What are the treatment options for bipolar disorder?

Treatment Options for Bipolar Disorder

First-line treatments for bipolar disorder include lithium, lamotrigine, quetiapine, or valproate as monotherapy, or combination therapies such as lithium + lamotrigine, lithium/valproate + aripiprazole, or olanzapine-fluoxetine combination. 1

Medication Management by Phase of Illness

Bipolar Depression

• First-line options:
  • Lithium monotherapy
  • Lamotrigine monotherapy
  • Quetiapine monotherapy
  • Olanzapine-fluoxetine combination 1
• Caution: Antidepressants are not recommended as monotherapy as they may trigger manic episodes 2

Acute Mania/Mixed Episodes

• First-line options:
  • Lithium (gold standard)
  • Olanzapine
  • Risperidone
  • Quetiapine
  • Valproate 1, 3, 4
• For severe symptoms with agitation, intramuscular olanzapine 10 mg can be used (max 3 doses 2-4 hours apart) 3

Maintenance Treatment

• First-line options:
  • Lithium (strongest evidence for long-term prophylaxis) 1, 5, 6
  • Lamotrigine (particularly effective for preventing depressive episodes) 7
  • Valproate
  • Quetiapine
  • Aripiprazole 1

Combination Therapy Approaches

When monotherapy is insufficient, consider these evidence-based combinations:

• Lithium + lamotrigine (effective for both manic and depressive episode prevention) 1, 7
• Lithium/valproate + aripiprazole 1
• Lithium + carbamazepine or valproate (may improve overall response rates) 7

Important caution: Avoid adding benzodiazepines to the combination of olanzapine and lithium due to risk of oversedation 1

Special Populations

Adolescents (13-17 years)

• Start with lower doses:
  • Olanzapine: 2.5-5 mg once daily (target: 10 mg/day) 3
  • Consider risperidone as an alternative 4, 5
• Note: The increased potential for weight gain and dyslipidemia in adolescents may lead clinicians to consider other medications first 3

Elderly Patients

• Target lower lithium plasma levels initially 8
• Avoid paroxetine and fluoxetine due to anticholinergic effects and risk of agitation 1
• Tertiary-amine TCAs are potentially inappropriate due to anticholinergic effects 1

Monitoring Requirements

Regular monitoring is essential for safe and effective treatment:

• Serum medication levels (particularly for lithium: target 0.6-0.8 mmol/L) 8
• Thyroid function
• Renal function
• Liver function
• Complete blood count
• Weight and BMI
• Blood pressure
• Fasting glucose
• Lipid panel 1

Non-Pharmacological Approaches

These should be used as adjuncts to medication therapy:

• Psychoeducation
• Cognitive-behavioral therapy
• Family interventions
• Social skills training 1
• Family-Focused Treatment for Adolescents (FFT-A) has shown efficacy in reducing manic symptoms 1

Common Pitfalls and Caveats

1. Delayed diagnosis and treatment: Early diagnosis and treatment are associated with better outcomes, but diagnosis is often delayed by approximately 9 years 2

2. Medication adherence issues: More than 50% of patients with bipolar disorder are non-adherent to treatment 2

3. Suicide risk: Annual suicide rate is approximately 0.9% among individuals with bipolar disorder, with 15-20% dying by suicide. Risk is highest during depressive and mixed episodes 1, 2

4. Medical comorbidities: Bipolar disorder is associated with increased risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease 1

5. Temporary discontinuation: Lithium should be temporarily discontinued during serious intercurrent illness that increases risk of acute kidney injury 1

6. Weight gain concerns: Several medications (clozapine, olanzapine, quetiapine, risperidone, lithium, valproate) are associated with weight gain 1

7. Drug interactions: Fluoxetine can cause serotonin syndrome when combined with other serotonergic medications 1

Lithium remains the gold standard for bipolar disorder treatment with the most robust evidence for preventing both manic and depressive episodes, as well as reducing suicide risk 5, 6.