Teratogenicity and hyperprolactinemia

Abstract

Byline: Chittaranjan. Andrade CME Questions A) Drugs should be prescribed with caution to women of childbearing age because of the risk of teratogenicity, should conception occur during treatment; this concern is particularly important when prescribing drugs that will be required for long periods, such as in the maintenance therapy of epilepsy, bipolar disorders, neuropathic pain, and migraine. Topiramate and valproate are sometimes prescribed as maintenance medications for certain or all of these indications. With this background, mark True or False against each of the following statements: *Topiramate monotherapy is safe during pregnancy. *The use of topiramate along with other antiepileptic drugs is associated with an unacceptably high teratogenic risk. *Valproate is one of the most teratogenic medications used in psychiatry. *The teratogenicity of valproate is substantially higher when the drug is used in combination with other antiepileptic medications. *The teratogenic risk of valproate is dose-dependent. *Valproate is teratogenic only during weeks 6-12 of gestation. *Exposure to valproate during pregnancy can be associated with low IQ in the offspring. B) Hyperprolactinemia is a common problem with different antipsychotic drugs. Hyperprolactinemia may lead to many adverse consequences, and may thereby jeopardize drug compliance. With this background, mark True or False against each of the following statements: *The normal prolactin level is 25 ng/ml and above. *Hyperprolactinemia may result in increased libido. *Hyperprolactinemia may result in osteoporosis. *Hyperprolactinemia is uncommon with paliperidone. *Aripiprazole augmentation reverses antipsychotic-induced hyperprolactinemia. View Answer CME Answers A) Teratogenicity Answers: 1. False; 2. True; 3. True; 4. True; 5. True; 6. False; 7. True. 1. Topiramate monotherapy during pregnancy Topiramate is a well-established teratogen in animals such as mice, rats, and rabbits. One study[sup] [1] examined the effects of first-trimester topiramate exposure in 52 pregnancies with 41 liveborn infants. Topiramate was observed to reduce birth weight without decreasing gestational age at delivery; there was no increase in the risk of structural birth defects. However, another larger and methodologically superior study[sup] [2] documented substantial teratogenicity with the drug. This study used data from the UK Epilepsy and Pregnancy Register. The subjects were 203 women with epilepsy who had been exposed to topiramate as monotherapy ( n =70) or as part of polytherapy ( n =133) during the first trimester of pregnancy, and who had been referred before the outcome of pregnancy was known. There were 178 live births; the risk of major congenital malformations with topiramate was 9% (95% CI, 5.6%-14.1%) in the entire sample, and 4.8% with topiramate monotherapy. In this context, studies suggest that the risk of major malformations is 2.7-3.5% in epileptic women who do not use antiepileptic drugs during pregnancy, and those who use antiepileptic drugs in monotherapy.[sup] [3],[4] 2. Teratogenicity of topiramate combined with other antiepileptic drugs In the UK Epilepsy and Pregnancy Register study[sup] [2] referred to above, major congenital malformations were more common in women exposed to topiramate combined with other antiepileptic agents (11.2%) than in those exposed to topiramate monotherapy (4.8%) during the first trimester of pregnancy. The highest risk of major malformations was when topiramate was used along with valproate (36%), or along with two or more other antiepileptic drugs (24%). Also, in women receiving topiramate in polytherapy, smallness for gestational age was associated with a higher dose of the drug. 3. Teratogenicity of valproate in monotherapy Data from the North American Antiepileptic Drug Pregnancy Registry,[sup] [4] the UK Epilepsy and Pregnancy Register,[sup] [3] and the Israeli Teratology Information Service database[sup] [5] suggest that the risk of major congenital malformations is 6-11% after first trimester exposure to valproate monotherapy. …