Teratogenic risk and contraceptive counselling in psychiatric practice: analysis of anticonvulsant therapy

<p>Background: Anticonvulsants have been used to manage psychiatric conditions for over 50 years. It is recognised that some, particularly valproate, carbamazepine and lamotrigine, are human teratogens, while others including topiramate require further investigation. We aimed to appraise the documentation of this risk by psychiatrists and review discussion around contraceptive issues.</p> <p>Methods: A retrospective review of prescribing patterns of four anticonvulsants (valproate, carbamazepine, lamotrigine and topiramate) in women of child bearing age was undertaken. Documented evidence of discussion surrounding teratogenicity and contraceptive issues was sought.</p> <p>Results: Valproate was most commonly prescribed (n=67). Evidence of teratogenic risk counselling at medication initiation was sub-optimal – 40% of individuals prescribed carbamazepine and 22% of valproate. Documentation surrounding contraceptive issues was also low- 17% of individuals prescribed carbamazepine and 13% of valproate.</p> <p>Conclusion: We found both low rates of teratogenic risk counselling and low rates of contraception advice in our cohort. Given the high rates of unplanned pregnancies combined with the relatively high risk of major congenital malformations, it is essential that a detailed appraisal of the risks and benefits associated with anticonvulsant medication occurs and is documented within patients’ psychiatric notes.</p&gt

The prescribing of antiepileptic drugs for pregnant Australian women

Background: It is not clear how widely it is appreciated in Australia that certain antiepileptic drugs, particularly valproate, are teratogenic

Clinical pharmacology consultation: a better answer to safety issues of drug therapy during pregnancy?

PURPOSE: drug safety classifications give a very basic estimation of risk and should only be used as general guideline when assessing risk of pregnancy-related drug exposure or planning treatment. We conducted a study to assess the strength of association between both the clinical pharmacologists' risk assessment and the FDA risk categorization, and adverse pregnancy outcomes. ----- METHODS: we retrospectively reviewed records of 1,076 patients consecutively referred to the clinical pharmacology outpatient clinic for pregnancy-related drug exposure (2000-2008). Clinical pharmacologists' risk assessments were reviewed in relation to FDA drug categorization and available pregnancy outcomes. ----- RESULTS: overall, clinical pharmacologists' risk estimation was in agreement with the FDA risk categorization system in only 28% of consulted women, and in only 9% of women with high-risk exposure (FDA DX). Clinical pharmacologists' risk assessment confirming high-risk drug exposure had a better positive predictive value for adverse pregnancy outcomes than the FDA DX categorization (25% vs 14% respectively), while the negative predictive values were similar (92% vs 94% respectively). Clinical pharmacologists' risk assessment was a better predictor of adverse pregnancy outcomes compared with FDA risk categorization (OR 2.11 [95%CI 1.5-3.1; p < 0.001] vs OR 1.52 [95%CI 1.1-2.1; p = 0.014] respectively). ----- CONCLUSIONS: additional evaluation beyond the FDA drug classification is essential for safer and more rational drug use in pregnancy. Clinical pharmacologists who have undergone rigorous medical training are ideally placed to consult on administration of medicines in pregnant women, thus making the prescribing of treatments in that patient category substantially safer and more rational

The teratogenic risk of antiepileptic drug polytherapy

Purpose: To compare the risks of fetal malformation during pregnancy associated with antiepileptic drug (AED) polytherapy and monotherapy. Methods: Statistical analysis of malformation rate and antiepileptic drug exposure data from the Australian Register of Antiepileptic Drugs in Pregnancy, and from the literature. Results: The calculated relative risk (RR) value for AED polytherapy compared with monotherapy was below 1.0 in only 3 of 14 literature publications. In the register, at 1 year postnatally there were fetal malformations in 5.32% of 282 AED polytherapy pregnancies, and in 7.84% of 791 AED monotherapy pregnancies, an RR of 0.68 [95% confidence interval (CI) 0.39-1.17). For pregnancies exposed to valproate, the RR of fetal malformation (0.39, 95% CI 0.20-0.89) was lower in polytherapy (7.26%) than in monotherapy (17.9%); the difference did not depend on valproate dosage. The RR values for fetal malformation were not significantly different for AED polytherapy and monotherapy when valproate was not involved. Logistic regression suggested that coadministration of lamotrigine may have reduced the malformation risk from valproate. Discussion: The fetal hazard of AED polytherapy relative to monotherapy may depend more on the degree of exposure to valproate than on the fact of polytherapy per se. Coadministration with lamotrigine may lower the fetal risk of valproate therapy