Roger P. Greenberg, PhD

Continuing Education Information

The idea that medications hold the key to repairing all manner of psychological and physical discomforts has been around for many decades. The acceptance of this idea has been reflected in steady, consistent sales data. For example, between 1960 and 1980 the sale of prescription drugs remained at a relatively stable percentage of the United States gross domestic product. However, in the following two decades sales escalated by a whopping 300% as serotonin reuptake inhibitor antidepressants zoomed into the top ten most prescribed drugs and the pharmaceutical industry became the most profitable business in the United States (Angell, 2005). The notion of quelling psychological problems through unraveling the physiological mysteries of the brain achieved an additional push when President George H.W. Bush designated the period 1990-1999 as the “Decade of the Brain.” This designation resulted in an increased effort by the National Institute of Mental Health and the Library of Congress “to enhance public awareness of the benefits to be derived from brain research.”

The rage for psychopharmacological treatments was also fueled by a combination of intense, clever marketing, the need for more effective treatments, and the perception that the approach was based on hard scientific studies. The appeal was understandable. It just seems easier to deal with emotional discomforts by taking a pill rather than having to endure the effort of spending weeks speaking to a psychotherapist about unpleasant, threatening experiences or unacceptable impulses. It is also comforting for patients to feel that unwanted emotions do not need to be linked with environmental, interpersonal events. By using medications, no blame or responsibility needs to be assigned to either the afflicted individuals or to significant people in their lives.

In general, medical practitioners also find ample reasons for welcoming the biochemical solutions. As I have noted elsewhere, the treatments are easy to put into practice, provide a clear, concrete response to patient demands to do something, supply an aura of medical respectability and are financially well-supported by the insurance and pharmaceutical industries (Greenberg & Fisher,1997). In sum, the motivation to believe in the power of the pill is sturdy and socially desirable. By comparison, the arguments mustered for the importance of psychological factors in creating “disorders” and the usefulness of psychotherapy to combat them has seemed to many to be less attractive, more effortful, and less based on hard science. Therefore, psychotherapy in its various forms, with roots in the psychodynamic tradition of attributing symptoms to an underlying psychosocial cause for disturbance, may appear to the biologically inclined to teeter as an acceptable, first-line approach for dealing with mental health problems like depression. As Cummings and Cummings (2013) suggest, the “Golden Age of Psychotherapy” of the 1950s and 1960s looked to be slipping away.

A Reversal of Fortune

Given the direction that things were headed, recent years in the professional literature have taken an unexpected twist with revelations that are thought provoking and startling! The world was turned upside down by the Journal of the American Medical Association meta-analysis article on antidepressants ( and the subsequent 2010 Newsweek article by Sharon Begley) suggesting that the benefits of antidepressants for most patients do not significantly exceed the benefits that they might receive from placebo treatments (Fournier et al., 2010). At the same time, the American Psychologist published an article by Jonathan Shedler (2010) demonstrating that there is good empirical evidence for the efficacy of psychodynamic psychotherapy. What was thought to be scientifically valid – A pure biological approach to treating depression – was now under intense scrutiny. What was thought to be less scientifically rooted – the psychodynamic approach to treatment – was now undergoing a scientific rejuvenation. What was going on here?

Supporters of the biological approach scrambled to denounce the negative finding produced by the critical meta-analysis with accusations of short-comings in the studies reviewed. They were of course correct. There were indeed short-comings, as there always are in research. However, it was surprising that the meta-analysis generated reactions as though the result was something new. I was the principal author of three comprehensive reviews of the antidepressant literature published in 1989, 1997, and 2009. Each of these reviews was quite consistent with the new meta-analysis in showing small to negligible differences in effects produced by antidepressants and placebos.

