Measurement of lithium response in patients with bipolar disorder using the Retrospective Assessment of Response to Lithium Scale (Alda scale): A narrative review

Lithium is the first-line medication for the treatment of bipolar disorder (BD), but its exact biological mechanisms have not been identified. One of the major obstacles in lithium-related research is the difficulty in precisely and reliably measuring the response to lithium. The Alda scale was developed to retrospectively measure lithium response in a standardized way. However, several aspects should be considered in understanding previous studies that used the Alda scale. In this narrative review, we aim to review previous studies and present the limitations of prior findings. Additionally, we suggest future strategies for applying the Alda scale in measuring lithium response. Initial studies using the Alda scale mainly included patients who were on lithium monotherapy for a long-term period. However, lithium monotherapy is relatively rare in clinical practice. More importantly, in clinical practice, if patients do not respond well to lithium, clinicians do not prescribe it for a long-term period. Thus, a modified approach to include diverse patients is necessary to identify true poor responders. Most previous studies also mainly included European populations, and ancestrally diverse populations should be included in the research. Furthermore, applying the same scale to explore the effects of other medications would also enhance our understanding of the neurobiological mechanisms of psychiatric medications in BD. Applying electronic health record data in evaluating lithium response would soon facilitate large-scale studies. Future studies that include diverse clinical populations reflecting the clinical practice are necessary to advance precision psychiatry.