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A Summary of Research on the Effectiveness of Antidepressants
and Psychotherapy

Michael Conner, PsyD
In a 2002 review of research, Kirsch and
Antonuccio (1) concluded that meaningful differences There is a significant gap between science and are lacking between antidepressants and placebos. In practice in the treatment of depression in America. 1998 Kirsch and Sapirstein (2) as well as Kirsch and Research internationally reports there is no valid or others (3) concluded the effects of antidepressant convincing evidence that antidepressants have a positive long term benefit with regard to depression or medication are weaker in children than in adults. Their suicide rates. The majority of improvement attributed to conclusions regarding children are consistent with antidepressants can be accounted for by factors of those found in all 7 prior reviews of the effects of hope, desire, belief, fortuitous events, passage of time antidepressants in depressed children (4,5,6,7,8,9,10). and behavioral changes made by patients over time. The response when treating children with anti- In 2002, Kirsch and others (11) reviewed all depressants is minimal and less than the response applications for antidepressant medications to the US reported in treatment of adults. A 12 week NIMH study Food and Drug Administration. An examination of all demonstrates that antidepressants are more effective submitted trials of newer antidepressant medications, than psychotherapy and that psychotherapy combined with antidepressants can help in treating adolescents found that the benefit of antidepressant medications with depression. Another NIMH study of adults was much smaller when all studies were considered demonstrates that a 16 week trial of psychotherapy is rather than when only the published studies. superior both clinically and economically to 16 weeks of antidepressants. Based on these findings and prior In 2004, the National Institute for Mental Health research we may expect that psychotherapy of (NIMH) (12) conducted a clinical trial of 439 sufficient duration with children may also be more adolescents with major depression at 13 sites effective than antidepressants. Evidence that nationwide. The study compared cognitive-behavioral antidepressants can reduce suicidal behavior or attempts is weak and there is some evidence that therapy (CBT) with Prozac which is the only suicide rates have increased since antidepressants antidepressant approved by the Food and Drug came into use. Isolated research on the effectiveness Administration for use in children and adolescents. At of antidepressants claiming positive findings in adults 12 weeks the combination of medication and and children may be misleading because many more psychotherapy was deemed the most effective studies show no statistically significant benefit. A majority of studies demonstrate that psychotherapy is treatment. Compared with placebo, the combination of effective, has a statistically significant benefit, and Prozac with CBT was statistically significant using the should be the first choice in treating mild, moderate Children's Depression Rating Scale-Revised. and severe depression. Contrary to marketing and Compared with Prozac alone and CBT alone, advertising claims, researchers and scientists have not demonstrated or claimed that depression is the result treatment using Prozac with CBT was superior. It was of a chemical imbalance or chemical insufficiency. concluded that Prozac alone was a superior treatment There is no valid evidence that antidepressants correct to CBT alone. Rates of response for Prozac with CBT any biochemical mechanism causing depression, or were 71%; Prozac alone, 60%; CBT alone, 43%; and that such a mechanism exists. The benefits of placebo, 35%. This study suggests that approximately antidepressants are not profound, lasting or predictable. Treatment using psychotherapy as a first 26% of people placed on Prozac alone will benefit by line treatment appears to be a prudent, cost effective the 12th week. But, 37% of the people placed on and a medically necessary course of action. Despite psychotherapy and Prozac will benefit by the 12th this, treatment recommendations over time by primary medical care to employ psychotherapy have declined. Based on research and practices internationally, it can In this same study, clinically significant suicidal be asserted that prescribing antidepressants without thinking, which was present in 29% of the sample at psychotherapy as a first-line treatment for depression baseline, improved significantly in all 4 treatment may be negligent. Psychotherapy has withstood the groups. Prozac with CBT showed the greatest test of time and has been demonstrated to be effective. Medications for depression have not. reduction. Seven (1.6%) of 439 patients attempted suicide and there were no completed suicides. The combination of Prozac with CBT offered the most favorable tradeoff between benefit and risk for of depression identified in primary medical care. Both adolescents with major depressive disorder. When the TCAs and SSRIs were considered effective for adults investigators used a broader definition of harm-related but the effect was small. This comprehensive review events to include suicidal and nonsuicidal behavior is also the first to show that low-dose TCAs are such self-harm, increase in suicidal ideas, or thoughts effective in