olanzapine and Abnormalities--Drug-Induced

To review available data on first-trimester exposure to olanzapine, quetiapine, risperidone and aripiprazole and risk of congenital malformations. We performed a systematic literature search in accordance with PRISMA guidelines identifying studies containing original data on first-trimester exposure and pregnancy outcome with respect to congenital malformations. Cumulated data for olanzapine were 1090 first-trimester-exposed pregnancies with 38 malformations resulting in a malformation rate of 3.5%. The corresponding numbers for quetiapine, risperidone and aripiprazole were 443/16 (3.6%), 432/22 (5.1%) and 100/5 (5.0%), respectively. Relative risk estimates and 95% confidence intervals were 1.0 (0.7-1.4) (olanzapine), 1.0 (0.6-1.7) (quetiapine), 1.5 (0.9-2.2) (risperidone) and 1.4 (0.5-3.1) (aripiprazole). First-trimester exposure to olanzapine is not associated with an increased risk of congenital malformation. Data for quetiapine and risperidone do not suggest a substantially increased risk, while the risk estimate for aripiprazole remains imprecise owing to a low amount of data.

Topics: Abnormalities, Drug-Induced; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Humans; Olanzapine; Pregnancy; Pregnancy Complications; Quetiapine Fumarate; Risperidone; Schizophrenia

Antipsychotic medications are being prescribed for a growing number of women with mental illnesses. However, evidence regarding their safety in pregnancy is still insufficient to provide adequate support for clinical practice, creating increasing concern among pregnant women and clinicians.. The aim of this article is to review published data regarding the safety of antipsychotic medications in pregnancy with a focus on the most commonly used atypical antipsychotics.. Given the potential harm of not treating severe psychiatric illnesses during pregnancy, careful administration of antipsychotics is recommended for pregnant women who suffer from severe mental disorders. The most frequently used antipsychotics in pregnancy are olanzapine, risperidone and quetiapine, and do not appear to cause consistent, congenital harm to the fetus. No specific patterns of fetal limb or organ malformation related to these drugs have been reported. There is some evidence suggesting an association between antipsychotic use in pregnancy and the development of gestational diabetes. Also there appears to be an association between antipsychotic medication use in pregnancy and increased neonatal respiratory distress and withdrawal symptoms. Further studies are needed for clinicians to balance good maternal mental health, healthy pregnancies and good infant health outcomes.

Topics: Abnormalities, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Maternal-Fetal Exchange; Mental Disorders; Olanzapine; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prospective Studies; Quetiapine Fumarate; Risperidone

Women who are pregnant and who have a history of psychosis are commonly managed with antipsychotic medications. The evidence regarding the use of antipsychotics in pregnancy has been insufficient to provide adequate support for this practice and is a concern for clinicians and women alike. This review presents literature surrounding the use of antipsychotic medications in pregnancy, providing an overview of the historical and contemporary perspectives which influence clinicians prescribing practices. Data were sourced from Medline, CINAHL, PsycINFo, using the terms antipsychotics with pregnancy and psychosis or schizophrenia. This was expanded to include the most common atypical antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone and aripiprazole. Literature was found reporting the use of antipsychotic medications in pregnancy since the introduction of antipsychotics in the 1950s, comprising mainly of authors' reviews of the literature, case studies, retrospective reports, drug company registries and more recently a prospective comparative study. This review identifies that the literature provides no clear answer for clinicians as to the risk associated with the use of antipsychotics in pregnancy. To this effect, recently in Australia, the National Register of Antipsychotic Medications in Pregnancy was established to prospectively collect information regarding outcomes for mother and baby, when antipsychotic medications have been used during pregnancy.

