Drug Injury Watch

New Medical Study About SSRI Antidepressants Used During Pregnancy And Autism Spectrum Disorder (ASD) In Children

JAMA Pediatrics Article Reports Increased Risk Is Greatest When These Depression Medicines Are Used By Mothers During The Second And/Or Third Trimester

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Some popular medications prescribed to treat depression are in the Selective Serotonin Reuptake Inhibitors, or SSRIs, class of drugs, including the following:

Wellbutrin (bupropion);
Celexa (citalopram);
Cipralex (escitalopram);
Prozac (fluoxetine);
Luvox (fluvoxamine);
Remeron (mirtazapine);
Paxil (paroxetine);
Effexor (venlafaxine); and,
Zoloft (sertraline).

A recent medical journal article discussed the extent to which these drugs, when used by women during pregnancy, are associated with an increased autism risk in children.

The bottom line is that using selective serotonin reuptake inhibitors (SSRIs) during the second or third trimester of pregnancy is associated with a heightened risk for autism spectrum disorder (ASD) in children. This is according to a JAMA Pediatrics study which is the subject of this article, "Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children", first published online in December 2015.

For that study the medical researchers used data from a population-based cohort study of women from Quebec who delivered 145,000 full-term singleton infants. Children were followed until a mean age of 6.2 years.

From the Abstract for the JAMA Pediatrics medical journal article about that study we get these details about its findings:

Importance  The association between the use of antidepressants during gestation and the risk of autism spectrum disorder (ASD) in children is still controversial. The etiology of ASD remains unclear, although studies have implicated genetic predispositions, environmental risk factors, and maternal depression.

Objective  To examine the risk of ASD in children associated with antidepressant use during pregnancy according to trimester of exposure and taking into account maternal depression.

Exposures  Antidepressant exposure during pregnancy was defined according to trimester and specific antidepressant classes.

Main Outcomes and Measures  Children with ASD were defined as those with at least 1 diagnosis of ASD between date of birth and last date of follow-up. Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios with 95% CIs.

Results  During 904 035.50 person-years of follow-up, 1054 children (0.7%) were diagnosed with ASD; boys with ASD outnumbered girls by a ratio of about 4:1. The mean (SD) age of children at the end of follow-up was 6.24 (3.19) years. Adjusting for potential confounders, use of antidepressants during the second and/or third trimester was associated with the risk of ASD (31 exposed infants; adjusted hazard ratio, 1.87; 95% CI, 1.15-3.04). Use of selective serotonin reuptake inhibitors during the second and/or third trimester was significantly associated with an increased risk of ASD (22 exposed infants; adjusted hazard ratio, 2.17; 95% CI, 1.20-3.93). The risk was persistent even after taking into account maternal history of depression (29 exposed infants; adjusted hazard ratio, 1.75; 95% CI, 1.03-2.97).

Conclusions and Relevance  Use of antidepressants, specifically selective serotonin reuptake inhibitors, during the second and/or third trimester increases the risk of ASD in children, even after considering maternal depression. Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy.

We will continue to monitor the apparent link between the use of antidepressant drugs such as Zoloft, Wellbutrin, Prozac, Paxil, and Effexor by women during pregnancy with the new side effect of autism spectrum disorder (ASD) in their children, and report significant developments here.

In addition, in an upcoming article we will be reporting on an important study by the Center for Disease Control and Prevention's (CDC's) National Center on Birth Defects and Developmental Disabilities. It was published in the British Medical Journal (BMJ) medical journal and addresses certain birth defects side effects associated with the SSRI drugs, especially Paxil and Prozac.

Of course, we welcome Comments for this article (which can be submitted below) from mothers and medical providers as well as any other people interested in the topic of SSRI use during pregnancy and autism spectrum disorder (ASD) in children.

 

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UK Drug Safety Regulator Issues New Warnings About The Use Of Depakote / Depacon / Depakene By Women During Pregnancy

Updates Information About Extent Of Serious Developmental Disorders Such As Autism Spectrum Disorders (ASD) As Well As Congenital Malformations And Birth Defects Like Spina Bifida

(Posted by Tom Lamb at DrugInjuryWatch.com)

Depakote, Depakote CP, and Depakote ER (divalproex sodium), Depacon (valproate sodium), and Depakene (valproic acid) are manufactured and sold by the drug company AbbVie Inc. (formerly Abbott).

