Why You Shouldn’t Take Antidepressants During Pregnancy
As a young doctor, I joked about a general warning that can still be seen in Danish package inserts for drugs: “Caution is advised during pregnancy.” What does that mean?
If you take a pill, it is too late to be cautious, and if you don’t take it, you don’t need to be cautious because you will be totally safe.
My joke was that caution meant placing the pill between the legs instead of swallowing it, which would also make it more difficult to become pregnant.
The authorities passed the buck. If your child is malformed, they can say that they did warn you.
Official statements that antidepressants are safe to take during pregnancy should be distrusted. No drug is safe. If drugs were safe, they would not be the leading cause of death, ahead of cardiovascular diseases and cancer.
In this article, I shall explain why it is wrong to recommend or take antidepressants during pregnancy.
The role of serotonin in the body
SSRIs stand for selective serotonin reuptake inhibitors, which is a misnomer. They are not selective at all. They have multiple effects throughout the body and are not directed against any chemical abnormality.
People do not become depressed because they have too little serotonin in the body, but mainly because they live depressing lives. Serotonin plays a very important role in many processes in the body, also in many primitive organisms.
It is usually a very bad idea to change the blood level of a chemical that has proved so useful during evolution.
Fetal development is a delicate process that can easily go wrong, which is why we tell pregnant women to avoid alcohol. A priori, we would expect any substance that affects serotonin levels to be harmful because serotonin is essential for fetal development.
This is basic biology, but we live in a world dominated by financial interests, which is why many pregnant women take antidepressants during pregnancy.
How a drug company fooled the drug regulators
The first SSRI approved for use in children was fluoxetine from Eli Lilly. It should never have been approved. When psychiatrist David Healy and I reviewed the confidential internal study reports for the two trials that led to approval of fluoxetine for children with depression, we found that fluoxetine is unsafe and ineffective.
In the first trial, the investigators had omitted two suicide attempts on fluoxetine in their published paper, and many of the 48 children on the drug experienced restlessness and had nightmares, which increased the risk of suicide and violence.
In the other trial, one child was severely harmed for every 10 children treated with fluoxetine. Fluoxetine increased the QTc interval on the electrocardiogram (P = 0.02), which increases the risk of sudden death, increased serum cholesterol and was an effective growth inhibitor, reducing the increases in height and weight over just 19 weeks by 1.0 centimeter and 1.1 kilograms, respectively (P = 0.008 for both).
The public does not have access to animal experiments with drugs because the drug companies know it would be bad for business if people saw the data.
When I got access to Merck’s animal studies for their HPV vaccine Gardasil in a U.S. lawsuit where I was an expert witness, I saw that the data supported what the patients had reported: Gardasil can cause serious neurological harm, and the vaccine adjuvant is also harmful.
However, drug regulators all over the world have declared that both the adjuvant and Gardasil are safe.
The European Medicines Agency (EMA) had serious concerns about approving fluoxetine for use in children, which is clear in an 86-page document about animal studies from August 2005 that is nowhere to be found on the Internet:
“Prozac Paediatric Indication. Arbitration Procedure No: EMEA/H/A-6(12)/671. Lilly Response to Questions from EMEA in Document EMEA/CHMP/175191/05.”
I have uploaded this document in the public interest. It illustrates the extent to which drug companies are willing to bend the truth for an economic gain and to harm children, including killing some of them, because antidepressants double suicides.
The EMA deemed Lilly’s data insufficient and asked for further studies and explanations.
They noted that a study on young rats showed a “very unfavourable profile” of the drug, which included severe effects on body weight gain, sexual maturation in males and females, testes, skeletal muscles, sperm concentration and reproductive performances, which appeared with no or low safety margins.
Moreover, the effects on the testes were not reversible.
When EMA noted that S-norfluoxetine, the active metabolite of fluoxetine, had caused testicular degeneration in six of 15 rats, Lilly replied that testicular effects were observed in the rat and the mouse, but not in the dog!
About the inhibition of skeletal growth, Lilly replied:
“Fundamental differences in bone physiology between rodents and humans (Kimmel 1996) limit the ability of rodent studies to accurately predict the response in the human skeleton. Human skeletal health is monitorable in the clinic and remains a focus of clinical investigation.”
This is bullshit. Inhibition of growth is a fact, and no amount of monitoring can prevent this.
The greatest concern related to growth inhibition with brain-active substances is, of course, that they could also cause irreversible brain injuries.
A large Dutch study found that prenatal SSRI use was associated with less cerebral gray matter in children that persisted a decade later and greater increases in volumes of the amygdala and fusiform gyrus that did not persist until early adolescence.
The EMA asked Lilly to take into account “all available non-clinical and clinical data, discuss whether potential effects on brain development and function are adequately addressed, or whether further data can be obtained.”
EMA’s concern should have killed fluoxetine, but this is not how drug regulation works.
Lilly replied that “Lilly considers the current nonclinical data package acceptable for the assessment of potential effects on brain development and function.”
