To Use or Not Use Antidepressants

Image by Lightsource

Image by Lightsource

I ran across a report from the National Center for Health Statistics when reading Saving Normal by Allen Frances that had some incredible facts about antidepressant use in the United States. The report said that 11% of Americans 12 years and over take antidepressant medication. Women were 2.5 times as likely to take antidepressants as men. Individuals 40 and over are more likely to take antidepressants than those younger than 40. “Twenty-three percent of women aged 40-59 take antidepressants, more than any other age-sex group.”

When the severity of depressive symptoms was considered, use of antidepressant medication rose as the severity of symptoms increases. This seems logical; the worse your depression is, the more likely you are to try medication. But look at the other end of symptom severity—7.6% of those taking antidepressants have NO REPORTED symptoms of depression. The Data Brief pointed out that this group could include people taking antidepressants for reasons other than depression and those who are being “successfully” treated with antidepressants, and just don’t have any symptoms currently. See the table below.

Depressive symptoms





























Allen Frances suggested that part of the problem was that drug companies capitalized on the placebo effect, that is: “people getting better because of positive expectations independent of any specific healing effect of the treatment.” Treating the “worried well” expanded the customer pool and guaranteed a pool of satisfied customers. “Placebo responders often become long-term loyalists to medication use even when the medication is perfectly useless.”

The best way to get great results with a pill is to treat people who don’t really need it—the highest placebo response rates occur in those who would get better naturally and on their own.

What’s at stake? The Statistics Portal indicated that the top ten selling antidepressants in 2011-2012 grossed 8.5 billion dollars. Considering that most of the antidepressants are off patent and not as profitable to the drug companies, this is an incredible haul. Another indication of the pervasiveness of antidepressant use in the U.S. is to look at the number of prescriptions written. The top antidepressant drugs in the U.S. based upon the number of dispensed prescriptions in 2011-2012 are given in the following chart, again from The Statistics Portal.



Celexa (citalopram hydrobromide)


Zoloft (sertaline hydrochloride)


Prozac (fluoxetine hydrochloride)


Trazadone (trazadone hydrochloride)






Paxil (paroxetine hydrochloride)


Effexor (venlafaxine hydrochloride ER)


Wellbutrin (bupropion hydrochloride XL)


Elavil (amitriptyline hydrochloride)


Returning to the NCHS Data Brief, once people start taking antidepressants, they tend to continue taking them. Sixty-one percent of Americans taking an antidepressant have been taking it longer than 2 years; 13.6% have been taking them ten or more years. The problem is that the widespread use of antidepressants and their long-term use may be actually causing depression.

Robert Whitaker commented in Anatomy of an Epidemic that prior to the appearance of antidepressant drugs, depression was seen as a rare problem with typically good outcomes over time. Now the NIMH says that an episode of major depression “can occur only once in a person’s lifetime, but more often, a person has several episodes.” In 2012, an estimated 16 million adults and 2.2 million adolescents had at least one depressive episode in the past year.

Whitaker noted how Italian psychiatrist, Giovanni Fava began in 1994 to look at the changing face of depression. In that article, Fava raised the possibility that “long-term use of antidepressant drugs may also increase the biochemical vulnerability to depression and decrease its likelihood of subsequent response to pharmacological treatment.” In a 2003 article, Fava suggested that antidepressants may, in some cases, actually cause depression.  “Whether one treats a depressed patient for 3 months or 3 years, it does not matter when one stops the drugs. A statistical trend suggested that the longer the drug treatment, the higher the likelihood of relapse.”

In a 2014 article, “Rational Use of Antidepressant Drugs,” Fava said that rational use of antidepressant drugs should consider all the potential benefits and harms. They should only be used with the most severe and persistent cases of depression. They should be used for the shortest possible duration. Using antidepressants to treat anxiety disorders should be reduced, unless a major depressive disorder is present or other treatments have been ineffective.

These suggestions may seem to be radically different from current guidelines such as those of the American Psychiatric Association, but they reflect the weighing of risk, responsiveness and vulnerability that should be applied to the use of AD [antidepressant drugs] in each individual case.

To use or not to use antidepressants, that is the question. There is serious potential harm that may occur with their use. And sometimes they can literally save a life. What seems to be clear is that current guidelines for their use can, in the long run, worsen the problem they were originally supposed to “treat.” Along with the above suggestions for the rational use of antidepressants given by Fava, I think there needs to be a change in how we think about psychiatric drugs. The current disease-centered model of drug action needs to be replaced by a drug-centered model of drug action. You can find more on this distinction in the writings of Joanna Moncrieff, such as The Myth of the Chemical Cure and my article, “A Drug is a Drug is a Drug.” Also see two longer articles on antidepressants available in the Counseling Issues section under the “Resources” link of this site.


