Quetiapine for Treatment-Resistant Mania

Ms. A was a 39-year-old married woman who was hospitalized for worsening mania after reduction of her trifluoperazine dose from 15 to 12 mg/day. Her symptoms included insomnia, racing thoughts, sexual preoccupation, impulsivity, irritability, increased energy, pressured speech, flights of ideas, paranoid ideation, auditory hallucinations, and suicidal ideation. She was also taking valproic acid, 2000 mg/day, and lithium carbonate, 1200 mg/day. Her blood levels of these drugs were 116 mg/ml and 1.2 meq/ml, respectively. Ms. A’s bipolar disorder had begun during her 20s, and she had initially responded to treatment with lithium carbonate. After several relapses, she started experiencing breakthrough symptoms while taking therapeutic doses of lithium, which required augmentation with both valproic acid and antipsychotic agents. These medications were poorly tolerated, causing weight gain, alopecia, hirsutism, mild oral tardive dyskinesia, and parkinsonism, both with standard antipsychotics and with olanzapine and risperidone. ECT had been minimally effective.

At admission Ms. A began treatment with quetiapine, which was titrated to 75 mg t.i.d., while she continued maintenance treatment with valproic acid, lithium carbonate, and 6 mg/day of trifluoperazine. Her manic symptoms decreased rapidly with minimal sedation. After discharge she was unable to immediately follow up with outpatient treatment and was readmitted 10 days later with an exacerbation of mania. Her quetiapine dose was increased to 150 mg b.i.d. and 200 mg at bedtime over 4 days. The trifluoperazine and valproate doses were decreased to 4 mg and 1500 mg at bedtime, respectively, to minimize sedation and sialorrhea. Ms. A was discharged after 8 days of hospitalization with full remission of her manic and psychotic symptoms. Over the next 6 months her doses of trifluoperazine and valproic acid were tapered off and discontinued. Her quetiapine dose was adjusted to 200 mg in the morning and 400 mg at bedtime, resulting in weight loss and a decrease in sedation. She has remained clinically stable with combined lithium and quetiapine therapy.