In aging bipolar patients, lithium looks superior to antipsychotics

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  • A multicenter, randomized, controlled trial showed similar tolerability for both lithium and divalproex (Depakote), but lithium led to a greater reduction in manic symptoms.

Why this matters

  • The results suggest that guidelines for older patients may need to emphasize lithium over antipsychotics in this population.

Study design

  • 112 inpatients, 112 outpatients aged 60 and older, randomly assigned to receive 300 mg/d lithium or 500 mg/d divalproex for 9 wk.
  • Doses titrated to achieve serum concentrations of 0.80-0.99 mEq/L.
  • Funding: NIH.

Key results

  • Attrition rates were similar for the 2 drugs (14% for lithium, 18% for divalproex at 3 wk; 51%, 44% at 9 wk, respectively; no statistically significant difference at either time point).
  • Sedation rates were similar for both drugs (P=.308).
  • The change from baseline in the Young Mania Rating Scale score favored the lithium group (change in score, 3.90; 95% CI, 1.71-6.09).
  • Response rates at 9 wk were similar in both groups (78.6% lithium, 73.2% divalproex; P=.31).
  • Both groups had infrequent need for adjunctive risperidone (Risperdal; 17% lithium, 14.3% divalproex; no statistically significant difference).


  • No placebo group.
  • The study was short.