The Quest for the Holy Grail of Psychiatry

Our brain: the final frontier. This is the unending quest of research into biomarkers. Its continuing mission: to explore strange new theories, to seek out new mental illnesses and new diagnoses, to boldly go where no psychiatric research has gone before.

The quest for biomarkers (measurable indicators of a biological state or condition) of mental disorders has gone on for decades without success. The recently proposed research strategy of the National Institute of Mental Health (NIMH) know as Research Domain Criteria (RDoC), has proposed to set aside the DSM diagnoses used to frame past mental health research and utilize data from neuroscience, genomics and behavioral science to spell out the etiology of mental illness.

Psychiatrist Giovanni Fava views the RDoC model as “the reflection of an intellectual crisis in psychiatry.” While its “blanket” approach aims to see that all possible biological and behavioral measurements are utilized, Fava thinks it will result in conflicting results that may be difficult to interpret. He said it was “misguided” to assume that nothing will be missed with such a strategy and that “innovative classification systems will ensue automatically.” The complexity of the new approach and the potential for interpretive problems it is illustrated by this recently published article in World Psychiatry, “Biomarkers and clinical staging in psychiatry.”

He pointed out that major clinical challenges were left without independent research. Among these challenges was the problem of the loss of clinical effects during long-term antidepressant treatment. And despite a lack of any evidence to support their superiority, antidepressant drugs are increasingly used as a first-line treatment for anxiety disorders. Studies on psychological treatment were also “scandalously under-supported.”

A major problem in the development of the Research Domain Criteria project has been the fact that its strong ideological endorsement by leading figures of the National Institute of Mental Health has resulted in suppression of an adequate debate. How many investigators who are likely to submit funding applications to that agency may afford disclosing that the emperor has no clothes and that the strategy may be a road to nowhere?

Fava et. al thought the exclusive reliance upon diagnostic criteria had impoverished the clinical process and did not reflect “the complex thinking that underlies decisions in psychiatric practice.” Current diagnostic definitions of psychiatric disorders are based on collections of symptoms from very heterogeneous populations and are likely to yield “spurious results when exploring biological correlates of mental disturbances.”

The large studies of biomarkers across diagnostic categories proposed by RDoC are anticipated to yield improved clinical information. But “such a view is based on the concept of assessment as a collection of symptoms devoid of any clinical judgment and interpretation.” There is no evidence to support the research direction taken by RDoC. Fava et al. noted that although Kapur, Phillips and Insel proposed that new biomarker-defined subtypes be identified, they were not able to “provide exemplifications suggesting that this approach was likely to yield meaningful clinical results in psychiatry.” Incidentally, Thomas Insel is the current director of the NIMH.

Using meta-analyses of biomarkers commonly used in cardiovascular medicine as an example, Fava et al. noted the presence of publication bias and selective reporting. They said biomarkers could end up being the result of various mechanisms and not necessarily the result of a specific disease process.

The complexity of the brain and the spurious nature of measurements that can be recorded constitute a major difficulty for psychiatry. Specifically, the neuroplastic properties make the brain a unique organ that essentially has to be studied and understood in a longitudinal, lifetime and transgenerational perspective.

Biological reductionism was said to have resulted in an approach that is far from the “explanatory pluralism” required by clinical practice. The exclusion of the methodological triad of observation (outer viewing), introspection (inner viewing), and dialogue (inter-viewing) makes this approach unscientific. Either the human realm was excluded from scientific inquiry or the scientific approach was conformed to the reductionistic, mechanistic requirements of the biomedical paradigm.

This restrictive ideology characterizes the Research Domain Criteria. It is time to enrich such criteria with clinically relevant dimensions and add clinical validity to the reliability and reductionism-focused mainstream of psychiatry research.

Elsewhere (“We Are But Thinking Reeds”) I’ve spoken of the necessity to see human nature as a psychosomatic unity of body (soma) and soul (psyche). The human mind is more than just a manifestation of brain activity. Any approach to “mental” illness research that fails to acknowledge this will never entirely succeed in its quest to find the holy grail of psychiatry.


