Quetiapine Outperforms Lithium in Resistant Depression

TOPLINE: 

In a 52-week trial among adults with treatment-resistant depression, quetiapine augmentation was more effective than lithium augmentation in reducing symptoms, offered greater cost-effectiveness, and showed comparable safety.

METHODOLOGY: 

• LQD was a pragmatic, open-label, parallel-group, randomised controlled superiority trial (2016-2021) that included 212 adults with treatment-resistant depression.
• Participants (mean age, 42.4 years; 46% men; 89% White) were randomly assigned to receive either quetiapine (n = 107) or lithium (n = 105) augmentation therapy.
• Co-primary outcomes were the overall burden of depressive symptom severity over 52 weeks and the time to all-cause treatment discontinuation; secondary outcomes included clinician-rated depression severity (measured using the Montgomery-Åsberg Depression Rating Scale [MÅDRS] total score), remission rates, health-related quality of life, work and social functioning (measured using the Work and Social Adjustment Scale [WSAS] total score), treatment adherence, safety, and adverse events.
• The cost-effectiveness of the two drugs was compared from two perspectives: An National Health Service and personal social services perspective and a broader societal perspective.

TAKEAWAY:

• The quetiapine group showed a significantly lower overall burden of depressive symptom severity than the lithium group (area under the between-group differences curve, −68.36; P =.0296). The time to medication discontinuation was comparable between the two groups (P =.1196).
• The quetiapine group had lower MÅDRS scores (P =.0435) and WSAS scores (P =.0071) at week 52 than the lithium group, indicating lower depression severity and functional impairment, respectively,.
• Among 32 serious adverse events observed in 18 participants, one was potentially linked to lithium. Safety outcomes were comparable between the two groups (15 events in 7% of participants in the quetiapine group and 17 events in 11% of participants in the lithium group).
• Quetiapine was more cost-effective than lithium from both perspectives considered in the analysis.

IN PRACTICE:

“Compared with lithium, quetiapine might be a more appropriate first-line augmentation for many people with treatment-resistant depression. Future research should investigate predictors of treatment response and discontinuation,” the authors wrote.

SOURCE:

This study was led by Anthony J. Cleare, PhD, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, England. It was published online in the April 2025 issue of The Lancet Psychiatry.

LIMITATIONS:

Substantial missing data for some secondary outcome measures and slightly more missing data in the lithium group at weeks 26 and 52 may have introduced a detection bias. The reduced representation of non-White ethnic groups in the study sample and a chance imbalance in sex and employment between the two groups may have affected the outcomes.

DISCLOSURES: 

This trial was funded by the National Institute for Health and Care Research Health Technology Assessment programme. Several authors reported having various ties with pharmaceutical companies and research organisations. Details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.