The Pill : Association of Hormonal Contraception With Depression

Are some side effects of birth control pills being kept secret ?

November 2016, JAMA Psychiatry published a Danish study that found a correlation between the use of hormonal birth control and being diagnosed with clinical depression. The study tracked hormonal birth control use and prescription of antidepressants over six years for over a million women. They found that women who were on hormonal birth control—be it the pill or a hormonal IUD or vaginal ring—were significantly more likely to be prescribed antidepressants.

These findings are only the latest in a long line of battles between women and their doctors over accurate information, broadly.vice reports in The Racist and Sexist History of Keeping Birth Control Side Effects Secret.

In 2018, the popularity of apps like Natural Cycles highlights the serious issues with contraceptives, the conversation reports.

Illustration by Eleanor Doughty, feature image credit broadly-images.vice.

Key Points

  • Question
    Is use of hormonal contraception associated with treatment of depression?
  • Findings
    In a nationwide prospective cohort study of more than 1 million women living in Denmark, an increased risk for first use of an antidepressant and first diagnosis of depression was found among users of different types of hormonal contraception, with the highest rates among adolescents.
  • Meaning
    Health care professionals should be aware of this relatively hitherto unnoticed adverse effect of hormonal contraception.

Abstract

Importance
Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women’s mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed.

Objective
To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital.

Design, Setting, and Participants
This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016.

Exposures
Use of different types of hormonal contraception.

Main Outcomes and Measures
With time-varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital.

Results
A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71).

Conclusions and Relevance
Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use.

En dehors de la science et de la justice, le bon sens peut parfois suffire

Pesticides, antidépresseurs et agnotologie du suicide

Publié par Luc Perino, médecin généraliste, humeur du 21/08/2018

Un retentissant procès vient de condamner Monsanto à verser 250 millions d’euros à un jardinier intoxiqué par le glyphosate. Cette sentence est considérée par la plupart des commentateurs comme une preuve définitive de la toxicité du glyphosate. Depuis des décennies, des milliers d’articles scientifiques ont formellement démontré la toxicité des pesticides en général et du glyphosate en particulier. Rares sont ceux qui ont eu un écho, et les plus commentés l’ont été cent fois moins que ce dernier procès. Certes, la science n’a pas le charme médiatique de la justice, mais ce serait là une trop rapide conclusion.

En réalité, la science n’émeut pas les multinationales, car elles en sont les premières productrices. Rien n’est plus facile que de décortiquer les petits biais consubstantiels à toute science et de produire de nouveaux biais. Cette science du doute s’appelle l’agnotologie et elle suffit à maintenir longtemps les institutions en sommeil. Surtout si ce sommeil est profitable à tous les sens du terme.

On pourrait en conclure que seule la justice peut émouvoir les multinationales. Ce pourrait être vrai si les condamnations visaient les dirigeants, mais les peines se résument toujours à d’anonymes indemnités qui ont été largement budgétées en amont. L’industrie pharmaceutique en est coutumière. Le laboratoire Glaxo a payé une amende de 3 milliards de dollars pour avoir dissimulé pendant des années les risques cardiovasculaires mortels liés à son hypoglycémiant (rosiglitazone). Pfizer a payé 2,3 milliards pour avoir promu hors autorisation de dangereux antiépileptiques pour des douleurs banales. Etc. Le procès du glyphosate semble ridicule aux côtés des milliards que paient avec discrétion les compagnies pharmaceutiques pour éviter les procès.

Pourtant, en dehors de la science et de la justice, le bon sens peut parfois suffire. La simple observation de la dévastation animale et végétale immédiate causée par les pesticides suffisait à en évaluer la toxicité. Les paysans du monde entier ne s’y sont pas trompés en choisissant les pesticides comme premier moyen de suicide. Les pesticides sont même responsables de plus d’un suicide sur sept dans le monde. Les antidépresseurs en provoquent probablement plus, mais la preuve est plus délicate, car l’agnotologie pharmaceutique est infiniment plus subtile que l’agnotologie agro-alimentaire.

