Quetiapine Dose Adjustments in Pregnant and Postpartum Women With Bipolar Disorder
Atypical antipsychotics are increasingly used to treat bipolar disorder (BD) in women of childbearing age. In the United States, the rate of atypical antipsychotic use in pregnancy more than doubled between 2001 and 2007.1 A study of medication treatment in the United States from 2006 to 2011 identified quetiapine as the most commonly used second-generation antipsychotic in pregnancy.2 In Denmark, the rate of quetiapine use increased to 83% among childbearing-aged women between 2009 and 2013, and in Australia, quetiapine use tripled among pregnant women between 2000 and 2011.3,4 Although BD and Schizophrenia are the FDA indications for treatment with quetiapine, off-label use of quetiapine has broadened, and it is increasingly prescribed for other diagnoses including insomnia, unipolar depression, and generalized anxiety disorder.5 The few clinical practice guidelines for atypical antipsychotic use in pregnancy address the risk of fetal malformation, but pharmacokinetic and pharmacodynamic data for atypical antipsychotics, such as quetiapine, to inform dosing for optimal treatment throughout pregnancy are lacking.6
The physiological changes of pregnancy that alter drug disposition include increased plasma volume, cardiac output, and glomerular filtration rate.7 Steroid hormones (eg, estradiol) also affect drug-metabolizing enzyme activities.8 The concentrations of many psychotropic agents including selective serotonin-reuptake inhibitors (eg, sertraline,9 citalopram,10 fluoxetine11), tricyclic antidepressants (eg, nortriptyline12) and mood stabilizers (eg, lamotrigine,13 lithium14), decrease across pregnancy. Dose changes are often necessary, because reduced plasma concentration-to-dose ratios of antidepressants and mood stabilizers in pregnancy are associated with increases in mood symptoms. This is particularly true for depressive symptoms for pregnant patients with bipolar disorder.10 In a case report of quetiapine plasma concentrations across pregnancy, the changes in the area under the concentration versus time curve in the first, second, and third trimester relative to 6 months postpartum were −27%, − 42%, and −18%, respectively.15 These data indicate that plasma concentrations of quetiapine are lower in pregnancy compared with postpartum and that doses may need to be increased in pregnancy to maintain consistent plasma concentrations and efficacy. To add to the 1 report in the literature, we present data on 10 cases of quetiapine dosing across pregnancy in women with DSM-IV diagnosed BD.