REVIEW OF: Patino LR et al, J Child Adolesc Psychopharmacol 2021;31(7):485–493

STUDY TYPE: Randomized double-blind controlled trial

Bipolar disorder (BD) often begins in adolescence. When a teenager presents with a first manic or mixed episode, it can be difficult to choose between a mood stabilizer and an antipsychotic. This study compared lithium versus quetiapine for acute mania in young people.

In this double-blind trial, researchers recruited 109 youths with a recent diagnosis of BD I currently in an acute manic or mixed episode from an inpatient or outpatient setting. Patients were between 10 and 17 years of age. The study randomized participants to lithium or quetiapine. Within one week, they reached a target dose of 1.0–1.2 mEq/L lithium serum level or 400–600 mg of quetiapine. The primary outcome was the change in Young Mania Rating Scale (YMRS) score at six weeks compared to baseline.

Of the 109 patients enrolled, 76 completed the study, with 30 on lithium (59%)and 46 on quetiapine (79%). Interestingly, more participants on lithium discontinued in the first three weeks (75%), whereas those on quetiapine discontinued more commonly after three weeks (64%). Lithium doses averaged 1023 mg/day with a serum level of 1.0 mEq/L, and quetiapine averaged 428 mg/day.

While lithium and quetiapine were both effective for mania, quetiapine was somewhat more effective early on. Quetiapine showed improvement over lithium on the YMRS as early as the first week and continued to outperform lithium throughout the six-week trial on this measure; however, by week four, the difference was no longer statistically significant. The authors wonder whether quetiapine seemed more effective because it was better tolerated and had fewer dropouts than lithium. 

Lithium increased thyroid-stimulating hormone and white blood cell count, whereas quetiapine did not. Unexpectedly, lithium caused a longer corrected QT interval than quetiapine, although none of the occurrences were clinically concerning. Quetiapine side effects included headaches, somnolence, weight gain of 3.7 kg, and higher cholesterol (LDL/HDL) ratio than lithium. 

CARLAT TAKE

Quetiapine treated acute mania in youth somewhat faster and more effectively than lithium for the first few weeks with a small to moderate effect size. While this might favor beginning treatment with quetiapine, lithium may nevertheless be a good longer-term maintenance medication if the patient can tolerate it.