Lamotrigine and Psychiatric Side Effects: Anxiety and Irritability
Yes, lamotrigine can cause both anxiety and irritability as side effects, though the evidence shows these occur relatively uncommonly and the drug is generally well-tolerated psychiatrically.
Evidence from Clinical Trials
Documented Side Effects in Autism Spectrum Disorder Studies
In a randomized controlled trial of lamotrigine in children with autism spectrum disorder (ages 3-11 years), the significant side effects reported were insomnia and hyperactivity, not anxiety or irritability 1. This is notable because the study was specifically targeting irritability as a treatment outcome, yet irritability did not emerge as a treatment-emergent side effect 1.
Psychiatric Adverse Effects: The Broader Picture
Lamotrigine can induce psychiatric symptoms including affective switches, acute psychotic episodes, and hallucinations, particularly in patients using it for mental disorders or epilepsy 2. However, anxiety and irritability specifically are not prominently featured in the psychiatric adverse effect profile documented in the literature 2.
Treatment-Resistant Depression Studies
Interestingly, when lamotrigine was used as augmentation therapy in treatment-resistant depression, irritability actually improved significantly rather than worsened 3. Patients showed statistically significant reduction in irritability scores as early as 30 days after lamotrigine addition, with sustained improvement at subsequent timepoints 3. This suggests lamotrigine may have mood-stabilizing effects that reduce rather than cause irritability in certain contexts 3.
Cocaine Dependence and Bipolar Disorder
In patients with bipolar disorder and cocaine dependence, lamotrigine was associated with significant improvement in mood symptoms without reports of anxiety or irritability as emergent side effects 4. The medication was well tolerated with no discontinuations due to side effects 4.
Clinical Context and Interpretation
Common vs. Rare Side Effects
The most commonly reported adverse events with lamotrigine in bipolar disorder maintenance studies are headache, nausea, infection, and insomnia—not anxiety or irritability 5. The drug does not appear to cause weight gain and has a preferable side-effect profile compared to lithium or carbamazepine 5, 6.
Important Caveat: Discontinuation Syndrome
While not a direct side effect of taking lamotrigine, discontinuation of SSRIs (not lamotrigine) can cause anxiety and irritability as part of withdrawal syndrome 1. This is relevant because patients may be on multiple medications, and symptoms attributed to lamotrigine might actually be from discontinuation of other agents 1.
Clinical Recommendation
Monitor for psychiatric symptoms when initiating lamotrigine, but anxiety and irritability are not expected common side effects. The more concerning psychiatric adverse effects to watch for are affective switches and psychotic symptoms 2. If anxiety or irritability develop after starting lamotrigine, consider:
- Alternative explanations: Underlying mood disorder progression, concurrent medication changes, or psychosocial stressors 2
- Timing: True drug-induced symptoms typically emerge within weeks of initiation or dose escalation 2
- Dose relationship: Most psychiatric side effects are dose-related 2
The most common reason for discontinuation is tiredness, not psychiatric symptoms 3.