On January 22, 2015 the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) issued a Drug Safety Alert, "Medicines related to valproate: risk of abnormal pregnancy outcomes", which has to do with these drugs.  The subtitle of this MHRA warning was plain and clear:

• Children exposed in utero to valproate are at a high risk of serious developmental disorders (in up to 30-40% of cases) and/or congenital malformations (in approximately 10% of cases).

From the "Risk of abnormal pregnancy outcomes" section of that MHRA January 2015 warning:

Valproate is associated with a dose-dependent risk of abnormal pregnancy outcomes, whether taken alone or in combination with other medicines. Data suggest that when valproate is taken for epilepsy with other medicines, the risk of abnormal pregnancy outcomes is greater than when valproate is taken alone.

The risk of congenital malformations is approximately 10% while studies in preschool children exposed in utero to valproate show that up to 30-40% experience delays in their early development such as talking, and/or walking, have low intellectual abilities, poor language skills and memory problems.

Intelligence quotient (IQ) measured in a study of 6 years old children with a history of valproate exposure in utero was on average 7-10 points lower than those children exposed to other antiepileptics.

Available data show that children exposed to valproate in utero are at increased risk of autistic spectrum disorder (approximately three-fold) and childhood autism (approximately five-fold) compared with the general study population. Limited data suggests that children exposed to valproate in utero may be more likely to develop symptoms of attention deficit/hyperactivity disorder (ADHD).

And from the "Future action" section of that MHRA January 2015 warning:

The product information will now be updated to reflect our current understanding of the available evidence and to make information as clear as possible.

For more details, one can read the January 2015 MHRA Dear Doctor Letter regarding valproate medicines such as Depakote / Depacon / Depakene.

In the US, back in May 2013 there was a so-called “Black-Box” warning and several other significant label revisions about serious risks for children whose mother used Depakote / Depacon / Depakene during pregnancy which were added to the Prescribing Information by FDA and the drug company AbbVie. In part those label changes concerned higher risks of neural tube defects like spina bifida, hypospadias, and other birth defects or congenital malformations.

Then in August 2014 the Prescribing Information, or drug labels, for Depakote / Depacon / Depakene were updated by the FDA and AbbVie Inc. to add a warning about the potential risk for autism spectrum disorders (ASD).

We will watch to see if there are any further Depakote / Depacon / Depakene label changes regarding autism and/or birth defects here in the US like those that are forthcoming in the UK, according the January 2015 Drug Safety Update regarding these valproate drugs.

For more about the safety issues concerning these drugs, see our Depakote / Depakene / Depacon drug information page.

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European Medicines Agency (EMA) Committee Recommends Further Restrictions On Use Of Depakote / Depakene / Depacon By Women Of Childbearing Age

Cites Higher Risks Of Neural Tube Defects Like Spina Bifida, Hypospadias, And Other Birth Defects As Well As Increased Risk Of Autism Spectrum Disorder

(Posted by Tom Lamb at DrugInjuryWatch.com)

More restrictions of the use of valproate drugs -- such as Depakote, as well as Depakene and Depacon, from AbbVie Inc. (formerly Abbott) -- by women who may become pregnant have been recommended by a European drug regulatory committee.

From an October 14, 2014 Medscape news report, "Restrict Valproate, EMA Committee Urges":

The European Medicine Agency (EMA)'s Pharmacovigilance and Risk Assessment Committee has recommended strengthening the restrictions on the use of valproate in women of childbearing age.

This is because of the risk for malformations and developmental problems in children exposed to valproate during pregnancy.

The committee recommends that valproate not be used to treat epilepsy or bipolar disorder in girls and women who are pregnant or who can become pregnant unless other treatments are ineffective or not tolerated....

The recommendations of the committee will now be sent the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human, which will adopt a final position. In the meantime, women currently taking valproate who have any questions about their treatment should speak with their doctor, the EMA says.

The review of valproate was started in October 2013 after the publication of new data on the risks of valproate exposure in the womb.

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We have written several articles about the birth defects or congenital malformations and developmental problems that have been associated with Depakote, Depakote CP, and Depakote ER (divalproex sodium), Depacon (valproate sodium), and Depakene (valproic acid).

