Effect of the Glutamate NMDA Receptor Antagonist Memantine as Adjunctive Treatment in Borderline Personality Disorder: An Exploratory, Randomised, Double-Blind, Placebo-Controlled Trial

Kulkarni, Jayashri; Thomas, Natalie; Hudaib, Abdul Rahman; Gavrilidis, Emorfia; Grigg, Jasmin; Tan, Raelene; Cheng, Jacinta; Gurvich, Caroline

doi:10.1007/s40263-018-0506-8

Cited by 18 publications

(6 citation statements)

References 41 publications

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“…From this review, novel agents have been tested for efficacy in treating not PIA but related conditions such as anger, hostility, and irritability. Such agents include 5-aminolevulinic acid phosphatase ( Higashikawa et al, 2020 ), fish oil ( Dean et al, 2014 ), and specific omega-3-fatty acids ( Bellino et al, 2013 ), the 5-HT 2c agonist lorcaserin ( Coccaro and Lee, 2019 ), the antiepileptic tiagabine ( Gowin et al, 2012 ), the benzodiazepine clobazam tested in Lennox–Gastaut Syndrome ( Paolicchi et al, 2015 ), and the glutamate NMDA receptor antagonist memantine ( Kulkarni et al, 2018 ). As an antagonist for neurokinin-1 (NK1) receptors upon which substance P acts, aprepitant, used as an antiemetic, could theoretically function as an AIAA but has yet to be tested ( Fanning et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacotherapy of Primary Impulsive Aggression in Violent Criminal Offenders

et al. 2021

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Primary impulsive aggression (PIA) can be implicated as a common factor that results in an arrest, disciplinary, and restraint measures during confinement, and criminal recidivism after release. Evidence suggests that anti-impulsive aggression agents (AIAAs) can diminish or prevent impulsive aggression even when occurring with personality pathology such as borderline or antisocial personality disorder (ASPD), common conditions in offender populations. A previous review identified agents that have been subjected to controlled drug trials of sufficient quality, and subsequently, a decisional algorithm was developed for selecting an AIAA for individuals with IA. This selection process began with the five agents that showed efficacy in two or more quality studies from the earlier review. Today, 8 years after the quality review study, the present authors undertook this follow-up literature review. The aims of the present review were to survey the literature to identify and assess: (1) drug trials of comparable quality published since the 2013 review, including trials of the previously identified AIAAs as well as trials of agents not included in the earlier review; (2) severity of aggressive outbursts; (3) the materiality of risks or side-effects that are associated with individual AIAAs as well as antipsychotic agents commonly used to control clinical aggression; (4) efficacy of these agents in special populations (e.g., females); and (5) cost and convenience of each agent. Improved pharmacotherapy of PIA by addressing risks, side effects and practicality as well as the efficacy of AIAAs, should promote the rehabilitation and reintegration of some pathologically aggressive offenders back into the community.

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Section: Discussionmentioning

confidence: 99%

Pharmacotherapy of Primary Impulsive Aggression in Violent Criminal Offenders

et al. 2021

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“…Its off-label use in the treatment of BPD is supported by the hypothesis of glutamate dysregulation and excitotoxicity of BPD core symptoms [ 103 ]. To date, only a double-blind placebo-controlled RCT showed that a dose of 20 mg of memantine per day added on to another usual drug treatment was well tolerated and improved BPD symptoms [ 104 ]. Given the existence of only one study, further research is needed to assess the efficacy of memantine compared to placebo and other treatments in patients with BPD.…”

