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The following is a summary of “Clinical and cost-effectiveness of lithium versus quetiapine augmentation for treatment-resistant depression: a pragmatic, open-label, parallel-group, randomised controlled superiority trial in the UK,” published in the April 2025 issue of Lancet Psychiatry by Cleare et al.

Lithium and quetiapine are first-line options for treatment-resistant depression. Direct comparisons beyond 8 weeks are lacking. 

Researchers conducted a retrospective study to compare the clinical and cost-effectiveness of quetiapine and lithium in treatment-resistant depression. The study assessed outcomes over 12 months. 

They conducted a pragmatic, open-label, parallel-group, randomized controlled trial at six NHS trusts in England with 212 adults aged ≥18 years. Participants had DSM-5 major depressive disorder, Hamilton score ≥14, and inadequate response to ≥2 antidepressants. They were randomized 1:1 to lithium or quetiapine using block randomization stratified by site, depression severity, and treatment resistance. Safety checks preceded medication initiation. Coprimary outcomes were depressive symptom severity over 12 months and time to all-cause discontinuation. Economic analysis assessed cost-effectiveness from NHS, social services, and societal perspectives. Analyses used the intention-to-treat population. 

The results showed 212 participants (97 male [46%], 115 females [54%]; mean age 42.4 years, SD 14.0) were assigned to quetiapine (n=107) or lithium (n=105). 188 (89%) were White, 7 (3%) mixed, 9 (4%) Asian, 4 (2%) Black, 3 (1%) Other, and 1 (1%) not recorded. The Quetiapine group had lower depressive symptom severity (AUC –68.36 [95% CI –129.95 to –6.76]; P=0.0296). Time to discontinuation showed no difference. Quetiapine was more cost-effective. 32 serious adverse events occurred in 18 participants; 1 possibly related to lithium. Overdose occurred in 3% of each group: 7 events (quetiapine), 5 events (lithium). 

Investigators found quetiapine to be more clinically effective than lithium for long-term symptom reduction in treatment-resistant depression. They also found it was probably more cost-effective. 

Source: thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00028-8/fulltext