Manic psychosis often requires neuroleptic (NL) treatment, and the NL doses used in mania are often high. A global objective of our work is to describe the lowest effective haloperidol (HAL) dose for acute mania. Lorazepam (LZP) augmentation may allow use of lower NL doses, so we will study the effects of adding LZP to two different doses of HAL> Also, we will study effects of adding lithium (Li) to HAL so that results about HAL dose will be generalizable to standard Li-NL treatment. Enough acutely psychotic bipolar manic subjects to obtain 60 completers will receive either HAL 25md/d (usual dose) or HAL 5mg/d (low dose) under double-blind conditions for 3 weeks. In addition to HAL, subjects will receive either placebo, LZP 4mg/d, or standard Li treatment, also under double blind conditions. HAL, Li and LZP blood levels will be measured weekly. Clinical ratings will include the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression, and Manic-State Rating Scale. Side effects will be rated with the Neurologic Rating Scale, Treatment Emergent Symptoms Scale, and an akathisia scale. We will test the hypotheses that: 1) Clinical improvement (on BPRS) is related to HAL dose (and blood level), i.e. HAL 25mg/d produces more improvement that HAL 5mg/d.; 2) HAL side effects are related to HAL dose (and blood level), i.e. HAL25mg/d produces more HAL side effects than HAL 5mg/d. 3) LZP increases clinical improvement, while Li does not. 4) LZP (or Li) increases HAL blood levels. 5) In LZP-treated patients LZP blood levels are related to clinical response, and LZP has both pharmacokinetic and pharmacodynamic interactions with HAL. 6) Li increases HAL side effects. As a secondary hypothesis, if HAL 25mg/d produces greater clinical improvement than HAL 5mg/d then, 7) Any advantage of HAL 25mg/d (alone) over HAL 5mg/d (alone) is made up by LZP augmentation.
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| Chou, J C; Czobor, P; Tuma, I et al. (2000) Pretreatment plasma HVA and haloperidol response in acute mania. J Affect Disord 59:55-9 |
| Chou, J C; Czobor, P; Charles, O et al. (1999) Acute mania: haloperidol dose and augmentation with lithium or lorazepam. J Clin Psychopharmacol 19:500-5 |
