Psychiatric drugs are one of the most prescribed medications by the medical profession. You would think that there would be more awareness of what they actually do. What is interesting is that reporting in the media is relatively absent in regard to some of the adverse effects or even the effectiveness of these medications. Over the years research has been published evaluating the side effects, as well as the effectiveness of these drugs. It is interesting to speculate as to why there is this lack of reporting in mainstream media. Some recent medical studies looking at the long-term safety of antidepressants is worrying. More worrying is the drug research data on which the effectiveness of antidepressants is based on.

Antidepressants vs Placebo –  Challenging current wisdom

In 1998, two psychology researchers, Irving Kirsch and Guy Sapirstein of the University of Connecticut, were interested in understanding the placebo effect. It seemed to them that depression was a good place to look for placebo effects. They were not interested in the drugs effect. They assumed, as everyone else did, that antidepressants were effective. There were scores of medical trials that demonstrated the effectiveness of antidepressants.

They examined 38 manufacturer-sponsored antidepressant studies involving just over 3,000 depressed patients. They were not surprised that there was a substantial placebo effect on depression. What surprised them was the minimal effect that the drug had on depression. Patients on a placebo improved about 75 percent as much as those on drugs. Kirsh recalls “We wondered, what’s going on? These are supposed to be wonder drugs and have huge effects.”

They published their results “Listening to Prozac but Hearing Placebo”. Being so controversial the editors of the journal Prevention & Treatment ran a warning with his paper, saying it used meta-analysis “controversially.” Not surprisingly, feedback to the article was scathing, they were accused of bias. They had only analysed some studies of antidepressants.

In 1998 the Freedom of Information Act was used to obtain data from the Food and Drug Administration (FDA). The request was for data submitted to the FDA from pharmaceutical companies, in the process of obtaining approval for six new generation antidepressants that accounted for the bulk of antidepressant prescriptions being written at the time. The total came to 47 company-sponsored studies—on Prozac, Paxil, Zoloft, Effexor, Serzone, and Celexa—that Kirsch and colleagues then pored over. What they discovered is short of unbelievable:

• only 43% of the clinical trials showed any statistically significant benefit of drug over placebo
• The remaining 57% were failed or negative trials
• about 40 percent of the clinical trials had never been published. That is significantly higher than for other classes of drugs
• their analysis once again found that 82% of the drug response was duplicated by placebo! This is higher than the 75% in the original study.
• more importantly this beneficial response was less than 2 points (1.8) on the Hamilton Depression scale. This is a scale where depression is scored between 0 to 53 points, that determines how depressed a patient is. Considering that a change in sleep pattern can make a six-point difference on the scale, 1.8 is minimal
• patients at the very extreme end of depression severity showed a slightly more beneficial response

So how did these trials get approved through the FDA? To understand this, you only need to look at the approval criteria used by the FDA. The FDA required two adequately conducted clinical trials showing a difference between the drug and placebo. But here is the catch:

• there is no limit to the number of clinical trials that can be conducted
• negative trials simply do not count
• the clinical significance of the findings is not considered, only the statistical significance

As an example, in 2011 the drug vilazodone was submitted to the FDA for approval.

• seven controlled clinical trials were conducted
• the first five failed to show any significant differences in depression
• the average drug to placebo difference in these studies was less than 0.5 point on the Hamilton Depression scale
• in two of the three trials, the outcome actually favoured the placebo
• two more studies were conducted which managed to obtain a small but significant drug-placebo differences (1.70 points)

This was sufficient for the FDA to grant approval. The information approved by the FDA for informing doctors and patients read, ‘‘The efficacy of VIIBRYD was established in two 8-week, randomized, double-blind, placebo-controlled trials.’’ No mention was made of the five failed trials that preceded the two successful ones.

