Can Lamictal (Lamotrigine) Worsen Anxiety?
Yes, lamotrigine (Lamictal) can worsen anxiety in some patients, as it is listed among the potential adverse effects in the FDA drug label, with anxiety occurring in approximately 4% of patients taking the medication.
Mechanism and Evidence
Lamotrigine is primarily used as an anticonvulsant and mood stabilizer for epilepsy and bipolar disorder. While not directly indicated for anxiety disorders, its effects on the nervous system can influence anxiety symptoms in several ways:
Direct Adverse Effect: According to the FDA drug label, anxiety is specifically listed as an adverse reaction that occurred in at least 2% of patients treated with lamotrigine and at a greater incidence than placebo 1.
Neurological Impact: Lamotrigine works by inhibiting voltage-sensitive sodium channels and reducing the release of excitatory neurotransmitters. This mechanism, while beneficial for seizure control and mood stabilization, can potentially disrupt the balance of neurotransmitters involved in anxiety regulation.
Behavioral Activation: Similar to SSRIs, lamotrigine can cause behavioral activation/agitation in some patients, which may present as or exacerbate anxiety symptoms 2.
Risk Factors for Anxiety with Lamotrigine
Certain factors may increase the likelihood of experiencing anxiety while taking lamotrigine:
Medication combinations: Particularly when combined with aripiprazole and antidepressants, lamotrigine has been associated with severe akathisia, anxiety, and even suicidal ideation 3.
Dosage and titration: Rapid titration or high doses may increase the risk of neuropsychiatric side effects including anxiety.
Pre-existing anxiety disorders: Patients with a history of anxiety may be more susceptible to medication-induced anxiety symptoms.
Management Approaches
If a patient develops or experiences worsening anxiety while on lamotrigine:
Evaluate titration schedule: Consider whether the medication was titrated too quickly. Slow titration may reduce the risk of adverse effects.
Dose adjustment: Lowering the dose may help alleviate anxiety symptoms while maintaining therapeutic benefit for the primary condition.
Time of administration: Changing the timing of lamotrigine administration (morning vs. evening) may help manage anxiety symptoms.
Medication review: Assess for potential drug interactions that might be contributing to anxiety symptoms.
Consider discontinuation: In cases of severe anxiety that significantly impacts quality of life, discontinuation of lamotrigine may be necessary, with appropriate tapering to avoid withdrawal seizures 2.
Therapeutic Alternatives
For patients who cannot tolerate lamotrigine due to anxiety:
Alternative mood stabilizers: Consider other options like valproate or lithium if lamotrigine was prescribed for bipolar disorder.
Alternative anticonvulsants: For epilepsy, medications like levetiracetam or carbamazepine may be considered 2.
Adjunctive therapy: In some cases, adding an anxiolytic medication might help manage anxiety while continuing lamotrigine if the benefits outweigh the risks.
Important Monitoring Considerations
When starting or adjusting lamotrigine therapy:
Monitor for early signs of anxiety, agitation, or behavioral activation, especially during the initial titration period.
Assess for suicidal ideation, as anxiety can be associated with increased suicide risk in vulnerable patients.
Distinguish between primary anxiety disorder symptoms and medication-induced anxiety.
Consider standardized anxiety rating scales to objectively track symptoms over time.
While lamotrigine can be an effective treatment for epilepsy and bipolar disorder, the potential for anxiety as an adverse effect should be carefully considered in the risk-benefit assessment, particularly in patients with pre-existing anxiety disorders or those taking multiple psychotropic medications.