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September 25, 2013

Antidepressants: Effective or Effectively Marketed

by Angel Pumila

Antidepressants: Effective or Effectively Marked

Reviewing Research Literature

The following is research on the effectiveness of antidepressants.  It is found that placebo effects may not be significantly different from that of antidepressant drugs themselves. Marketing companies that perform the research have an unfair bias against the outcomes of their studies.  New research finds that the cause of depression may not just be biochemical.  There are many psychological factors involved that cannot be treated by these drugs alone.  This project is intended review the current research on the use of antidepressants and in the end be able to clarify if these drugs are a marketing ploy or actually reduce the risk of suicide in patients.

This topic was previously visited by a researcher by the name of John Salamone from the University of Connecticut.  His article, Antidepressants and Placebos: Conceptual Problems and Research Strategies focuses on what he claims may exaggerated effect sizes.  Salamone analyzes the work of Kirsh and outcomes of his study.  “In the present commentary, depression is discussed in terms of neurochemical systems that promote interaction with the environment, and the view allows for recognition of the importance of environmental stimulation, placebo effects, and drug actions” (Salamone, 2002).

Salamone continues explaining his conflicting feelings by explaining that, “I cannot escape the feeling that some of Kirsh’s claims and implications are exaggerated and that some of his points are overly simplistic or misleading. Moreover, it appears to me as though this pattern of polemical exaggeration is taking place in the context of the evolution of the placebo issue from a scientific debate into a sort of political campaign. Currently, there are several political forces at play within psychology and psychiatry, including debates about prescription rights for psychologists, insurance reimbursements, and the utility of various models, including the “medical model,” for therapeutic interventions. In the wake of the psychopharmacology revolution of the last five decades, we appear now to be in the midst of a backlash. Amidst all of these swirling political forces, coupled with the popular press attention to this issue, I fear that some of the essential scientific points are being underemphasized or lost (Salamone, 2002).”

Salamone determines through his own analysis that there could be a bias among those who conducted these original experiments because the effects of antidepressants are so small. He concluded that improvements at the highest doses of antidepressants were no different than improvements at the lowest doses. He states that the improvements should have been different between doses and subjects, and therefore refutes the findings.

This author hypothesizes that drug manufacturers have done an outstanding job of selling antidepressants not only to doctors but to the general public and that their effectiveness when compared with inert placebos has been somewhat overestimated. Many of the early studies of the effectiveness and side effects were funded by drug manufacturers and therefore are not reliable, according to the Salamone.

“Some might suggest that comparing antidepressants and placebos after only six weeks of treatment is unfair to the active drug condition and that longer-term outcome will surely favor the medication. However, data from the National Institute of Mental Health Collaborative Depression Study suggest otherwise. The 18-month follow-up data from that multisite trial (Shea, 1992) found patients assigned to placebo (plus clinical management) had intent-to-treat outcome comparable to that in the active drug condition (plus clinical management),” (Antonuccio, Burns, Danton, 2002).

They add that, “The silver lining in these results for psychiatry is that the psychiatrist, or at least something about the psychiatric relationship, and not the pill, appears to facilitate improvement in depression. Figuring out ways to enhance the therapeutic alliance, originally pioneered but recently marginalized by organized psychiatry, may prove more fruitful than modifying the selectivity of antidepressants” (Antonuccio, Burns, Danton, 2002).

These authors’ research was conducted relatively safely, although the ethics involved in the research still seems questionable. It seems that science had not played as significant a role as it should have and that marketing played a bigger role in the rise in the use of antidepressants to treat depression, thereby making the authors hypothesis correct.

In the article by Elizabeth T. McNeal and Peter Cimbolic, title, “Antidepressants and Biochemical Theories of Depression,” the authors conduct a case study in which they hypothesize that “there may be multiple biochemical and psychological pathways to depression” (McNeal, Cimbolic, 1986).

They conclude that, “Over the last few decades, much has been learned about the monoamine systems in depression. Extensive research on the effects of antidepressants on the uptake and metabolism of NE and 5-HT have suggested that these neurotransmitters are involved in some way in at least some depressive syndromes. The evolution of a new generation of antidepressants that do not show these effects necessitated the development of other theoretical possibilities in order to explain their actions. This also had the effect of redirecting research into studies of the effects of antidepressant treatments on receptor systems in the brain. This work has been very fruitful. We have learned a great deal about the responsiveness of receptor systems to neurotransmitters, especially NE and 5-HT. As it became clear that long-term effects of antidepressants differed from short-term effects, research was also focused in this direction. Chronic treatments with “typical” and “atypical” drugs have yielded some interesting consistencies” (McNeal, Cimbolic,1986).

