Kulkarni 2018.

Study characteristics
Methods	8‐week trial with 2 arms: memantine hydrochloride + treatment‐as‐usual placebo + treatment‐as‐usual Duration of trial: 8 weeks + 4 weeks for washout Country: Australia Setting: outpatient
Participants	Methods of recruitment of patients: "Participants were recruited primarily via doctor referral, and via printed and electronic advertisements on noticeboards at various sites of The Alfred Hospital (Melbourne, VIC, Australia), and were primarily from Alfred Psychiatry outpatient units and community clinics". (Kulkarni 2018, p. 182) Overall sample size: 34 Diagnosis of borderline personality disorder: DSM‐IV Means of assessment: Zan‐BPD Mean age: 34.4 years (SD = no information; range = no information) Sex: 85.29% women Comorbidity: bipolar II disorder Inclusion criteria Both genders Aged 16‐65 years Diagnosis of BPD according to Zan‐BPD Proficiency in reading and writing English Exclusion criteria Clinical evidence of CNS pathology, neurological disorder, head injury, epileptic seizures or convulsions Currently pregnant or breastfeeding A current DSM‐IV‐TR diagnosis of substance abuse or dependence disorder, or another axis I disorder including a past or current diagnosis of schizophrenia, delusional (paranoid) disorder, schizoaffective disorder, bipolar I (mixed, manic, depressed or euthymic) or psychotic depression. Individuals with bipolar II were included. Clinically significant and active evidence of liver or kidney disease, or haematological, respiratory, endocrine or cardiovascular disease Use of prescription drugs that may cause relevant drug interactions with the trial drug according to the summary of product characteristics: NMDAR antagonist (amantadine, ketamine, dextromethorphan), L‐dopa, dopamine agonist and cholinergic agonist Commencing new psychotherapy or new medication during trial period History of mental retardation or documented IQ below 75
Interventions	Experimental group Treatment name: memantine‐hydrochloride + treatment‐as‐usual Number randomised to group: 17 Duration: 8 weeks Control/comparison group Comparison name: placebo + treatment‐as‐usual Number randomised to group: 17 Duration: 8 weeks Both groups Concomitant psychotherapy: psychotherapy and other psychosocial interventions as usual treatment Concomitant pharmacotherapy: Treatment‐as‐usual consisted of medications of antidepressants (selective serotonin reuptake inhibitors, tricyclics, monoamine oxidase inhibitors noradrenergic and specific serotonin antagonist and serotonin noradrenaline reuptake inhibitors), mood stabilisers and antipsychotics, as well as psychotherapy and other psychosocial interventions. Proportions of participants taking standing medication during trial observation period: no information
Outcomes	Primary outcomes: BPD severity, measured by Zan‐BPD. Assessed at baseline and at week 2, 4, 6 and 8 (EOT) Secondary outcomes Attrition, measured in terms of patients lost after randomisation in each group Adverse effects, measured by "An adverse effects questionnaire, administered fortnightly to assess adverse effects known to be related to memantine use" (Kulkarni 2018, p. 4).
Notes	Sample calculation: yes Ethics approval: yes Funding source: funded by grants from universities, authorities or research foundations Conflicts of interest: No conflicts of interest were reported. Comments from trial authors (limitations) Exploratory study "[...] small sample size with inherent potential for statistical error (type I/type II)" (Kulkarni 2018, p. 185) "[...] plateau of total scores was not reached in either active or placebo groups." (Kulkarni 2018, p. 185) [...] blood plasma levels of memantine were not analysed in the study, which could confirm adherence to the medication and expose any potential individual variability in drug pharmacokinetics." (Kulkarni 2018, p. 185) Comments from review authors: supplemental information provided by trial author through email correspondence (Kulkarni 2020 [pers comm])
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “All participants were individually randomized by The Alfred Clinical Trials Pharmacy to receive either a 10 mg “run‐in dose” for 7 days followed by oral daily memantine hydrochloride 20 mg, or oral placebo according to a computer‐generated randomization list”. (Kulkarni 2018, p. 182)
Allocation concealment (selection bias)	Low risk	Comment: central allocation by pharmacy‐controlled randomisation
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: “All study personnel and participants remained blinded to treatment assignment for the duration of the study”. (Kulkarni 2018, p. 182) Comment: The article referred to the trial as being double‐blind but did not provide information on how blinding was secured.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: The article referred to the trial being double‐blind, however, there was insufficient information on how blinding of outcome assessors was carried out and maintained to permit a judgement of low or high risk of detection bias.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: Intent‐to‐treat imputation method mentioned in abstract. 26.5% discontinued the intervention. From the flow diagram – 8 discontinued from 34 ‐ still 33 analysed
Selective reporting (reporting bias)	High risk	Comment: NCT02097706 ‐ Two secondary outcomes (Cogstate (cognitive assessment) & Borderline Evaluation of Severity over Time) were mentioned in the protocol but not included in the full report. No mention of adverse effects as a secondary outcome in protocol
Vested Interest (funding and/or author affiliations)	Low risk	Comment: reported no conflicts of interest
Other bias	Low risk	Comment: no others sources found