Mood Stabilizers with 15+ Years of Clinical Use
Lithium, valproate (valproic acid), and carbamazepine are the three mood stabilizers with extensive clinical use spanning 15 years or more for long-term mood stabilization in bipolar disorder. 1, 2, 3
Primary Mood Stabilizers with Established Long-Term Use
Lithium
- Lithium is the gold standard and only FDA-approved mood stabilizer for bipolar disorder in patients age 12 and older, with the longest track record of efficacy and safety data 4, 3
- Lithium is indicated for treatment of manic episodes and maintenance therapy in Bipolar Disorder, reducing the frequency and intensity of manic episodes 3
- Lithium demonstrates superior evidence for prevention of both manic and depressive episodes in long-term maintenance therapy compared to other agents 2, 4
- Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties 2
- Median survival time without relapse is 81 months for lithium, significantly longer than valproate (36 months) or carbamazepine (42 months) 5
Valproate (Valproic Acid)
- Valproate is recommended by the American Academy of Child and Adolescent Psychiatry as a first-line treatment for acute mania and maintenance therapy in bipolar disorder 1, 2
- Valproate shows higher response rates (53%) compared to lithium (38%) and carbamazepine (38%) in children and adolescents with mania and mixed episodes 2
- Valproate is particularly effective for irritability, agitation, aggressive behaviors, and dysphoric/mixed mania 2, 6
- Six controlled studies demonstrate efficacy of valproate in acute mania treatment 7
- Valproate prophylaxis data, though based on uncontrolled studies, appear equally promising to carbamazepine for preventing both manic and depressive episodes 7
Carbamazepine
- Carbamazepine is recommended as a mood stabilizer option for bipolar mania by WHO and the American Academy of Child and Adolescent Psychiatry 1, 2
- Nineteen double-blind studies demonstrate carbamazepine's efficacy in acute mania 7
- Fourteen controlled or partially controlled studies suggest carbamazepine is effective in preventing both manic and depressive episodes 7
- Carbamazepine is widely recognized as a major therapeutic tool for lithium-nonresponsive bipolar illness 7
- Carbamazepine may be particularly useful for rapid cyclers, dysphoric mania, patients with comorbid substance abuse, and those without family history of bipolar illness 7
Clinical Context and Comparative Efficacy
- All three medications—lithium, valproate, and carbamazepine—have been used clinically for decades and represent the conventional mood stabilizers with the most extensive long-term data 7, 6, 8
- Lithium remains the mainstay of pharmacologic therapy for the majority of patients with bipolar disorder, though significant numbers fail to respond to lithium monotherapy 6
- The hazard of experiencing relapse is 66% higher for patients taking valproate compared to lithium after controlling for symptom covariates 5
- Polypharmacy combining these mood stabilizers (lithium plus valproate, lithium plus carbamazepine, or valproate plus carbamazepine) is commonly used when monotherapy fails 8
Important Clinical Considerations
- Maintenance therapy with lithium or valproate should continue for at least 12-24 months after mood stabilization, with some patients requiring lifelong treatment 1, 2
- Withdrawal of maintenance lithium therapy is associated with dramatically increased relapse risk, especially within 6 months following discontinuation, with >90% of noncompliant adolescents relapsing 2, 4
- Treatment with lithium should be initiated only in settings where personnel and facilities for close clinical and laboratory monitoring are available 1
- Regular monitoring is essential: for lithium, check levels, renal and thyroid function every 3-6 months; for valproate, monitor serum drug levels, hepatic function, and hematological indices every 3-6 months 2