What is the recommended treatment for mania?

Treatment for Mania

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

First-Line Monotherapy Options

Lithium

• Lithium remains the gold standard with the most robust long-term evidence, showing efficacy for acute mania with response rates of 38-62% and superior prophylaxis against both manic and depressive episodes. 1, 3
• Initiate lithium only in settings with personnel and facilities for close clinical and laboratory monitoring, including baseline complete blood count, thyroid function tests, urinalysis, BUN, creatinine, and serum calcium. 4, 1
• Monitor lithium levels, renal and thyroid function, and urinalysis every 3-6 months during maintenance therapy. 1
• Lithium is FDA-approved for patients age 12 and older. 1

Valproate (Divalproex)

• 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, 5
• Obtain baseline liver function tests, complete blood cell counts, and pregnancy test before initiating valproate. 4, 1
• Monitor serum drug levels, hepatic function, and hematological indices every 3-6 months. 4, 1
• Avoid valproate in women of childbearing potential when possible due to teratogenic risk and association with polycystic ovary disease. 1, 6

Atypical Antipsychotics

• Haloperidol or chlorpromazine should be routinely offered as first-line options in resource-limited settings. 4
• 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, 7, 2, 8
• Risperidone is effective at doses of 1-6 mg/day for acute mania, with no additional benefit above 3 mg/day in most patients. 2
• Atypical antipsychotics have superior neurological tolerability compared to typical antipsychotics but require vigilant metabolic monitoring. 8, 9
• Monitor body mass index monthly for 3 months then quarterly, and blood pressure, fasting glucose, and lipids at 3 months then yearly. 1

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 and treatment-resistant mania. 1, 8
• Risperidone 1-6 mg/day combined with lithium or valproate (therapeutic ranges 0.6-1.4 mEq/L for lithium, 50-125 mcg/mL for valproate) demonstrated superiority over mood stabilizers alone in controlled trials. 2
• Quetiapine plus valproate is more effective than valproate alone for adolescent mania. 1
• Avoid neuroleptic-lithium combinations initially as they offer no clear advantages over monotherapy and carry increased neurotoxicity risk. 3

Treatment Duration and Maintenance

• Continue antipsychotic treatment for at least 12 months after beginning of remission. 4
• Maintenance therapy with lithium or valproate should continue for at least 2 years after the last episode, with lithium showing superior evidence for long-term prophylaxis. 4, 1
• Withdrawal of maintenance lithium therapy dramatically increases relapse risk, with >90% of noncompliant adolescents relapsing versus 37.5% of compliant patients. 1
• Continue the regimen that effectively treated the acute episode for maintenance, as this approach maximizes long-term stability. 1

Adjunctive Treatments

• Anticholinergics should not be used routinely for preventing extrapyramidal side effects; reserve short-term use only for significant acute or severe symptoms when dose reduction and switching have failed. 4
• Psychological treatments including relaxation therapy, cognitive behavioral therapy principles, psychoeducational programs, and family counseling may be considered as adjunctive treatment. 4
• Psychoeducation and psychosocial interventions should accompany pharmacotherapy to improve outcomes. 1

Critical Pitfalls to Avoid

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