Is it acceptable to use Lamictal (lamotrigine) in conjunction with lithium for the treatment of bipolar disorder when lamotrigine alone is insufficient?

From the Guidelines

Yes, it is often appropriate to use Lamictal (lamotrigine) together with lithium for bipolar disorder when Lamictal alone isn't providing adequate symptom control. This combination therapy is a well-established treatment approach for bipolar disorder, particularly when monotherapy has proven insufficient. The medications work through different mechanisms - lithium stabilizes mood by affecting neurotransmitter systems and intracellular signaling, while Lamictal works primarily by inhibiting glutamate release and stabilizing neuronal membranes. This complementary action can provide more comprehensive mood stabilization than either medication alone.

Key Considerations

• The combination of lamotrigine and lithium should only be initiated under close medical supervision, as dosing must be individualized and carefully titrated 1.
• Lamictal typically requires slow titration (starting at 25mg daily and gradually increasing) to reduce the risk of serious rash, while lithium requires regular blood level monitoring (target levels usually 0.6-1.2 mEq/L) to ensure effectiveness while avoiding toxicity.
• Side effects should be monitored, including potential neurological symptoms, skin reactions, and thyroid or kidney function changes.
• Regular follow-up appointments with your psychiatrist are essential to assess response and adjust treatment as needed.

Monitoring and Safety

• Baseline laboratory assessment should include complete blood cell counts; thyroid function tests; urinalysis; blood urea nitrogen, creatinine, and serum calcium levels; and a pregnancy test in female adolescents 2.
• Once a stable lithium dose is obtained, lithium levels, renal and thyroid function, and urinalyses should be monitored regularly (every 3-6 months) 2.
• For valproate, baseline liver function tests, complete blood cell counts, and pregnancy tests are recommended, with serum drug levels, plus hepatic and hematological indices, monitored periodically (every 3-6 months) 2.

Treatment Approach

• Medication trials should be as systematic as possible, with the duration of trials sufficient to determine the agent's effectiveness 2.
• A 6- to 8-week trial of a mood-stabilizing agent is recommended, using adequate doses, before adding or substituting other mood stabilizers 2.
• Care should be taken to avoid unnecessary polypharmacy, in part by discontinuing agents that have not demonstrated significant benefit 2.

From the Research

Efficacy of Lamictal and Lithium Combination

• The combination of lamotrigine (Lamictal) and lithium for the treatment of bipolar disorder has been studied in several trials 3, 4, 5.
• A systematic review found that lamotrigine may be superior to placebo as a treatment modality for bipolar disorder, but its efficacy in comparison to lithium was similar, except for recurrence of mania episodes, which was higher in the lamotrigine group 3.
• Another study found that lamotrigine was effective in delaying time to intervention for any mood episode, including depressive episodes, but showed limited efficacy in delaying time to intervention for manic/hypomanic episodes compared to placebo 4.

Safety and Tolerability

• The incidence of adverse effects was similar between the lamotrigine group and the placebo group, with low- to moderate-certainty evidence suggesting that lamotrigine is well-tolerated 3, 4.
• A review of the evidence for the efficacy and safety of lamotrigine in the treatment of bipolar disorder found that indications for safety, tolerability, and patient acceptability are relatively favorable, provided there is slow dose escalation to reduce the probability of skin rash 6.

Combination Therapy

• A prospective study found that the combination of lithium and valproate or carbamazepine was the most common prophylactic treatment for bipolar I and II disorders, and that polytherapy was prescribed mainly to patients with bipolar I disorder, a high number of previous episodes, and lifetime psychotic symptoms 5.
• The study also found that the annual frequency of recurrences decreased significantly after entering the study in the overall sample, and that the reduction was significantly higher in patients on lithium plus valproate or carbamazepine compared with the valproate or carbamazepine group 5.

Clinical Implications

• The evidence suggests that lamotrigine may be a useful adjunct to lithium in the treatment of bipolar disorder, particularly for patients who have not responded to lithium alone 3, 4.
• However, the decision to use lamotrigine in combination with lithium should be based on individual patient needs and circumstances, taking into account the potential benefits and risks of combination therapy 3, 6, 5.