Biochemical and psychiatric predictors of Li⁺ response and toxicity in Li⁺ -treated bipolar patients

Background: It has not been determined whether biochemical or psychological variables predict clinical response and toxicity to Li⁺ treatment. Methods: From 30 Li⁺-treated bipolar patients, we measured biochemical variables in red blood cells (RBCs) that encompassed the cell membrane abnormality and the Li⁺/Mg²⁺ competition mechanism. Psychiatric measures of depression, mania, and side effects of Li⁺ toxicity were correlated with these biochemical variables. Physician classification of Li⁺ response and toxicity for each patient were used for determining whether significant differences in biochemical variables and psychiatric measures existed between full and partial responders, and as well as toxic and non-toxic Li⁺-treated bipolar patients. Results: Serum [Li⁺ ] ([Li⁺]_e), the ratio of intracellular RBC to serum Li⁺, [Li⁺]_i/[Li⁺]_e, and phosphatidylcholine shared moderate proportions of variance (10-15%) with several of the psychiatric measures. Physician assessment of full response was predicted by higher levels of [Li⁺]_e and lower scores on the Hamilton Slowing subscale (95.6% accuracy), whereas higher lithium-binding constants and higher Hamilton total scores perfectly predicted physician classification of partial response. Higher scores on Hamilton Slowing subscale and General Side Effects (GSE scale were strongly predictive of physician classified Li⁺ toxicity (80% accuracy), whereas lower levels of [Li⁺]_e and lower scores on the Hamilton Symptom Severity subscale perfectly predicted physician rated non-toxicity in these patients. Conclusions: We found distinct [Li⁺]_e levels that predict response and/or toxicity. Specifically, when [Li⁺]_e was in the range of 0.93-1.42 mM, full response without toxicity was predicted; higher values predicted toxicity; lower values predicted partial response.