The revelation of small differences in outcomes for antidepressant and placebo treatments is not an isolated finding. Several authors have acknowledged the overselling of solutions based on a pure biological impact (e.g., Abramson, 2004; Angell, 2005; Antonuccio et al., 1995, 1999; Greenberg et al., 1992, 1994; Greenberg & Fisher, 1989, 1997; Healy, 2004; Hollon et al., 2002; Jackson et al., 2004). In fact, two studies by Irving Kirsch and his colleagues (2002, 2008) support the conclusion of meager antidepressant- placebo differences that are perhaps even smaller than the modest results shown in the published literature. For their first report they were able to obtain information from the Food and Drug Administration (FDA) on the results of all the trials (both published and unpublished) that had been submitted in gaining initial approval for the six most widely used antidepressants. These were drugs that gained approval between 1987 and 1999. Differences favoring the medications in these trials were quite small; only about two points on the sixty-two point Hamilton Rating Scale. Some regard a difference of this size as not reflecting much clinical change. Moreover, 90 percent of the studies showed no advantage at all for the new drugs in patients with mild to moderate levels of depression. In a second more recent meta-analysis looking at the issue of depression severity, Kirsch et al. (2008) again found no differences in treatment outcomes for those with moderate levels of depression and only small differences in those with the most severe depression. Once more they raised questions about whether even these differences were large enough to be clinically meaningful. Repeatedly studies of this type indicate that significant and equivalent gains can be had with either psychosocial or biological interventions.

Another piece of troubling information appeared in a study reported in The New England Journal of Medicine (Turner et al., 2008). This report indicated that the published information on the effectiveness of antidepressants is misleading because it presents an inaccurate picture of what has been learned from the effectiveness trials that have been done. When the investigators looked at all the trials in the FDA database – both published and unpublished – for agents that were approved between 1987 and 2004, they discovered that only about half of them actually showed any significant differences between drugs and placebos. However, the published literature did not reflect this result because it did not report on 92% of the negative results and thereby, implied that almost all trials (94%) were positive. In addition, because of the selective reporting, the published literature suggested an effect size that was about one-third larger than the one that would be obtained by including all the trials in the FDA database.

The search to unravel and downplay the mystery of the lack of superior findings for antidepressant pills reminds me of the old story of the optimistic boy who noticed a large pile of horse manure that had been deposited in his back yard. Running from his house he leaped into the pile and began digging furiously. His father ran after the boy and shouted, “What are you doing?” The boy shouted back, “There must be a pony in there somewhere.”

Merging Elements in Psychopharmacology and Psychotherapy

So our quest is to answer the question, “Is there a pony in there?” I would argue that there may be a miniature horse in there, but it does not look like what people have been taught as conventional wisdom about antidepressants. Actually, I believe the horse looks a lot less like a pure-bred Kentucky Derby winner (a biological creature) than like Mr. Ed, the 1960’s TV talking horse noted for his ability to interact psychosocially. My argument is that the success of the antidepressant approach rests on a large psychosocial component. Please note that the argument is not that antidepressants are ineffective. They do result in improvements. The issue is whether the gains can be attributed solely to their chemical composition.

A few decades ago, I co-authored an article titled, “How are an Orange and a Banana Alike? Comparative Observations on Psychoanalytic and Biological Research.” (Greenberg & Fisher. 1994). The article noted that it is not often realized that psychoanalytic and biological researchers face similar problems.

Antidepressant drug treatments tend to be thought of as hard science. They conjure up images of chemistry, test tubes, equations, and treatment specificity. Frequently unrecognized is the fact that although biological treatments are delivered with particular dosage levels and chemical composition, they are administered in an interpersonal context and outcomes (just as in psychotherapy) are measured in terms of “judgments” about feelings and behaviors. Thus, there is an intrusion of interpersonal, psychosocial elements in what was thought to be an unsullied biological approach. Finding that the biological interventions may not stand alone as superior depression treatments is nothing to be ashamed about. A psychosocial point of view does not need to be regarded as based on second rate science. As observed in an American Psychologist article, the physical sciences do not necessarily show greater precision or reliability in research findings than do the social sciences (Hedges, 1987).

