Lamotrigine for Depression and Gabapentin for Anxiety
Lamotrigine is effective for bipolar depression but not for unipolar depression, while gabapentin has not been shown to be effective for anxiety disorders and should not be used for this indication.
Lamotrigine for Depression
Lamotrigine is FDA-approved for maintenance treatment in bipolar disorder and has demonstrated efficacy specifically for bipolar depression, but it is not indicated for unipolar major depressive disorder. 1
Evidence for Bipolar Depression
Lamotrigine showed superior efficacy to placebo in treating bipolar depression, with response rates (>50% improvement on MADRS) of 56% for the 200 mg/day dose and 48% for the 50 mg/day dose, compared to 29% for placebo. 2
The antidepressant effect became evident after 3 weeks of treatment, and importantly, lamotrigine did not destabilize mood or precipitate manic episodes, a critical advantage over traditional antidepressants. 2, 3
In maintenance therapy, lamotrigine significantly delayed time to intervention for depressive episodes in patients with bipolar I disorder across two large 18-month randomized controlled trials. 4, 5
Lamotrigine demonstrated efficacy in both recently manic/hypomanic and recently depressed bipolar patients, making it particularly valuable for preventing depressive recurrence. 4
Critical Limitations
Lamotrigine has NOT demonstrated efficacy in acute mania treatment. 4, 5, 3
There is no evidence supporting lamotrigine use for unipolar major depressive disorder—its benefits are specific to the depressive phase of bipolar disorder. 2, 4
Dosage must be titrated slowly over 6 weeks to 200 mg/day to minimize the risk of serious rash, including Stevens-Johnson syndrome (incidence 0.1%). 4, 5
Dosage adjustments are required when co-administered with valproate (slower titration needed) or carbamazepine (faster titration needed). 4, 5
Gabapentin for Anxiety
Gabapentin should NOT be used for anxiety disorders—controlled studies have found it ineffective for psychiatric indications including anxiety.
Evidence Against Use
Controlled studies in adults have not found gabapentin to be helpful for bipolar disorder or related psychiatric conditions. 1
Preliminary data indicated that lamotrigine was more effective than gabapentin in treating bipolar depression, further undermining gabapentin's psychiatric utility. 2
While older anecdotal reports suggested potential benefit, gabapentin should be reserved only for patients with bipolar disorder unresponsive to traditional therapies until randomized controlled trial data become available. 6
Established Indications
Gabapentin's evidence-based uses are limited to neuropathic pain conditions (such as painful diabetic neuropathy and postherpetic neuralgia) and seizure disorders, not anxiety. 1
For neuropathic pain, gabapentin requires careful dose titration due to nonlinear pharmacokinetics from saturable absorption. 1
Clinical Bottom Line
For depression: Use lamotrigine ONLY if the patient has bipolar disorder with depressive episodes. Do not use for unipolar depression. Ensure slow titration over 6 weeks and monitor for rash. 2, 4, 5
For anxiety: Do not use gabapentin. Instead, use evidence-based treatments such as SSRIs, SNRIs, or benzodiazepines for acute management. 1
When treating anxiety symptoms in patients with major depressive disorder, second-generation antidepressants (fluoxetine, paroxetine, sertraline, venlafaxine) show equivalent efficacy and are appropriate first-line choices. 1