primary care. As such, prescribing a or acts of harm to others or property, they found a tricyclic or SSRI antidepressant in primary care is a significantly higher rate in the Prozac groups (13). more effective clinical activity than prescribing In 2004 Kirsch and Antonuccio (14) testified placebo - but only 13 to 18% more than placebo. before the Food and Drug Administration stating there While statistically significant, this is not a profound are a total of 12 published randomized clinical trials (RCT) in the entire world literature of treating In 2005, during a study of 240 patients, DeRubeis children with antidepressants. Eight of these 12 trials and others (17) reported that cognitive therapy worked failed to find any significant benefit of medication as well as a popular antidepressant for moderate to over inert placebo. Only 4 of the RCTs claimed severe depression. In the study, patients on medication significant differences between drug and placebo, and got better quicker. At eight weeks, the response rate those did so only on clinician rated measures, not was 50 percent for Paxil, 43 % for cognitive therapy patient rated measures. Three of the clinical trials did and 25 % for placebo. But by 16 weeks, 58 % of not report means and/or standard deviations, leaving 9 patients in both treatment groups were feeling better. for a meta-analysis. When these nine studies are Patients who got 16 weeks of cognitive therapy also combined the improvement attributed to placebo was had about the same relapse rate a year later as people 87%. Overall, this means that no more than 13% of who took an antidepressant the whole time. If people people who improved actually benefited from quit taking Paxil after 16 weeks, their relapse rate was antidepressants. No more that 25 % of people who twice that of therapy patients who had 16 weeks of improved responded to SSRIs like Prozac. This meta- psychotherapy. These findings suggest that analysis indicates that Tricyclic Antidepressants psychotherapy is more effective and will cost less in (TCAs) have no significant pharmacological effect on depression in children. In effect, 75% of the SSRI Following their study, and during an interview response and 97% of the TCA response is placebo or with the Philadelphia Inquirer on April 4, 2005, consequences that are associated with the passage of DeRubeis and Hollon (18) stated that the American time. While the effects of Selective Serotonin Psychiatric Association should change its treatment Reuptake Inhibiters (SSRIs) like Prozac are guidelines for moderate to severe depression, which statistically significant, there was no evidence in these currently call for antidepressants as the first-line studies that the use of these drugs was clinically In 2005, Moncrieff and Kirsch (19) reported that In 2004, Pampallona and others (15) conducted a longitudinal follow-up studies show very poor meta-analysis and found that combined psychotherapy outcomes for people treated with antidepressants for and medications with adults were more effective than depression both in hospital (20) and in their psychotherapy alone. They also found that community, (21), and most importantly, that the psychotherapy can help keep patients in drug therapy overall prevalence of depression is rising despite They recommended further research to explore increased use of antidepressants (22). “Two studies interventions that might serve as a “treatment that prospectively assessed outcome in depressed compliance mechanism” for drug therapy. patients treated naturalistically by general In 2005, after an extensive review, Arroll and practitioners and psychiatrists found that people others (16) found only 15 studies based in primary prescribed antidepressants had a slightly worse care that met inclusion criteria and provided evidence outcome than those not prescribed them, even after for the comparative efficacy of tricyclics and SSRIs vs baseline severity had been taken into account placebo. Adult patients responded to 56% to 60% to (23,24).” No comparable studies could be found that antidepressants compared with 42% to 47% for showed a better outcome in people prescribed placebo. 40 to 44% did not improve at all. As such, only 13 to 18% of adults actually benefited from an In their 2005 review Moncrieff and Kirsch (19) antidepressant. This systematic review is the first also found that some authors have suggested a causal comparing antidepressants with placebo for treatment association between increased antidepressant prescribing since 1990 and reduction of overall correct this problem. Furthermore, there is no valid suicide rates observed in some countries. However, evidence to support the conclusion that depression is other researchers have pointed out that drops in the result of a “chemical imbalance.” overall suicide rates started long before this period, Lacasse and Leo suggest that despite a lack of and suicide rates have increased in some age groups evidence, and even evidence to the contrary, the and some countries despite increased antidepressant pharmaceutical industry markets and educates the prescribing. Meta-analyses of data from controlled public, schools and health care describing a cause and trials have not found reduced rates of suicide or treatment for depression that is not substantiated by suicidal behavior in drug use compared with placebos. The positive effect of antidepressants on suicide rates Does Psychotherapy Work?