Donald Kiesler (1966), in a classic paper in the Psychological Bulletin, called attention to several myths in psychotherapy research. One of them was the “therapist uniformity assumption” wherein it is assumed that all analysts using the same treatment model display therapy behaviors and outcomes that are similar. Reviews of research evidence on Freud’s ideas (Fisher & Greenberg, 1985; 1996) supported the idea that therapist uniformity is a myth. It turned out that analysts are very diverse and rarely display consensus about anything. Surprisingly, the same unreliability appears in the psychiatric medication literature where there are interesting studies showing that the same medication, presumably prescribed in the same way, can show different results depending on the specific clinic and the specific clinician who prescribes them! An early example of this appears in a multi-center study comparing results at three different hospitals using the same three antidepressants and the same criteria for the selection of depressed patients (Greenblatt, Grosser, and Wechsler, 1964). The rank order of treatment effectiveness among the hospitals was the same no matter which treatment was used. One setting consistently produced the best results and another produced the worst. For instance, one of the antidepressants was effective 67% of the time at the most effective medical center and only 31% of the time at the least effective hospital. It is evident that something other than the chemical composition of the drugs was affecting outcome in the different settings.

Over time it has become clear that psychosocial factors operate in drug treatments as well as psychotherapy treatments (Greenberg, 1999; Greenberg & Dewan, 2014). One example of this occurred in the well-known NIMH Depression Treatment study that compared outcomes for two forms of psychotherapy with antidepressants and placebos (Elkin et al., 1989). The investigators noticed that some of the clinicians conducting antidepressant treatment were getting better results than other clinicians prescribing the same drugs. They worked hard to get the physicians to take their personality styles out of the drug treatments they provided in order to achieve uniform outcomes. They were unsuccessful. Some were just better at it than others.

Another example of parallel findings is revealed in the critical reviews of the outcome literatures for both psychotherapy and antidepressant medications. There it has been shown that judgments about outcomes can be swayed by the investigators’ vested interests in the success of a particular type of treatment. In response, drug treatment advocates have pointed to double-blind studies – where neither patients nor clinicians are informed about who is receiving the active drug and who the placebo – as offering protection from accusations of rater bias. The rejoinder has been evidence showing that the double-blind isn’t really blind.

Reviews of “blinded” antidepressant studies, where patients and clinicians were asked to guess whether active drugs or placebos were being delivered, revealed that the participants were able to do so with a high degree of accuracy….often more than 80 % (Greenberg & Fisher, 1989, 1997). It was speculated that one tip-off was the experiencing of side-effects in those taking medication. In the few studies using an “active placebo,” which mimics side effects like dry mouth, the identification of the active drug is more camouflaged and made more difficult. Under these conditions, ratings of antidepressant-placebo outcome differences tend to shrink even more, down to a level that may not be clinically meaningful.

Oddly enough, despite the writing in articles and books for over a decade about lack of blindness in the outcome ratings of drug researchers (as well as psychotherapists), it was only within the past few years that the American Journal of Psychiatry (March, 2010) finally acknowledged in a commentary that the double-blind isn’t really blind.

Some Additional Pertinent Observations from the Research Literature

Advocates of biological treatments for depression are sometimes drawn to downplaying the modest results for antidepressants relative to placebos by suggesting that medications are likely to be more effective in “real life” than in tightly controlled research studies because of the freedom physicians would have to change dosages or drugs. This idea has not been supported. Studies addressing this speculation have produced evidence that the medications may be even less effective in everyday life than they are in drug trials (Teasdale et al., 1984; Brugha et al., 1992; Fava et al., 2003; Rush et al., 2004; Rush et al., 2006). Similarly, antidepressant trials relying primarily on clinician judgment for outcome ratings (such as with the Hamilton Scales) may make the results look better than trials that rely on patient ratings (such as with the Beck Scales). In short, practitioners tend to see significantly more benefit from the treatments than patients do (Greenberg & Fisher, 1989, 1997).

