Central nervous system-related safety and tolerability of add-on ketamine to standard of care treatment in treatment-resistant psychotic depression in patients with major depressive disorder and bipolar disorder.

Background: Psychotic treatment-resistant depression represents a complex and challenging form of mood disorder in clinical practice. Despite its severity, psychotic depression is frequently underdiagnosed and inadequately treated. Ketamine has demonstrated rapid and potent antidepressant effects in clinical studies, while exhibiting a favorable safety and tolerability profile. Although there is limited literature available on the use of ketamine in psychotic TRD, reports on its efficacy, safety, and tolerability profile are of great interest to clinicians. The aim of this study is to investigate the relationship between dissociative symptomatology and psychomimetic effects in inpatients with treatment-resistant major psychotic depression and treatment-resistant bipolar psychotic depression, who receive intravenous ketamine treatment alongside psychotropic medication, both during and after treatment. Materials and methods: A total of 36 patients diagnosed with treatment-resistant unipolar (17 patients) or bipolar (18 patients) depression with psychotic features were treated with eight intravenous infusions of 0.5 mg/kg ketamine twice a week over 4 weeks. Ketamine was given in addition to their standard of care treatment. The severity of depressive symptoms was evaluated using the MADRS, while dissociative and psychomimetic symptoms were assessed using the CADSS and BPRS, respectively. Results: There were no statistically significant changes observed in MADRS, CADSS, and BPRS scores within the study group during ketamine infusions. However, significant improvements in MADRS, CADSS, and BPRS scores were observed during ketamine infusions in both the unipolar and bipolar depression groups. Conclusion: This study provides support for the lack of exacerbation of psychotic symptoms in both unipolar and bipolar depression.

Case Report: Repeated Series of Ketamine Infusions in Patients With Treatment-Resistant Depression: Presentation of Five Cases.

Purpose: Approximately 30% of patients with major depressive disorder (MDD) are treatment resistant. There is an unquestionable need for new treatment strategies. Subanesthetic doses of intravenous (IV) ketamine have a rapid antidepressant effect in treatment-resistant depression (TRD). This paper describes the efficacy of repeated series of intravenous ketamine infusions as an add-on treatment in five TRD inpatients. Methods: Eligible patients aged 43-63 were given eight ketamine infusions as an add-on treatment for patients with MDD. The subjects have readministered the intervention due to worsening depressive symptoms. Results: Of the five inpatients given ketamine as a series of eight infusions, one underwent three, and four had two treatment series. Four patients achieved remission after first series and three after the second series of ketamine infusions. The adverse reactions were mild and transient with no sequelae. Limitations: Presented case series applies to short-term intervention with IV ketamine as an add-on therapy. The results cannot be generalized to the long-term maintenance treatment nor other ketamine formulations as well as different administration schedules and dosing. Conclusions: This case series showed efficacy and safety of the repeated series of IV ketamine treatment in TRD in MDD and bipolar disorder type I. The subsequent interventions were safe and observed adverse events were mild and transient. Interestingly, the IV ketamine treatment at successive administrations seems to alter the major depression severity of the next affective episode. There is a critical need for further research regarding IV ketamine treatment effectiveness and long-term safety in future studies.