Pilot Study Investigates Lithium vs Quetiapine for Bipolar Spectrum Disorder

Medicine, pills
Medicine, pills
This pilot study demonstrates the potential efficacy and safety of lithium as a treatment option for bipolar disorder.

The use of lithium to treat patients with bipolar spectrum disorder warrants further large-scale studies after a pilot study showed similar effectiveness and tolerability compared to treatments of quetiapine immediate release monotherapy. Findings from this study are published in the Journal of Clinical Psychopharmacology.  

Researchers in this randomized, rater-blinded study evaluated the safety, tolerability, and effectiveness of lithium when compared with quetiapine immediate release monotherapy to treat bipolar I, bipolar II, or subthreshold bipolar disorder over a 16-week time frame. Screening included collection of demographic information, mental status and suicidal severity data, clinical interviews, laboratory testing, and medical history. Patients in the lithium arm (n=18) received incremental dose increases until their blood lithium level reached 0.6 mEq/L or greater. Patients in the quetiapine arm (n=24) received incremental dose increases until they reached 300 mg a day, and if this was not tolerated, dosages could be reduced to 100 mg a day. Researchers assessed tolerability by discontinuation and effectiveness by symptom severity, quality of life, and changes in blood chemistry.

At screening, the lithium arm had more white patients (61.1%; P =.01), more older patients (mean age=44.7 years old; P =.05), fewer patients with previous suicide attempts (22.2%; P =.03), and fewer patients with substance use disorders (5.6%; P =.05). The mean blood lithium level of patients taking 600 mg per day (n=13) was 0.5 mmol/L (range=0.3 to 1.05 mmol/L), and in patients with adjusted dosages (n=7), the mean blood lithium level was 0.8 mmol/L (range=0.4 to 1.0 mmol/L). The mean dose of quetiapine was 327.78 mg per day (range=100 to 900 mg).  The mean time to discontinuation was 7.7 ± 1.1 weeks in the lithium arm and 8.4 ± 0.8 weeks in the quetiapine arm (P =.54).

Symptom severity and quality of life improved from baseline to weeks 8 and 16 in both arms with the only significant difference being changes in the Clinical Global Impression-Efficacy Index score from baseline to week 16, both overall (P =.02) and in patients with depression (P =.04). Metabolic changes, safety measurements, and inflammatory markers were similar between the two groups, with the only significant difference being a larger decrease in total cholesterol in the lithium arm. Adverse events were comparable between the two arms with lithium having more cases of nausea (P =.02) and upset stomach (P =.01) and quetiapine having more cases of dry mouth (P <.01).

Related Articles

Future studies need to increase sample size to draw meaningful conclusions and have a longer follow up time to demonstrate real-world results.

In conclusion, this pilot study demonstrates the potential efficacy and safety of lithium as a treatment option for patients with bipolar spectrum disorder and warrants further comprehensive studies.

This study was supported by the Young Investigator Award from Brain and Behavior Research Foundation and from the Cleveland Foundation. Please refer to reference for a complete list of authors’ disclosures.


Gao K, Goto T, Yuan C, et al. A pilot study of the effectiveness of lithium versus quetiapine immediate release monotherapy in patients with bipolar spectrum disorders. J Clin Psychopharmacol. 2018;38(5):422-434.