What is the treatment algorithm for mania?

Treatment Algorithm for Mania

For acute mania, initiate treatment with either lithium (0.8-1.2 mEq/L target), valproate (50-125 μg/mL target), or an atypical antipsychotic (olanzapine 10-15 mg/day, risperidone 2-3 mg/day, quetiapine, aripiprazole, or ziprasidone) as monotherapy, with combination therapy reserved for severe presentations or inadequate monotherapy response. 1, 2

Initial Treatment Selection

First-Line Monotherapy Options

Mood Stabilizers:

• Lithium: Target serum level 0.8-1.2 mEq/L for acute treatment, with response rates of 38-62% in acute mania 1, 2. Lithium demonstrates superior long-term efficacy for maintenance and reduces suicide attempts 8.6-fold and completed suicides 9-fold 1.
• Valproate: Shows higher response rates (53%) compared to lithium (38%) in children and adolescents with mania and mixed episodes 1, 2. Target therapeutic range 50-125 μg/mL 3.

Atypical Antipsychotics (provide more rapid symptom control):

• Olanzapine: 10-15 mg/day (range 5-20 mg/day), superior to placebo and effective in combination with lithium or valproate 1, 3, 4
• Risperidone: Initial dose 2-3 mg/day, effective range 1-6 mg/day 1, 5, 4
• Quetiapine, aripiprazole, ziprasidone: All FDA-approved for acute mania 1, 4

When to Choose Combination Therapy

Immediate combination therapy is indicated for:

• Severe manic presentations with psychotic features or extreme agitation 1, 6
• Treatment-resistant mania (failed adequate monotherapy trial of 6-8 weeks) 1, 6
• Mixed episodes (consider valproate plus atypical antipsychotic) 1, 7

Combination approach: Mood stabilizer (lithium or valproate) PLUS atypical antipsychotic 1, 3, 4. Olanzapine 5-20 mg/day combined with lithium (0.6-1.2 mEq/L) or valproate (50-125 μg/mL) demonstrates superior efficacy to mood stabilizers alone 3.

Adjunctive Medications for Acute Agitation

Benzodiazepines (lorazepam 1-2 mg every 4-6 hours PRN) provide rapid control of agitation when combined with antipsychotics, with superior efficacy compared to either agent alone 1, 8. Use cautiously with clear maximum daily limits (typically ≤2 mg lorazepam equivalent) and frequency restrictions (2-3 times weekly for PRN use) 1.

Special Clinical Situations

Mixed Episodes

• Prefer valproate over lithium as first-line mood stabilizer 7
• Consider carbamazepine or atypical antipsychotics 7
• Some guidelines do not differentiate mixed from pure manic episodes 7

Adolescents (Ages 13-17)

• Lithium is the only FDA-approved agent for bipolar disorder in this age group 1, 2
• Atypical antipsychotics commonly used but require careful metabolic monitoring 1, 2
• Olanzapine 2.5-20 mg/day (mean effective dose 8.9 mg/day) demonstrated efficacy in adolescent trials 3

Intramuscular Treatment for Severe Agitation

• Olanzapine for injection 10 mg IM demonstrated superiority to placebo at 2 hours post-injection 3
• Patients may receive up to 3 injections in 24 hours, with minimum 2-hour interval between doses 3

Maintenance Therapy (Critical for Preventing Relapse)

Continue the regimen that effectively treated the acute episode for minimum 12-24 months 1, 2. Some patients require lifelong treatment when benefits outweigh risks 1.

Maintenance Medication Selection

• Lithium shows superior evidence for preventing both manic and depressive episodes 1, 2
• Lamotrigine particularly effective for preventing depressive episodes 1, 9
• Continue atypical antipsychotic if used successfully in acute phase 2

Critical Relapse Prevention Data

• >90% of noncompliant adolescents relapsed versus 37.5% of compliant patients 1
• Withdrawal of lithium increases relapse risk, especially within 6 months of discontinuation 1, 2

Monitoring Requirements

Lithium Monitoring

• Baseline: Complete blood count, thyroid function, urinalysis, BUN, creatinine, serum calcium, pregnancy test in females 1
• Ongoing (every 3-6 months): Lithium levels, renal and thyroid function, urinalysis 1, 2

Valproate Monitoring

• Baseline: Liver function tests, complete blood count, pregnancy test 1
• Ongoing (every 3-6 months): Serum drug levels, hepatic function, hematological indices 1

Atypical Antipsychotic Monitoring

• Baseline: BMI, waist circumference, blood pressure, fasting glucose, fasting lipid panel 1
• Follow-up: BMI monthly for 3 months then quarterly; blood pressure, glucose, lipids at 3 months then yearly 1, 2

Critical Pitfalls to Avoid

• Never use antidepressant monotherapy - triggers manic episodes or rapid cycling 1, 2, 9
• Avoid premature discontinuation - inadequate maintenance duration leads to >90% relapse rates 1, 2
• Do not underdose or undertrial - systematic 6-8 week trials at adequate doses required before concluding ineffectiveness 1
• Monitor metabolic effects vigilantly - atypical antipsychotics carry significant weight gain and metabolic syndrome risk 1, 2, 4
• Screen for comorbidities - substance use disorders, anxiety, ADHD complicate treatment and require specific management 1, 2
• Avoid typical antipsychotics as first-line - inferior tolerability with 50% risk of tardive dyskinesia after 2 years in young patients 1, 8

Psychosocial Interventions (Essential Adjunct)

Combine pharmacotherapy with psychoeducation about symptoms, course, treatment options, and critical importance of medication adherence 1, 2, 9. Cognitive-behavioral therapy demonstrates strong evidence for both mood and anxiety components 1, 9. Family-focused therapy assists with medication supervision, early warning sign identification, and reducing access to lethal means 1, 9.