Oral versus Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia and Special Populations at Risk for Treatment Nonadherence: A Systematic Review
Long-acting injectable antipsychotics (LAIs) should offer better efficacy and tolerability, compared to oral antipsychotics due to improved adherence and more stable pharmacokinetics. However, data on LAIs has been mixed, with some studies finding that they are more effective and tolerable than oral antipsychotics, and others finding the contrary. One possibility for the disparate results may be that some studies administered different antipsychotics in the oral and injectable form. The present systematic review examined the efficacy and tolerability of LAIs versus their oral equivalents in randomized and naturalistic studies. In addition, it examined the impact of LAIs on special populations such as patients with first-episode psychosis, substance use disorders, and a history of violence or on involuntary outpatient commitment. Randomized studies suggest that not all LAIs are the same; for example, long-acting risperidone may be associated with equal or less side effects than oral risperidone, whereas fluphenazine decanoate and enanthate may be associated with equal or more side effects than oral fluphenazine. They also suggest that LAIs reduce risk of relapse versus oral antipsychotics in schizophrenia outpatients when combined with quality psychosocial interventions. For their part, naturalistic studies point to a larger magnitude of benefit for LAIs, relative to their oral equivalents particularly among first-episode patients. 1. Introduction Schizophrenia is a severely disabling psychiatric disorder that often includes hallucinations, delusions, cognitive deficits, poor insight, and comorbid substance use disorder (SUD) [1–3]. The first decade of illness in schizophrenia patients is often characterized by repeated episodes of psychosis with varying levels of remission between episodes and increased disability following each episode [3–5]. Moreover, the bulk of functional deterioration tends to occur in the first five years after onset of schizophrenia, after which the illness typically progresses into a stable phase, wherein positive symptoms are decreased and negative, and cognitive symptoms become predominant [3]. Antipsychotics—drugs that block dopamine D2 receptors—attenuate positive symptoms in schizophrenia and help improve outcomes, especially in the early stages of illness [4, 6–8]. For example, a pivotal study by May [8] revealed that treatment with antipsychotics or electroconvulsive therapy increased the rate of release from the hospital, reduced the length of hospital stay, and decreased the need for sedatives and hydrotherapy in newly
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