in the long term is unclear. Moncrieff and Kirsch also conclude that recent meta-analyses show SSRI’s have In one of the first reviews of psychotherapy no clinically meaningful advantage over placebo. outcomes, Hampe and others (27) in 1973 evaluated Claims that antidepressants are more effective in more the progress of 62 phobic children 1 and 2 yrs after severe cases of depression have little evidence to termination of treatment or waiting period. 80% were either symptom free or significantly improved; only 7% still had a severe phobia. Successfully treated Antidepressants: Reality or Myth ?
patients tended to remain symptom free and to be free Why do professionals and the public believe that from other deviant behaviors as well. 60% of the antidepressants are an effective first-line treatment failures at termination continued to receive treatment approach? There are a number of research designs and methodology errors that can explain isolated findings Smith and Glass (28) in 1977 analyzed the results as well as why research can be perceived as positive of 375 controlled evaluations of psychotherapy and by professionals and lay people. John (25) described counseling. The findings provide convincing evidence how false findings may be the majority or the vast of the efficacy of psychotherapy. On the average, the majority of published research. It can be proven that typical therapy client is better off than 75% of most positive research findings are false. For example, untreated individuals. Few important differences in the probability that any research finding is true effectiveness could be established among very depends on the prior probability that it is true. Isolated positive findings may in fact be false if the In 1979, Lesser (29) reviewed traditional preponderance of prior studies is negative. Negative psychotherapy outcome studies, which show that findings from single studies are generally not psychotherapy is more effective than placebo, long- published. Therefore, patients, professionals and term psychotherapy is as effective as brief, and limited hard data are available as to the effectiveness of the John describes how distorted reporting and weak psychotherapies used. Cost-benefit studies show that definitions of improvement are among the most brief psychotherapy is cost effective, while long-term typical forms of bias. For example, an ordinal rating psychotherapy clearly reduces hospitalization costs. system is typically used to measure response to In 1981, Andrews and others (30) analyzed the medications. A person with a score of 40 may be more results of 81 controlled psychotherapy trials. The depressed than a score of 20 but this does not mean condition of the typical patient after treatment was they are twice as depressed. Other biases include the better than that of 77% of untreated controls measured researcher’s profession, career interests, funding at the same time, and the rate of relapse in the first 2 sources, size of the study and the complexity of Also in 1981, Tramontana (31) describes and In 2005, Lacasse and Leo (26) provide evidence critically evaluate studies on individual, group, and and present expert opinions that there is no evidence family therapy that were published from 1967 through to support widely promoted claims regarding the cause of depression, the effectiveness of methodological scope and rigor. The greater weight of antidepressants, and how antidepressant work. available evidence on adolescents does point toward Lacasse and Leo cite studies, experts and leading the superiority of psychotherapy over no-therapy scientists who conclude there is insufficient evidence conditions, with the median rate of positive outcome to support a belief that depression is the result of a serotonin deficiency and that drugs like Prozac can with psychotherapy being approximately 75%, generally defined as hope, desire or a belief that compared with a rate of 39% without psychotherapy. In 1982, Smith (32) applied meta-analysis to 475 In an extensive review of research, Hunsley (37) in studies of the effectiveness of psychotherapy and 112 2003 outlined how “empirical evidence has studies of the comparative effects of psychotherapy demonstrated that psychological interventions can and psychoactive drugs. Their analysis showed that effectively treat a wide range of child and adult health psychotherapy is effective in enhancing psychological problems. The focus of this review is on cost issues well-being, regardless of the way it is measured by associated with psychological interventions, including researchers. Drug therapy, while combining well with cost-effectiveness and cost offset (i.e., a reduction in psychotherapy, is not more effective than health care costs attributable to effective psychotherapy alone. intervention).” Hunsley concluded that evidence thus In 1985, Casey and others (33) examined 75 far has demonstrated “that psychological interventions studies. Results show that therapy with children was can be more cost-effective than optimal drug similar in effectiveness to therapy with adults; treated treatment. For example, although having comparable children achieved outcomes about two-thirds of a effectiveness, cognitive-behavioral treatments for standard deviation better than untreated children. panic disorder and for depression have been estimated Although behavioral treatments appeared to be more to cost approximately one-third less than effective than non-behavioral treatments, this apparent pharmacological treatment. Most important he points superiority was due largely to the