Effectiveness of long-acting injectable antipsychotics: a clinical perspective.

INTRODUCTION The personal and societal costs of schizophrenia spectrum disorders are immense. Affected individuals may experience positive, negative and mood symptoms; medical and substance use comorbidities; and cognitive impairment that significantly impair social and occupational functioning. Globally, schizophrenia is a leading cause of years lost to disability, with a particularly large burden among adolescents and young adults. Treatment of schizophrenia spectrum disorders aims at improved functioning and recovery across the lifespan, but symptom reduction and relapse prevention are important interim goals. Although antipsychotic medications reduce psychotic symptoms and greatly decrease the risk of relapse, their effectiveness in real-world practice is decreased by non-adherence. A meta-analysis of studies that used trained personnel to measure antipsychotic medication adherence found that not ‘regularly taking medications as prescribed’ is prevalent in an average of 41% of participants across 10 studies. Despite this high prevalence, providers are often unaware of this issue and generally overestimate medication adherence in their patients. Long-acting injectable (LAI) formulations of antipsychotic medications were developed to improve adherence. The first LAIs, fluphenazine enanthate and decanoate, were introduced in 1966 in the context of large-scale deinstitutionalisation of patients with serious mental illnesses and the consequent need for effective community-based treatment. Numerous LAI antipsychotics have been developed and marketed in the meantime. Table 1 lists the LAI antipsychotic medications currently available in the USA and the UK. 6 LAIs reduce the frequency at which a patient has to decide whether to take medication. Rather than deciding to take a medication once or twice daily, the patient must only decide to have an injection administered once or twice monthly. Pharmacokinetically, LAIs provide a more stable steady-state concentration of medication in the blood compared with daily oral dosing. Clinicians who are considered using LAIs in their practice want to know: Do LAIs improve patient outcomes compared with oral antipsychotics and if so, which outcomes? Are newer LAIs more effective than older ones? Who should receive LAIs? This review will draw lessons from decades of research that compares the effectiveness of LAIs to oral medications and to other LAIs. LAIS VERSUS ORAL ANTIPSYCHOTIC MEDICATIONS: ADHERENCE Numerous researchers have examined whether LAIs improve adherence as compared with oral medications, but there is no definitive answer. While LAIs decrease how often a patient has to decide whether to take a medication, they do not eradicate adherence issues, as patients may choose to discontinue the monthly or bimonthly injections. Observational studies, though subject to confounding, provide suggestive evidence that LAIs improve medication adherence in routine practice. For example, Brnabic et al conducted a post hoc analysis of a prospective observational study that collected data at 31 international sites. The study matched 40 participants taking an LAI to an equal number taking an oral antipsychotic medication. The study found that compared to those treated with LAIs, twice as many on oral medications switched, augmented or discontinued their medications. Randomised controlled trials (RCTs), however, have not found improved adherence with LAIs. A systematic review and meta-analysis by Leucht et al identified five RCTs that reported results on adherence and found no significant difference in adherence between those on LAIs and those on oral medications, although adherence was typically not measured rigorously. The methodological differences between observational studies and RCTs that may explain these conflicting findings are described below.