Lithium Found Significantly Superior to Newer Bipolar Drugs

By John Henry Dreyfuss, MDalert.com staff.

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  • Patients taking lithium had lower rates of self-harm and unintentional injury versus those taking valproate, olanzapine, or quetiapine.
  • Patients diagnosed with bipolar disorder are 15x more likely to die by suicide and 6x more likely to die by accidental injury than people in the general population.
  • People taking valproate, olanzapine, or quetiapine were 40% more likely to harm themselves compared to patients taking lithium.
  • People taking valproate or quetiapine were 32% to 34% more likely to suffer an unintentional injury.

Lithium (Figure 1) has been found superior to many newer mood stabilizers for patients with bipolar disorder (BPD), according to a study published recently in JAMA Psychiatry. Patients taking lithium had lower rates of suicide, self-harm, and unintentional injury according to results of a propensity score (PS)-adjusted and PS-matched longitudinal cohort study conducted in the United Kingdom (UK).

Figure 1. Lithium carbonate is the only drug FDA approved
for treatment of bipolar disorder in children.
(Source: Wikipedia.)

“This finding augments limited trial and smaller observational study results. It supports the hypothesis that lithium use reduces impulsive aggression in addition to stabilizing mood,” the authors explained.

Patients taking lithium had lower rates of self-harm and unintentional injury compared to those taking other drugs for treatment of BPD (Figure 2), such as valproate, olanzapine, or quetiapine, said lead researcher Joseph Hayes, a fellow of psychiatry at University College London.

Figure 2. Dynamic remodeling of dendritic arbors
in GABAergic interneurons of adult visual cortex.
(Source: Wikipedia/Creative Commons.)

"This is important because people with bipolar disorder are 15x more likely to die by suicide and 6x more likely to die by accidental injury than the general population," Dr. Hayes explained.

Patients taking a mood stabilizer other than lithium were 40% more likely to harm themselves compared with those taking lithium, the authors found. Patients taking valproate or quetiapine were 32% to 34% more likely to suffer an unintentional injury while experiencing a manic episode, the researchers said.

The Analysis

Self-harm is one of the most common causes of morbidity among patients with BPD (Figure 3). It is strongly associated with suicide and evidence continues to accumulate showing that lithium use may reduce suicidal behavior. Additionally, there is concern among researchers and clinicians that the use of anticonvulsants as mood stabilizers may increase self-harm among patients with BPD.

Figure 3. Bipolar disorder.
(Source: Wikipedia/NIH.)

The investigators conducted a PS-adjusted and PS-matched longitudinal cohort study among a nationally representative UK sample. They used electronic health records data collected between January 1, 1995, and December 31, 2013. Included in the study were all patients diagnosed as having bipolar disorder who were prescribed lithium, valproate, olanzapine, or quetiapine as maintenance mood stabilizer treatment during this period. The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide.

Among the 14,396 individuals diagnosed with BPD during the study period, 6671 were included in the cohort. Of these patients, 2148 were prescribed lithium, 1670 were prescribed valproate, 1477 were prescribed olanzapine, and 1376 were prescribed quetiapine as a maintenance mood stabilizer.

Self-harm rates were lower in patients prescribed lithium (205; 95% confidence interval [CI], 175-241 per 10 000 person-years at risk [PYAR]) compared with those prescribed valproate (392; 95% CI, 334-460 per 10 000 PYAR), olanzapine (409; 95% CI, 345-483 per 10 000 PYAR), or quetiapine (582; 95% CI, 489-692 per 10 000 PYAR).

This association was maintained after PS adjustment (hazard ratio [HR], 1.40; 95% CI, 1.12-1.74 for valproate, olanzapine, or quetiapine vs lithium) and PS matching (HR, 1.51; 95% CI, 1.21-1.88). After PS adjustment, rates of unintentional injury were lower for patients taking lithium compared with those who received valproate (HR, 1.32; 95% CI, 1.10-1.58) and quetiapine (HR, 1.34; 95% CI, 1.07-1.69) but not olanzapine.

The suicide rate among these patients was 14 (95% CI, 9-21) per 10 000 PYAR. Although this rate was lower among patients in the lithium group than for those who received other treatments, “there were too few events to allow accurate estimates,” the researchers wrote.


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