Parenteral Valproate for Control of Acute Mania
Valproate is a safe and effective antiepileptic and thymoleptic drug. An intravenous form has been available since December 1996; it is approved for the treatment of complex partial and absence seizures but not for bipolar disorder (package insert, Abbott Laboratories). A recent case report discusses using intravenous valproate for controlling agitation in an 8-year-old autistic patient (1). We are not aware of any literature on its use for mania.
Ms. A was an 81-year-old nursing home resident with a long history of bipolar disorder, including approximately 10 hospitalizations for manic episodes; her condition was maintained with divalproex and haloperidol therapy. She had recently developed Alzheimer’s dementia.
The dementia manifested in growing apathy, with Ms. A often sitting for long periods fully awake but with her eyes closed. It was thought that she was becoming lethargic, and her haloperidol dose was tapered off. This brought no dramatic change, so her divalproex dose was tapered and discontinued. Within a week, Ms. A was euphoric, loud, argumentative, grandiose (“I’m the greatest lion tamer in the Ringling Brothers Circus!”), paranoid, and hallucinating. Soon she refused to take her medications, and a hasty attempt to restart divalproex therapy failed. Finally, she refused all food and fluids, necessitating hospitalization.
Ms. A was admitted to the psychiatric department. Her manic symptoms continued. Attempts to persuade her to take nutrition, fluids, or medications orally failed, and intravenous fluid replacement was begun. Because of her declining nutritional status and persistent agitation, we decided her condition constituted an emergency. With family consent, we began intravenous haloperidol, 1 mg b.i.d. This lessened her agitation but had no effect on her mania or psychosis.
As Ms. A’s nutritional status continued to deteriorate, we decided, again with family consent, to administer valproate intravenously. We began with 125 mg of valproate in 100 cc of 5% dextrose in water, infused over 1 hour every 6 hours, and increased the infusion to 200 mg after the first two doses. After 2 days (nine doses), Ms. A’s mania cleared. She began eating, drinking, and taking her medications, including divalproex, orally. In the few days until discharge, Ms. A exhibited her baseline playful and pleasantly disoriented dementia (“Get me a beer!”), with no evident psychosis, grandiosity, or other indication of mania. The nine intravenous doses brought her serum valproate level to 53 μg/ml, which had historically been therapeutic for her. She experienced no untoward effects. Ms. A was discharged back to her nursing home with the manic episode resolved.
When acute mood stabilization is required, but the oral route is unavailable, parenteral valproate appears to be a safe and effective alternative. Oral and intravenous total daily doses are equivalent (package insert, Abbott Laboratories). The rapid response in this case suggests that a loading effect might be achieved expeditiously with intravenous administration (presumably with diminished gastrointestinal side effects), although aggressive intravenous dosing for routine control of mania would merit further study for safety.
1. Hilty DM, Rodriguez GD, Hales RE: Intravenous valproate for rapid stabilization of agitation in neuropsychiatric disorders (letter). J Neuropsychiatry Clin Neurosci 1998; 10:365–366Crossref, Medline, Google Scholar
