Summary
Although several antidepressants have been listed and are widely used in patients with treatment-resistant depression (TRD), about 70% of them fail to achieve remission after the initial treatment and require augmentation treatments. However, previous studies investigating the effectiveness of augmentation therapy were limited
Methods
e conducted a population-based cohort study using a target trial emulation framework. Eligible patients from the National Health Insurance Database (NHID) include patients diagnosed with depression who had previously received two antidepressants within one year between January 1, 2009, and December 31, 2020. Patients with dementia, schizophrenia, bipolar disorder, and alcohol, drug abuse within the past year were excluded to avoid misclassification of antipsychotic exposure. The index date was defined as the first date patients received either an antipsychotic or a third-line antidepressant. The outcomes were the suicide attempt and the complete suicide. We used propensity score (PS) 1:1 matching by the duration of antidepressants and baseline characteristics. This is to conduct pairwise comparisons across patients who received antipsychotics and third-line antidepressants to estimate hazard ratios (HR) and 95% confidence intervals (95% CIs). Furthermore, we used both the Fine and Gray model and the cause-specific hazard model to estimate the subdistribution hazard (SDH) and cause-specific hazard ratio (CSH), respectively. We conducted sensitivity analysis by excluding either low dose sulpiride (150 mg/day) or trazodone during cohort identification.
Results
We included a total of 103 022 patients with TRD. Subsequent to PS matching, 37,855 patients had either antipsychotics or antidepressants. The mean age was 52.4 (SD 16.1) years, and 38.7% were male. Compared to patients who received third-line antidepressants, patients receiving antipsychotics were associated with reduced risk of the suicide attempt (SDH adjusted HR: 0.70; 95% CI: 0.66–0.75; CSH adjusted HR: 0.71; 95% CI: 0.64–0.78). Compared to patients who received third-line antidepressants, patients receiving antipsychotics were not associated with increased risk of the complete suicide (adjusted HR: 1.17; 95% CI: 0.99–1.39). The results of the sensitivity analysis were consistent with the main analysis.
Conclusions
The study showed that controlling the condition with antipsychotics may even reduce the risk of the suicide attempt in patients with TRD. The finding warrants further investigation into the use of antipsychotics in patients with TRD to reduce unintended outcomes.
