Part II Do Psychotropic Medications Cause More Harm than Good?

July 7, 2023

What Do Studies on Psychotropic Medications Show?

With every research publication, there is some level of unavoidable inherent bias.  You may read one source in complete support of an intervention and another in complete opposition.  Most articles rely on information and conclusions read by the author without the author’s further investigation or in-depth analysis into the source of actual research’s hard data.  In depth analysis of a paper’s hard data is time consuming and not often done by physicians, yet it is essential to verify an author’s conclusion.

The topic “antidepressants are controversial” is demonstrated by decades of analytical research showing many adverse effects and many adverse opinions.  The literature is voluminous and yet studies on the whole are not well done, hence leading to misconstrued data information or flawed conclusions.

Though consequences of psychotropic medications can be serious and catastrophic, they may benefit some people, but determining who they may benefit, who they may harm, and why, are remaining questions this series of blogs attempts to answer.  The task of reviewing thousands of studies has been formidable.

Psychotropic Medications: Studies Questioning Possible Lethal Potential?

The link between psychotropic medications and agitation, homicide, and suicide has been established.  The below recent eye-opening studies add to the current need to bring further investigation to the topic and further caution when it comes to prescribing psychotropic drugs.

  • A 2016 systematic review and meta-analysis in the Journal of the Royal Society of Medicine screened 5787 publications looking at healthy adults without mental disorders who were started on antidepressants.  The authors concluded:
    • “Antidepressants double the risk of suicidality and violence, and it is particularly interesting the volunteers in the studies we reviewed were healthy adults with no signs of a mental disorder.”
    • It is a “potentially lethal misconception” these drugs are not dangerous for adults.
  • The above 2016 review is in direct opposition to the majority of psychiatrists who believe increased suicide risk is only present until the age of 24 and is actually not an adverse effect of the drug but a sign the drug is working. This belief is based off trial data published by the FDA in 2006 and 2004.
    • In 2004, the FDA ”issued a black box warning on antidepressants indicating they were associated with an increased risk of suicidal thinking, feeling, and behavior in young people…based on a meta-analysis of 372 randomized clinical trials involving 100,000 participants showing the rate of suicidal behavior was 4 % receiving antidepressants versus 2% receiving placebo.” Black box warnings are required by the FDA for medications carrying serious safety risks.
    • After the FDA published the 2006 meta-analysis, data was re-analyzed and estimated there were likely 15 times more suicides than was reported in the original FDA report, questioning the validity of the original FDA data and conclusions.
    • Reasons for underreporting by the FDA were:
  • “…the FDA trusted data sent to them by the companies doing the research, however, the companies did not include any suicides occurring 24 hours after the randomized phase was over.”

Hence, the FDA relied on relayed information rather than taking time to properly self-      analyze hard-core data.

