Acute Mania: Haloperidol Dose and Augmentation With Lithium or Lorazepam

Abstract

Antipsychotic dosing for acute mania has not been well studied. Combined treatment with lithium and an antipsychotic is the most common treatment, but additional antimanic efficacy of a lithium-antipsychotic combination beyond that of an antipsychotic alone has not been well demonstrated. Furthermore, the possibility that lithium could affect antipsychotic dose requirement is believed to have never been studied. In this study, 63 acutely psychotic bipolar manic inpatients were randomly assigned to receive double-blind treatment with 1 of 2 haloperidol doses, 25 mg/day or 5 mg/day, for 21 days. In addition to haloperidol, subjects were randomly assigned to receive concomitant treatment with placebo, standard lithium, or lorazepam 4 mg/day. The high haloperidol dose produced greater improvement and more side effects than did the low dose. Lithium added to the low dose produced a markedly greater clinical response than did the low dose alone. Lorazepam did not improve the outcome for the patients receiving low-dose haloperidol. The clinical response produced by high-dose haloperidol was not enhanced by adding either lithium or lorazepam. All treatment effects emerged by the fourth day of treatment and persisted. Used alone, a haloperidol dose of 5 mg/day is too low for most manic patients, but concomitant lithium produces a dose-dependent enhancement of haloperidol response. Lorazepam 4 mg/day was insufficient to produce an advantage when added to low-dose haloperidol.

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2009 on the Treatment of Acute Mania

“…In a small double-blind study lorazepam's efficacy was comparable to that of haloperidol as an add-on to lithium (Lenox et al 1992). However, used as an add-on medication to haloperidol, lorazepam was less efficacious than lithium add-on treatment (Chou et al 1999). In a small, double-blind, randomised monotherapy but not placebo-controlled 2-week comparison with clonazepam, lorazepam appeared more efficacious in treating acute mania (Bradwejn et al 1990).…”

Acute bipolar mania: a systematic review and meta‐analysis of co‐therapy vs. monotherapy

“…Another was a small trial comparing lithium with a combination of lithium and carbamazepine in 10 patients; outcomes were inadequately reported and were not consistent with the outcomes that we report in this review (19). One compared six different treatment arms and combined three arms each into a high-and low-dose group to make statistical comparisons, we were unable to extract data for individual treatment groups (20).…”

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

“…Lithium (0.6-1.4 mEq/l) has been reported to be both superior to quetiapine IR up to 800 mg daily [79] and inferior to quetiapine IR above 800 mg daily [313] and haloperidol [193]. Also, haloperidol 25 mg/day was superior to 5 mg/day against acute mania (response rate 41 vs. 24 % at day 4; 78 vs. 48 % at day 21) but with more side effects [108]. Aripiprazole showed superior levels of response and tolerability to haloperidol in the treatment of an acute manic episode, but that study put much emphasis on tolerability [525].…”

“…One study reports that the combination of lithium and haloperidol at low dose (5 mg/daily) but not at high dose (25 mg/daily) increases the efficacy against acute mania. Lorazepam has no effect neither on the low dose nor on the high dose [108]. Adding haloperidol to lithium was similar to adding lorazepam [308], but this was not a placebocontrolled study.…”