Psychopharmacology Reviews: Intravenous Propofol For Severe, Refractory Mania

David L. Ginsberg, MD

Director of Outpatient Services, Tisch Hospital’s Department of Psychiatry, New York University Medical Center

Intravenous (IV) anesthetic propofol, also known as 2,6-diisopropylphenol, is sometimes used for the management of delirium tremens. Now comes a report that suggests that IV propofol may also be efficacious for the treatment of severe, refractory mania.

A 49 year-old woman with a history of bipolar I disorder was admitted with 3 weeks of elevated mood, grandiosity, decreased sleep, loud and pressured speech, racing thoughts with flight of ideas, distractibility, and psychomotor agitation. Admission labs revealed normal complete blood count and basic metabolic panel, a negative urine drug screen, and serum valproic acid level of 72.5 µg/mL. The patient was initially treated with divalproex sodium and lorazepam, with symptom improvement after 8 days. Subsequently she consented to participate in a study protocol in which divalproex and lorazepam were tapered. Manic symptoms reemerged and the study protocol was discontinued.

Following an extended medical odyssey during which she was treated with divalproex sodium, risperidone, lorazepam, and haloperidol; suspected of early neuroleptic malignant syndrome and had her neuroleptics withdrawn; given ECT interspersed with cholorpromazine, chloral hydrate, and amobarbital; and during which her agitation became increasingly severe, the patient was, on her 55th day of hospitalization, transferred to the medical intensive care unit and started on IV propofol

The rate was titrated in order to achieve full sedation and was increased to 65 µg/kg per minute within 1 hour and was then further increased to 75 µg/kg per minute after another 7 hours. The rate was maintained between 75 and 85 µg/kg per minute over the next 51 hours, at which point propofol was tapered and discontinued. Subsequently the patient was extubated and divalproex sodium was started at 750 mg by mouth BID. Throughout her 5 day stay in the MICU, CPK levels were within normal limits.

She was then transferred back to the psychiatric ward. She was still irritable, but markedly improved. She tolerated divalproex sodium, chlorpromazine, and olanzapine, and was discharged on the 72nd hospital day, 13 days after the completion of 60 hours of general anesthesia with IV propofol.

Propofol’s mechanism of action is believed to involve facilitation of GABA_A receptor activity and depression of glutamate synaptic transmission. It acts quickly and is rapidly cleared with little bioaccumulation. While additional studies on its safety and efficacy for this condition are indicated, for cases of severe, refractory mania, IV propofol may sometimes provide a viable option, but should only be administered in collaboration with expert colleagues, such as anesthesiologists and others, depending upon the medical status of the patient.