Open-label study of the effect of combination quetiapine/lithium therapy on lithium pharmacokinetics and tolerability

The aim of this study was to assess the effect of oral quetiapine on the steady-state pharmacokinetics of lithium.

This was an open-label trial in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who had demonstrated tolerability to combination lithium/ antipsychotic therapy. Patients received lithium for at least 1 week before screening and throughout the 18-day trial. Quetiapine was coadministered in fixed, stepwise, increasing doses of 25 to 250 mg TID on days 4 through 11, and maintained at 250 mg TID on days 12 through 14. Blood samples were drawn to monitor plasma concentrations of lithium and quetiapine. Psychiatric assessments included the Brief Psychiatric Rating Scale, the Clinical Global Impression severity of illness item, and the modified Scale for the Assessment of Negative Symptoms. Neurologic function was assessed using the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Other assessments included clinical laboratory testing, electrocardiography, physical examinations, and monitoring for spontaneously reported adverse events.

Nine men and 1 woman (mean [SE] age, 32.8 [1.9] years; mean [SE] body weight, 87.6 [3.3] kg) entered and completed the 18-day trial. Eight patients had bipolar disorder, 1 had paranoid schizophrenia, and 1 had schizoaffective disorder. Morning trough concentrations of lithium in serum (days 2, 6, 8, 10, 12, 14, and 17), as well as quetiapine and 2 of its metabolites in plasma (days 12, 13, and 14), did not appear to vary noticeably. Small increases were observed in the mean values of the area under the 12-hour serum lithium concentration-time curve and the maximum and minimum observed serum lithium concentrations when quetiapine was added to the lithium regimen. However, the increases were not considered clinically relevant by the investigators and were not statistically significant. A total of 91 adverse events were reported, 67 (73.6%) of which were not attributed to trial treatment. The most commonly reported adverse events during coadministration of lithium and quetiapine were somnolence (90.0% [9/10]), asthenia (70.0% [7/10]), dry mouth (30.0% [3/10]), nausea (30.0% [3/10]), vomiting (30.0% [3/10]), dizziness (30.0% [3/10]), tremor (30.0% [3/10]), and insomnia (20.0% [2/10]). There were no serious adverse events.

Measures of lithium and quetiapine concentrations did not vary significantly during combination therapy. Coadministered lithium and quetiapine were well tolerated in the patients studied.