Can Patients Safely Take Lithium and Lamictal Together?
Yes, patients with bipolar disorder can absolutely be on lithium and lamotrigine (Lamictal) simultaneously—this combination represents a rational, evidence-based maintenance strategy that targets both manic and depressive poles of the illness. 1, 2
Evidence-Based Rationale for This Combination
The American Academy of Child and Adolescent Psychiatry recognizes lamotrigine as an approved maintenance therapy option for bipolar disorder, particularly effective for preventing depressive episodes. 1
Lithium shows superior evidence for prevention of both manic and depressive episodes in maintenance therapy, with the strongest anti-suicide effects of any mood stabilizer (reducing suicide attempts 8.6-fold and completed suicides 9-fold). 1
The lithium-lamotrigine combination provides complementary coverage: lithium primarily prevents mania while lamotrigine primarily prevents depression, making this pairing theoretically optimal for comprehensive prophylaxis. 2
Clinical Trial Evidence Supporting This Combination
In a placebo-controlled 18-month trial, both lamotrigine and lithium were superior to placebo for preventing relapse of mood episodes in bipolar I disorder, with lamotrigine specifically superior for preventing depressive episodes and lithium superior for preventing manic/hypomanic/mixed episodes. 3
A retrospective case series of 21 patients treated with lithium plus lamotrigine for a mean of 55.7 weeks showed acute antidepressant benefit in 48% of patients and overall prophylactic benefit in 29%, though this was a treatment-resistant population where 87% had failed at least one previous mood stabilizer. 4
Another case series demonstrated that lamotrigine combined with lithium was generally well tolerated, with 62% of patients showing much or very much improvement in overall illness severity after 3 months of treatment. 5
Practical Implementation Algorithm
Starting the Combination
If adding lamotrigine to existing lithium therapy, use the standard slow titration schedule to minimize risk of Stevens-Johnson syndrome: start 25mg daily for 2 weeks, then 50mg daily for 2 weeks, then 100mg daily for 1 week, then target dose of 200mg daily. 1
If lamotrigine was discontinued for more than 5 days, restart with the full titration schedule rather than resuming the previous dose to minimize risk of serious rash. 1
Maintain therapeutic lithium levels of 0.8-1.2 mEq/L during acute treatment; some patients respond at lower concentrations for maintenance (typically 0.6-0.8 mEq/L). 1
Dosing Considerations
Mean effective doses in clinical studies were lithium 963 mg/day and lamotrigine 179 mg/day, though lamotrigine is typically titrated to 200mg daily for maintenance. 4
Each mood stabilizer may be given at lower doses when used in combination, potentially reducing side effect burden and improving compliance. 2
Monitoring Requirements
For lithium: monitor lithium levels, renal function (BUN, creatinine), thyroid function (TSH), and urinalysis every 3-6 months. 1
For lamotrigine: monitor weekly for any signs of rash, particularly during the first 8 weeks of titration. 1
Baseline labs before starting lithium should include complete blood count, thyroid function tests, urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females. 1
Drug Interactions and Safety
Lamotrigine has few significant drug interactions with lithium, making it a safe addition to lithium-based regimens. 1
The combination was generally well tolerated in clinical studies, with cognitive problems being the most common side effect (29% in one series), though this may be attributable to either medication. 4
Discontinuation rates due to adverse events were 31% for lamotrigine plus lithium in one study, with tolerability concerns primarily related to lithium rather than the combination itself. 5
Clinical Phenotypes That Benefit Most
Lithium-responsive patients typically have episodic course without rapid cycling, while lamotrigine-responsive patients more commonly have rapid cycling, panic attacks, and substance abuse comorbidity. 6
The combination may be particularly valuable for patients with mixed features or those who experience breakthrough depression despite adequate mania control, or breakthrough mania despite adequate depression control. 2
Patients with predominantly depressive episodes may benefit most from this combination, as lamotrigine provides robust antidepressant effects while lithium prevents manic switches. 3
Critical Pitfalls to Avoid
Never rapid-load lamotrigine to reach therapeutic doses faster—this dramatically increases risk of Stevens-Johnson syndrome, which can be fatal. 1
Do not discontinue lithium abruptly if adding lamotrigine—withdrawal of maintenance lithium therapy is associated with increased relapse risk exceeding 90% in noncompliant patients, especially within 6 months following discontinuation. 1
Avoid premature discontinuation of the combination—maintenance therapy must continue for at least 12-24 months after stabilization, with some patients requiring lifelong treatment. 1
Do not conclude treatment failure before completing a 6-8 week trial at adequate doses of both medications. 1
When This Combination May Not Be Optimal
If the patient has predominantly manic presentations with minimal depressive episodes, lithium plus an atypical antipsychotic may provide superior acute and maintenance control compared to lithium plus lamotrigine. 1
For acute mania, lamotrigine is not effective—first-line treatments include lithium, valproate, or atypical antipsychotics, with lamotrigine reserved for maintenance therapy. 1
Patients with severe renal impairment may not tolerate lithium, necessitating alternative combinations such as valproate plus lamotrigine. 1
Long-Term Maintenance Strategy
Continue the combination for a minimum of 12-24 months after achieving mood stabilization, as premature discontinuation leads to high relapse rates. 1
Schedule monthly follow-up visits for 6-12 months after symptom resolution, then every 3 months once stable, assessing for early warning signs of relapse including sleep changes, increased goal-directed activity, and mood lability. 1, 7
If discontinuation is necessary, taper lithium gradually over 2-4 weeks minimum to minimize rebound risk, while maintaining lamotrigine to provide continued mood stabilization during the transition. 1