Evidence continues to mount that antidepressants are ineffective, harm brain function and carry risks of serious side effects when taking or stopping the drugs.

A new study of Americans with depression found no significant difference in the overall well-being and health-related quality of life over time between those treated with antidepressant drugs and those who did not take the drugs.  The findings are relevant to the physicians of the 45 million Americans currently prescribed antidepressant drugs, including 2.2 million children under the age of 18.

Omar A. Almohammed and colleagues from the departments of pharmacy at several universities in Saudi Arabia and the United States used data from the U.S. Medical Expenditures Panel Survey for adults with depression during the years 2005-2016 to investigate whether the use of antidepressants actually improved the quality of life of those suffering from depression. 

The data comprised an average of 17.5 million adults each year, 58% of whom took antidepressants.  Quality of life was measured with data from a separate survey, using patient-reported physical outcome measures that focused on physical health problems, bodily pain, general health, and energy/fatigue, and mental outcome measures that focused on emotional problems, psychological distress, and psychological well-being.

Publishing their results in the journal PLOS One, the researchers reported no significant difference in changes in the physical and mental well-being over two years of follow-up between those who took antidepressants as treatment and those who did not.

“The real-world effect of using antidepressant medications does not continue to improve patients’ HRQoL [health-related quality of life] over time, as the change in HRQoL was comparable to patients who did not use any antidepressant medications,” they wrote.

They further cite other meta-analyses that were conducted to assess the change in outcomes for patients treated with antidepressants.  Those studies found that the benefit from taking antidepressants was minimal, that “most of the improvement in symptoms (about 80%) came from the placebo effect,” and that “when data from unpublished studies were combined with data from published studies the difference became statistically insignificant, or even clinically undetectable,” according to the Almohammed team.

“The real-world effect of using antidepressants does not continue to improve patients’ health-related quality of life over time, as the change is comparable to patients who did not use antidepressants.”
– Omar Almohammed, PharmD, PhD, Clinical Pharmacology, King Saud University

The researchers recommended that doctors should rethink the prescribing of antidepressants as first-line treatment for depressed patients and instead consider non-drug interventions. “Physicians, mainly primary care providers who are caring for most of these patients, may need to reconsider referring patients with depression to receive some kind of non-pharmacological therapy,” they wrote.

The Almohammed study’s findings are consistent with a review of meta-analyses of newer generation SSRI and SNRI antidepressants by Mark Horowitz, Ph.D., of the Division of Psychiatry at University College London, and Michael Wilcock, pharmaceutical researcher at Royal Cornwall Hospitals NHS Trust.   Writing in the BMJ Drug and Therapeutics Bulletin in 2021, they reported finding no clinically significant difference in measures of depression symptoms between adults treated with antidepressants and those taking placebos, whether over a shorter or longer timeframe and regardless of the study participants’ depression severity. 

Their review further concluded that studies purporting to find antidepressant efficacy in children and adolescents were “even less convincing.”  The researchers observed that published results of clinical studies involving adolescents exaggerated benefits by various means, such as changing the outcomes reported from the ones initially specified for investigation.  They also claimed that risks were under-reported in studies, such as by coding suicide attempts by study participants taking antidepressants as “emotional lability” (mood swings).

Even more recently, researcher John Read, Ph.D., professor of psychology at the University of East London, and Joanna Moncrieff, a psychiatrist and researcher at University College London, reviewed evidence on the use of antidepressants for treating depression and concluded the drugs are ineffective, harmful to brain function, and rest on assumptions of brain dysfunction that have never been proven.

“Despite claims by professional organizations and the pharmaceutical industry that depression is due to a chemical imbalance that can be rectified by drugs, there is no evidence that there are any neurochemical abnormalities in people with depression let alone abnormalities that might cause depression,” they wrote in Psychological Medicine earlier this year.

In keeping with the more recent research findings on antidepressants, draft guidance published in November by the London-based National Institute for Health and Care Excellence advised British physicians that antidepressant drugs should not be considered first-line treatment.  Instead, people with depression should be offered and able to choose from a variety of treatment options, including such non-drug options as exercise and mindfulness.

The Citizens Commission on Human Rights (CCHR) database of psychiatric drug side effects currently lists 283 research studies and 155 drug regulatory agency warnings about adverse effects from antidepressants.  Those harmful side effects include insomnia, emotional dulling, sexual dysfunction, anxiety, irritability, hostility, aggressiveness, loss of judgment, and the impulsivity and mania that can lead to violence and suicidal thoughts and actions.  A 2016 study led by Nordic Cochrane Centre researcher Andreas Bielefeldt found that giving SSRI antidepressants to healthy adult volunteers with no signs of depression doubled their risk of suicidality and violence. 

Patients taking antidepressants also face the risk of severe and long-lasting withdrawal symptoms when discontinuing the drugs, even when slowly tapering off them under the supervision of a physician.  A study published in 2020 in the Journal of Osteopathic Medicine  advised that “with extended use, [antidepressants] can be notoriously difficult to quit because they can produce a state of physical dependence.” 

Depending on the drug and the length of time taken, those withdrawal effects may include hypertension, seizures, stroke-like symptoms, amnesia, agitation, fear, anger, aggression, hallucinations, delirium, and suicidal thoughts.

Researchers James Davies, Ph.D., co-founder of the U.K.-based Council for Evidence-based Psychiatry, and John Read, Ph.D., of the University of East London, conducted an analysis of 23 earlier peer-reviewed studies on the withdrawal from antidepressants.  Their study, published in Addictive Behaviors in 2019, found that more than half (56%) of people who attempt to come off antidepressants experience withdrawal effects, with nearly half (46%) of them rating those effects as “severe.” 

The withdrawal symptoms can also be long-lasting.  A study led by Tom Stockmann, published in the International Journal of Risk & Safety in Medicine in 2018, analyzed reports of withdrawal symptoms on an Internet forum and found that on average, symptoms when discontinuing SSRI antidepressants lasted close to two years (90.5 weeks) and lasted nearly a year (50.8 weeks) for those discontinuing SNRI antidepressants.

Because of the very real risk of severe and long-lasting withdrawal symptoms, both patients and their doctors are often reluctant to start or carry through on discontinuation of antidepressants, leading to much longer use than wanted.  What’s more, the withdrawal effects can be misdiagnosed as a return or worsening of the depression, causing the person to stay on the drugs.  The number of long-time antidepressant users is swelling as a result.

“Some 15.5 milllion American have taken antidepressants for at least five years,” according to science reporter Benedict Carey, writing in the New York Times in 2018.  “The rate has almost doubled since 2010 and more than tripled since 2000.”

Researchers led by Carolien Wentink of the psychiatry department of Radboud University Medical Center in the Netherlands published a study in the journal BMC Family Practice in 2019, in which they cited evidence on the long-term use of antidepressants and concluded that the rising number of antidepressant users is mainly due to the increase in chronic users.

WARNING: Anyone wishing to discontinue or change the dose of an antidepressant or other psychiatric drug is cautioned to do so only under the supervision of a physician because of potentially dangerous withdrawal symptoms.

CCHR recommends that individuals experiencing depression ask their physician for a complete physical examination with lab tests to find any underlying physical condition that could be causing the mental symptoms that might otherwise be misdiagnosed as a psychiatric disorder.

CCHR advocates for the full disclosure of the risks of serious side effects and withdrawal symptoms from antidepressants and other psychiatric drugs, so that patients can make fully informed decisions about taking or discontinuing the drugs.