Safety of Antidepressant Medications

A recent research paper, Carcinogenicity of Psychotrophic Drugs, found:

• 63.6% of antidepressants were associated with carcinogenicity, specifically mirtazapine, sertraline, paroxetine, citalopram and escitalopram, duloxetine and bupropion.
• 90% of antipsychotics agents were associated with carcinogenicity. All agents were associated with carcinogenicity except clozapine.
• 70% of benzodiazepines/hypnotics were associated with carcinogenicity, specifically clonazepam, zolpidem, zaleplon, diazepam, eszopiclone, oxazepam and midazolam
• 25% amphetamines/stimulants were associated with carcinogenicity, with methylphenidate specifially associated.
• 85.7% of anti-convulsants (“mood stabilizers”) were associated with carcinogenicity. The only agent not associated with carcinogenicity was lamotrigine. Specific agents associated with carcinogenicity were valproate, carbamazepine, gabapentin, pregabalin, oxcarbazepine and topiramate.

It is only when you bother to look for what these drugs are doing more widely, that you realise that they can have huge ramifications on other body systems. The effect of drugs on the body has been compared to a spiders’ web. We think we can tug only on a single thread of the web – but by tugging on one thread the whole web is disturbed.

In elderly patients those who were prescribed quetiapine (Seroquel), risperidone (Risperdal), or olanzapine had an almost 2-fold increased risk for hospitalization for acute kidney injury within the next 90 days vs those who did not receive these prescriptions. In addition, patients who received any of these oral atypical antipsychotics had increased risk for acute urinary retention, hypotension, and even death.

“.. we demonstrate, what is to our knowledge the first time, an altered microbiota associated with chronic olanzapine treatment.”

Pregnant women

Early pregnancy is a critical time in the baby’s development. Women considering getting pregnant should discuss safety issues regarding their medication well before getting pregnant. They should also have a comprehensive health assessment to see if there is an underlying cause for their depression. There are many conflicting studies regarding the use of psychiatric medications in pregnancy. Unfortunately, since there is no consensus, there is also a false perception of safety in pregnancy.

A recent study has linked two antidepressants to birth defects in children. Fluoxetine has been associated with heart wall defects and craniosynostosis. There are five previously reported birth defects associated with paroxetine, including heart defects, anencephaly, and abdominal wall defects.

Another recent study has reported that mothers on selective serotonin reuptake inhibitors (SSRIs) during pregnancy were significantly more likely to have children that develop Chiari type I brain malformation. Although most children with this type of malformation, do not have significant problems, some experience headaches and problems with balance severe enough to require surgery.

It is still unclear whether it is depression or the use of antidepressants in pregnancy as the cause of the link to autism. In this current study the use of selective serotonin reuptake inhibitors (SSRIs), during the second and/or third trimester, was found to increase the risk of ASD in children.

Safety of Psychiatric Medications in Children

With 7% of boys and 5% of girls in the USA medicated with psychotropics, and toddlers under 3 prescribed stimulants, it is time to ask some serious questions. Why are we medicating so many children? Are these medications safe? A study published in 2001, often referred to as study 239, was designed to promote the prescription of SSRIs to children. Re-evaluation of the original data revealed the complete opposite to the original conclusion. Eleven years after its publication, Glaxo Smith Kline was ordered to pay a 3 billion dollar fine (part of the largest health care fraud settlement in US history) for misrepresenting evidence of increased suicidality in treated children (11 of those treated engaged in suicidal behaviour vs 1 in the placebo group), in addition to falsely representing Paxil as outperforming placebo.

To be noted the supposedly flawed research by Dr Andrew Wakefield (whose gastrointestinal research has since been replicated by other researchers) was retracted by The Lancet. Incredibly, study 329 has not been retracted, despite misrepresenting evidence and being ordered to pay a billion dollar fine. When you have money you have influence.

According to the Centre of Disease Control (CDC), antipsychotics are implicated in causing almost four times more adverse drug event (ADE) emergency department visits than stimulants. According to a 2015 JAMA Psychiatry online report, antipsychotics were implicated in ADE emergency department visits at a rate 3.9-fold higher than stimulants in children and 3.8-fold higher than stimulants in adolescents.

I have already written previously on the level of ADHD medication and the United Nations concerns regarding Australia’s level of over prescription of ADD and ADHD drugs to children.

Are Prescription Drugs Killing Us?

