Subcutaneous ketamine reduces suicide risk and improves functioning in depression: A proof-of-concept study.

This investigation explores the efficacy of subcutaneous ketamine for mitigating depressive symptoms and suicidal ideation, addressing a crucial need for rapid-onset treatments in severe depression cases. It introduces an innovative approach to administering an NMDA receptor antagonist, significantly advancing psychopharmacological methods for treating suicidal behaviors as distinct entities, even within depressive episodes. The study's objective is to assess the impact of subcutaneous ketamine on diminishing suicidal thoughts and mood symptoms during depressive episodes through a naturalistic, prospective observational design. Conducted at Hospital de Clínicas de Porto Alegre, Brazil, between 2021 and 2023, the study involved 26 patients undergoing a current depressive episode. Of these, 23 completed the acute phase of treatment, and 18 were followed up for 6 months. The treatment regimen commenced with a ketamine dose of 0.5 mg/kg, which was adjusted according to individual responses under psychiatric supervision. The findings revealed substantial decreases in Columbia Suicide Severity Rating Scale scores following multiple ketamine sessions, with most patients achieving remission after approximately eight sessions. A notable reduction in depressive symptoms was also observed. A clear dose-response relationship was established, indicating that higher doses of ketamine were associated with more significant improvements in depressive symptoms, suicidal ideation, and overall functionality. Follow-up assessments suggested that these improvements were sustained over time. The subcutaneous administration of ketamine was generally well-tolerated, with minor and short-lived side effects. The study posits that subcutaneous ketamine may present a promising solution for treating severe depression accompanied by suicidal tendencies, particularly considering its positive influence on patient functionality and well-being. This method could offer a cost-effective and accessible treatment alternative, especially relevant in settings with limited resources. Given its potential in reducing long-term disability and economic viability, the study advocates for its broader application and further validation through larger, controlled trials. Trial Registration: ClinicalTrials.gov NCT05249309.

Aripiprazole for patients with schizophrenia and schizoaffective disorder: an open-label, randomized, study versus haloperidol.

INTRODUCTION: Aripiprazole, a dopamine D2 receptor partial agonist, has also partial agonist activity at serotonin (5-HT)1A receptors and antagonist activity at 5-HT2A receptors. METHODS: In this 8-week, multicenter, randomized, parallel-group, open-label, flexible-dose study, patients diagnosed with schizophrenia or schizoaffective disorder were randomized to aripiprazole 15-30 mg/day or haloperidol 10-15 mg/day. RESULTS: Patients treated with both aripiprazole and haloperidol improved from baseline in Positive and Negative Syndrome Scale total, positive, and negative scores as well as in Clinical Global Impressions scores (all P<.001). At the end of the study, the percentage of patients classified as responders--according to >or=40% reduction in the Positive and Negative Syndrome Scale negative subscale score--was significantly higher in the aripiprazole group (20%) than in the haloperidol group (0%) (P<.05). Additionally, a higher number of patients receiving haloperidol required more anticholinergic medications (P<.001) than aripiprazole-treated patients, whereas more aripiprazole (45.5%) than haloperidol-treated patients (12.9%) required benzodiazepines (P=.002). At endpoint, rates of preference of medication were higher in the aripiprazole group (63.2%) than in the haloperidol group (21.7%), as expressed by patients and caregivers (P=.001). CONCLUSION: Aripiprazole and haloperidol had similar efficacy in terms of reduction of overall psychopathology. Although aripiprazole has been demonstrated to be superior concerning negative symptoms and in terms of tolerability (extrapyramidal symptoms) and preferred by patients and caregivers than haloperidol, significantly more aripiprazole-treated patients required benzodiazepines.

An open trial of reboxetine in HIV-seropositive outpatients with major depressive disorder.

BACKGROUND: The prevalence of major depressive disorder (MDD) in human immunodeficiency virus (HIV)-seropositive patients is higher than in the general population. The treatment of comorbidities of HIV infection, such as depression, is an important target in the clinical management of these patients. The use of antidepressants in HIV patients can be complicated by the pharmacokinetic interaction between antidepressants and antiretroviral agents. Several antidepressants and antiretrovirals are metabolized by cytochrome P450 (CYP450). Reboxetine is a noradrenergic antidepressant that is not metabolized by CYP450 and may offer a valuable option in the treatment of MDD in HIV-seropositive patients. METHOD: Twenty HIV-infected outpatients with MDD according to DSM-IV criteria were treated with reboxetine, 8 mg/day, for 12 weeks within an open trial design. Outcome measures included the Montgomery-Asberg Depression Rating Scale (MADRS) and a side effect profile. Data were gathered from July 2000 to March 2001. RESULTS: Seventy-five percent of patients (N = 15) completed the trial. All patients who completed the trial had an improvement equal to or higher than a 50% reduction in their MADRS scores at endpoint. The most frequent adverse effects were insomnia, sweating, and shivering. CONCLUSION: Within this open trial, reboxetine was found to be effective in reducing depressive symptoms in HIV illness. The rate of dropout (25%) suggests that reboxetine may be well tolerated in this population.