Topics: Abnormalities, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes, Gestational; Dibenzothiazepines; Female; Humans; Infant, Newborn; Olanzapine; Piperazines; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

Pregnancy presents a special problem to the clinician treating bipolar disorders in women. Since the first episode of mania typically occurs before the age of 30, many women in their prime childbearing years may be exposed to potentially teratogenic mood-stabilizing agents. This exposure may also continue for the nursing infant during lactation. Pregnancy itself can exacerbate bipolar symptoms and also alter the pharmacokinetics of mood-stabilizing drugs. Risks to mother and fetus can be reduced with a number of simple strategies, including monotherapy with the lowest effective dose of a drug for the shortest period necessary, periconceptional use of multivitamins with folate, prescription of drugs with established safety records, and avoidance of exposure to antimanic agents during the first trimester of pregnancy. In this article, we review existing evidence on the risks to fetuses and nursing infants of mothers taking specific mood-stabilizing agents, and we present appropriate management guidelines designed to minimize these risks.

Topics: Abnormalities, Drug-Induced; Acetates; Adult; Amines; Antimanic Agents; Benzodiazepines; Breast Feeding; Carbamazepine; Cyclohexanecarboxylic Acids; Female; Fetus; Gabapentin; gamma-Aminobutyric Acid; Haloperidol; Humans; Infant, Newborn; Lithium; Mood Disorders; Olanzapine; Pirenzepine; Placenta; Pregnancy; Risk Factors; Valproic Acid

Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.. To evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes.. This cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022.. One or more first-trimester dispensing of any atypical, any typical, and individual antipsychotic drugs.. Any major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization.. A total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions.. In this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.

Topics: Abnormalities, Drug-Induced; Adult; Antipsychotic Agents; Chlorprothixene; Cohort Studies; Female; Gastroschisis; Heart Defects, Congenital; Humans; Infant; Olanzapine; Pregnancy; Scandinavian and Nordic Countries; Young Adult

To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM).. A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models.. Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results.. Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.

Topics: Abnormalities, Drug-Induced; Antipsychotic Agents; Birth Cohort; Female; Finland; Humans; Logistic Models; Olanzapine; Pregnancy

Antipsychotic prescription in pregnancy is a complex topic and raises a great deal of anxiety in professionals. There is limited data about atypical antipsychotic prescription in pregnancy and its possible teratogenicity. There are no randomised controlled studies of atypical antipsychotic use in pregnancy due to obvious reasons of ethical issues. We present two cases where a choice had to be made as to whether to prescribe Olanzapine during pregnancy, with different results.

Topics: Abnormalities, Drug-Induced; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chlorpromazine; Female; Hand Deformities, Congenital; Humans; Infant, Newborn; Lithium Carbonate; Olanzapine; Pregnancy; Pregnancy Complications; Risk Assessment; Schizophrenia, Disorganized

Psychosis frequently occurs in women of childbearing potential who may have unplanned pregnancies. Understanding the risk of prenatal antipsychotic exposure can be of benefit in selecting therapies. The authors evaluated the in utero and lactation exposure effects of olanzapine, a novel antipsychotic that is used in treating schizophrenia, bipolar disorder, and other conditions and that may have expanded use in the childbearing population. All prospectively and retrospectively ascertained pregnancy reports were collected as a registry in the Lilly Worldwide Pharmacovigilance Safety Database. Outcomes were available from 23 prospectively ascertained olanzapine-exposed pregnancies. Spontaneous abortion occurred in 13%, stillbirth in 5%, major malformation in 0%, and prematurity in 5%, all within the range of normal historic control rates. There were 11 retrospectively ascertained cases of pregnancy. Two retrospectively ascertained cases of lactation exposure did not suggest infant risk. The early experience with olanzapine use in pregnancy and lactation is encouraging in that no obvious added risk to the fetus or infant was observed. Additional cases of pregnancy and lactation exposure need to be evaluated to determine whether these early findings are representative of the risks of olanzapine exposure to the fetus and infant. At this time, olanzapine should only be used during pregnancy and lactation when the potential benefit justifies the potential risk to the fetus or infant.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Female; Humans; Lactation; Olanzapine; Pirenzepine; Pregnancy; Pregnancy Complications; Prospective Studies; Retrospective Studies