Evidence-Based Treatment … Lacks Evidence

21828750_sEvidence-based medicine (EDM) began in the early 1990s and was seen as a revolutionary movement that would improve patient care. It grew to become the buzz-word for all medical and behavioral health care—make sure treatment is evidence-based! And yet, there is little evidence that EDM has achieved its aim. Health care costs have soared and there is a distinct lack of “high-quality evidence suggesting that EBM has resulted in substantial population-level health gains.”

Given that EBM firmly favours an empirical approach over expert opinion and mechanistic rationale, it is ironic that its widespread acceptance has been based on expert opinion and mechanistic reasoning, rather than EBM ‘evidence’ that it actually works.

The article from which the above critique was taken suggested that the lack of evidence for the overall benefit of EBM was a consequence of it not being implemented effectively. A cornerstone of EBM methodology—the randomized trial—has been corrupted by vested interests.  The authors, Every-Palmer and Howick, defined EBM as “the conscientious and judicious use of current best evidence in conjunction with clinical expertise and patient values to guide health care decisions.” They singled out the field of psychiatry for specific concern, where “the problems with corruption of randomized trials are dramatic.”

Most of the medical psychiatric evidence base has been funded by the pharmaceutical industry, often without the relationships being disclosed. “Between two-thirds and three-quarters of all randomized trials in major journals have been shown to be industry funded.” One of the consequences of this has been publication bias: positive results are published; negative results are not. The best current estimate is that half of all completed clinical trials have never been published in academic journals. Some trials are never registered.

There is also evidence that industry-funded studies exaggerate the treatment effects in favor of the product preferred by their sponsor. One study reviewed industry-funded studies of atypical antipsychotics and found that 90% of the trials showed superiority of the sponsor’s drug. The studies had been designed “in a way that would virtually guarantee the favoured drug would ‘win.’”

Among their recommendations, Every-Palmer and Howick suggested that all clinical trials should be registered and reported. There needs to be more investment in independent research. Evidence-ranking schemes also need to be modified to account for industry bias. These suggestions would be helpful corrections for the corruption of the randomized trial methodology, but what if there are additional problems? For example, merely correcting problems with the misuse of randomized trials would not address concerns related to clinical expertise or patient values.

If current medical science is reaching its limits with some complex illnesses, as Every-Palmer and Howick said was one possibility for the lack of progress with EBM, then further gains will be hard to come by. This would seem to be true with mental illness and addiction, which are diagnosed with the Diagnostic and Statistical Manual (DSM), 5th edition. DSM diagnoses are consensus-based decisions about clusters of symptoms and do not have any objective laboratory measure. Thomas Insel, the Director of the National Institute of Mental Health (NIMH), said that diagnosis with the DSM was equivalent to “creating diagnostic systems based on the nature of chest pain or the quality of fever.”

A further compounding error could be when the role of clinical judgment is neutralized as a result of an overreliance upon the trump of scientific—real or imagined—evidence. Kiene and Kiene noted how the reputation of clinical judgment in medicine has undergone a “substantial transformation” over the last century with the rise of modern research methodology.  “A primary mission [in medical progress] therefore became ‘to guard against any use of judgement’, and it was executed through clinical trials.”

Giovanni Fava pointed to the increasing crisis in psychiatric research and practice because “Psychopathology and clinical judgment are often discarded as non-scientific and obsolete methods.” He noted how the concept of evidence-based medicine has achieved widespread endorsement in all areas of clinical medicine, including psychiatry. But randomized trials were not intended to answer questions about the treatment of individual patients. “The results may show comparative efficacy of treatment for an average randomized patient, but not for pertinent subgroups formed by characteristics such as severity of symptoms, comorbidity and other clinical nuances.”

An aura of authority is given to collections of “best available evidence”, which can in turn lead to major abuses that produce “inappropriate guidelines” for clinical practice. The risk is especially serious as a result of the substantial financial conflicts of interest in medical societies and with the authors of the medical guidelines for clinical practice within those societies.

Special interest groups are thus using evidence-based medicine to enforce treatment through guidelines, advocating what can be subsumed under the German language term of “ Leitkultur ”, which connotes the cultural superiority of a culture, with policies of compulsory cultural assimilation. In psychiatry, such process has achieved strong prescribing connotations, with a resulting neglect of psychosocial treatments.

Given the existing crisis within psychiatry, especially with the questionable validity and reliability of diagnosis within the DSM, evidence-based treatment guidelines that were developed and disseminated within such a culture require radical revision or should be used with extreme caution. The evidence for their efficacy is lacking.