised by fluctuations in mood, such as bipolar disorder.
Previous findings from small-scale studies of mood stabilisers in BPD suggested lamotrigine may be clinically effective for BPD over the short-term. To address this uncertainty, a larger randomised placebo-controlled trial, with a longer one-year follow-up, was funded by NIHR.
What did this study do?
The LABILE trial recruited 276 participants from secondary care mental health services across England. Adult participants were included if they met the DSM-IV diagnostic criteria for BPD.
Participants were randomised to receive lamotrigine (up to 200mg daily) or a placebo. The main outcome was the Zanarini Rating Scale for BPD at one year (ZAN-BPD), a score for describing symptoms and behavioural problems associated with BPD. In addition, depressive symptoms, deliberate self-harm and social functioning were measured.
The trial was designed carefully. To reduce the risk of bias, all patients, carers, referring psychiatrists and study investigators collecting and analysing the data were unaware of the treatment assignments. The self-reported adherence of participants to the study medication was low (only 34% took medication as per protocol).
What did it find?
- By one year, there was no significant difference in the ZAN-BPD score. The range is from 0 to 35 with higher scores indicating worse symptoms. The average score for those on lamotrigine was 11.3 compared with 11.5 in the placebo group (adjusted mean difference 0.1, 95% confidence interval ‑1.8 to 2.0).
- There was no significant difference between the groups for the trial’s secondary outcomes (depressive symptoms, deliberate self-harm and social functioning) at any follow-up time point.
- The average total cost of care was £12,244 in the lamotrigine group and £8,495 in the placebo group; however, the difference in cost was not statistically significant. Differences in QALYs (calculated using health-related quality of life scores) were also not statistically significant between groups.
- Sensitivity analyses adjusted for treatment adherence and for differences in baseline variables, considered outcomes at all follow-up visits, and used imputation of missing data (a statistical method that estimates what the likely data should have been). These analyses also supported a lack of treatment effect.
What does current guidance say on this issue?
NICE 2009 guidelines do not recommend the use of drug treatment for BPD or for the symptoms or behaviour problems associated with the disorder (for example, repeated self-harm, marked emotional instability, risk-taking behaviour and transient psychotic symptoms). Specifically, NICE do not recommend mood stabilisers, such as lamotrigine, for the treatment of BPD and rule out antipsychotic drugs for medium and long-term use in this condition.
What are the implications?
This randomised controlled trial provides strong evidence, with long-term follow up, showing lamotrigine to be clinically ineffective for the treatment of BPD.
The study responds to NICE’s call for more high-quality research in this area and supports current guidance which does not recommend the use of lamotrigine for BPD.
Citation and Funding
Crawford MJ, Sanatinia R, Barrett B, et al. Lamotrigine for people with borderline personality disorder: a RCT. Health Technol Assess. 2018;22(17):1-68.
This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 10/103/01).
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