So does the repeated finding that psychosocial aspects of treatment are very alive and evident in biochemical approaches mean that we should despair about the results? I think not. Perhaps when assessing whether therapies are useful it is time to downgrade the idea that a clear discrimination between biological and psychosocial effects must be maintained at all costs. The literature demonstrates how hard it often is in psychiatry and psychology to make a clear distinction between the effects created by psychotropic drugs and those that can be attributed to placebos or psychological mechanisms. In reality all effects occur in tissue and one is no more biologically real than others. In this sense response to psychotherapy, placebo or psychotropic medications can all be seen as biological. Research has also provided evidence consistent with the idea that psychological interventions can lead to physiological change. Consider the discovery that placebo effects are physiologically linked to changes in endorphin levels (Evans, 1985); or that placebo analgesia of pain is connected to an endogenous opiate- related mechanism (Sauro & Greenberg, 2005); or that there are parallel brain imagery changes that occur in successful treatment of obsessive-compulsive disorder treated by either psychotherapy or medications (Baxter et al., 1992); or that similar patterns of brain-scan changes can be seen in depressed patients who responded to either placebo or antidepressants (Mayberg et al., 2002).

The impact of psychosocial elements on medical outcomes is not limited to psychiatric drug studies. Unanticipated effects have also been reported for sham surgery, where patients were exposed to a surgical intervention that was not specific to the condition being treated. It was astonishing to discover that sham surgeries for osteoarthritis of the knee turned out to be just as effective for reducing knee pain as the conventionally accepted arthroscopic knee surgery had been (Mosely et al., 2002). Likewise, investigators found that double-blind sham surgery for stem-cell replacement in patients with Parkinson’s disease produced results that were judged to be strong and lasting (McRae et al., 2004).

Conclusions and Practical Suggestions for Moving Forward Clinically

The aim of this piece has been to point out that the mental health field, after a concerted drive toward a biomedical model, appears to be moving back to recognition that the human condition, as reflected in illness, disease, or mental disorders, is affected by a complex mix of biological, psychological and social factors. Using this viewpoint, symptom causation and the therapies to remediate emotional discomforts can therefore be seen through multiple lenses.

The idea of a biopsychosocial model was first put forth by psychiatrist George Engel in a 1977 paper in the journal Science and later detailed in a1980 article he wrote in the American Journal of Psychiatry. He argued for the need to create a new model, one that is not based only on biological understanding but includes the contributions of psychological and social factors. Emerging research continues to suggest that Engel was on to something important.

Take, for example, the case of depression. The pharmacological treatment of depression has been largely sold to the public as useful because of the idea that depression results from a chemical imbalance in the brain. The simple reasoning typically presented is that since there is a chemical imbalance, then imbibing new chemicals in the form of pills will help to restore biological stability. This is a straightforward explanation that leads to a straightforward easy solution. The problem is that there is no persuasive evidence that any imbalance actually exists (Valenstein, 2005; Healy, 2009; Kirsch, 2009; Paris, 2010).

Furthermore, there is clear evidence that taking the same pill prescribed by different people produces different results. Why? The answer appears to lie in the nature of the doctor-patient relationship. This was nicely shown in the NIMH Treatment of Depression Program that I previously mentioned (Elkin et al., 1989). In that project, decrease in the measures of depression turned out to be just as related to the quality of the doctor-patient relationship for those receiving medication as it was for those receiving psychotherapy. The quality of the relationship experienced by patients was significantly more related to whether patients would show improvement than was the type of treatment they received. The more the providers were seen as empathic, caring, open and sincere, the better the outcome (Blatt et al., 1996a). Another report, derived from the same project, indicated that ratings of the treatment alliance had a “very large” impact on outcome independent of whether the treatment was psychotherapy or medication. (Krupnick et al., 1996). A third publication looked at the most effective clinicians and determined what characteristics they possessed (Blatt et al., 1996b). Once more, it did not matter which type of treatment they delivered. Those who were most effective turned out to be those who had a psychological rather than a biological orientation to treatment of depression, those who placed less emphasis on medication per se in their usual way of working with patients, and those who expected treatment to last for a longer time period than did the less effective clinicians.

The bottom line suggested by the evidence briefly reviewed above is that it is time for clinicians to once again acknowledge and pay closer attention to the interpersonal side of what is going on in their encounters with patients whether they are delivering psychotherapy treatments or psychiatric medications. As Mintz (2005) stresses, it is important for psychiatric trainees to learn that it is “crucial” to develop an understanding of interpersonal and intrapsychic dynamics, even for those who believe they are delivering only somatic treatments. A similar point is made by Chaplin and colleagues (2007) in emphasizing the need for mastering “negotiating styles” and developing strong interpersonal skills when prescribing antipsychotic medications.

