Ketamine has shown effectiveness as a rapid-acting antidepressant with antisuicidal effects in terms of reduction of suicidal ideation in the short term. However, the evidence for long-term maintenance ketamine therapy for treatment-resistant depression (TRD) and suicidal behavior is limited. This case series (N=13) highlights the role of adjunctive serial maintenance ketamine infusions in restoring functionality in treatment-resistant unipolar and bipolar (mixed) depression with significant suicide risk and multiple comorbidities, including alcohol dependence. Two cases of TRD achieved functional remission with long-term maintenance ketamine treatment. The first case illustrates the potential synergistic interaction between ketamine and lamotrigine to achieve a sustained antidepressant response in the patient for 7 months. The second case may possibly be the longest reported case of maintenance ketamine therapy, with treatment continuing for 5 years to date. Ketamine treatment showed acute effectiveness in another 7 cases, especially in terms of reduction of suicidal ideation, albeit without significant long-term antidepressant effect. Factors that may contribute to lack of effectiveness of serial ketamine include inadequate mood stabilization in TRD in bipolar spectrum diagnoses, concomitant benzodiazepine use, complex comorbidities, and adverse effects such as significant hypertension and severe dissociation. Future systematic controlled studies are warranted to establish the efficacy and safety profile of long-term ketamine as maintenance therapy for TRD with suicidal behavior.
Background Systemic lupus erythematosus (SLE) patients are a high-risk population for suicide. Glutamatergic neurosystem genes have been implicated in the neurobiology of depression in SLE and suicidal behaviour in general. However, the role of glutamate receptor gene polymorphisms in suicidal behaviour among SLE patients remains unclear in the context of established clinical and psychosocial factors. We aimed to investigate the association of NR2A gene polymorphism with suicidal ideation in SLE while accounting for the interaction between clinical and psychosocial factors. Methods A total of 130 SLE patients were assessed for mood disorders (MINI International Neuropsychiatric Interview), severity of depression (Patient Health Questionnaire-9), suicidal behaviour (Columbia-Suicide Severity Rating Scale), socio-occupational functioning (Work and Social Adjustment Scale), recent life events (Social Readjustment Rating Scale) and lupus disease activity (SELENA-SLE Disease Activity Index). Eighty-six out of the 130 study participants consented for NR2A genotyping. Results Multivariable logistic regression showed nominal significance for the interaction effect between the NR2A rs2072450 AC genotype and higher severity of socio-occupational impairment with lifetime suicidal ideation in SLE patients ( p = 0.038, odds ratio = 1.364, 95% confidence interval = 1.018-1.827). However, only the association between lifetime mood disorder and lifetime suicidal ideation remained significant after Bonferroni correction ( p
Background: Oxidative stress markers are found to be linked with depression and suicide attempts in bipolar disorder (BD), although the role of DNA damage as a marker of suicidal ideation and attempt has yet to be determined. We aim to investigate the association between DNA damage and suicidal behaviour, i.e., suicidal ideation and suicide attempt, among suicidal ideators in BD patients while accounting for clinical and psychosocial risk factors. Methods: A cross-sectional study was conducted in the Universiti Kebangsaan Malaysia Medical Centre on 62 consecutive BD patients diagnosed using the M.I.N.I. Neuropsychiatric Interview and 26 healthy control participants. Socio-demographic and clinical assessments were performed using the Columbia Suicide Severity Rating Scale (C-SSRS) for lifetime suicidal ideation and attempt, Quick Inventory of Depressive Symptomatology (QIDS) for depression severity, Clinical Global Impression for Bipolar Disorder (CGI-BD) for illness severity [both mania (CGI-Mania) and major depressive episode (CGI-MDE)], Social Readjustment Rating Scale (SRRS) for change in life events, and Barratt Impulsiveness Scale (BIS) for behavioural impulsivity. The degree of DNA damage in peripheral blood samples was determined using a standard protocol of comet assay. Results: Multivariable logistic regression revealed higher scores of CGI-MDE as the sole significant factor for lifetime suicidal ideation (OR = 1.937, 95% CI = 1.799-2.076). Although initial bivariate analysis showed a significant association between DNA damage, malondialdehyde (MDA), catalase (CAT), and suicidal behaviour, the findings were not seen in multivariable logistic regression. Bivariate subgroup analysis showed that moderate and severe DNA damage (p = 0.032 and p = 0.047, respectively) was significantly associated with lifetime suicide attempts among lifetime suicidal ideators. The study is the first to look at the connexion between DNA damage and suicidal risk in bipolar patients. It is limited by the small sample size and lack of information on illicit substance use. Conclusions: More severe DNA damage was significantly associated with lifetime suicide attempts among lifetime suicidal ideators in BD. However, the severity of depression was found to be independently associated with lifetime suicidal ideation per se rather than DNA damage in BD. Larger prospective studies are required to ascertain the potential of DNA damage as a biomarker for the transition from suicidal ideation to a suicide attempt.