Use of lithium carbonate in treatment-resistant depression: current evidence

Abstract

Treatment-resistant depression (TRD) represents a major clinical challenge, characterized by the lack of therapeutic response following adequate antidepressant trials. In this context, augmentation strategies have been widely employed, with lithium carbonate standing out as one of the most traditional interventions. This study aimed to conduct an integrative review of the literature on the efficacy, safety, and therapeutic positioning of lithium in the management of TRD. The methodology was based on the Whittemore and Knafl (2005) framework, with searches conducted in PubMed/MEDLINE, ScienceDirect, and SciELO, including studies published between 2016 and 2025. Clinical trials, observational studies, systematic reviews, and meta-analyses were included, with 11 studies selected for the final sample. The findings indicate that lithium demonstrates consistent efficacy as an augmentation agent, although without clear superiority over contemporary strategies such as second-generation antipsychotics and rapid-acting agents, including ketamine and esketamine. Its anti-suicidal effect and relevance in specific subgroups are notable. However, safety concerns, the need for monitoring, and methodological variability across studies influence its clinical positioning. It is concluded that lithium remains a relevant but non-central therapeutic strategy, requiring individualized use based on patient profile and critical integration of available evidence.