PATTERNS OF REAL-WORLD ANTIPSYCHOTIC SWITCHING AFTER INITIATING ADJUNCTIVE CARIPRAZINE OR LUMATEPERONE IN ADULTS WITH MAJOR DEPRESSIVE DISORDER

In major depressive disorder (MDD), patients receiving adjunctive treatment may switch between atypical antipsychotics (AA), a practice associated with worse outcomes (eg, relapse and hospitalization). Understanding real-world AA switching patterns may optimize treatment and improve outcomes. We investigated AA switching patterns among individuals with MDD initiating adjunctive cariprazine or lumateperone.

Methods

The Komodo Research Database Plus was utilized to identify claims data (12/20/2020-7/31/2025) for adults with MDD who initiated adjunctive cariprazine or lumateperone (first dispensing=index) on or after 12/20/2021. Inclusion criteria included ≥12 months of continuous insurance enrollment prior to index date (baseline period), ≥2 pharmacy claims for the index AA, evidence of concurrent use of an antidepressant, and ≥3 months of postindex follow-up. Exclusion criteria included ≥1 bipolar disorder or schizophrenia diagnosis during the baseline period or on the index date, ≥1 record of a nonindex AA within 14 days preindex, or treatment with a long-acting injectable antipsychotic within 3 months preindex. Baseline demographic and clinical characteristics of AA cohorts were balanced with inverse probability of treatment weighting based on propensity scores. Switching prevalence was assessed at 3, 6, 9, or 12 months postindex, with switch defined as ≥2 postindex dispensings of a nonindex AA. A sensitivity analysis was also performed with switch defined as ≥1 postindex dispensing. Odds ratios (OR), their CIs and P values were estimated using logistic regression models comparing switch rates between cohorts.

Results

At all timepoints, AA switching was less frequent among patients who initiated cariprazine (n=24,270) than in those who initiated lumateperone (n=1787). In the weighted cohorts, switch rates among patients who initiated cariprazine and lumateperone were 7.8% and 13.3% at 3 months, 12.9% and 21.5% at 6 months, 16.8% and 27.0% at 9 months, and 19.6% and 29.4% at 12 months, respectively. Patients were 45% less likely to switch at 3 months after initiating cariprazine compared with lumateperone (OR [95% CI]=0.55 [0.48, 0.64], P < .001), 46% less likely at 6 months (0.54 [0.47, 0.61], P < .001), 46% less likely at 9 months (0.54 [0.48, 0.62], P < .001), and 42% less likely at 12 months (0.58 [0.51, 0.67], P < .001). A sensitivity analysis where the definition of a switch was relaxed to ≥1 postindex dispensing of a nonindex AA showed similar results, with significant ORs at 3, 6, 9, and 12 months. Patients that switched AAs most commonly switched to aripiprazole (cariprazine cohort: 5.0%; lumateperone cohort: 6.0%), brexpiprazole (2.8%; 2.5%), and lurasidone (2.0%; 3.7%). Of all patients initiating lumateperone, 4.4% switched to cariprazine, whereas 1.0% of the patients initiating cariprazine switched to lumateperone.

Conclusions

In patients with MDD, initiating adjunctive cariprazine was associated with a significantly lower likelihood of switching to a different AA compared to adjunctive lumateperone at 3, 6, 9, and 12 months.