First-Line Mood Stabilizers for Treatment
Lithium, valproate (divalproex sodium), and atypical antipsychotics are the first-line treatment options for patients requiring a mood stabilizer, with lithium having the strongest evidence for long-term efficacy in preventing both manic and depressive episodes. 1, 2
Primary Mood Stabilizer Options
Lithium
- FDA approved for acute mania and maintenance therapy in patients 12 years and older 1
- Only medication shown to be efficacious in preventing any mood episodes, manic episodes, and depressive episodes in randomized trials not enriched for prior response 2
- Requires baseline laboratory assessment including complete blood cell counts, thyroid function tests, urinalysis, blood urea nitrogen, creatinine, and serum calcium levels 1
- Regular monitoring of lithium levels, renal and thyroid function every 3-6 months is necessary 1
Valproate (Divalproex Sodium)
- Generally better tolerated than other mood stabilizers 1
- Initial dosage: 125 mg twice daily; titrate to therapeutic blood level (40-90 mcg/mL) 1
- Requires monitoring of liver enzyme levels, platelets, prothrombin time, and partial thromboplastin time 1
- Effective for control of problematic delusions, hallucinations, severe psychomotor agitation, and combative behaviors 1
Atypical Antipsychotics
- FDA approved for acute mania in adults: aripiprazole, olanzapine, risperidone, quetiapine, and ziprasidone 1
- Olanzapine is also approved for maintenance therapy 1
- Associated with significant weight gain and metabolic problems (type 2 diabetes, hyperlipidemia) 1
- Require monitoring of body mass index, waist circumference, blood pressure, fasting glucose, and lipid panel 1
Second-Line Options
Carbamazepine
- Initial dosage: 100 mg twice daily; titrate to therapeutic blood level (4-8 mcg/mL) 1
- Has more problematic side effects than valproate 1
- Requires regular monitoring of complete blood cell count and liver enzyme levels 1, 3
- Strong inducer of hepatic enzymes, leading to numerous drug interactions 3
Lamotrigine
- Approved for maintenance therapy in adults with bipolar disorder 1
- More evidence for efficacy in preventing depressive episodes than manic episodes 4
- Limited evidence from open trials for efficacy in controlling behavioral symptoms 5
Treatment Selection Algorithm
Assess specific presentation:
Consider patient factors:
Monitoring requirements:
- All mood stabilizers require systematic medication trials with duration sufficient to determine effectiveness (6-8 weeks) 1
- Regular monitoring of drug levels, side effects, and laboratory parameters is essential 1
- Baseline and follow-up assessment of weight and metabolic parameters for atypical antipsychotics 1
Important Clinical Considerations
- Medication trials should be systematic with adequate duration (6-8 weeks) and dosing before adding or substituting other mood stabilizers 1
- Phase of illness is an important consideration when choosing a medication 1
- Care should be taken to avoid unnecessary polypharmacy 1
- Most patients with bipolar I disorder will require ongoing medication therapy to prevent relapse; some individuals will need lifelong treatment 1
- Attempts to discontinue prophylactic therapy should be done gradually with close monitoring for relapse 1
Common Pitfalls to Avoid
- Inadequate dosing or premature discontinuation before therapeutic effect can be achieved 1
- Failure to monitor appropriate laboratory parameters, potentially missing serious adverse effects 1
- Unnecessary polypharmacy without systematic trials of individual agents 1
- Discontinuing effective treatment too early, as >80% of patients with a manic episode will have at least one relapse 1
- Using medications without established efficacy (e.g., gabapentin or topiramate have not shown efficacy in controlled studies) 1