Constatant le long et tortueux chemin de la vérité avec la science ou la justice comme seul attelage, nous comprenons aisément pourquoi la très grande majorité des humains se réfugie derrière les dogmes. L’industrie agro-alimentaire est là pour nous nourrir. L’industrie pharmaceutique est là pour nous soigner. Voilà des dogmes qui, en plus d’être immuables, sont vraiment reposants.

En Savoir Plus

Le “condition branding” de l’industrie pharmaceutique

Addiction suprême après les jeux-vidéo

Publié par Luc Perino, médecin généraliste, humeur du 02/07/2018

Le critère essentiel et indispensable dans le diagnostic d’addiction a toujours été la présence d’un syndrome de sevrage. Autrement dit, l’addiction ne peut concerner que des toxiques (alcool, tabac, drogues) dont l’arrêt brutal provoque de graves troubles physiopathologiques.

Mais avec les dérives verbales et diagnostiques caractérisant nos sociétés surmédicalisées, le terme d’addiction est de plus en plus souvent utilisé pour des comportements. Après le sport, le pari et le sexe pathologiques, voici le jeu-vidéo pathologique des enfants, officialisé par l’OMS en juin 2018.

Comment expliquer un tel laxisme terminologique au sein d’une discipline qui ne cesse de revendiquer le statut de science exacte ?

Un minimum de sens de l’observation nous montre que tout cela relève du “condition branding” : terme intraduisible désignant ce que font les marketeurs de l’industrie pharmaceutique pour vendre des maladies au même titre que d’autres vendent une marque (brand) de chaussures ou de parfum.

La psychiatrie en est devenue le terrain favori après que les plus banales anxiétés et dépressions aient été déclinées avec tant de succès en diverses maladies. Il n’y a aucune limite prévisible à cette mentalisation pharmacologique, car rien n’est plus flou que les troubles mentaux.

  • Le trouble dysphorique prémenstruel a été promu pour recaser la fluoxétine (Prozac),
  • le trouble d’anxiété sociale pour créer une niche à la paroxétine (Deroxat),
  • le trouble panique pour élargir les indications de l’alprazolam (Xanax).

Ces campagnes où le nom du produit n’est jamais directement prononcé sont nommées “unbranded campaigns”. Même les médias publics, les ministères et l’OMS sont des acteurs ingénus ou subornés de ces campagnes invitant les citoyens à reconnaître au plus vite des “maladies” injustement méconnues comme l’ostéoporose, la DMLA, l’hyperactivité ou le déficit cognitif mineur.

N’en doutons pas, dans les mois ou années qui viennent, un médicament sera proposé pour soigner cette nouvelle addiction aux jeux-vidéo. Il s’agira, soit d’une nouvelle niche pour un produit existant, soit de la promotion d’un nouveau produit.

Cette nouvelle “maladie” vient gonfler la liste des centaines de troubles mentaux pour lesquels on vante une intervention pharmacologique. Bien que les régressions spontanées soient fréquentes et que les psychothérapies restent les meilleures options dans la très grande majorité des troubles de l’humeur et du comportement.

Le but de toutes ces savantes orchestrations est d’établir l’addiction suprême pour le plus grand nombre. Une addiction aux psychotropes (tranquillisants, neuroleptiques et antidépresseurs) qui est certainement la plus fréquente et la plus irrémédiable de toutes.

Peu importe alors que la cause initiale soit comportementale ou toxicologique, notre aveuglement face au “condition branding” aboutit généralement à une addiction aux psychotropes. Au sens le plus strict du terme.

En Savoir Plus

Maternal antidepressant use associated with increased risk of miscarriage

Major depression, antidepressant use, and male and female fertility : Cohort study

2018 Study Abstract

Objective
To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments.

Design
Cohort study, DOI: https://doi.org/10.1016/j.fertnstert.2018.01.029, May 2018.

Setting
Clinics.

Patient(s)
Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility).

Intervention(s)
Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD.

Main Outcome Measure(s)
Primary outcome: live birth. Secondary outcomes: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS).

