What is the recommended management for an acute manic episode?

Management of Acute Manic Episode

For acute mania, initiate treatment with lithium, valproate, or an atypical antipsychotic (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) as first-line monotherapy, with combination therapy (mood stabilizer plus antipsychotic) reserved for severe presentations or inadequate response to monotherapy. 1, 2

First-Line Monotherapy Options

Lithium

• Lithium remains the gold standard with response rates of 38-62% in acute mania and superior long-term prophylaxis against both manic and depressive episodes. 2, 3
• Target serum level of 0.8-1.2 mEq/L for acute treatment, with levels checked 5 days after initiation and dose adjustments. 1
• FDA-approved for patients age 12 and older. 1, 2
• Lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties. 1
• Requires baseline complete blood count, thyroid function tests, urinalysis, BUN, creatinine, and serum calcium before initiation. 1, 2
• Monitor lithium levels, renal and thyroid function, and urinalysis every 3-6 months during maintenance. 1, 2

Valproate

• Demonstrates response rates of 53% in acute mania, superior to lithium (38%) in some pediatric studies, particularly effective for mixed or dysphoric mania. 1, 2
• Initial dosing: 20 mg/kg/day or 125 mg twice daily, titrate to therapeutic blood level (40-90 mcg/mL). 1
• Obtain baseline liver function tests, complete blood cell counts, and pregnancy test before initiating. 1, 2
• Monitor serum drug levels, hepatic function, and hematological indices every 3-6 months. 1, 2
• Avoid in women of childbearing potential when possible due to teratogenic risk and association with polycystic ovary disease. 2

Atypical Antipsychotics

• Second-generation antipsychotics (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone) are FDA-approved for acute mania in adults and provide more rapid symptom control than mood stabilizers alone. 1, 4, 2
• Aripiprazole has a favorable metabolic profile compared to olanzapine and provides rapid control of psychotic symptoms and agitation. 1
• Risperidone: Initial dose 2-3 mg/day for adults, effective dose range 1-6 mg/day; for pediatrics, start 0.5 mg once daily, target 1-2.5 mg/day. 5
• Olanzapine: 10-15 mg/day provides rapid symptomatic control, dose range 5-20 mg/day. 1
• Monitor body mass index monthly for 3 months then quarterly, and blood pressure, fasting glucose, and lipids at 3 months then yearly. 1, 2

Combination Therapy for Severe or Treatment-Resistant Mania

• Combination therapy with lithium or valproate plus an atypical antipsychotic represents a first-line approach for severe presentations and treatment-resistant mania. 1, 2
• Quetiapine plus valproate is more effective than valproate alone for adolescent mania. 1, 2
• Risperidone in combination with either lithium or valproate is effective in open-label trials. 1
• Olanzapine in combination with lithium or valproate is more effective than monotherapy with mood stabilizers for acute mania, particularly indicated for patients with severe agitation or psychotic symptoms. 1

Adjunctive Management for Acute Agitation

• Benzodiazepines such as lorazepam 1-2 mg every 4-6 hours as needed, combined with antipsychotics, provide superior acute control of manic agitation compared to either agent alone. 1
• The combination achieves faster sedation and prevents paradoxical excitation sometimes seen with benzodiazepines alone in manic patients. 1
• Prescribe with clear instructions regarding maximum daily dosage (typically not exceeding 2 mg lorazepam equivalent) and frequency limitations (not more than 2-3 times weekly for PRN use). 1

Treatment Duration and Maintenance

• Continue the regimen that effectively treated the acute episode for at least 12-24 months after stabilization. 1, 2
• Continue antipsychotic treatment for at least 12 months after beginning of remission. 2
• Withdrawal of maintenance lithium therapy dramatically increases relapse risk, with >90% of noncompliant adolescents relapsing versus 37.5% of compliant patients. 1, 2
• Some individuals may need lifelong treatment when benefits outweigh risks. 1

Critical Pitfalls to Avoid

• Never use antidepressant monotherapy in bipolar disorder, as this triggers manic episodes or rapid cycling. 1, 2
• Conduct systematic medication trials with 6-8 week durations at adequate doses before concluding an agent is ineffective. 1, 2
• Do not prematurely discontinue maintenance therapy, as inadequate duration leads to relapse rates exceeding 90%. 1, 2
• Monitor for metabolic side effects of atypical antipsychotics, particularly weight gain, diabetes risk, and dyslipidemia. 1, 2
• Avoid unnecessary polypharmacy while recognizing that many patients require combination therapy for optimal control. 1, 2

Psychosocial Interventions

• Psychoeducation about symptoms, course of illness, treatment options, and importance of medication adherence should accompany all pharmacotherapy. 1, 2
• Cognitive-behavioral therapy has strong evidence for both anxiety and depression components of bipolar disorder. 1
• Family intervention helps with medication supervision, early warning sign identification, and reducing access to lethal means in patients with suicide risk. 1

Resource-Limited Settings

• Haloperidol or chlorpromazine should be routinely offered as first-line options in resource-limited settings, with second-generation antipsychotics preferred when available. 1, 2