Well, the EMA had just told Lilly that they had a different view, but Lilly didn’t reply at all. They wrote that a study had reported long-lasting behavioral changes after fluoxetine treatment in mice, but considered the clinical relevance of these findings for children “questionable.”
Lilly noted that the mice were administered saline or fluoxetine from postnatal day 4 through 21 and that this period of brain development is considered equivalent to a human third-trimester fetus through a two-year-old child, adding that this “does not replicate the recommended age range for fluoxetine administration.”
This is unbelievable. A mouse study showing irreversible changes in behavior long after the drug is stopped was dismissed with a nonsense argument.
The EMA noted that statistically significant delayed growth and delayed puberty had been reported in placebo-controlled trials in children.
In addition, there had been spontaneous reports to Lilly of growth retardation, delay in puberty, menstrual disorders and sexual disorders: “These data are representing a signal which cannot be ignored.”
But Lilly ignored all the harms signals and did what drug companies always do when presented with damning evidence of serious harms of their drug: They promise to do additional studies.
Spineless drug regulators approve harmful drugs on that condition, even though they know that it is unlikely that relevant studies are ever carried out. A systematic review of 117 novel drugs that the U.S. Food and Drug Administration (FDA) had approved based on limited evidence showed that for one-third of the drugs, a post-approval study was not carried out.
Moreover, most of the studies that were carried out were inadequate: 70 percent used active comparators, and 89 percent used surrogate outcomes as primary endpoints.
I have not seen any relevant fluoxetine studies of the type EMA requested in the medical literature, and Lilly’s explanations were pathetic.
Lilly noted that “Protocol HCLT is being developed as a Phase IV commitment with the FDA to investigate the effects of fluoxetine treatment on height and weight in paediatric patients.”
A Phase IV trial is a study conducted after a drug has been approved and after it has been marketed.
Lilly argued that there would be “considerable recruitment challenges arising out of recent public discussion regarding the use of SSRIs in the child and adolescent population. This concern over recruitment challenges makes the manner and timeframe for this study uncertain.”
Lilly gave the drug regulator the fuck finger again. Their bullshit is short for: “Rest assured that we will never do the study.”
It cannot possibly be difficult to recruit children for a study that shall only measure their height and weight, and if it is difficult because of safety concerns, the drug should not be used.
Moreover, the study is superfluous, as we already knew that fluoxetine is a strong growth inhibitor. When I searched for the name of the protocol for the study, B1Y-MC-HCLT, there was nothing on the Internet.
Lilly conveniently said nothing about the harms related to the development of puberty and to people’s sex life. In half the patients, the sex life is impaired, and when I lectured in Australia in 2015, a pediatrician told me about three boys who had all attempted suicide because they could not get an erection the first time they tried to have sex.
Some people have committed suicide because the sexual harms can become permanent.
Wearing off EMA’s attack, Lilly even argued that they had agreed with the regulator to insert this statement in the Summary of Product Characteristics:
“In addition, long-term safety data in children and adolescents concerning growth, maturation, and cognitive and behavioral development are lacking.”
This is seriously misleading. Short-term data show substantial growth inhibition, and as most children take SSRIs for many years, they will become irreversibly growth-retarded.
In October 2005, two months after Lilly had responded to the EMA, the rapporteurs issued a 39-page assessment report, which concluded:
“It is not recommended to grant an indication to fluoxetine for the treatment of depression in children and adolescents because the benefit/risk balance in the claimed indication is deemed negative.
Concerns about safety issues were not resolved, specifically concerns about suicide related behaviours, including suicide attempt and suicidal ideation, and, from non-clinical data, about the effect on growth, sexual maturation, cognitive and emotional development.
The limited evidence concerning longterm safety is a concern as well, especially given these safety signals.”
It is tragic and a huge mistake that Lilly nonetheless succeeded in having fluoxetine approved for use in children, which paved the way for the approval of other harmful SSRIs.
Harms when SSRIs are used in pregnancy
In 2012, obstetrician Adam Urato and colleagues published a study that, like many earlier studies, found many harms of SSRIs, including elevated risk of miscarriage, preterm birth, neonatal health complications and possible long-term behavioral abnormalities, including autism.
There is also a strong signal of congenital abnormalities, which in 2005 prompted the FDA to ask GlaxoSmithKline to change the labelling for paroxetine so that it showed that there is a demonstrated risk to the fetus.
An increased risk of pregnancy-induced hypertension and preeclampsia, and respiratory distress and withdrawal symptoms in the newborn have also been demonstrated, and neonatal death and stillbirth are more common, both in animal and in human studies.
Urato has told me that the most consistent findings related to growth are lower birth weight and smaller head circumference in the SSRI-exposed groups, and that the problem with many large epidemiological studies is that they define exposure as having a prescription, which could be just one or two.
The studies where the women have taken the SSRI throughout the whole pregnancy are much more likely to show harms.
Even though around 400,000 children in the US are born each year to mothers who took depression pills during pregnancy, it took another 13 years and a new administration before the FDA was finally asked to do something about it.
This is taken from a long document. Read the rest here childrenshealthdefense.org
Bold emphasis added
Header image: Everyday Health