Effect of the Glutamate NMDA Receptor Antagonist Memantine as Adjunctive Treatment in Borderline Personality Disorder: An Exploratory, Randomised, Double-Blind, Placebo-Controlled Trial
Borderline personality disorder (BPD) is a complex, severe and highly stigmatised psychiatric illness. Several lines of evidence highlight the causal link between chronic stress, glucocorticoid response to stress and glutamatergic overactivity as a key event in the pathophysiology of BPD. Therefore, molecular mechanisms capable of regulating glutamate excitotoxicity represent novel and potentially promising treatment targets. Memantine-HCl is a voltage-dependent N-methyl-d-aspartate (NMDA) receptor ‘channel blocker’ that selectively blocks pathological glutamate overactivity.
The aim of the current study was to determine if memantine can improve BPD symptoms.
An 8-week, double-blind, placebo-controlled trial of adjunctive memantine to treatment as usual was conducted. Treatment as usual comprised antidepressants (selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, noradrenergic and specific serotonin antagonists and serotonin noradrenaline reuptake inhibitors), mood stabilisers and antipsychotics, as well as psychotherapy and other psychosocial interventions. Sixteen participants received oral placebo while 17 participants received daily oral memantine 10 mg for 7 days, with subsequent titration to daily oral memantine 20 mg. Eligibility criteria included men and women aged between 16–65 years, with a diagnosis of BPD according to the Diagnostic Interview for Borderline Patients. Primary outcome measures included the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), assessed fortnightly. Secondary measures included an adverse effect questionnaire administered fortnightly to assess adverse effects known to be related to memantine use.
According to intention-to-treat, latent growth curve analyses, a significant change in total score of ZAN-BPD symptom severity was observed in the memantine group at 20 mg/daily across time, compared with placebo (p = 0.02). No adverse effects were significantly more frequent among participants receiving active memantine than among those receiving placebo.
Memantine at a 20-mg daily dose is a well tolerated drug that can improve BPD symptomatology and may be a promising novel therapeutic for its treatment. Further studies are needed to explore the efficacy of memantine versus placebo, as well as in comparison with other potential treatments for BPD.
ClinicalTrials.gov identifier: NCT02097706.
Author Kulkarni participated in the conception and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript and critical revision of the manuscript for important intellectual content. Author Thomas participated in the acquisition of data, analysis and interpretation of data, drafting of the manuscript and significantly contributed to the writing and editing of this review. Author Hudaib undertook the analyses and writing of the study results. Author Gavrilidis provided assistance in the setup of the study including ethics and budget as well as acquisition of data. Author Grigg contributed to the initial stages of this research including protocol development and data acquisition. Authors Cheng, Tan and Arnold recruited patients, provided clinical assistance and assisted with data acquisition. Author Gurvich participated in the interpretation of data and critical revision of the manuscript. All authors contributed to and have approved the final manuscript. We would like to thank the participants and their families for their generous involvement in the study.
Compliance with Ethical Standards
Conflict of interest
The authors (Jayashri Kulkarni, Natalie Thomas, Abdul- Rahman Hudaib, Emorfia Gavrilidis, Jasmin Grigg, Raelene Tan, Jacinta Cheng, Amelia Arnold and Caroline Gurvich) have no conflicts of interest to declare.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
National Health and Medical and Research Council (NHMRC) Project Grant: 1129815 and Private Philanthropic Grant provided by Dr. Jeff Wolinski, C/o Monash University Fundraising Department, Faculty of Medicine, Nursing and Health Sciences.
Written informed consent was obtained from all individual participants included in the study.
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