Aripiprazole Lauroxil, a Novel Injectable Long-Acting Antipsychotic Treatment for Adults with Schizophrenia: A Comprehensive Review

Abstract

Purpose of Review. This is a comprehensive review of the literature regarding the use of Aripiprazole lauroxil for schizophrenia. This review presents the background, evidence, and indications for using aripiprazole lauroxil to treat schizophrenia in the context of current theories on the development of schizophrenia. Recent Findings. Schizophrenia is a chronic mental health disorder that currently affects approximately 3.3 million people in the United States. Its symptoms, which must be present for more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Aripiprazole lauroxil is a long-acting intramuscular injection that works as a combination of partial agonist activity at D2 and 5-HT1A receptors combined with antagonist activity at 5-HT2A receptors. It can be dosed as a 4-, 6-, or 8-week injection, depending on oral dosage. Aripiprazole lauroxil was FDA approved in October of 2015. Summary. Schizophrenia is a severe psychiatric disorder if left untreated. There are multiple medications to help treat schizophrenia. One antipsychotic agent, aripiprazole lauroxil, offers long duration injections that optimize and improve compliance. Known side effects include weight gain, akathisia, neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension. Aripiprazole lauroxil is an FDA-approved drug that can be administered monthly, every six weeks, or every two months and has been shown to be both safe and effective.

Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole

“…47,48 And ARI displays a higher affinity for the dopamine receptor than the serotonin receptor. 49,50 Hippocampal hyperactivity has been reported to increase dopamine release from the ventral tegmental area (VTA) to the NAc, 51 which is associated with hyperlocomotion. 52 This regulation may occur through a disinhibition of dopamine neuron activity in the VTA.…”

“…ARI is an atypical antipsychotic that acts as an antagonist of both 5‐HT2A and postsynaptic dopamine type 2 (D2) receptors as well as a partial agonist of 5‐HT1A and presynaptic D2 receptors 47,48 . And ARI displays a higher affinity for the dopamine receptor than the serotonin receptor 49,50 . Hippocampal hyperactivity has been reported to increase dopamine release from the ventral tegmental area (VTA) to the NAc, 51 which is associated with hyperlocomotion 52 .…”

Prodrugs as empowering tools in drug discovery and development: recent strategic applications of drug delivery solutions to mitigate challenges associated with lead compounds and drug candidates

“…52). 76,77,238 After injection of 5ab to SD rats at 5.0 mg per kg equimolar dose of parent, 5aa, 5ab and 5ad were all detected in the systemic circulation, indicating conversion of 5ab to the N-CH 2 OH intermediate 5ad, which subsequently degrades to 5aa with the release of formaldehyde. 239 In phase I clinical trials, PK parameters were evaluated in adult patients with schizophrenia following injection of 5ab as an aqueous suspension into the gluteal muscle over 24 weeks based on a schedule of seven 441 mg injections [q4wk], five 882 mg injections [q6wk] or four 1064 mg injections [q8wk], with the last dose administered at the 24th week.…”

“…LAIs are becoming especially popular for the treatment of schizophrenia. 77,78 An increased understanding of the biological barriers that hinder tissue-specific drug delivery has subtended the development of targeting strategies based on small molecule-, nucleic acid-, peptide-, antibody-, and cell-based approaches. 79 Drug candidates can fail because of efficacy issues attributed to poor accumulation in target organs and safety issues associated with high accumulation in off-target organs.…”

Risk of Drug-induced Movement Disorders with Newer Antipsychotic Agents

“…Aripiprazole lauroxil is administered from prefilled syringes ranging from 441 to 882 mg every 4–8 weeks intramuscularly [ 131 ]. Aripiprazole acts as a partial agonist at 5-HT 1A Rs and as an antagonist at 5-HT 2A Rs with a complex interaction at D2Rs [ 132 ]. At D2Rs, this drug acts as a partial antagonist at high extracellular dopamine concentrations and as a partial agonist at low extracellular dopamine concentrations [ 133 ].…”