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Antipsychotic polypharmacy in psychotic disorders is widespread despite international guidelines favoring monotherapy. Previous evidence indicates the utility of low-dose partial dopamine agonist (PDAs) add-ons to mitigate antipsychotic-induced metabolic adverse effects or hyperprolactinemia. However, clinicians are often concerned about using PDAs combined with high-potency, full dopaminergic antagonists (FDAs) due to the risk of psychosis relapse. We, therefore, conducted a literature review to find studies investigating the effects of combined treatment with PDAs (i.e. aripiprazole, cariprazine and brexpiprazole) and FDAs having a strong D-2 receptor binding affinity. Twenty studies examining the combination aripiprazole - high-potency FDAs were included, while no study was available on combinations with cariprazine or brexpiprazole. Studies reporting clinical improvement suggested that this may require a relatively long time (similar to 11 weeks), while studies that found symptom worsening observed this happening in a shorter timeframe (similar to 3 weeks). Patients with longer illness duration who received add-on aripiprazole on ongoing FDA monotherapy may be at greater risk for symptomatologic worsening. Especially in these cases, close clinical monitoring is therefore recommended during the first few weeks of combined treatment. These indications may be beneficial to psychiatrists who consider using this treatment strategy. Well-powered randomized clinical trials are needed to derive more solid clinical recommendations. Copyright (C) 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Cariprazine is a new dopamine D2 and D3 receptor partial agonist antipsychotic. Meta-Analytic evidence of efficacy in acute schizophrenia and specific groups of patients is lacking. We carried out a meta-Analysis in patients with acute schizophrenia to evaluate the efficacy of cariprazine over placebo and active comparators in overall symptoms, positive and negative symptoms and quality of life. Low and high (≥6 mg/day) doses were tested separately. The possible effect of clinical-demographic modulators was also tested. Four studies (2144 patients) were included. Both high and low cariprazine doses proved superior to placebo in all symptom domains. The standardized mean difference (SMD) to placebo showed a modest impact on overall symptoms compared with meta-Analytic results for other antipsychotics (SMD was similar to lurasidone, asenapine, ziprasidone and aripiprazole, but lower than risperidone, quetiapine and olanzapine). The SMD to placebo on negative symptoms was superior to many antipsychotics including aripiprazole, with a slightly more relevant effect of cariprazine low doses. This effect was probably on secondary negative symptoms since the short-Term follow-up of the studies included. Meta-regression data further refined the compound clinical profile, suggesting that cariprazine may be particularly useful in young patients with a relatively short duration of disease.