Can oxcarbazepine (anticonvulsant) be used for mood and anxiety disorders?

Oxcarbazepine for Mood and Anxiety Disorders

Direct Recommendation

Oxcarbazepine is NOT recommended for the treatment of mood and anxiety disorders. There is insufficient evidence from adequately powered, double-blind, placebo-controlled trials to support its use for these indications, and it is not included in any major clinical practice guidelines for mood or anxiety disorders 1.

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Evidence-Based Rationale

Lack of Guideline Support

• No major psychiatric guidelines recommend oxcarbazepine for mood or anxiety disorders. The American Society of Clinical Oncology guideline on anxiety and depression does not mention oxcarbazepine 1.
• The Japanese Society of Anxiety and Related Disorders explicitly states that antiepileptics (including oxcarbazepine) "have not been adequately studied and are thus not included in the guideline with or without recommendations" for social anxiety disorder 1.
• The American College of Physicians guideline on depression treatment does not include oxcarbazepine among second-generation antidepressants or recommended agents 1.

Limited and Weak Evidence Base

• A systematic Cochrane review found insufficient evidence to support oxcarbazepine in bipolar disorder, with no difference between oxcarbazepine and placebo in the primary outcome (≥50% reduction in Young Mania Rating Scale scores) 2.
• The review concluded: "Currently, there are insufficient trials of adequate methodological quality on oxcarbazepine in the acute treatment of bipolar disorder to inform us on its efficacy and acceptability" 2.
• Studies on oxcarbazepine for bipolar disorder have "small samples of patients, with insufficient follow-up periods and other methodological weaknesses" 3.
• There is a "lack of double-blind, placebo-controlled studies" for oxcarbazepine in mood disorders 3.

Comparison to Evidence-Based Alternatives

For mood disorders (bipolar disorder):

• The American Academy of Child and Adolescent Psychiatry recommends lithium, valproate, or atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) as first-line treatments for acute mania 4.
• Lithium shows superior evidence for long-term efficacy in maintenance therapy 4.
• Oxcarbazepine has "substantially weaker evidence" compared to established mood stabilizers, with no controlled trials for acute mania 4.

For anxiety disorders:

• SSRIs (fluoxetine, sertraline, paroxetine, escitalopram) and SNRIs (venlafaxine) are recommended as first-line pharmacotherapy for social anxiety disorder, with high treatment response rates (NNT = 4.70 for SSRIs, NNT = 4.94 for SNRIs) 1.
• For anxiety in patients with intellectual disability, SSRIs remain the treatment of choice, with α-agonists and β-blockers sometimes used, but anticonvulsants are not recommended 1.

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Safety Concerns with Oxcarbazepine

Serious Dermatological Reactions

• Oxcarbazepine carries risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with reporting rates exceeding background incidence by 3- to 10-fold 5.
• The median time of onset for serious skin reactions is 19 days after treatment initiation 5.
• Patients carrying the HLA-B*1502 allele (prevalent in Han Chinese, Thai, Filipino, and some Malaysian populations at 2-15%) are at increased risk 5.

Hyponatremia

• Oxcarbazepine may reduce serum sodium concentrations, particularly when combined with other medications that lower sodium 5.
• Symptoms include nausea, tiredness, confusion, and increased seizure frequency 5.

Neuropsychiatric Adverse Effects

• Higher incidence of neuropsychiatric adverse effects compared to placebo (17-39% vs. 7-10%) 2.
• Common side effects include sedation (40%), dizziness, nausea, and headache 6.
• Like all antiepileptic drugs, oxcarbazepine increases risk of suicidal thoughts or behavior approximately 2-fold (adjusted RR 1.8,95% CI: 1.2.7) 5.

Treatment Discontinuation

• High discontinuation rates due to side effects: 52% of patients stopped treatment in one naturalistic study, mostly due to adverse effects 6.

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Recommended Treatment Algorithm

For Mood Disorders (Bipolar Disorder)

First-line options:

• Lithium (target level 0.8-1.2 mEq/L for acute treatment) 4
• Valproate (therapeutic level 40-90 mcg/mL) 4
• Atypical antipsychotics: aripiprazole (5-15 mg/day), olanzapine (5-20 mg/day), risperidone (2 mg/day), quetiapine, or ziprasidone 4

For severe presentations:

• Combination therapy with lithium or valproate plus an atypical antipsychotic 4

Maintenance therapy:

• Continue effective acute treatment for at least 12-24 months 4
• Lithium shows superior evidence for relapse prevention 4

For Anxiety Disorders

First-line pharmacotherapy:

• SSRIs: fluoxetine, sertraline, paroxetine, or escitalopram 1
• SNRIs: venlafaxine (if SSRIs ineffective) 1

Adjunctive non-pharmacological interventions:

• Cognitive-behavioral therapy (CBT) has strong evidence for anxiety disorders 1
• Psychoeducation about symptoms and treatment options 1

For comorbid mood and anxiety:

• Treat depressive symptoms first, as this often improves anxiety symptoms concurrently 1
• Consider unified CBT protocol combining approaches for both conditions 1

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Critical Clinical Considerations

When Oxcarbazepine Might Be Considered (Rarely)

• Only as add-on treatment in treatment-refractory bipolar disorder when multiple evidence-based treatments have failed 3, 6.
• Only in patients who cannot tolerate adequate dosages of standard approved treatments 3.
• Even in these scenarios, the evidence remains weak and inconclusive 3, 2.

Monitoring Requirements If Used

• Baseline and periodic serum sodium levels 5
• Baseline liver function tests, complete blood count, and pregnancy test in females 4
• Weekly assessment for skin reactions, particularly during first 8 weeks 5
• Consider HLA-B*1502 genetic testing in at-risk populations before initiating treatment 5
• Monitor for suicidal ideation, particularly in first weeks of treatment 5

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Common Pitfalls to Avoid

• Do not use oxcarbazepine as first-line treatment for mood or anxiety disorders when evidence-based alternatives (lithium, valproate, SSRIs, SNRIs) are available 1, 4, 2.
• Do not assume oxcarbazepine has similar efficacy to carbamazepine despite structural similarity—the evidence base is substantially weaker 4, 3.
• Do not overlook the risk of serious skin reactions, particularly in patients of Asian descent who may carry HLA-B*1502 allele 5.
• Do not combine with other medications that lower sodium without careful monitoring 5.
• Do not use in patients with known hypersensitivity to carbamazepine, as 25-30% will also react to oxcarbazepine 5.