Let me be clear. I am not indicating that antidepressants should not be used in treating depression. There are debated findings in the research literature suggesting that they may offer some unique benefits with severely depressed patients, such as those with vegetative symptoms like difficulty eating and sleeping. It is also wise to keep in mind that patient treatment preferences are important. In fact, the American Psychological Association encourages clinicians to keep such preferences in mind (APA, 2006). It has been demonstrated that patients do better in terms of forming stronger treatment alliances, refraining from dropping out of treatment, and achieving more positive outcomes when they receive the type of treatment that they prefer (Greenberg & Goldman, 2009). Even given these facts, though, antidepressants are not magic pills. Spending a few minutes with a patient and writing a prescription does not substitute for building a treatment alliance and inquiring about what is going on in a patient’s life.

Several years ago Steven Hollon and Robert DeRubeis (1981) published an intriguing paper where they compared the outcomes for patients receiving psychotherapy and those receiving psychotherapy plus placebos. According to data derived from several studies they discovered that psychotherapy plus placebos was less effective than psychotherapy delivered alone. Why? My speculation is that many patients are prone to work less hard in dealing with their problems if they assume that pills alone are all that is needed to derail their anxieties and depression. To gain maximum treatment effectiveness, it is most often necessary for clinicians to emphasize the psychosocial, human part of treatment. This idea also dovetails nicely with the research showing that relapse back into depression is more likely after pills are stopped than when psychotherapy is terminated. Apparently treatments that provide learning experiences for patients are more protective than those that just adjust biochemistry for a while (Greenberg & Goldman, 2009).

In this article I have focused most attention on the diagnosis and treatment of depression, though similar arguments can and have been made for other disorders (Fisher & Greenberg, 1997). I have made depression the focus here because of the prominence and prevalence of the depression diagnostic category among all the specified diagnoses, its tenuous connection with brain research findings and the elevation of antidepressant drugs to the list of the most prescribed physiological remedies for any disorders. It is also true that research has shown that the media and the advertising industry have greatly oversold the value of these medications by using such labels as “miracle drugs” in their marketing campaigns. In fact, inspection of pronouncements made in advertisements to the public and mental health professionals has shown that the claims made are neither well supported by the empirical literature nor carefully inspected by government oversight (Donohue et al., 2007; Spielmans et al., 2008).

Let me end with two pieces of good news. First, in recognition of the idea that pure brain research will not adequately explain the complexities of human behavior, a new international effort was launched to spur trans-disciplinary research that includes professions such as psychology, the social sciences, neuroscience, cognitive science, computer science,, robotics and others. The effort has been labeled the Decade of the Mind and is focused on gaining financial support for research conducted over the decade 2012 to 2022 (Albus et al., 2007).

The second piece of good news may depend on your point of view. It reflects the fact that drug companies have done a wonderful job in convincing practitioners and the public that pills are a very potent solution to the problem of depression. Research published in 2009 by Reif and colleagues showed that the rate of response to placebos has increased dramatically. Effect sizes in placebo treated groups more than doubled between 1980 and 2005!

So, it appears to be back. Just as with the rejuvenation of Coke Classic, the Ford Mustang, and the Aflac Duck, we are witnessing the return of appreciation for the importance of psychosocial elements in human experience.


Dr. Greenberg is a Distinguished Professor at State University of New York (SUNY) Upstate Medical University where he has served as a mentor, teacher, and clinical supervisor to hundreds of psychology trainees, psychiatric residents, and medical students. For more than 35 years, Dr. Greenberg has assessed programs and student performance, serving as a site visitor for accreditation of psychology training programs. Dr. Greenberg received his PhD from Syracuse University and completed his internship at the Veteran Affairs Medical Center in Syracuse, NY. In addition to publishing more than 250 highly influential articles, books, and presentations, he co-authored "The Scientific Credibility of Freud's Theories and Therapies," which was selected as one of the ten best books in behavioral sciences by the National Library Association and Psychology Today. Dr. Greenberg has been credentialed by the National Register since 1975.


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