Lithium efficacy in bipolar depression with flexible dosing: A six-week, open-label, proof-of-concept study

Abstract

Lithium has a narrow therapeutic index with a subtle balance between effectiveness and adverse effects. Current guidelines recommend the use of lithium as a treatment for acute bipolar depression; however, the therapeutic range for the treatment has not been fully defined. Recently, the adjunctive lower lithium dose in bipolar depression has revealed potential efficacy; however, no study has investigated it predominantly in monotherapy. In this open-label, proof-of-concept study, 31 individuals with bipolar disorder during a depressive episode were randomized and 29 were followed up for six weeks with flexible lithium dosing. All subjects had a 21-item Hamilton Rating Scale for Depression (HAM-D) score of ≥18 at baseline. Subjects were divided into two groups, with higher (Li ≥0.5 mEq/l) or lower (Li <0.5 mEq/l) blood lithium levels. Response and remission rates were evaluated using the HAM-D scores. Following 6 weeks of lithium treatment, the remission rate for all patients was 62.0%. The plasma lithium levels did not impact the clinical response. However, subjects with higher blood lithium levels had an increased prevalence of nausea, restlessness, headaches and cognitive complaints. The results indicate that the lithium dose for the treatment of bipolar depression in an individual should be based on the clinical efficacy and side-effects. In the context of personalized psychiatric treatments, it is necessary to evaluate the therapeutic action of lithium with individual regimens in order to develop more tolerable and effective treatment approaches.

Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder

“…Exclusion criteria included rapid cycling BD, current substance (including alcohol) abuse or dependence, with the exception of tobacco, previous electroconvulsive therapy, presence of neurological disorders or any medical disorder that could affect the CNS, mental retardation, medications with CNS effects, vitamins and contraindications for MRI scanning 23 .…”

Lithium chloride ameliorated spatial cognitive impairment through activating mTOR phosphorylation and inhibiting excessive autophagy in the repeated cerebral ischemia‑reperfusion mouse model

“…Lithium, a commonly applied therapeutic agent for depression ( 13 ), has been demonstrated to exert protective effects on neuronal cells both in vitro and in vivo ( 14 ). A previous study has reported that lithium chloride can ameliorate deficits in spatial learning and memory induced by repeated cerebral IR injury by increasing Akt and GSK3β phosphorylation in addition to increasing BDNF expression in hippocampal neurons ( 15 , 16 ).…”

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies

“…Of the remaining studies, 73 publications met the inclusion criteria and were further investigated in detail. The search found 16 publications on anticonvulsants [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], 20 on atypical antipsychotics [ 21 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], 2 on lithium [ 49 , 50 ], 28 on antidepressants [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , …”