Efficacy and tolerability of aripiprazole versus D2 antagonists in the early course of schizophrenia: a systematic review and meta-analysis

Abstract

Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D2 receptor (D2R) partial agonists and D2R antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare D2R partial agonists with D2R antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified D2R partial agonist, and was not significantly different from pooled D2R antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled D2R antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation D2R antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole’s efficacy did not differ substantially from D2R antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other D2R partial agonists with D2R antagonists in early stages of schizophrenia.

Antipsychotic utilization trajectories three years after initiating or reinitiating treatment of schizophrenia: A state sequence analysis approach

“…Unfortunately, the available literature on the consequences of medication change is limited 65,66 . For instance, little is known about emergent treatment resistance following AP switches or reexposition 67 . Even less known is the impact of those AP sequences use on side effects incidence.…”

“…65,66 For instance, little is known about emergent treatment resistance following AP switches or reexposition. 67 Even less known is the impact of those AP sequences use on side effects incidence. However, the current study highlights that switching rates could possibly be reduced by an appropriate choice of initial antipsychotic treatment, oral clozapine and LAI SGAs being the treatments with the best continuation and adherence trajectories, challenging the usual trial and error's approach still commonly used in psychiatry but also in medicine.…”

Place of the partial dopamine receptor agonist aripiprazole in the management of schizophrenia in adults: a Delphi consensus study

“…Negative symptomatology constitutes an important dimension of schizophrenia and its adequate management remains an important unmet medical need in the treatment of schizophrenia [ 29 – 32 ]. Patients with pronounced negative symptoms tend to be less functional and have poorer outcomes than those in whom such symptoms are milder [ 11 , 33 – 37 ]. It has been clear for several decades that negative symptoms respond less well to antipsychotic medication than acute psychotic symptoms.…”

“…For instance, there is also some evidence that aripiprazole improves quality of life to a greater extent than certain SGAs [ 10 ]. Importantly, the adverse event profile of aripiprazole is different from that of some of the mixed dopamine-serotonin antagonists [ 11 – 13 ]. In addition, it has been postulated that it may be of particular use in certain specific clinical domains, such as in patients with persistent negative symptoms, comorbid substance abuse or in partial responders to other antipsychotic drugs [ 14 , 15 ].…”

Network Analysis of the Structure of the Core Symptoms and Clinical Correlates in Comorbid Schizophrenia and Gambling Disorder

“…Medication use is other related important factor, since impulsive responses have been associated in some patients within the impulsive spectrum disorders with dopamine agonist therapy during chronic treatments (Napier & Persons, 2019 ). Pharmacological research published in the last 20 years has related the increase in impulsivity-related problems in SCZ patients to dose response to some dopamine agonist drugs (Kim et al, 2021 ; Kishi et al, 2021 ; Pahwa et al, 2021 ), including clinical cases with dual mental conditions (Clerici et al, 2018 ). These studies show that aripiprazole (an atypical anti-psychotic drug), as well as other dopamine replacement therapies, contributes to the development of impulsive responses, and these medications therefore constitute risk factors for the onset and progression of GD among SCZ populations.…”