From the Research
Lamictal (lamotrigine) can be an effective adjunct treatment with SSRIs for treatment-resistant depression, as evidenced by a comprehensive meta-analysis showing significant improvements in Hamilton Rating Scale for Depression scores and response rates 1. When adding lamotrigine to an SSRI regimen, start at 25 mg daily for two weeks, then increase by 25 mg every two weeks until reaching a target dose of 100-200 mg daily (divided into two doses if needed). This slow titration is essential to minimize the risk of serious rashes, including Stevens-Johnson syndrome. Some key points to consider when using lamotrigine as an adjunct treatment include:
- Patients typically need 4-6 weeks at therapeutic doses to determine efficacy
- Common side effects include headache, dizziness, blurred vision, and nausea
- Patients must be monitored for rash development, particularly in the first 8 weeks of treatment
- Lamotrigine works by stabilizing mood through inhibition of voltage-sensitive sodium channels and modulation of glutamate release, which complements the serotonergic effects of SSRIs
- This combination is particularly helpful for patients with bipolar depression or those with depression featuring prominent mood cycling
- Blood levels don't need routine monitoring, but dose adjustments may be necessary with certain medications that affect lamotrigine metabolism, such as valproate (which increases levels) or carbamazepine (which decreases levels) 2, 3, 4. It's also worth noting that lamotrigine augmentation may be more effective in patients with more severe illness and longer duration of illness, and when used in combination with selective serotonin reuptake inhibitors rather than serotonin-norepinephrine reuptake inhibitors 1.