• Significantly Increased Risk Of Autism Spectrum Disorder (ASD) In Children Whose Mothers Used Depacon / Depakene / Depakote During Their Pregnancy
• Higher Risks Of Birth Defects Spina Bifida And Hypospadias Found To Be Dose-Related For Depacon / Depakene / Depakote / Stavzor
• Depacon / Depakene / Depakote: 400% Increased Risk Of Birth Defects Compared To Other Anti-Seizure Medications Used By Mothers With Epilepsy
• Depakote Or Depakene Taken During Pregnancy May Cause Congenital Malformations Or Birth Defects Such As Neural Tube Defects Like Spina Bifida
• Anti-Epileptic Drugs Associated With Birth Defects And Fetal Death

We will continue to monitor the safety profile of these valproate medications for seizures, epilepsy, bipolar disorder, and (until recently) migraine headaches. 

In addition, we are investigating possible drug injury legal cases against the responsible drug company AbbVie Inc. (formerly Abbott).

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb)

Significantly Increased Risk Of Autism Spectrum Disorder (ASD) In Children Whose Mothers Used Depacon / Depakene / Depakote During Their Pregnancy

August 2014 Label Change By AbbVie Inc. (formerly Abbott) For These Valproate Migraine, Epilepsy/Seizure, And Bipolar Medications Was Done Rather Quietly

(Posted by Tom Lamb at DrugInjuryWatch.com)

Without much notice, e.g., no FDA Drug Safety Communication was issued, in August 2014 the Prescribing Information, or drug labels, for Depakote, Depakote CP, and Depakote ER (divalproex sodium), Depacon (valproate sodium), and Depakene (valproic acid) were updated by the drug company AbbVie Inc. (formerly Abbott) to add a warning about the potential risk for autism spectrum disorders (ASD).

In the label approved by the FDA on August 20, 2014 for Depakote (accessed 9/25/14), this new warning about autism spectrum disorders can be found at Section 8.1 Pregnancy:

An observational study has suggested that exposure to valproate products during pregnancy may increase the risk of autism spectrum disorders. In this study, children born to mothers who had used valproate products during pregnancy had 2.9 times the risk (95% confidence interval [CI]: 1.7-4.9) of developing autism spectrum disorders compared to children born to mothers not exposed to valproate products during pregnancy. The absolute risks for autism spectrum disorders were 4.4% (95% CI: 2.6%-7.5%) in valproate-exposed children and 1.5% (95% CI: 1.5%-1.6%) in children not exposed to valproate products. Because the study was observational in nature, conclusions regarding a causal association between in utero valproate exposure and an increased risk of autism spectrum disorder cannot be considered definitive.

The medical study referenced in this new "valproate drugs used during pregnancy - risk of autism spectrum disorders" warning seems to be the subject of this article, "Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism", which was published by the Journal of the American Medical Association (JAMA) in April 2013. From the Conclusions section of this JAMA medical journal article:

Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism in the offspring, even after adjusting for parental psychiatric disease and epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.

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And for a better understanding of this still relatively "new" Depacon / Depakene / Depakote - autism side effect issue, we refer you to the very informative National Institute of Mental Health (NIMH) web page "What Is Autism Spectrum Disorder?":

Autism spectrum disorder (ASD) is characterized by:

• Persistent deficits in social communication and social interaction across multiple contexts;
• Restricted, repetitive patterns of behavior, interests, or activities;
• Symptoms must be present in the early developmental period (typically recognized in the first two years of life); and,
• Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.

The term “spectrum” refers to the wide range of symptoms, skills, and levels of impairment or disability that children with ASD can have. Some children are mildly impaired by their symptoms, while others are severely disabled....

Previously, in a May 2013 post, we reported that children born to mothers who took any of the valproate medications -- valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics -- may have other serious side effects:

Depakote Or Depakene Taken During Pregnancy May Cause Congenital Malformations Or Birth Defects Such As Neural Tube Defects Like Spina Bifida 

In Addition, There Are FDA Warnings That Using Depakote Or Depakene While Pregnant May Put Child At Risk For Having A Lower IQ Score Later In Life

As regards lawsuits and legal claims, we expect that the Depacon / Depakene / Depakote drug injury litigation which previously was focused on certain types of birth defects or congenital malformations will expand to include cases of autism spectrum disorder (ASD) and autism.
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