Review of clinical medication adherence in patients with schizophrenia

Table 1 Comparative effectiveness of long-acting injectable vs oral antipsychotics

Ref.	Population	Key outcomes (LAI vs OAP)	Effect size/statistical significance	Key limitations
Greene et al[38], 2018	Schizophrenia (n = 5638)	Adherence (PDC ≥ 0.8): 33.9% vs 25.5%	Adjusted mean PDC: + 5% (LAI superior, P < 0.001)	Unmeasured clinical differences (e.g., baseline severity) may bias results; medicaid-only population
		mean PDC: 0.55 vs 0.50
		Discontinuation: 63.2% vs 72.0%	Discontinuation risk: 20% lower for LAI (HR = 1.20, P < 0.001)
		Time to discontinuation: 196 vs 123 days
	Bipolar disorder (n = 11344)	Adherence (PDC ≥ 0.8): 30.9% vs 21.5%	Adjusted mean PDC: + 5% (LAI superior, P < 0.001)	Same limitations as schizophrenia cohort
		mean PDC: 0.51 vs 0.45
		Discontinuation: 67.9% vs 77.4%	Discontinuation risk: 19% lower for LAI (HR = 1.19, P < 0.001)
		Time to discontinuation: 149 vs 99 days
Bossie et al[40], 2015	Schizophrenia (meta-analysis of 11 studies)	Pragmatic trials: Consistently favored LAI for relapse prevention, hospitalization reduction, and adherence. Explanatory trials (RCTs): Often showed no significant difference in efficacy	ASPECT-R score (pragmatism): LAI-superior studies: 31.6 ± 6.4	Limited representation of 1st-gen LAIs; ratings based on published reports (not protocols)
			Non-superior studies: 11.9 ± 1.9, P = 0.007
			Most differentiating domain: Participant compliance assessment (P = 0.005)

LAI: Long-acting injectable; OAP: Oral antipsychotics; PDC: Proportion of days covered; HR: Hazard ratio; RCTs: Randomized controlled trial; ASPECT-R: A study pragmatic-explanatory characterization tool-rating.