[Switching from antipsychotics to aripiprazole and risk of agitation]

The exact modalities of switching between two antipsychotics are rarely studied despite the high frequency of this issue in clinical practice. In this context, description of clinical cases may be enlightening. We report on three new cases of agitation after replacing a dopaminergic antagonist with aripiprazole. A literature review indicated no other predictive clinical feature associated with a higher risk of agitation than therapeutic history. In fact, patients who previously received a greater dose of antipsychotic are more at risk to present paradoxical agitation when switching to aripiprazole. This has led to the hypothesis of dopaminergic hypersensitivity: dopaminergic antagonists could increase the number of receptors to be activated by a partial agonist-like aripiprazole. In one of the cases described here, the patient had received aripiprazole two years previously without any particular side effects. The reintroduction of aripiprazole after a treatment by risperidone was followed by agitation. Other pharmacological hypotheses to explain this agitation involve cholinergic and histaminergic rebounds as well. The frequency of these paradoxical reactions is probably underreported, and psychiatrists should be more attentive to them. During the replacement, aripiprazole should be prescribed at the maximal posology from the start, and the previous antipsychotic should be maintained and slowly decreased in no fewer than four weeks.