Result(s)
Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception.

Conclusion(s)
Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant.

Why prescription drugs are now the third leading cause of death and the pharmaceutical manufacturers dominance of mental healthcare

James Moore interviews Professor Peter Gøtzsche, Nordic Cochrane Centre Director, 2017

James Moore was keen to talk to Prof. Peter Gøtzsche about his background in research, his views on antidepressant prescribing and how pharmaceutical manufacturers have influenced mental healthcare.

Overview

  • Professor Gøtzsche’s background in clinical trials within the Pharmaceutical industry.
  • How the pharmaceutical manufacturers were manipulating clinical trial data for their own gain.
  • How drug manufacturers have denied for more than 20 years that benzodiazepines and antidepressant drugs cause dependance.
  • How the UK drug regulator (MHRA) also denied this in 2003 at the same time that the World Heath Organisation reported that 3 antidepressants were in the top 30 list of drugs that create dependance.
  • That surveys of patients show that between 50% and 66% of those taking antidepressants experience dependance.
  • The similarities between the pharmaceutical industry and the tobacco industry.
  • That stopping an antidepressant suddenly can be very dangerous.
  • How prescription drugs have become the third leading cause of death behind heart disease and cancer.
  • How pharmaceutical manufacturers have used their power and influence to the detriment of patient safety.
  • That the best science shows that there is no doubt that psychiatric drugs have killed millions of people over the years.
  • How psychotherapy is shown to reduce the risk of suicide but instead we prescribe pills that increase the suicide risk for all ages of patients.
  • That the chemical imbalance lie is still being propagated amongst psychiatrists even thought here is no scientific evidence whatsoever so support it.
  • How psychiatric drugs should be used for acute/emergency situations only.
  • That the medication centred approach of psychiatry does more harm than good.
  • How patients should avoid psychiatric drugs unless they are used for a very short time or that the patient really feels that they need them.
  • That when you look at the randomised controlled trials, there is a large risk of bias in these trials and that antidepressant efficacy has been overstated.
  • That the Cochrane Collaboration undertook the most rigorous meta analysis ever undertaken of 131 trials involving 27,422 patients taking SSRI’s, this analysis showed that antidepressants do not have any meaningful effects and their harms outweigh any benefits there might be.

Sources

Antidepressant use during pregnancy and psychiatric disorders in offspring

Danish nationwide register based cohort study, 2017

What is already known on this topic

  • Several studies have linked selective serotonin reuptake inhibitor use during pregnancy to autism spectrum disorder in offspring, although results have been conflicting
  • The potential explanation for this association is that selective serotonin reuptake inhibitors cross the placental barrier and affect the development of the fetal brain
  • If this holds true, in utero exposure to selective serotonin reuptake inhibitor and other classes of antidepressants may increase risk for various psychiatric disorders besides autism spectrum disorder

What this study adds

  • Antidepressant use during pregnancy was associated with increased risk for various diagnostic groups of psychiatric disorders in offspring
  • The observed associations may be attributable to the severity of underlying maternal psychiatric disorders in combination with in utero antidepressant exposure

Study Abstract

Objective
To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders.

Design
Population based cohort study.

Setting
Danish national registers.

Participants
905 383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×106 person years at risk.

Exposures for observational studies
Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy).

Main outcome measure
First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models.

Results
Overall, psychiatric disorders were diagnosed in 32 400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group.

Conclusions
In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive.

  • Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study, BMJ 2017;358:j3668, 06 September 2017.
  • Characteristics of study population according to maternal antidepressant use before and during pregnancy. Values are numbers (percentages) unless stated otherwise, featured image credit bmj.

Selective Uptake and Bioaccumulation of Antidepressants in Fish

How antidepressants are ending up in Great Lakes fish

Antidepressant drugs, making their way through an increasing number of people’s bodies, getting excreted in small amounts into their toilets, and moving through the wastewater treatment process to lakes and rivers, are being found in multiple Great Lakes fish species’ brains.

