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UNDERUTILIZED AUGMENTERS IN POLYPHARMACY REGIMENS: THE CASE FOR LITHIUM

Nassir Ghaemi — Tufts University/Harvard Medical School

2026 ASCP Annual Meeting

Lithium is an underutilized medication in general, especially in monotherapy. When used, it is more commonly added to other agents in polypharmacy, as in augmentation of antidepressants in unipolar depression, or when added to antipsychotics or anticonvulsants in bipolar illness. One of the advantages of lithium in polypharmacy is pharmacokinetic; since it is not metabolized by the liver, but is excreted unchanged in the kidney, it does not have liver-based drug interactions with antipsychotics, anticonvulsants, and antidepressants. It is thus safer in polypharmacy rather than combining two anticonvulsants or two antipsychotics. Further, because of its second messenger mechanisms, it has different pharmacodynamic effects than most standard psychiatric drugs, which tend to have synapse-based mechanisms. These different mechanisms likely allow for more synergy for efficacy. Clinical trial data in bipolar illness support the idea that the most effective polypharmacy regimens involve lithium as a core agent, while polypharmacy regimens without lithium are less effective. Similar data, though less replicated, exist in unipolar depression. In this lecture I will examine these pharmacological and clinical lines of evidence supporting the unique utility of lithium in polypharmacy treatment of mood illnesses. One added line of clinical practice is the use of lithium specifically for prevention of suicide and dementia, in very low doses. This additional utility of lithium, added to other standard treatments, also will be reviewed.

References

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