Lamotrigine for Augmenting Anxiety Treatment
Lamotrigine is not recommended for augmenting anxiety treatment based on current clinical practice guidelines, which do not include it as a standard or alternative option for anxiety disorders. The available evidence is limited to small case reports and studies focused on depression rather than anxiety disorders.
Guideline-Based Recommendations for Anxiety Treatment
First-Line Pharmacotherapy
Current clinical practice guidelines for anxiety disorders consistently recommend:
- SSRIs (escitalopram, sertraline, paroxetine, fluvoxamine) as first-line pharmacotherapy 1
- SNRIs (venlafaxine) as first-line or second-line options 1
- Pregabalin (an antiepileptic analog) is listed as a first-line option specifically in Canadian guidelines 1
Second-Line Options
When first-line treatments fail, guidelines recommend:
- Benzodiazepines (alprazolam, bromazepam, clonazepam) as second-line agents 1
- Gabapentin (another antiepileptic) as a second-line option 1
- Switching to another SSRI or SNRI if the initial agent is inadequate 1
Combination Treatment
- CBT plus SSRI is recommended preferentially over monotherapy for children and adolescents with anxiety disorders, and this principle extends to adult treatment 1
Why Lamotrigine Is Not Recommended
Absence from Guidelines
Lamotrigine is notably absent from all major anxiety disorder treatment guidelines 1. The 2023 Japanese guidelines explicitly state that antiepileptics (other than pregabalin and gabapentin) "have not been adequately studied and are thus not included in the guideline with or without recommendations" 1.
Negative Evidence
The Canadian guidelines specifically deprecate levetiracetam (another antiepileptic) based on negative evidence, suggesting caution with antiepileptics not specifically studied for anxiety 1.
Limited and Concerning Research Evidence
The available research on lamotrigine for anxiety is extremely limited:
- One small case series (4 patients) with panic disorder showed mixed results: only 1 drug-naive patient improved significantly, while 2 of 3 patients on augmentation therapy showed minimal improvement 2
- Case reports document serious adverse effects: Two patients with mood disorders developed severe akathisia, increased anxiety, and suicidal ideation when lamotrigine was combined with aripiprazole and antidepressants 3
Primary Indication Is Bipolar Depression
Lamotrigine's established efficacy is for bipolar disorder maintenance treatment, particularly preventing depressive episodes, not for anxiety disorders 4. While one meta-analysis showed efficacy for lamotrigine augmentation in treatment-resistant unipolar depression 5, 6, this does not translate to anxiety disorder treatment.
Clinical Algorithm for Treatment-Resistant Anxiety
When patients fail initial anxiety treatment, follow this sequence:
- Optimize current SSRI/SNRI: Ensure adequate dose and duration (6-12 weeks at therapeutic dose) 1
- Add CBT if not already implemented 1
- Switch to alternative SSRI/SNRI if first agent fails 1
- Consider pregabalin or gabapentin as evidence-based antiepileptic options 1
- Add benzodiazepine for short-term relief if needed 1
- Evaluate for comorbid conditions that may require different treatment approaches 1
Important Caveats
- Guidelines acknowledge a research gap: There are "few studies of pharmacotherapy for inadequate response or intolerance to SSRIs and SNRIs" 1
- Monitoring is essential: Any augmentation strategy requires close monitoring by a physician with expertise in anxiety disorder treatment 1
- Risk of adverse effects: The case reports of increased anxiety and suicidal ideation with lamotrigine combinations raise significant safety concerns for anxiety patients 3
In summary, lamotrigine should not be used for anxiety augmentation given the absence of supporting evidence, exclusion from clinical guidelines, availability of better-studied alternatives (pregabalin, gabapentin), and concerning case reports of worsening anxiety.