2017 Study Abstract

The continuous release of pharmaceuticals and personal care products (PPCPs) into freshwater systems impacts the health of aquatic organisms.

This study evaluates the concentrations and bioaccumulation of PPCPs and the selective uptake of antidepressants in fish from the Niagara River, which connects two of the North American Great lakes (Erie and Ontario).

The Niagara River receives PPCPs from different wastewater treatment plants (WWTPs) situated along the river and Lake Erie. Of the 22 targeted PPCPs, 11 were found at part-per-billion levels in WWTP effluents and at part-per-trillion levels in river water samples.

The major pollutants observed were the antidepressants (citalopram, paroxetine, sertraline, venlafaxine, and bupropion, and their metabolites norfluoxetine and norsertraline) and the antihistamine diphenhydramine. These PPCPs accumulate in various fish organs, with norsertraline exhibiting the highest bioaccumulation factor (up to about 3000) in the liver of rudd (Scardinius erythrophthalmus), which is an invasive species to the Great Lakes.

The antidepressants were selectively taken up by various fish species at different trophic levels, and were further metabolized once inside the organism. The highest bioaccumulation was found in the brain, followed by liver, muscle, and gonads, and can be attributed to direct exposure to WWTP effluent.

  • How antidepressants are ending up in Great Lakes fish, Detroit Free Press, Sept. 1, 2017.
  • Selective Uptake and Bioaccumulation of Antidepressants in Fish from Effluent-Impacted Niagara River, ACS Journal, Environ. Sci. Technol., DOI: 10.1021/acs.est.7b02912, August 16, 2017.

The BMJ Research looks at prenatal antidepressant use and risk of ADHD in children

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study

Previous reports might have overestimated the association between gestational use of antidepressants and ADHD in offspring because they have failed to control for shared family factors. Although we cannot completely discount the possibility that gestational use of antidepressants is a causal factor, our findings raise the possibility that confounding by indication might at least partially explain the observed association. We propose that if a causal association exists, then the size of the effect is probably smaller than that previously reported. However, decision making about antidepressant use in pregnancy remains important and requires an assessment of the risks and benefits in the context of the individual woman and family.

What is already known on this topic

  • Whether to prescribe drugs for depression during pregnancy is a complex decision
  • Prenatal use of antidepressants is considered a risk factor for attention-deficit/hyperactivity disorder (ADHD) in children, but evidence is inconclusive
  • The negative consequences of untreated maternal depression might also affect childhood development

What this study adds

  • The risk of ADHD was similar between the offspring of mothers who used antidepressants during pregnancy and those who used before pregnancy only, whereas the risk was higher for offspring of mothers with psychiatric disorders irrespective of whether antidepressants were used
  • Evidence suggests that the association between prenatal antidepressant use and risk of ADHD may at least partially be explained by confounding by indication of antidepressants
  • If there was a causal association; then the size of the effect is probably smaller than what has been reported previously

2017 Study Abstract

Objective
To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring.

Design
Population based cohort study.

Setting
Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System.

Participants
190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015.

Main outcome measure
Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years).

Results
Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30).

Conclusions
The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication of antidepressants. If there is a causal association, the size of the effect is probably smaller than that reported previously.

Antidepressant Use in Pregnancy and Preterm Birth, ASD, ADHD in Offspring

Is first-trimester maternal antidepressant use related to offspring birth problems, neurodevelopmental problems, or both?

1. Association Between Maternal Use of SSRI Medications and Autism in Their Children

In the February 2016 issue of JAMA Pediatrics, Boukhris and colleagues reported that in utero exposure to selective serotonin reuptake inhibitors (SSRIs) was associated with a significantly increased risk for autism. The authors examined all pregnancies from 1998 to 2009 in the Québec Pregnancy/Children Cohort database that resulted in children with autism spectrum disorder (ASD) as the primary outcome. Among 145 456 full-term infants included in the analysis, 1054 children were diagnosed with ASD by the mean age of 6.2 years (SD, 3.2 years) at follow-up, including 1008 cases of ASD among 140 732 children (0.72%) who were not exposed to antidepressants, and 31 cases of ASD among the 2532 (1.2%) children who were exposed to SSRIs during the second or third trimester. Based on these results, the authors concluded that second- or third-trimester exposure to SSRIs was associated with increased risk for ASD (adjusted hazard ratio, 1.87; 95% CI, 1.15-3.04).

