Long-acting injectable antipsychotics in schizophrenia: Literature review and practical perspective, with a focus on aripiprazole once-monthly

Introduction: Prevention of relapse is a major challenge in schizophrenia, a disease characterized by poor adherence to antipsychotic medication leading to multiple rehospitalizations and a substantial burden-of-care. Methods: We narratively review published clinical data from the development of long-acting injectable (LAI) formulations of antipsychotic drugs and examine the comparative effectiveness of oral versus LAIs in schizophrenia, with a focus on the second- generation LAI antipsychotic aripiprazole. Evidence is presented from studies with naturalistic/pragmatic as well as explanatory trial designs, supported by the clinical experience of the authors. Results: LAI formulations of antipsychotic drugs offer advantages over oral medications and there is good evidence for their use as a first-choice treatment and in younger patients. Key phase III studies have shown aripiprazole once-monthly 400 mg (AOM 400) to be effective and well tolerated, with high rates of adherence and low rates of impending relapse. In a recent randomized trial with a ‘‘naturalistic’’ study design more representative of routine clinical practice, AOM 400 was well tolerated and had significantly greater effectiveness than paliperidone LAI overall and in younger patients aged ≤35 years. Conclusion: Results across the ‘‘full spectrum’’ of efficacy in traditional clinical trials as well as those encompassing the concept of effectiveness in a more naturalistic setting of real-life clinical practice support the use of AOM 400 as a valid long-term treatment option in schizophrenia overall, as well as earlier in the treatment course, and not solely in situations of poor adherence or when oral antipsychotics have failed.