What is a commonly recommended mood stabilizer for the treatment of mania?

Mood Stabilizer for Mania

Lithium is the most strongly recommended mood stabilizer for acute mania, with FDA approval for this indication and the most robust long-term evidence for preventing both manic and depressive episodes. 1, 2

First-Line Treatment Selection

For acute mania, lithium, valproate, or atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) are all recommended first-line options by the American Academy of Child and Adolescent Psychiatry. 1 However, lithium stands out as the only FDA-approved mood stabilizer specifically indicated for treating manic episodes of Bipolar Disorder and for maintenance therapy. 2

Lithium's Superior Profile

• Lithium demonstrates response rates of 38-62% in acute mania and is significantly more effective than placebo at inducing response (OR 2.13) and remission (OR 2.16). 3
• Lithium shows superior evidence for long-term efficacy in maintenance therapy compared to other agents, preventing both manic and depressive episodes in non-enriched trials. 1
• Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties. 1
• Lithium produces normalization of manic symptomatology within 1 to 3 weeks when given during an acute episode. 2

Valproate as Alternative

• Valproate shows higher response rates (53%) compared to lithium (38%) specifically in children and adolescents with mania and mixed episodes. 1
• Valproate is particularly effective for mixed or dysphoric mania and is generally better tolerated than other mood stabilizers. 1
• Valproate has been shown to be as effective as lithium for maintenance therapy in bipolar disorder. 1

Dosing and Monitoring Algorithm

Lithium Initiation

• Target serum level of 0.8-1.2 mEq/L for acute treatment, with the therapeutic range lying between 0.30 and 1.30 mmol/L. 1, 4
• Single daily administration should be considered over multiple daily doses to minimize long-term renal damage and enhance compliance, with no significant differences in efficacy or adverse effects between regimens. 5
• Baseline monitoring must include complete blood count, thyroid function tests, urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females. 1
• Ongoing monitoring requires lithium levels, renal and thyroid function, and urinalysis every 3-6 months. 1

Valproate Initiation

• Initial dosage of 125 mg twice daily, titrate to therapeutic blood level (40-90 mcg/mL). 1
• Baseline assessment requires liver function tests, complete blood cell counts, and pregnancy test in females. 1
• Regular monitoring (every 3-6 months) should include serum drug levels, hepatic function, and hematological indices. 1

Combination Therapy Considerations

For severe presentations, combination therapy with lithium or valproate plus an atypical antipsychotic is recommended and represents a first-line approach for treatment-resistant mania. 1

• Quetiapine plus valproate is more effective than valproate alone for adolescent mania. 1
• Risperidone in combination with either lithium or valproate is effective in open-label trials. 1
• Lithium augmentation may improve overall response rates to treatment with carbamazepine or divalproex, with each mood stabilizer given at lower doses when combined, resulting in reduced side effects. 6

Critical Adverse Effects to Monitor

Lithium

• Lithium is more likely than placebo to cause tremor (OR 3.25) and somnolence (OR 2.28). 3
• The lower limit of risk for intoxication is 1.50 mmol/L, requiring careful monitoring given lithium's narrow therapeutic index. 4

Valproate

• Monitor liver enzyme levels regularly, as minor elevations of transaminases are frequent and dose-related, with potential for serious hepatotoxicity. 7
• Valproate is associated with polycystic ovary disease in females, an additional concern beyond weight gain. 1
• Rare but serious risks include acute pancreatitis, hyperammonemia, and Stevens-Johnson syndrome. 7

Maintenance Duration

Maintenance therapy must continue for at least 12-24 months after the acute episode, with some individuals requiring lifelong treatment when benefits outweigh risks. 1

• Withdrawal of maintenance lithium therapy is associated with increased relapse risk, especially within 6 months following discontinuation. 1
• More than 90% of adolescents who were noncompliant with lithium treatment relapsed, compared to 37.5% of those who were compliant. 1

Common Pitfalls to Avoid

• Inadequate duration of maintenance therapy leads to high relapse rates—systematic medication trials require 6-8 weeks at adequate doses before concluding ineffectiveness. 1
• Failure to monitor for metabolic side effects of medications, particularly atypical antipsychotics when used in combination. 1
• Antidepressant monotherapy can trigger manic episodes or rapid cycling and should never be used without a mood stabilizer. 1