Throughout the article, the authors refer to all of the major studies that have been done since depression was first diagnosed as a mental disorder, and their research is obviously in-depth from the numerous references they provide. Their study seems to be ethical, and their approach seems honest. While their hypothesis that there are numerous biochemical and psychological pathways to depression does seem to be proved through their research, these authors admit that after all of their studies, they (and no one else) can really provide a concrete answer as to the effectiveness of antidepressants.

“Though much has been learned,” they state, “this information might be considered just the tip of the iceberg. We still have very little knowledge about the etiology of depression or, more specifically, the various pathways to depression. There is much suggestive evidence that a number of amine transmitter systems are involved in the development of some depressions. Biochemical and neurohormonal data indicate that several neurotransmitter systems may be acting either alone or in combination to produce depressive symptoms. Studies of the effects of antidepressants have contributed much to our knowledge to date, but one must remember that these effects can be misleading. One does not necessarily discover causes of a disease by studying the effects of biochemicals that can cure it” (McNeal, Cimbolic,1986).

With regard to the use of antidepressants to prevent patients from committing suicide, the steady rate of suicide among depressed people speaks for itself. While many researchers and experts would expect that suicide rates would decrease with the use of antidepressants, this did not happen. In fact, in some regions, suicide rates increased. In his article, “Why Has the Antidepressant Era Not Shown a Significant Drop in Suicide Rates,” H. M. van Praag states that “Khan et al. (2000) reported that rates of suicide and attempted suicide did not significantly differ in depressed patients treated with either placebo or an antidepressant. They analyzed studies with seven new antidepressant drugs, (i. e., fluoxetine, sertraline, paroxetine, venlafaxine, nefazadone, mirtazapine, and bupropion) using the USA Food and Drug Administration database. The study encompassed 19,639 patients” (van Praag, 2002). van Praag goes on to say that, “Stress, produced by traumatic events or situations together with inadequate coping skills, is probably an important etiological factor in many cases of depression. Suicidality, thus, might be not so much a feature of depression as such, but rather a consequence of preexisting personality traits” (van Praag, 2002).

The author then expresses his consternation with the paradox that exists between the use of antidepressants and suicide rates. “Taking into account that depression is a major suicide precursor, and that over the past 20 years antidepressants have been employed on an ever-increasing scale, it is puzzling that suicide rates have not dropped accordingly. Over the past decades the rate of completed suicide has remained quite stable, whereas that of suicide attempts seems to have increased (to the extent it has been studied in defined regions). These are puzzling observations, since depression is the major suicide precursor and since antidepressants have been increasingly used over the years in the treatment of depression (van Praag, 2002).

In an article titled, “Depression and Suicidal Behavior,” Tamás Zonda agrees that more and more people are being treated for depression, but the author notes that, “Depressive diagnoses (“affective spectrum”) have increased significantly in the last decade. Nowadays, a mental disorder can hardly be found that wouldn’t have an affective “touch” to a certain degree. New depressive disorders appear from time to time, the last being premenstrual dysphoria. Depression is over-diagnosed in general and in the suicidal process. We read in the literature that depressive disorders are present in 50 to 90 percent of suicidal events. Studies do not take into account two special psychiatric conditions: The presuicidal-syndrome and/or the crisis situation. These conditions are not depression, however, they are regarded as depression in the course of a psychological autopsy. So we can rightly suppose that depressive disorders are over-diagnosed among suicide victims” (Zonda, 2005). This author believes that there is no way to positively determine how the use of antidepressants and suicide rates correlate because antidepressants are used for a variety of disorders unrelated to suicidal tendencies. This article also addresses the fact that there are many other factors that are not associated with depression that can cause people to commit suicide, including sudden trauma and pre-existing suicidal tendencies. Therefore, one could deduce that the use of antidepressants do not prevent suicide attempts.

“Data from international studies do not support the antidepressant theory, “Zonda explains.  “For example, Slovenian data show no relationship between sales of the antidepressants and the trends of suicide rates (Oravecz, 2003). In the United Kingdom from 1987 to 1998, the suicide the rate has decreased by 15 percent, while in Ireland it increased by 39 percent. Is it possible that GPs did not hear about antidepressants in Ireland and do not prescribe them?” (Zonda, 2005). Zonda’s question, while somewhat sarcastic, does make a point. No one is quite sure why suicide rates are higher in some countries and lower in others and what role antidepressants play in those rates. The studies that have been conducted seem to be subjective and do not include all possible factors that could affect patients or influence them to attempt suicide.

