A 32-year-old woman comes to the office for prenatal counseling. The patient recently married and hopes to start a family soon. She has a history of severe bipolar disorder and chronic insomnia. The patient has been treated previously with quetiapine, valproate, and citalopram. After several hospitalizations for severe manic and depressive episodes in her late 20s, she has been stable on lithium for the past 2 years. She also takes lorazepam occasionally for sleep. The patient has a history of 2 suicide attempts. She says, "I can't wait to be a mother, but I am worried about the effects of medication on the baby. I also don't want to get manic or depressed again. Being in the hospital is so awful and I am doing so well now. I have such a supportive husband and my work is going well." The patient receives counseling regarding management of her condition and treatment options during pregnancy. Which of the following is the most important medication to avoid prescribing at this time?

Question

A 32-year-old woman comes to the office for prenatal counseling.  The patient recently married and hopes to start a family soon.  She has a history of severe bipolar disorder and chronic insomnia.  The patient has been treated previously with quetiapine, valproate, and citalopram.  After several hospitalizations for severe manic and depressive episodes in her late 20s, she has been stable on lithium for the past 2 years.  She also takes lorazepam occasionally for sleep.  The patient has a history of 2 suicide attempts.  She says, "I can't wait to be a mother, but I am worried about the effects of medication on the baby.  I also don't want to get manic or depressed again.  Being in the hospital is so awful and I am doing so well now.  I have such a supportive husband and my work is going well."  The patient receives counseling regarding management of her condition and treatment options during pregnancy.  Which of the following is the most important medication to avoid prescribing at this time?

Quizplus · Accepted Answer

Explanation: All psychotropic medications cross the placenta, and the risks of using psychotropics in pregnancy must be weighed against the benefits of treating the psychiatric condition. Psychiatric illness itself has been associated with negative outcomes, including preterm birth and lower Apgar scores. General guidelines for prescribing psychotropics in pregnancy include avoiding first-trimester exposure, if possible, and using the lowest doses and as few agents as possible. The anticonvulsant valproate is commonly used as a mood stabilizer in the acute and maintenance treatment of bipolar disorder. It should be avoided in pregnancy if possible due to its high risk of major congenital malformations, especially neural tube defects (eg, spina bifida). 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%). Compared with valproate, other psychotropic agents used to treat bipolar disorder, including lithium, have lower teratogenic potential. (Choices A and D) Most systematic reviews have not shown a significantly increased risk of major malformations with the use of most antidepressants (eg, citalopram) or antipsychotics (eg, quetiapine). These drugs are not considered major teratogens and can be used during pregnancy when clinically indicated. Their risks and benefits must be weighed against the risks of untreated psychiatric illness to the mother and fetus (eg, suicide, inadequate self-care and nutrition). (Choice B) Lithium is potentially teratogenic and has been associated with an increased risk of Ebstein anomaly, characterized by apical displacement of the tricuspid valve leaflets and atrialization of the right ventricle. However, the absolute risk of Ebstein anomaly is very low due to the rarity of the condition. This patient has severe bipolar illness that has stabilized only with the use of lithium. Her risk of recurrence without treatment is significant and could negatively impact her ability to care for herself and a fetus, especially if she were to become suicidal again. The risks of recurrence may therefore outweigh the low risk of Ebstein anomaly. Patients with severe bipolar illness that is responsive to lithium may elect to continue this medication with close monitoring. (Choice C) Benzodiazepines (eg, lorazepam) are not associated with an increased risk of congenital malformations. However, chronic use close to delivery can cause neonatal withdrawal. Educational objective: The anticonvulsant valproate, used to treat epilepsy and bipolar disorder, is a teratogen associated with a wide range of malformations, particularly neural tube defects. Women taking this medication should be warned that it is a teratogen and advised to plan their pregnancies. References: Managing your own mood lability: use of mood stabilizers and antipsychotics in pregnancy. (http://www.ncbi.nlm.nih.gov/pubmed/26685903) Sodium valproate and the fetus: a case study and review of the literature. (http://www.ncbi.nlm.nih.gov/pubmed/19892633) Teratogenesis associated with antibipolar agents. (http://www.ncbi.nlm.nih.gov/pubmed/19330496)

A 32-Year-Old Woman Comes to the Office for Prenatal Counseling