Evidence for Topiramate as a Mood Stabilizer
Topiramate is not recommended as a mood stabilizer due to controlled studies in adults showing it is not helpful for bipolar disorder, with only equivocal evidence in children and adolescents. 1
Quality of Evidence
The quality of evidence supporting topiramate as a mood stabilizer is poor and does not support its use for this indication:
- The American Academy of Child and Adolescent Psychiatry practice parameter explicitly states that "controlled studies in adults have not found gabapentin or topiramate to be helpful" for bipolar disorder 1
- The only study of topiramate in children and adolescents with bipolar disorder was described as "equivocal" 1
- While there are several open-label studies suggesting possible efficacy, these represent low-quality evidence compared to controlled trials
Available Research
The research on topiramate as a mood stabilizer consists primarily of:
- Open-label trials suggesting 50-65% response rates for refractory bipolar mania and 40-56% response for refractory bipolar depression when used as add-on treatment 2
- Small open-label studies showing some potential benefit as adjunctive therapy 3, 4, 5
- A preliminary phase II dose-finding study that failed to show statistical significance on its primary efficacy endpoint (change from baseline Y-MRS total scores) 2
- Only post-hoc analyses after excluding antidepressant-associated manias showed some benefit at higher doses (512 mg/day) 2
FDA Approval Status
Topiramate is not FDA-approved for bipolar disorder or as a mood stabilizer. According to guidelines, treatment for bipolar disorder should begin with agents approved by the FDA for this indication 1, which include:
- Lithium (approved down to age 12 for acute mania and maintenance)
- Aripiprazole, valproate, olanzapine, risperidone, quetiapine, and ziprasidone (approved for acute mania in adults)
- Lamotrigine and olanzapine (approved for maintenance therapy in adults)
- Olanzapine-fluoxetine combination (approved for bipolar depression in adults)
Clinical Considerations
When considering topiramate, clinicians should be aware of:
- Common side effects including paresthesias, cognitive impairment (attention, concentration, memory problems), fatigue, sedation, word-finding difficulties, nausea, and anorexia 2
- Weight loss potential, which may be beneficial in some patients but problematic in others 3
- Contraindications in pregnancy and glaucoma 6
- Need for monitoring serum bicarbonate levels (risk of metabolic acidosis), kidney function (risk of kidney stones), and pregnancy testing in women of childbearing potential 6
Current Clinical Role
While topiramate is not recommended as a primary mood stabilizer, it may have limited utility in specific clinical scenarios:
- As an adjunctive agent in treatment-resistant cases where weight gain from other mood stabilizers is problematic
- In patients with comorbid conditions for which topiramate is indicated, such as migraine headaches 6
- When combined with phentermine specifically for weight management in patients with obesity 6, though this combination is not indicated for mood stabilization
Bottom Line
The quality of evidence for topiramate as a mood stabilizer is poor. Guidelines recommend using FDA-approved agents for bipolar disorder, which do not include topiramate. Controlled studies have failed to demonstrate efficacy, and only open-label trials suggest potential benefit, representing low-quality evidence that is insufficient to support its use as a primary mood stabilizer.