A 36-year-old woman comes to the office for follow-up of bipolar I disorder. The patient was diagnosed at age 20 following a manic episode and has a history of 2 hospitalizations at age 24 and 33 for major depressive episodes. Her mood has been stable on valproate for the past 2 years; she takes no other medications. The patient recently got married and has been functioning well. She hopes to become pregnant and would like to stop her oral contraceptive in the next few months. She says, "I do not want to risk having another hospitalization, so I would like to keep taking medication during my pregnancy." After discussion of treatment options, the patient decides to stop the valproate and switch to a different medication. Which of the following is the most appropriate treatment option for this patient?
In women contemplating pregnancy, treatment options for mood disorders should be informed by any adverse medication effects (eg, teratogenicity) as well as prior medication trials and their effects on mood stabilization. This patient with bipolar disorder is euthymic on valproate maintenance therapy; however, the risks of fetal exposure to this medication should be considered.
Valproate, an anticonvulsant commonly used as a mood stabilizer in the acute and maintenance treatment of bipolar disorder, is a teratogen associated with neural tube defects (eg, anencephaly, myelomeningocele). Women exposed to valproate in the first trimester—the critical period of organogenesis—are at particularly high risk, with studies indicating up to a 20-fold increase over the general population (an absolute risk of 1%-2%). Therefore, switching to lamotrigine, a mood stabilizer with a favorable pregnancy safety profile, is an appropriate treatment option for euthymic patients who do not wish to continue valproate during pregnancy.
In patients who switch to another medication, pregnancy should be delayed for 3-6 months to assess the efficacy of the medication. If affective stability is maintained with the new medication, pregnancy can be attempted.
(Choices A and F) Systematic reviews have not typically shown a significantly increased risk of major malformations with the use of most antidepressants (eg, bupropion, sertraline). However, antidepressant monotherapy should be avoided in patients with bipolar I disorder due to the risk of antidepressant-induced mania.
(Choice B) The anticonvulsant carbamazepine is also associated with neural tube defects and should be avoided in pregnancy.
(Choice C) Antipsychotics are not major teratogens; however, haloperidol—a first-generation antipsychotic agent—is not indicated for bipolar maintenance. Second-generation antipsychotics (eg, quetiapine, risperidone) can be considered.
(Choice E) Although lithium is potentially teratogenic (Ebstein anomaly), the absolute risk is very low due to the rarity of the condition. Patients with severe bipolar illness who are stable on lithium when they conceive may elect to continue this medication during pregnancy, with close monitoring. However, it would be inappropriate to recommend switching this patient to lithium when other alternatives with lower teratogenic risk are available.
Educational objective:
The anticonvulsant valproate is a teratogen associated with major congenital malformations, particularly neural tube defects. Patients trying to become pregnant who are taking valproate and require maintenance pharmacotherapy for bipolar disorder should be switched to a medication with a lower risk of teratogenicity (eg, lamotrigine).