Lithium Loading Dose in Acute Mania

When quetiapine is already on board, faster lithium isn’t faster treatment

STUDY: Moghimi-Sarani E et al, BMC Psychiatry 2026;

STUDY TYPE: Randomized, single-blind controlled trial

FUNDING: Shiraz University of Medical Sciences

Background

Valproate loading achieves faster responses in hospitalized mania, but what about rapid titration of lithium? Here’s the first trial to test it.

The Study

Sixty hospitalized adults with bipolar I disorder in a moderate-to-severe manic episode were randomized to lithium loading (20 mg/kg on day 1, maximum 1,800 mg, then standard dosing) or standard titration starting at 300 mg/day. Both strategies were combined with quetiapine titrated to 400–800 mg/day.

Both groups improved substantially over 14 days. The loading group showed a larger mean YMRS reduction from baseline (−17.70 vs. −13.96), but absolute scores at days 3, 7, and 14 did not differ significantly between groups. Therapeutic lithium levels were reached sooner in the loading group (day 5: 0.82 vs. 0.65 mEq/L), and aggressive behavior scores were lower by day 14 (0.06 vs. 0.53).

Surprisingly, there was no difference in adverse events, and no lithium toxicity occurred in either group.

Limitations: Small (n=60), and the loading group had somewhat higher baseline YMRS scores.

Practice Implications

1. This is a negative trial, with a few positive signals.
2. On the other hand, it’s not a fair test of the strategy, as quetiapine may have washed out any benefit from lithium loading.
3. The lack of adverse effects may be unique to this hospital. In practice, slow titration is better tolerated, particularly regarding nausea.