Dr. Peter Gotzsche, co-founder of the Cochrane Collaboration (the world’s most foremost body in assessing medical evidence), has come out strongly on the lack of efficacy and safety of psychiatric medication. He believes these medications offer few benefits compared with placebo and may cause more than half a million deaths per year in the United States and Europe.

Consequently, 98% of psychotropic drugs should be dropped. These include all antidepressant, attention-deficit/hyperactivity disorder, and dementia drugs and all but 6% of the antipsychotics and benzodiazepines currently in use.

According to Professor Gotzsche, here’s a list of things you want to avoid:

• Antidepressants for all, because they probably don’t work for severe cases of depression
• All brain-active drugs in children
• Anti-psychotics and other brain-active drugs for the elderly. Psychotropic drugs should be used as little as possible and mostly in very acute situations, as they are very harmful when used long term

More worrying, however, is the widespread underreporting of deaths associated with psychiatric drugs. Dr Gøtzsche estimates that there have been 15 times more suicides among people taking antidepressants than reported by the US Food and Drug Administration.

I don’t know if it should be concerning or enlightening that that even the editors of prestigious journals are making public comments on the pharmaceutical industry:

 “The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness.” – Dr. Richard Horton, the current Editor-In-Chief of the Lancet (source)

The medical profession is being bought by the pharmaceutical industry, not only in terms of the practice of medicine, but also in terms of teaching and research. The academic institutions of this country are allowing themselves to be the paid agents of the pharmaceutical industry. I think it’s disgraceful. – Arnold Seymour Relman (1923-2014), Harvard Professor of Medicine and Former Editor-in-Chief of the New England Medical Journal (source)

Have the public been unwittingly enrolled into an uncontrolled and unconsented ongoing long-term experiment?

Below are some comments from commentators that are disputing the statistical analysis.

“Doctors and patients know what works and what does not.”

(C. Vargas, February 27, 2008, PLoS Medicine)

“Clinical practice plus millions of content patients can’t be that wrong.”

(R. Werner, February 27, 2008, PLoS Medicine)

As a medical scientist it is unbelievable that millions of dollars have been spent on trials involving hundreds of thousands of individuals, to produce studies that show no or barely minimal effect of antidepressants, with serious side effects. The results being accepted by the FDA (who you would think would have the public’s health and wellbeing foremost) and accepted blindly by doctors (that have been educated by the pharmaceutical companies) with prescription pads, prescribing millions of doses of a medication that has been described as no better than a “Tic Tac”!

OK as painful as it is I can accept that.

What I can’t accept is the rhetoric around treating our children with behavioural or neurological disorders. It is OK to prescribe psychotrophic medications to children that:

• have little research of their effectiveness
• is “off-label” (not approved for children or the condition being treated)
• include cocktails of two or more medications (these are increasingly being prescribed)
• have few long-term studies of the effects of these medications
• that the side effects can be extremely serious
• not publish or disclose negative study results

The medical profession is quick to use its position of authority to convince parents that certain alternative treatments are “not proven” and potentially “dangerous”. They are doctors, they must know – right? Wrong!

• diet is effective in treating ADHD
• dietary modification is a promising treatment in ASD children and gaining acceptance
• specific supplements have been shown to benefit subgroups of children
• children improve when you address their gut issues
• children improve when you improve their sleep
• children improve when you treat their nutritional deficiencies

There is a huge foundation of anecdotal evidence that these approaches work. Unfortunately, no one has the millions of dollars that pharmaceutical companies have to do the research and “cherry pick” the few studies that suit them. However, the research IS out there – if you bother to look for it. The research is very robust and shows that these “alternative treatments” (I prefer the term biomedical) are effective for the vast majority of children. True science takes note of anecdotal evidence and explores it further. These days unless there are financial gains associated with the science, there is virtually no interest in pursuing it further.

In days gone by, parents and individuals relied totally on advice given by medical professionals and the media. The internet has changed that. It is a new playing field. Studies and information that has been held back from the public AND the medical professionals are on the internet and can no longer be hidden. Previously this knowledge was “buried”, and was worthless as no one knew it was there. Now that it has been released and found by professionals that can analyse these results independently, the game has changed.