Adding valproic acid to lithium.
- Lithium is eliminated by the kidney for about 95%. Changes in the rate of excretion can cause unwanted effects.
- Valproic acid is principally metabolized by CYP2C9, CYP2C19, CYP2A6 and UDP-glucuronosyltransferases. Valproic acid is an inhibitor of the enzymes CYP2C9, epoxide-hydroxylase and UDP-glucuronosyltransferases.
- Lithium and valproic acid are the most commonly used mood-stabilizing agents.
- The combination of lithium and valproate appears to be well tolerated and effective in treating bipolar illness.
- Addition of valproate to lithium has been recognized as a first-line treatment for mania that is refractory to lithium monotherapy.
- The addition of valproate is most effective for patients with rapid cycling or mixed episodes.
- This combination may be synergistic.
- Lithium’s pharmacokinetics are not changed by valproate.
- There may be additive adverse reactions due to this combination, such as weight gain, sedation, gastrointestinal complaints, and tremor.
- Start valproic acid according to the general dosing advice.
- Farmacotherapeutisch Kompas - lithium (dutch)
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- Farmacotherapeutisch Kompas; Toxicologie (dutch)
- KNMP; Informatorium Medicamentorum 2015; Monografie "valproaat" (Dutch)
- Freeman et al. Mood stabilizer Combinations: A Review of Safety and Efficacy. Am J Psychiatry 1998;155:12-21
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