Patients affected by severe manic episode, often with delusional symptoms, are commonly treated with a combination of mood stabilizers, antipsychotics and other sedatives. The choice of a specific drug, dose and term is still debated.

A naturalistic study on a sample of 84 inpatients affected by acute severe mania treated with a combination therapy.

To compare efficacy and tolerability of haloperidol/risperidone/quetiapine in association with lithium and/or valproate.

Eighty-four bipolar inpatients affected by a manic episode according to DSM-5 criteria. Drugs administered according to our best practice. Clinical course weekly monitored with Young Mania Rating Scale (YMRS) for 4weeks. Extrapiramidal side effects (EPSE) monitored with Saint Hans Rating Scale (SHRS).

Twenty-five men (29.76%) and 59 women (70.24%); mean age 43.37 ± 13.58 years. Mean YMRS score T0 40.27 ± 9.04. Forty-one patients (48.81%) treated with haloperidol (3.4 mg/die); 16 (19.05%) with risperidone (4.3 mg/die); 27 (32.14%) with quetiapine (438 mg/die). The 3 groups showed no difference regarding clinical characteristics and YMRS basal scores. Chi2 analysis confirmed an higher response rate (50% of reduction of YMRS final score compared to T0) with haloperidol (χ2 = 14.88; P = 0.00). The repeated-measures model analysis showed a significant decrease (P < 0.05) in YMRS scores in haloperidol vs. risperidone vs. quetiapine patients for all time points from second week. No statistical difference for EPSE was found.

We suggest that haloperidol could be advisable in the treatment of severe mania, with rapid efficacy, even with low doses. Occurrence of EPSE was not considerable during the acute treatment. Studies with a larger sample size, randomization, fixed doses, double blind design are needed.

The authors have not supplied their declaration of competing interest.