Real-world effectiveness of clozapine for intellectual disability: results from a mirror-image and a reverse-mirror-image study

Background: Comorbid mental illness is common in patients with intellectual disability. Antipsychotics are widely used for these conditions, but the effect of clozapine remains largely unknown. Aims: We aimed to investigate the effectiveness of clozapine on naturalistic outcomes in patients with intellectual disability. Methods: By combining the national health registers, we identified all patients in Denmark with intellectual disability initiating clozapine treatment during the period 1996–2012. We used a mirror-image model to test whether initiation of clozapine treatment was associated with reduction in psychiatric admissions and inpatient days, reduction in the number of individuals performing intentional self-harm or overdose, and less frequent use of concomitant psychopharmacological treatment. Similar outcome measures were used in a reverse mirror-image model to investigate the effects of clozapine termination. Results: A total of 405 patients with intellectual disability redeemed clozapine. After initiation of clozapine the number of psychiatric admissions were reduced by 0.65 admissions (95% CI: 0.31–1.00) and the inpatient days were reduced by 67.2 days (95% CI: 51.2–83.3), with a similar decrease for patients with intellectual disability without psychiatric comorbidity. Clozapine treatment was not found to reduce the number of individuals with intentional self-harm, incidents of overdose, or the use of concomitant psychotropics. In cases where clozapine treatment was terminated, the number of psychiatric admissions increased by 0.57 admissions (95% CI: 0.01–1.12). Conclusion: This nationwide study, which is the largest to date, suggests that treatment with clozapine is associated with a reduction in psychiatric admissions and inpatient days in patients with intellectual disability. Further studies evaluating the effects of clozapine in patients with intellectual disability are warranted