Lamotrigine and Increased Sexual Arousal
Lamotrigine can indeed cause increased sexual arousal and sexually oriented behavior, though this is a rare adverse effect. In your patient taking both lamotrigine 200 mg daily and bupropion for bipolar II disorder, the hypersexuality is most likely attributable to lamotrigine, as bupropion is actually associated with improved or neutral sexual function rather than hypersexuality.
Evidence for Lamotrigine-Induced Hypersexuality
Two documented cases of acute hypersexuality occurred in male patients taking lamotrigine as add-on therapy 1. Importantly, these patients had:
- No prior psychiatric history predisposing them to this response
- No brain damage
- Hypersexuality that was not part of hypomania or broader psychiatric disturbance
In one case, the hypersexuality completely resolved after discontinuing lamotrigine without any additional treatment. In the second case, reducing the lamotrigine dose decreased the intensity of hypersexuality 1.
Distinguishing from Mania/Hypomania
Critical caveat: You must first rule out that this represents activation of mania or hypomania, which is a known risk with lamotrigine in bipolar disorder 2. Assess for:
- Decreased need for sleep
- Racing thoughts
- Increased goal-directed activity beyond sexual behavior
- Impulsivity in other domains
- Elevated or irritable mood
If these features are present, this represents mood destabilization requiring immediate intervention, not a simple adverse effect.
Bupropion's Role
Bupropion is unlikely to be the culprit here. The evidence consistently shows bupropion has significantly lower rates of sexual adverse events compared to SSRIs 3. In fact, bupropion is used therapeutically to treat SSRI-induced sexual dysfunction, with response rates of 46% in women and 75% in men 4. Bupropion may even enhance sexual function in some individuals 5.
Management Algorithm
If this is isolated hypersexuality without manic features:
First-line approach: Reduce lamotrigine dose incrementally (e.g., decrease by 50-100 mg) while monitoring for:
- Decreased intensity of hypersexuality
- Maintenance of mood stability
- No emergence of depressive symptoms
If dose reduction is insufficient or causes mood destabilization: Discontinue lamotrigine and transition to an alternative mood stabilizer, as lamotrigine's primary benefit is in preventing depressive episodes in bipolar disorder 6, 7
Continue bupropion: There is no reason to discontinue or reduce bupropion, as it is not contributing to the hypersexuality and provides antidepressant coverage
If manic/hypomanic features are present:
- This represents activation of mania/hypomania 2
- Consider adding an antimanic agent (antipsychotic or lithium) rather than simply adjusting lamotrigine
- Reassess the appropriateness of continuing lamotrigine, as it has limited efficacy for manic episodes (RR 2.13 for manic recurrence vs lithium) 7
Important Clinical Considerations
The mechanism by which lamotrigine causes hypersexuality remains unclear 1. However, lamotrigine has been shown to improve sexual function in some epilepsy patients, particularly in women, with improvements in desire, pleasure, arousal, and orgasm 8. This suggests lamotrigine has complex, dose-dependent effects on sexual function that can manifest as either improvement or pathological hypersexuality.
Monitor closely after any intervention, as lamotrigine is effective for maintenance treatment of bipolar disorder (RR 0.84 for relapse/recurrence vs placebo) 7, and discontinuation may increase risk of depressive relapse.