International journal of psychiatry in clinical practice
April 29, 2026
David Eckert, Siegfried Kasper
A narrative review presents a decision-making framework for three pharmacological augmentation strategies for treatment-resistant depression: lithium, quetiapine, and esketamine. The agents differ in pharmacological profile, monitoring requirements, and clinical application, though their mechanisms appear to converge on neuroplasticity pathways. Treatment selection may be guided by psychiatric presentation, somatic comorbidity, and practical feasibility. Validated predictive markers for differential response are currently lacking.
Figshare
January 23, 2026
David Eckert, Siegfried Kasper
Treatment-resistant depression is a major clinical challenge, and guidelines recommend different pharmacological augmentations. A systematic review of head-to-head studies comparing lithium, quetiapine, and esketamine found only four trials: three comparing lithium and quetiapine, and one comparing esketamine and quetiapine. All three agents are effective, with a descriptive superiority of esketamine over quetiapine and of quetiapine over lithium. The results argue for re-evaluating treatment algorithms, but because the drugs differ in side effects, contraindications, and pharmacological profiles, embedding them in a comprehensive clinical context is important.
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
January 22, 2026
David Eckert, Siegfried Kasper
For treatment-resistant depression, lithium, quetiapine, and esketamine are all effective augmentation options. A systematic review of head-to-head studies found only four trials: three comparing lithium and quetiapine, and one comparing esketamine and quetiapine. The evidence suggests a descriptive superiority of esketamine over quetiapine and of quetiapine over lithium. However, because the three drugs have fundamentally different properties, side effects, and contraindications, the choice should be made in a comprehensive clinical context. The findings argue for re-evaluating existing treatment algorithms in guidelines.