Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study

Abstract

Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses.

Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors.

Methods: The STAR Network 'Depot Study' was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively.

Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4-44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3-43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4-84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6-40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6-27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742-0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003-4.634; p = 0.049).

Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation.

Fig. 1

Distribution of participants receiving a first long-acting injectable antipsychotic prescription by diagnostic category. Error bars represent 95% confidence intervals. FGA first-generation antipsychotic, LAI long-acting injectable antipsychotic. *Haloperidol LAI n = 85, fluphenazine LAI n = 27, zuclopenthixol LAI n = 16, perphenazine LAI n = 2

Fig. 2

Kaplan–Meier survival estimate of the probability of continuing antipsychotic long-acting injectable antipsychotics during the 12 months after initial prescription. *Statistically significant difference between risperidone LAI and paliperidone LAI (HR 2.014; 95% CI 1.152–3.522; p = 0.014). **Statistically significant difference between olanzapine LAI and paliperidone LAI (HR 2.363; 95% CI 1.170–4.774; p = 0.017). CI confidence interval, FGA first-generation antipsychotic, HR hazard ratio, LAI long-acting injectable antipsychotic