Identifying differential predictors for treatment response to amisulpride and olanzapine combination treatment versus each monotherapy in acutely ill patients with schizophrenia: Results of the COMBINE-study.

BACKGROUND: Extensive research has been undertaken to predict treatment response (TR) to antipsychotics. Most studies address TR to antipsychotics in general and as monotherapy, however, it is unknown whether patients might respond favourably to a combination of antipsychotics. AIMS: This study aimed to identify differential predictors for TR to monotherapy with amisulpride or olanzapine compared to a combination of antipsychotics. METHODS: Post-hoc analysis was conducted of data collected from the COMBINE-study, a double-blind, randomized, controlled trial. Demographic and disease-related measures were gathered at baseline to predict TR after eight weeks defined by the Positive and Negative Syndrome Scale. Missing values were accounted for by a random replacement procedure. Attrition effects and multicollinearity were analysed and sets of logistic regression models were calculated for different treatment groups. RESULTS: Of the 321 randomized patients, 201 completed procedures until week eight and 197 were included in the analyses. For all treatment groups, early TR after two weeks and high subjective well-being under antipsychotics at baseline were robust predictors for TR. The propensity for early side effects also indicated a higher risk of later non-response. Specific parameter estimates were rather similar between treatment groups. CONCLUSION: Early TR, drug-related subjective well-being, and early side effect propensity evolved as predictors for later TR whether to monotherapy or combination strategy. Accordingly, due to a lack of differential predictors, early and close monitoring of targeted and unwanted effects is indicated to guide respective treatment decisions.

Ketamine in multiple treatment-resistant depressed inpatients: A naturalistic cohort study.

BACKGROUND: Ketamine has emerged as an effective treatment option for patients with treatment-resistant depression. However, there is limited evidence of the benefits of ketamine in inpatients with multiple treatment resistance (MTR), who far exceed the formal criteria for treatment resistance and suffer from extensive psychiatric comorbidities. OBJECTIVE: The aim of this naturalistic study was to provide preliminary evidence for the use of ketamine in the treatment of MTR depression in a naturalistic inpatient setting. METHODS: Seventy-seven patients (mean age 45.1 ± 13.8 years) were treated with intravenous or intranasal ketamine (1068 administrations) twice weekly for five weeks, followed by maintenance therapy if clinically indicated. Treatment effects were assessed with the BDI, and side effects were assessed by clinicians. We analyzed dose- and route of application-related changes in depression severity, response and remission rates as well as effects on suicidality and frequency of adverse events. RESULTS: Depression severity and suicidality decreased in the acute treatment phase and these changes persisted during the maintenance therapy phase. A total of 28.9 % of the patients met the criteria for response, and 15 % met the criteria for remission. The initial treatment response was highly predictive of the outcome at the end of the acute treatment phase. None of the reported side effects required medical intervention. High-dose intravenous ketamine (0.75-1 mg/kg) resulted in the most pronounced clinical effects. LIMITATIONS: This observational, retrospective, and naturalistic study may be subject to bias and did not allow control of external variables. CONCLUSIONS: We outlined a clinically feasible, high-dose ketamine treatment regimen for hospitalized patients with MTR depression.