Editorial Type:
Article Category: Research Article
 | 
Online Publication Date: 01 Aug 2013

Toolbox: Psychotropic use in pregnancy and lactation

PharmD, BCPP and
PharmD, BCPS, BCACP
Page Range: 45 – 57
DOI: 10.9740/mhc.n164620
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When designing treatment regimens for patients with psychiatric illness, recommendations for treatment of pregnant or breastfeeding women can be particularly complicated. Safe and appropriate medication use in this patient population may vary based on the patient's stage of pregnancy and whether or not she plans to breastfeed. The pharmacist is often asked to help guide these decisions and to recommend medications that will minimize toxicity to the fetus or newborn child while also ensuring efficacy and control of the patient's psychiatric symptoms. The appendices on the following pages were designed to help the psychiatric pharmacist quickly review the FDA's pregnancy categories as well as current data regarding the use of psychiatric medications in a pregnant or breastfeeding patient. The appendices include:

  • Psychotropic use in pregnancy and lactation: pregnancy categories

  • Psychotropic use in pregnancy and lactation: lactation categories

REFERENCES

    APPENDIX A. PSYCHOTROPIC USE IN PREGNANCY AND LACTATION: PREGNANCY CATEGORIES

    Explanation of FDA Pregnancy Categories and Inclusion of Briggs Criteria

    The FDA pregnancy categories were first implemented in 1979 and required all marketed drugs be assigned to one of 5 categories, A, B, C, D or X depending on risk of reproductive or developmental adverse effects.1 In 1997, the FDA held a public hearing to obtain feedback on the practicality and utility of the pregnancy categories. Due to concerns raised at this forum about the effectiveness and utility of the categories, the FDA decided to revise the labeling for use in pregnancy and lactation to more accurately convey the actual risks associated with exposure. The new format is to include a clinical management statement, risk assessment summary, and discussion of available data. While the proposed changes and format were announced in 2008, they have yet to be fully implemented.

    Briggs' Pregnancy and Lactation reference, currently in its 9th edition, no longer cites the FDA pregnancy letter categories. Beginning with the 7th edition, printed in 2005, the authors began assigning recommendations of risk for use in pregnancy and lactation for each drug included in the reference in addition to the pregnancy letter categories. The authors felt that the letter categories were insufficient in defining the potential risks and were poorly written. For instance, risks associated for category C and D drugs in particular may be the same as those labeled category X, but have more benefit for use in certain situations. However, as currently written, one might conclude incorrectly that risk proportionately increases from category A to X or that all drugs labeled in a given category share the same risks. Thus, both FDA pregnancy categories and Briggs recommendations of risk are included in this table to further explain where risk truly lies in the face of currently existing data.

    FDA Pregnancy Classifications1

    • Category A – Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).

    • Category B – Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

    • Category C – Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

    • Category D – There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

    • Category X – Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits

    Brigg's Pregnancy Ratings2:

    • Compatible —Human pregnancy data is sufficient to demonstrate risk to the embryo/fetus is very low or nonexistent; animal reproduction data are not relevant.

    • No (limited) human data-Probably compatible —Human pregnancy data may or may not exist, but characteristics of the drug suggest there is not significant risk to the embryo/fetus; animal reproduction data are not relevant.

    • Compatible if maternal benefit>>embryo/fetal risk —Human pregnancy data may or may not exist, but the potential maternal benefit outweighs the known or unknown embryo/fetal risk; animal reproduction data are not relevant.

    • Human data suggest low risk —Limited human pregnancy data suggests that the drug does not represent a significant risk of developmental toxicity at any time in pregnancy; limited human pregnancy data outweighs animal reproduction data.

    • Animal data suggest low risk —Either no human pregnancy data or few human pregnancy exposures have not been associated with developmental toxicity and the drug does not cause developmental toxicity in all animal species studied at ≤10 times the human dose based on body surface area (BSA) or AUC.

    • Animal data suggest moderate risk —Either no human pregnancy data or few human pregnancy exposures have not been associated with developmental toxicity but the drug causes developmental toxicity in one animal species studied at ≤10 times the human dose based on BSA or AUC.

    • Animal data suggest risk --Either no human pregnancy data or few human pregnancy exposures have not been associated with developmental toxicity but the drug causes developmental toxicity in two animal species studied at ≤10 times the human dose based on BSA or AUC.

    • Animal data suggest high risk --Either no human pregnancy experience or few human pregnancy exposures have not been associated with developmental toxicity but the drug causes developmental toxicity in three or more animal species studied at ≤10 times the human dose based on BSA or AUC.

    • Contraindicated—1st trimester —Human exposures in the 1st trimester, either to the drug itself or similar drugs, have been associated with developmental toxicity; the drug should be avoided.

    • Contraindicated—2nd/3rd trimesters —Human exposures in the 2nd and 3rd trimesters, either to the drug itself or similar drugs, have been associated with developmental toxicity; the drug should be avoided.

    • Contraindicated —Human exposures at any time during pregnancy, either to the drug itself or similar drugs, have been associated with developmental toxicity. Animal reproduction data, if available, confirm the risk and the drug should not be used in pregnancy.

    • Human data suggest risk in 1st/3rdtrimester -- Evidence for the drug or similar drugs suggests there may be fetal risk for developmental toxicity in the 1st and 3rd trimester or close to delivery but not in the 2nd trimester.

    • Human data suggest risk in the 2nd/3rdtrimester -- Evidence for the drug or similar drugs suggests there may be fetal risk for developmental toxicity in the 2nd and 3rd trimester or close to delivery but not in the 1st trimester.

    • Human data suggest risk in 3rdtrimester —Evidence for the drug or similar drugs suggests there may be fetal risk for developmental toxicity in the 3rd trimester or close to delivery but not in the 1st and 2nd trimesters.

    • Human (and animal) data suggest risk —Human data for the drug or similar drugs suggest there may be risk for developmental toxicity throughout pregnancy. Use in pregnancy should be avoided unless the maternal condition requires the drug.

    APPENDIX B. PSYCHOTROPIC USE IN PREGNANCY AND LACTATION: LACTATION CATEGORIES

    Copyright: © 2013 College of Psychiatric and Neurologic Pharmacists
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