  • A 2005 meta-analysis by independent researchers screened 702 randomized trials totaling 87,650 patients finding 345 trials with usable information for fatal and non-fatal suicide attempts.  In reviewing these trials, researchers found many suicide attempts were not counted in the data because researchers did not look for them or did not report them in their trials if suicide presented shortly after treatment was stopped.  The authors concluded:
  • There was more than a twofold increase in rate of suicide attempts in patients receiving SSRIs compared to placebo or therapeutic interventions other than tricyclic antidepressants.
  • Patients receiving SSRIs compared with placebo had a significant increase in odds of suicide attempts (odds ratio 2.28).
  • The ability to detect significant differences in subgroups was limited due to reduced sample sizes but odds ratios exceeded 1.0 for all trials except those with participants with mean age of over 60.
  • The odds ratio for non-fatal suicide attempts was significant at 2.70 whereas for fatal suicide attempts, there was no significant difference between placebo and SSRIs at 0.95.
  • Estimates for patients with major depression receiving SSRIs favored a decrease in suicides.
  • No significant differences were identified between SSRIs and tricyclic antidepressants when comparing suicide attempts.
  • “A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events…Doctors rely on published reports for their treatment decisions, making open and complete reporting scientifically and ethically essential.”
  • Another meta-analysis by independent researchers from 2005 including 40,826 patients found no evidence SSRIs increased risk of suicide. However, even in this meta-analysis, increased risk of suicide cannot be excluded as companies had seriously underreported suicide risk, suicidality, and non-fatal self-harm from their trials compared to actual reported suicides. The authors conclude:
    • “Increased risks of suicide and self-harm caused by SSRIs cannot be ruled out,
    • .. larger trials with longer follow up are required to assess the balance of risks and benefits fully…
    • When prescribing SSRIs, clinicians should warn patients of the possible risk of suicidal behavior and monitor patients closely in the early stages of treatment.”
  • As the efficacy and safety of antidepressants has been questioned, a 2017 study published in the British Medical Journal and Journal of Epidemiology Community Health, was conducted to assess whether young violent offenders aged 15-18 were more likely to have used an antidepressant prior to their first violent offense. The authors concluded:
  • Boys were convicted for non-violent and violent crimes more often than girls
  • Prior antidepressant use to violent crime was more common among convicted persons than non-convicted
  • Prior antidepressant use was more common among boys with repeated violent crimes
  • After adjusting for background characteristics, the association decreased but was still present and most notable for SSRIs
  • The strongest predictor of crime conviction was the child being in psychiatric care prior to age 15
  • A re-evaluation of the original clinical trials is warranted
  • Reported in a 1999 article entitled, “Guns and Doses,” “Although the list of school-age children who have gone on violent rampages is growing at a disturbing rate…few have been willing to talk about the possibility the heavily prescribed drugs and violence may be linked.”
  • The largest antidepressant effectiveness trial ever conducted, STAR*D, showed just 2.7% of patients had an initial remission lasting up to 12 months. This trial, however, is controversial because of poor design and its data is not well accepted.

Summary

The harm psychiatric drugs can do is easily demonstrated in clinical trials by a multitude of adverse effects, some serious and life-threatening.

Studies required to prove safety and efficacy by the FDA are highly flawed,

  • not representing normal use of the drug in practice,
  • are short only lasting around 3-8 weeks,
  • typically exclude potentially suicidal or violent high-risk patients,
  • use only one drug even though multiple are often combined in practice,
  • are ultimately evaluated by the drug manufacturers rather than researchers.
  • As trials are short-lived from 3-8 months, no evidence exists on long-term antidepressant therapy.

Patients taking antidepressants are more likely to relapse than those taking no medication, 2011 study.

A 2008 meta-analysis evaluated all antidepressant-controlled trials conducted during the approval process by the FDA showing they did not perform better than placebo “except in a relatively small group of the most extremely depressed patients.”  This was a slight difference and may not translate to clinical significance.

In December 2011, Thomas Insel, Director of the National Institute of Mental Health published an article entitled “Antidepressants: A Complicated Picture.”  In it, he wrote:

  • “…even under research conditions, clinical trials for antidepressants use rating scales that may be weak or imprecise indicators of efficacy.
  • Mild depression tends to improve on placebo so the difference between antidepressant use and placebo effect is very small, or at times, absent.
  • In more severe forms of depression, antidepressants show greater efficacy.
  • The bottom line is these medications appear to have a relatively small effect in patients broadly classified as having depression.”

Is this potentially “small effect” worth the risk of the serious adverse effects and unknown long-term effects?  Are there better ways in which to deal with mental health?

Conclusions

Out of thousands of studies, no studies to date have adequately supported the use of antidepressants over placebo for mild to moderate depression.

Many patients end up on a combination of psychotropic medications though this is not supported as combination therapy has not been well studied.

Antidepressants may have a place for severe depression for a short period of time though there are no long-term studies to show this nor short-term studies showing the difference is clinically significant.

Antidepressants carry a black box warning of which everyone should be aware.

The need for further studies with better study design is essential and necessary to draw accurate conclusions as to how antidepressants may be best utilized in mental health disorders.

Posted in Medications