2017 Study Abstract

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.

Design, Setting, and Participants
We conducted a register-based study of an ongoing population-based cohort, the Québec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Québec from January 1, 1998, to December 31, 2009. A total of 145 456 singleton full-term infants born alive and whose mothers were covered by the Régie de l’assurance maladie du Québec drug plan for at least 12 months before and during pregnancy were included. Data analysis was conducted from October 1, 2014, to June 30, 2015.

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.

2. Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring

Key Points

Findings
In this retrospect cohort study of 1 580 629 Swedish offspring using multiple statistical and methodical approaches to adjust for confounding, first-trimester antidepressant exposure was significantly associated with preterm birth (odds ratio, 1.3 in a sibling comparison analysis) but not with risk of being born small for gestational age or later autism spectrum disorder or attention-deficit/hyperactivity disorder.

Meaning
After accounting for confounding factors, first-trimester antidepressant exposure, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.

2017 Abstract

Importance
Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding.

Objective
To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems.

Design, Setting, and Participants
This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations.

Exposures
Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations.

Main Outcomes and Measures
Preterm birth (< 37 gestational weeks), small for gestational age (birth weight < 2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring.

Results
Among 1 580 629 offspring (mean gestational age, 279 days; 48.6% female; 1.4% [n = 22 544] with maternal first-trimester self-reported antidepressant use) born to 943 776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons.

Conclusions and Relevance
Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.

Image credit Jamie Campbell.

Brain Changes found in Newborns exposed to Antidepressants

Antidepressive treatment during pregnancy can affect newborn brain activity

A first of its kind neuroscience study, published this month in Cerebral Cortex, found changes in the brain electrical activity of infants exposed to SSRI antidepressants during pregnancy. The changes are associated with less-organized communication between the brain’s hemispheres and are comparable to the effects found in previous animal studies.

New Study Finds Brain Changes in Newborns Exposed to Antidepressants, madinamerica, June 17, 2016.

The researchers call for more critical evaluations of the prescription of antidepressants during pregnancy and suggest that non-pharmacologic and therapeutic alternatives should be the preferred treatment.

Abstract

Newborn Brain Function Is Affected by Fetal Exposure to Maternal Serotonin Reuptake Inhibitors, cercor.oxfordjournals, doi: 10.1093/cercor/bhw153, June 6, 2016.

Recent experimental animal studies have shown that fetal exposure to serotonin reuptake inhibitors (SRIs) affects brain development. Modern recording methods and advanced computational analyses of scalp electroencephalography (EEG) have opened a possibility to study if comparable changes are also observed in the human neonatal brain. We recruited mothers using SRI during pregnancy (n = 22) and controls (n = 62). Mood and anxiety of mothers, newborn neurology, and newborn cortical function (EEG) were assessed. The EEG parameters were compared between newborns exposed to drugs versus controls, followed by comparisons of newborn EEG features with maternal psychiatric assessments. Neurological assessment showed subtle abnormalities in the SRI-exposed newborns. The computational EEG analyses disclosed a reduced interhemispheric connectivity, lower cross-frequency integration, as well as reduced frontal activity at low-frequency oscillations. These effects were not related to maternal depression or anxiety. Our results suggest that antenatal serotonergic treatment might change newborn brain function in a manner compatible with the recent experimental studies.

Antidepressive treatment during pregnancy can affect newborn brain activity, University of Helsinki, 15.6.2016. Photo Sampsa Vanhatalo.

The present EEG findings suggest links at the level of neuronal activity between human studies and animal experiments. These links will also enable bidirectional translation in future studies on the neuronal mechanisms and long-term neurodevelopmental effects of early SRI exposure.