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 (~11 weeks), while studies that found
symptom worsening observed this happening in a shorter timeframe (~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.