ABSTRACT
BACKGROUND: Despite high prevalence rates among women of mood disorders and of infertility, there is a paucity of systematic data to inform the treatment of women at risk for psychiatric morbidity in the context of assisted reproductive technologies (ART). The objective was to delineate predictors of depressive relapse in women with histories of mood disorders during ART, including the role of psychotropic medication continuation. METHODS: This was a prospective observational study of women undergoing ART with past diagnoses of major depressive disorder (MDD) or bipolar depression. For 6-months, follow-up included assessments of mood, perceived stress, and partner support. A subsample participated in biomarker collection. Depressive relapse was confirmed using Mini-International Neuropsychiatric Interview. RESULTS: N = 38 were evaluable. Participants with MDD (N = 25) experienced a depressive relapse rate of 44.0%. Relapse rates among antidepressant maintainers (N = 15; relapse rate = 40.0%) and antidepressant discontinuers (N = 10; relapse rate = 50.0%) were not significantly different. Among participants with bipolar disorder (N = 13), the overall relapse rate was 30.8%. Among psychotropic medication maintainers (N = 10), 40.0% relapsed, and among discontinuers (N = 3), none relapsed. Scores on the Perceived Stress Scale correlated with relapse risk (odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.08-1.26, p = 0.0065). C-reactive protein was associated with relapse (OR = 1.92, 95% CI: 1.43-2.55, p < 0.0001); blood cortisol and interleukin-6 were not. CONCLUSIONS: Risk of depressive relapse among women undergoing ART is considerable. Medication continuation does not adequately confer relapse prevention. Stress and inflammation appear to contribute to risk of relapse. Additional strategies to mitigate depressive relapse in at-risk women undergoing ART are needed.
Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major , Infertility, Female , Reproductive Techniques, Assisted , Stress, Psychological , Adult , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/physiopathology , Female , Humans , Infertility, Female/psychology , Infertility, Female/therapy , Massachusetts/epidemiology , Prospective Studies , Psychiatric Status Rating Scales , Recurrence , Reproductive Techniques, Assisted/psychology , Reproductive Techniques, Assisted/statistics & numerical data , Risk Assessment , Secondary Prevention , Stress, Psychological/diagnosis , Stress, Psychological/etiology , Stress, Psychological/physiopathology , Stress, Psychological/prevention & controlABSTRACT
OBJECTIVE: Second-generation antipsychotics are used to treat a spectrum of psychiatric illnesses in reproductive-age women. The National Pregnancy Registry for Atypical Antipsychotics was established to determine the risk of major malformations among infants exposed to second-generation antipsychotics during pregnancy relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity. METHOD: Women were prospectively followed during pregnancy and the postpartum period; obstetric, labor, delivery, and pediatric medical records were obtained. Eligible enrollees were pregnant women ages 18-45. The Registry is based at the Center for Women's Mental Health at Massachusetts General Hospital. Women were recruited through provider referral, self-referral, and the Center's web site. RESULTS: As of December 2014, 487 women were enrolled: 353 who used second-generation antipsychotics and 134 comparison women. Medical records were obtained for 82% of participants. A total of 303 women had completed the study and were eligible for inclusion in the analysis. Of 214 live births with first-trimester exposure to second-generation antipsychotics, three major malformations were confirmed. In the control group (N=89), one major malformation was confirmed. The absolute risk of major malformations was 1.4% for exposed infants and 1.1% for unexposed infants. The odds ratio for major malformations comparing exposed infants with unexposed infants was 1.25 (95% CI=0.13-12.19). CONCLUSIONS: The results suggest that it would be unlikely for second-generation antipsychotics to raise the risk of major malformations more than 10-fold beyond that observed in the general population or among control groups using other psychotropic medications. If the estimate stabilizes around the null with ongoing data collection, findings may be reassuring for both clinicians and women trying to make risk-benefit treatment decisions about using atypical antipsychotics during pregnancy. These findings are timely given the renewed focus of regulatory agencies on reproductive safety.