Section: Discussionmentioning

confidence: 99%

Current Clinical Psychopharmacology in Borderline Personality Disorder

Casale

Bonanni

Bargagna

et al. 2021

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Background: Patients with Borderline Personality Disorder (BPD) manifest affective and behavioural symptoms causing personal distress, relationship difficulties, and reduced quality of life with global functioning impairment, mainly when the disease takes an unfavourable course. A substantial amount of healthcare costs is dedicated to addressing these issues. Many BPD patients receive medications, mostly those who do not respond to psychological interventions. Objective: Our aim was to assess the efficacy of the most used strategies of pharmacological interventions in BPD with a comprehensive overview of the field. Methods: We searched the PubMed database for papers focused on the most used psychotropic drugs for BPD. We included randomized controlled trials and open studies in adult patients with BPD, focusing on the efficacy and tolerability of single classes of drugs with respect to specific clinical presentations that may occur during the course of BPD. Results: Specific second-generation antipsychotics (SGAs) and/or serotonergic antidepressants can be effective for different core symptoms of BPD, mainly including mood symptoms, anxiety, and impulse dyscontrol. Some atypical antipsychotics can also be effective for psychotic and dissociative symptoms. Specific antiepileptics can be useful in some cases in treating specific BPD symptoms, mainly including mood instability, impulsiveness, and anger. Conclusions: No medication is currently approved for BPD, and clinicians should carefully assess the benefits and risks of drug treatment. Further studies are needed to identify specific personalized treatment strategies, also considering the clinical heterogeneity and possible comorbidities of BPD.

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“…As an NMDA receptor antagonist, it is thought that memantine can slow or halt the constant NMDA activation that is brought about by excessive glutamate release at the postsynaptic receptor site (Stahl et al, 2018). Neuronal toxicity is present with excessive glutamate; it is hypothesized that the blockade of excessive glutamate that memantine provides slows cognitive loss in ASD and AD patients (Kulkarni et al, 2018). Memantine is approved for use in moderate to severe AD, and also used off label in mild AD and other memory and cognitive disorders (Stahl et al, 2018).…”

Section: Memantinementioning

confidence: 99%

Update on Neurodegenerative Diseases and Glutamate: A PMHNP Single Case Study Report of a Diagnostically Complex Adult Patient, Interventions, and Unexpected Outcomes

Kroll¹,

Bennett

Klinefelter³

2021

J Am Psychiatr Nurses Assoc

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OBJECTIVE: While dysfunction of serotonin and dopamine neurotransmitters has been studied in depth, in regard to the etiology of mental illness, the neurotransmitter glutamate and its dysfunction is now being explored as contributing to neurodegenerative psychiatric diseases, schizophrenia, autism, depression, and Alzheimer’s disease. This article explains its synthesis, neurotransmission, and metabolism within the brain and subsequent dysfunction that is responsible for neurocognitive loss associated with several psychiatric disorders. METHOD: The case study will report on the screening for pseudobulbar affective (PBA) disorder in a 29-year-old male with bipolar disorder, autism spectrum disorder, and intellectual developmental disability who was experiencing extreme, uncontrolled emotional outbursts requiring continuous family isolation (pre-COVID-19) for safety. With the positive screen for PBA, the patient was subsequently treated with a glutamatergic drug, dextromethorphan/quinidine. RESULTS: The patient’s unexpected response to this treatment including the acquisition of language, increased cognition, and improved executive functioning is presented. At 2 years post the initiation of treatment, his PBA screening score is reduced, uncontrolled outbursts and aggression have subsided, and the family can spend time outside of their home. CONCLUSIONS: Neurodegeneration and its impact is being researched and treated with medications affecting glutamate. The addition of a glutamatergic medication to this young man’s medication regimen has improved both his and his family’s quality of life. The psychiatric diagnoses, medications, and treatments associated with glutamate are explained in depth. The importance of nurses’ understanding of glutamate, its synthesis, transmission, and dysfunction causing excitotoxicity and brain cell death and its impact on patients’ behavior and safety is explained.

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Effect of the Glutamate NMDA Receptor Antagonist Memantine as Adjunctive Treatment in Borderline Personality Disorder: An Exploratory, Randomised, Double-Blind, Placebo-Controlled Trial

Cited by 18 publications

References 41 publications

Pharmacotherapy of Primary Impulsive Aggression in Violent Criminal Offenders

Pharmacotherapy of Primary Impulsive Aggression in Violent Criminal Offenders

Current Clinical Psychopharmacology in Borderline Personality Disorder

Update on Neurodegenerative Diseases and Glutamate: A PMHNP Single Case Study Report of a Diagnostically Complex Adult Patient, Interventions, and Unexpected Outcomes

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