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Persistent psychotic disorders: avoid combining neuroleptics

Combining oral neuroleptics cumulates adverse effects but offers no proven benefits.

In adult patients with psychotic disorders associated with a psychiatric condition such as schizophrenia, there is no evidence that one oral neuroleptic is particularly more effective than another. In monotherapy, the choice between neuroleptics is mainly guided by the drugs' adverse effect profile weighed against both the observed beneficial effects on clinical outcomes and any adverse effect that occurred during previous treatment. When distressing symptoms persist after well-managed monotherapy, a combination of two oral neuroleptics is sometimes considered.

In two randomised trials involving a total of 170 adults with schizophrenia and related disorders, combinations of so-called first-generation neuroleptics improved clinical outcomes compared to monotherapy.

In fifteen other trials, there was no evidence that combinations of so-called second-generation neuroleptics offered any benefits compared to monotherapy.

Combinations of neuroleptics expose the patient to an accumulation of serious adverse effects, including antimuscarinic, cardiac, extrapyramidal, sedative and metabolic effects, as well as neuroleptic malignant syndromes, rhabdomyolysis and drug interactions. In the absence of well-established efficacy, it is wise to avoid combining neuroleptics.

When a combination of neuroleptics seems justified, it is best to prescribe the lowest possible doses, taking into account foreseeable drug interactions, and to monitor the occurrence of adverse effects, especially cardiac effects.

©Prescrire 1 January 2020

"Persistent psychotic disorders and neuroleptics. Additive adverse effects when neuroleptics are combined" Prescrire Int 2020; 29 (211): 24-25. (Pdf, subscribers only).

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