Long-Acting Injectable Antipsychotics in Schizophrenia: Literature Review and Practical Perspective, with a Focus on Aripiprazole Once-Monthly

Abstract

IntroductionPrevention 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.MethodsWe 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.ResultsLAI 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.ConclusionResults 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.

Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia

“…Clinical trials show that antipsychotic medications significantly improve psychotic symptoms for patients with schizophrenia [ 221 , 222 , 223 ]. Atypical antipsychotics may partially normalize ROS metabolism and oxidative stress [ 75 ].…”

“…The drug acts as a dopamine D2 and serotonin 5-HT1A receptor agonist and as a serotonin 5-HT2A receptor antagonist [ 228 , 229 ]. Aripiprazole displays high affinity for serotonin 5-HT1A and 5-HT2A receptors and dopamine D2 and D3 receptors [ 223 ]. The drug is unlikely to cause weight gain, sedation, or other changes in metabolism [ 226 , 230 , 231 , 232 ].…”

Can We Rely on AGNP Therapeutic Targets Also For LAI Antipsychotics?

“…We believe, however, that the updated guidelines have missed the important opportunity to face with, and to provide useful information on, the emerging issue of long-acting injectable (LAI) formulations of atypical antipsychotics. The role of LAI formulations -which have been developed as alternative to oral regimens, to sustain the release of the drug over a period of weeks, increasing the dosing interval time and improving patient adherence -is indeed growing [2][3][4][5].…”

Medication Adherence and Discontinuation of Aripiprazole Once-Monthly 400 mg (AOM 400) Versus Oral Antipsychotics in Patients with Schizophrenia or Bipolar I Disorder: A Real-World Study Using US Claims Data

“…Currently eight LAI agents are FDA approved for the treatment of schizophrenia [first-generation LAIs: fluphenazine decanoate, haloperidol decanoate; second-generation LAIs: aripiprazole monohydrate (Abilify Maintena ® ; AOM 400) [ 18 ], olanzapine pamoate, paliperidone palmitate 4 week (Invega Sustenna ® ) [ 19 ], risperidone microspheres (Risperdal Consta ® ) [ 20 ], aripiprazole lauroxil (Aristada ® ) [ 21 ], and paliperidone palmitate 12 week (Invega Trinza ® ) [ 22 ] ], and of these, AOM 400 and risperidone LAI are approved for the maintenance treatment of BD-I. AOM 400 is the more recently approved of the two agents (2013 for schizophrenia, 2017 for BD-I) and offers patients a once-monthly alternative that has been shown to be both effective and well-tolerated [ 23 – 25 ]. Current treatment guidelines for schizophrenia recommend that clinicians consider LAIs, not only in patients who are inadequately adherent to pharmacological therapy [ 26 – 30 ], but also in patients who prefer such treatment [ 31 ].…”