What are the guidelines for taking Abilify (aripiprazole) and Lamictal (lamotrigine) together?

Aripiprazole and Lamotrigine Combination Therapy

The combination of aripiprazole (Abilify) and lamotrigine (Lamictal) is generally safe and well-tolerated, with no significant pharmacokinetic interactions requiring dose adjustments of either medication. 1, 2

Pharmacokinetic Interactions

• Aripiprazole's FDA label specifically states that "no dosage adjustment is necessary for lamotrigine when co-administered with aripiprazole" 1
• Clinical studies confirm that aripiprazole has no meaningful effect on lamotrigine's steady-state pharmacokinetics in patients with bipolar I disorder 2
• When lamotrigine is co-administered with aripiprazole, there are no significant changes in lamotrigine's maximum plasma concentration or area under the concentration-time curve 2

Clinical Applications

• This combination is commonly used in mood disorders, particularly bipolar disorder, where lamotrigine is often used for depression prevention and aripiprazole for mania management 3, 4
• Lamotrigine is primarily effective as part of combination therapy for maintenance treatment in bipolar disorder, showing benefits when combined with other mood stabilizers 4
• Aripiprazole has proven efficacy for acute mania and prevention of manic episodes but has limited evidence supporting its use in bipolar depression 3

Monitoring and Safety Considerations

• Important safety concern: Monitor closely for development of akathisia, increased anxiety, and suicidal thoughts, particularly when initiating aripiprazole in patients already on lamotrigine and antidepressants 5
• Begin aripiprazole therapy with low doses when adding to an existing lamotrigine regimen to minimize risk of adverse effects 5
• The most common adverse effect reported when combining these medications is insomnia (observed in approximately one-third of patients in clinical studies) 2
• If severe akathisia, anxiety, or suicidal ideation develops, discontinuation of aripiprazole should be considered 5

Drug Interactions with Other Medications

• Aripiprazole levels may be affected by strong CYP3A4 inhibitors/inducers and CYP2D6 inhibitors, requiring dose adjustments 1
• Carbamazepine and other strong CYP3A4 inducers can decrease aripiprazole exposure, potentially requiring increased aripiprazole dosing 1
• Lamotrigine levels may be decreased by enzyme-inducing antiepileptic drugs (like carbamazepine, phenytoin, phenobarbital) 6
• When combining with benzodiazepines like lorazepam, monitor for increased sedation and orthostatic hypotension 1

Specific Patient Populations

• For patients with hypertension, monitor blood pressure closely as aripiprazole has alpha-adrenergic antagonism that may enhance the effect of antihypertensive medications 1
• In women of reproductive potential, be aware that enzyme-inducing medications may decrease the effectiveness of hormonal contraceptives when used with lamotrigine 6
• For patients with epilepsy and mood disorders, lamotrigine can be used for both conditions, while aripiprazole should be monitored for potential impact on seizure threshold 6

This combination therapy can be effective for bipolar disorder management but requires careful monitoring, particularly during initiation, with special attention to neuropsychiatric side effects that may impact morbidity, mortality, and quality of life.