title: Duloxetine and pregnancy outcomes: safety surveillance findings.
abstract: BACKGROUND
  Duloxetine hydrochloride is approved for the treatment or management of major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, chronic musculoskeletal pain, and fibromyalgia in the United States. These conditions affect millions of women, including those of childbearing potential. In pregnancy, pharmacological treatment is justified only if the potential benefits outweigh potential risks to mother and fetus, neonate or infant. There are no adequate and well-controlled studies in pregnant women treated with duloxetine. Post-marketing surveillance is an important tool for the assessment of drug safety in pregnancy in a naturalistic setting.
  
  
  OBJECTIVE
  Using safety surveillance and spontaneous adverse events reporting databases, to provide pregnancy outcomes statistics as they relate to duloxetine exposure.
  
  
  METHODS
  This was an analysis of pregnancy outcome data captured in Lilly Safety System (LSS) (a safety database for the collection, storage, and reporting of adverse events involving Lilly Products), through October 31 2011 and the FDA Adverse Events Reporting System (AERS) database through September 30 2011. Both databases provided spontaneous reporting data from the time of first duloxetine marketing authorization in 2004; in addition, the LSS Database includes serious adverse event and pregnancy data from clinical trials since the creation of the database in 1983.
  
  
  METHODS
  Patients who had received duloxetine during pregnancy and reported pregnancy outcomes.
  
  
  METHODS
  Normal and abnormal pregnancy outcomes. Abnormal outcomes comprised spontaneous abortion, premature/post-term birth, congenital anomaly, perinatal/post-perinatal complication, still birth, and ectopic pregnancy. Descriptive statistics are provided for LSS data. A disproportionality analysis was performed using the Empirical Bayes Geometric Mean (EBGM) for the AERS data. The lower bound of the 90% confidence interval of EBGM (EB05) ≥1 was used as the threshold to determine disproportionality.
  
  
  RESULTS
  In the LSS analysis, 400 pregnancy cases with a known pregnancy outcome were identified. Of the 233 prospectively reported cases, 170 (73%) were spontaneous reports; the remainder were reported from clinical trials (58 [25%]) or post-marketing studies (5 [2%]). In most of these cases (74%), patients received duloxetine for the treatment of depression. Pregnancy outcomes were normal in 143 cases, and abnormal in 90 cases. Abnormal pregnancy outcomes were mainly spontaneous abortions (n=41), post/perinatal conditions (n=25) or premature births (n=19). In patients with abnormal pregnancy outcomes, relevant concomitant medication use and relevant medical history were more frequently reported, compared to those with normal pregnancy outcomes (p<0.05). For the AERS database analysis, EB05 was less than one for all clusters of abnormal pregnancy outcomes; there was no disproportionality of reporting adverse pregnancy outcomes for patients treated with duloxetine versus all other drugs or selected antidepressants.
  
  
  CONCLUSIONS
  While limitations of these data are recognized, the information available to date from these two data sources suggest that the frequency of abnormal outcomes reported in duloxetine pregnancy cases is generally consistent with the historic control rates in the general population.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA. hoog_sharon_l@lilly.com
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hoog
authors.forename: Yingkai
authors.initials: Y
authors.lastname: Cheng
authors.forename: John
authors.initials: J
authors.lastname: Elpers
authors.forename: Sherie A
authors.initials: SA
authors.lastname: Dowsett
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003865:Major Depressive Disorder / Q000188:drug therapy; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D011256:Pregnancy Outcome / Q000453:epidemiology*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride
keywords: antidepressants; birth defects; duloxetine.; pregnancy outcomes; safety surveillance