Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what is the evidence?

Lithium and anticonvulsants are used as adjunctive agents to antipsychotic medications for the treatment of schizophrenia. However, the evidence supporting this 'off-label' use is relatively shallow and inconsistent. Early reports of the usefulness of lithium as an adjunctive agent have been negated by later studies. Similarly, large trials of adjunctive valproate and adjunctive lamotrigine completed in the wake of early and promising efficacy signals from smaller studies have failed to replicate the initial findings. Also problematic is the dearth of large trials of adjunctive mood stabilizers in treatment-refractory schizophrenia or persistent aggressive behavior in schizophrenia, two populations for which there remains a pressing therapeutic need for effective medication regimens. Nevertheless, on an individual patient basis there may be some benefits to be gained by adding a mood stabilizer to a medication regimen, but these must be weighed against potential adverse effects, and outcomes closely monitored so that discontinuation of the mood stabilizer is prompt should benefits not accrue.