types of outcome out that a recent meta-analysis of 91 research studies and target problems included in behavioral studies. published between 1967 and 1997 found that average health care cost savings due to psychological In 1986, Howard and others (34) analyzed data intervention were in the range of 20–30% across based on more than 2,400 patients, covering a period studies, and 90% of the studies reported evidence of a of more than 30 yrs of research. Results indicated that medical cost offset. As of 2003 there is overwhelming by 8 sessions approximately 50% of patients were evidence that psychological treatments (a) can be cost- measurably improved, and approximately 75% were effective forms of treatment and (b) have the potential to reduce health care costs, as successfully treated In 2002, Wampold and others (35) conducted a patients typically reduce their utilization of other meta-analysis of studies that compared Cognitive Therapy (CT) to ‘other therapies’ in an earlier meta- Hunsley also describes how many effective analysis, except that in this meta-analysis “other psychological services result in a net cost benefit to therapies” were classified as bona fide and non-bona health care systems. This is how it should be in any fide. Bona fide treatments were defined as treatments health care system that truly aims to improve the with therapeutic rationale for depression. The benefits health of the population through effective treatments of CT were found to be approximately equal to the to reduce pain, distress, suffering, and disability. benefits of bona fide non-CT and behavioral “Psychological interventions work for an enormous treatments, but superior to non-bona fide treatments. range of health problems and, although attempts to The results of this study support the conclusion that all promote greater access to these services must include bona fide psychological treatments for depression are arguments based on cost-effectiveness and cost offsets, they should not be (and have not been) totally In 2003 Hubble, Duncan and Miller (36) published a comprehensive review and analysis of
psychotherapy process and outcomes. They Treatment Issues in America
determined the proportion of improvement in
In 2000, Berndt and others (38) examined 2222 psychotherapy was the result of (a) the techniques persons employed as data processors at multiple sites used, 15%, (b) patient expectations and placebo, 15%, nationwide. The average daily productivity of (c) the relationship with a therapist (30%) and (d) employees with 1 or more mental disorders for which environmental and patient resources such as social they were receiving treatment was no different from support, fortuitous events, and patient strengths, 40%. that of employees with no mental disorders. Despite Placebo and expectancy effects in psychotherapy are this finding, which suggests the effectiveness of less than those found in treatment with anti- treatment, the cost data were striking: "controlling for depressants. Placebo and patient expectation are age and sex, employees with more than 1 mental health disorder have total medical expenditures about 10 times those of employees with no mental disorder." completely eradicate the somatic preoccupations of When considered alone, the expenditures associated with 4 solo mental disorders. Anxiety, depression, In 2002, Olfson and others (52) found that between adjustment disorders, and other mental disorders 1987 and 1997 there was a marked increase in the (mainly substance abuse) were similar in magnitude to proportion of the population who received outpatient one another, each averaging about 4.5 times the total treatment for depression. Treatment was characterized medical expenditures of those with no mental by greater involvement of physicians, greater use of medications, and expanding availability of third-party Depression is the world's fourth most prevalent payment, but fewer outpatient visits and less use of health problem (39) costing the United States $30 to psychotherapy. The proportion of treated individuals $50 billion in lost productivity and direct medical who used antidepressant medications increased from costs each year (40,41). Persons who are depressed 37.3% to 74.5%, whereas the proportion who received miss work because of illness at twice the rate of the psychotherapy declined significantly from 71.1% to general population (42). Health service costs are 50% 60.2. The average number of depression treatment to 100% greater for depressed patients than for visits per patient declined significantly from 12.6 to comparable patients without depression. These 8.7 per year. An increasingly large proportion of increased costs are caused by higher medical patients, 68.9% to 87.3%, were treated by physicians utilization, not by specialty mental health care (43, for their condition, and treatment costs covered by 44). Additional costs associated with depression third-party payers increased from 39.3% to 55.2%. include impaired concentration, failure to advance in In their 2005 review, Keesler and other (53) found educational and vocational endeavors, increased that no significant changes occurred between 1990- substance abuse, impaired or lost relationships, and 1992 and 2001-2003 in suicidal ideation, plans, gestures, or attempts, whereas plans among ideators In 2000, the Agency for Health Care Policy and increased significantly from 19.6% to 28.6%, and Research (AHCPR), the Veterans Health conditional prevalence of gestures among planners Administration/Department of Defense (VHA-DOD), decreased significantly from 