M. David Rudd and Liliana Cordero take that idea one step further in, “What Every Psychologist Should Know About the Food and Drug Administration’s Black Box Warning Label for Antidepressants,” by suggesting that studies are seriously flawed. The authors state that, “In 2004, the Food and Drug Administration (FDA) placed a black box warning label on all antidepressant drugs (including selective serotonin reuptake inhibitors [SSRIs]) used with children and adolescents (FDA Center for Drug Evaluation and Research [CDER], 2004). In 2007, the label was updated and expanded to include young adults up to 24 years of age (FDA CDER, 2007). The current label targets the risk for “suicidal thinking and behavior (suicidality)” (FDA CDER, 2007) in children, adolescents, and young adults. The expanded label also includes information about the benefits of antidepressants with older adults (ages 65 and older) along with a reminder that “suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide” (Rudd and Cordero, 2009).

The authors explain that this increased risk in more noticeable in adolescents and young adults but does not include the stated risk of death and that the risk is more pronounced in the first few months of use. “The FDA black box warning label does not indicate an increased risk for death by suicide, only for suicidality (defined as suicidal thinking and behaviors). This is true for children, adolescents, and young adults. There were no suicides in the child and adolescent aggregated trials, and although there were suicides in the adult trials, there was no conclusive data that the medications elevated the risk for death by suicide beyond that seen with a placebo. The rates were comparable for adults across the clinical and placebo arms” (Rudd and Cordero, 2009).

These authors then discuss the merits of the FDA’s research and state that all evidence is really to the contrary. They note that SSRIs have been shown to reduce thoughts of suicide and suggest that there is not enough context for the FDA’s findings. “As part of the debate, it is important for all mental health clinicians to be aware that recent evidence in the literature actually demonstrates a reduction in suicide risk with SSRI use, with markedly low rates of SSRI antidepressants reported in the toxicology results of suicide cases (Ryan, 2005). Erlangsen, Candudas-Romo, and Conwell (2008) found that only 1 in 5 older adults were taking antidepressants at the time of suicide. Additionally, they discovered that the male suicide rate declined by 9.7 suicides per 100,000 for men taking antidepressants and by 3.3 suicides per 100,000 for women, essentially a 10 percent decline in both groups. The net result is that antidepressants were found to reduce risk in a significant fashion with the elderly, consistent with the often unrecognized element in the FDA warning label and medication guide” (Rudd and Cordero. 2009).

The conclusions of these researchers seem to be that there is no conclusive data that supports the assumption that the use of antidepressants increases or decreases suicide rates. Some studies support an increase (The Food and Drug Administration study), while others suggest that presuicidal syndrome or situational crises may influence suicide rates more than the use of antidepressants. Still other studies indicate that antidepressants decrease suicide rates. It is difficult to know which study to believe, which makes it difficult to know whether one should take antidepressants or not. When even the researchers are confused, there is cause for concern. Further research is certainly indicated, and I will try to get some reliable answers through my own research.

 

 

References

Salamone, John D.; Prevention & Treatment, Vol 5(1), Jul, 2002. ArtID 24. Antidepressants and placebos: Conceptual problems and research strategies.

 

Antonuccio, David O.; Burns, David D.; Danton, William G.; Prevention & Treatment, Vol 5(1), Jul, 2002. ArtID 25. Antidepressants: A triumph of marketing over science?

 

McNeal, Elizabeth T.; Cimbolic, Peter; Psychological Bulletin, Vol 99(3), May, 1986. pp. 361-374. [Journal Article] Antidepressants and biochemical theories of depression.

 

van Praag, H. M.; Crisis: The Journal of Crisis Intervention and Suicide Prevention, Vol 23(2), 2002. pp. 77-82. 

 

 Zonda, Tamás; Crisis: The Journal of Crisis Intervention and Suicide Prevention, Vol 26(1), 2005. pp. 34-35. 

 

Rudd, M. David; Cordero, Liliana; Professional Psychology: Research and Practice, Vol 40(4), Aug, 2009. pp. 321-326.

 

Goldney, Robert; Crisis: The Journal of Crisis Intervention and Suicide Prevention, Vol 26(2), 2005. pp. 97-98. Antidepressants and Suicide: A Commentary on a Significant Contribution to this Debate.

 

Kirsch, I. (2002). Yes, There Is a Placebo Effect, but Is There a Powerful Antidepressant

Drug Effect? Prevention & Treatment, 5, Article 22. Available on the World Wide Web:

http://www.journals.apa.org/prevention/volume5/pre0050022i.html

 

Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. S. (2002). The emporer’s new drugs:

An analysis of antidepressant medication data submitted to the U.S. Food and Drug

Administration. Prevention & Treatment, 5, Article 23. Available on the World Wide Web:

http://www.journals.apa.org/prevention/volume5/pre0050023a.html.

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