21.4% to 6.4%. and the American Psychiatric Association (APA) Treatment increased dramatically among ideators who published evidence-based recommendations for made a gesture from 40.3% to 92.8% and among depression treatment. Pharmacotherapy and ideators who made an attempt from 49.6% to 79.0%. psychotherapy (combination treatment) are But despite a dramatic increase in treatment, no recommended when treating moderate to severe significant decrease occurred in suicidal thoughts, depression. When the depression is mild to moderate plans, gestures, or attempts in the United States during and the patient is motivated to work on psychological and interpersonal issues, psychotherapy is warranted In 2005, Robinson and others (48) found that primary care physicians as a whole initiated Schulberg and other (39) in 1999 concur with the antidepressant interventions more frequently than any AHCPR guidelines and concluded that referral to a other treatment for depression. In particular, the mental health professional should be a part of physicians prescribed antidepressants for an average depression treatment, especially when patients exhibit of 52% of their newly diagnosed depressed patients, severe depressive symptoms (e.g., suicide risk; combination treatment (pharmacological and comorbid medical, psychiatric, or substance use psychological) for an average of 27% of the patients, disorder; or failure to respond to appropriate and psychotherapy alone for only 4% of the In his review of “cost offset” in the treatment of Discussion
depression, Pomerantz (51) in 2001 stated that “antidepressants do not cure the ‘medicalization of Depression in children and adults is without life’, which is something Thomas Szasz warned about question a serious problem that has a significant more than a quarter of a century ago. Furthermore, negative impact on health care and the economy of the antidepressants do not alleviate problems of living United States. In response to this public health (e.g., pain associated with chronic arthritis or diabetic problem, antidepressants are the first line treatment neuropathy, low self-esteem, a rejecting spouse) or despite evidence that psychotherapy is more effective and less expensive in the long run. There is also reason to suspect that the treatment of (3) Kirsch I., Moore T., & Scoboria A., Nicholls S. depression by physicians has not had a profound or positive effect on reducing suicidal behavior. More antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention In the United States, physician prescribing of & Treatment 2002 5: Article 23. Available at: antidepressants for depression is increasing while http://journals.apa.org/prevention/volume5/pre00 referrals for psychotherapy are decreasing. This is the reverse of what might be expected since there is (4) Ambrosini, P.J., Bianchi, M.D., Rabinovich, H., limited and minimal evidence that antidepressants are & Elia, J. Antidepressant treatment in children effective with adults and children. Psychotherapy and adolescents: I. Affective Disorders. Journal appears to be effective and more effective for both adults and children than antidepressants. Practically speaking, all competent psychotherapies for (5) Duvjone, V.F., Barnard, M.U., & Rapoff, M.A. Pharmacological and cognitive-behavioral How then can our health care system recommend approaches in the treatment of childhood medications without psychotherapy knowing that depression: A review and critique. Clinical medications do not alleviate problems in living? Some possible reasons for the higher use of antidepressants (6) Fisher, R.L. & Fisher, S. Antidepressants for may include (a) the introduction of SSRIs such as children: Is scientific support necessary? The Prozac that have fewer side effects than tricyclics, (b) Journal of Nervous and Mental Disease, 1996, aggressive pharmaceutical industry advertising, (c) research publication bias, (d) errors in research (7) Hazell, P., O'Connell, D., Heathcote, D., methodology, (e) an increased level of screening for Robertson, J., & Henry, D. Efficacy of tricyclic depression, (f) third party reimbursement for drugs in treating child and adolescent depression: medications, and (g) a greater number of physicians a meta-analysis. British Medical Journal, 2005 willing to treat depression in primary medical care. There is clear evidence that antidepressants can (8) Kastelic, E.A., Labellarte, M. J., & Riddle, M.A. help some patients. There is sufficient evidence to (2000). Selective serotonin reuptake inhibitors suggest that competent psychotherapy should be the for children and adolescents. Current Psychiatry first line treatment for depression. There is also evidence that psychotherapy alone can be prescribed for severe cases of depression and that a combination (9) Michael, K.D. & Crowley, S.L. How effective of psychotherapy and antidepressants can be are treatments for children and adolescent prescribed for severe and unresponsive patients. depression? A meta-analytic review. Clinical Psychology Review, 2002 22, 247-269. These findings suggest that there is a significant gap between science and treatment of depression in (10) Sommers-Flanagan, J. & Sommers-Flanagan, R. America. Current guidelines and recommendations for Efficacy of antidepressant medication with the treatment of depression in the United States should depressed youth: What psychologists should be revised in light of research findings internationally. know. Professional Psychology: Research and Practice, 1996, 27, 145-153. References
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