Reassessing SSRIs

Separating Hype from Fact About Antidepressants

Magazine Issue
September/October 2004
Reassessing SSRIs

For the last decade, there’s been a spectacularly successful advertising campaign to convince the public that the selective serotonin reuptake inhibitors (SSRIs), including Prozac, Zoloft, Celexa, Lexapro, Luvox, and Paxil, have revolutionized the treatment of depression. In response, antidepressant use has doubled and requests for antidepressant treatment have tripled in the last 10 years. Today, 74 percent of those seeking help with depression in the United States are treated with medication. Incredibly, 28 million Americans have taken an SSRI, including 500,000 children. In fact, researcher James Coyne of the University of Pennsylvania has pointed out that more people fill prescriptions each year for antidepressants than research indicates fit the diagnosis of depression, suggesting the widespread use of these medications for other conditions, even though these uses remain wholly untested.

Meanwhile, the remarkable growth in use of the SSRIs has paralleled a significant decrease in the use of psychotherapy to treat depression. The proportion of those being treated for major depressive disorder or dysthymic disorder with psychotherapy declined from 71 percent to 60 percent over a recent 10-year period.

But do these pills work as advertised for most people? SSRIs have fewer side effects than older generations of antidepressants (the tricyclics), and overdoses tend not to be lethal, making them safer for physicians to prescribe. However, the research provides little support for the notion that these drugs are a breakthrough in the treatment of depression. The key findings of the latest research indicate that:

– SSRIs are no more effective than the older tricyclic antidepressants, such as Elavil or Tofranil, which have been around for decades. For example, a metanalysis by several researchers at the Evidence Based Practice Center at the University of Texas at San Antonio found that the SSRIs help 63 percent of patients, compared to 60 percent for tricyclics. So, while SSRIs may have fewer side effects, they’re no more effective than older generations of drugs, and they’re more expensive.

– The impact of SSRIs on depression in children and adolescents is minimal. Recent surveys of treatment research indicate impact no better than placebo.

– Taking SSRIs increases the risk of suicide and suicidal ideation, especially in children and adolescents. Rates of suicidal ideation have been as high as 9 percent in a trial of Lustral, an SSRI manufactured by Pfizer. This rate is much higher than the rate of suicidal ideation among subjects receiving a placebo.

– Although lacking the side effects of the tricyclics, SSRIs often result in loss of libido, a side effect found in as much as 70 percent of those taking these medications. Many find this so distressing they discontinue use.

– SSRIs often lead to intense anxiety, lethargy, and distress when medication is discontinued. There’s increasing evidence of at least a psychological dependency on these medications, which leads to considerable discomfort when clients stop taking them. This, in turn, makes discontinuing these medications more difficult.

Despite this research, the general public continues to overestimate the effects of the SSRIs. Because the pharmaceutical industry not only spends millions of dollars in advertising, but also funds much of the research on their products, it can largely control the flow of information to the public, which remains unaware of research findings. The New York Times recently reported Forest Laboratories’ failure to release research showing low levels of impact on children and adolescents for its SSRI Celexa. Under pressure, Forest then released data from a study showing a similar lack of impact for Lexapro, another Forest antidepressant, in children and adolescents. The data demonstrating the small impact and increased risk in children for all SSRIs recently led to a decision by Great Britain’s Medicine and Health Care Products Regulatory Agency to warn against prescribing SSRIs for depressed children and adolescents.

Nevertheless, the combined results of all the studies on adults treated with SSRIs do indicate that, though these aren’t “wonder drugs,” they do help the majority of adult clients with major depressive disorder or dysthymic disorder. Therefore, many professionals and organizations, including the American Psychiatric Association and the American College of Neuropsychopharmacology, argue strongly for the efficacy of SSRIs.

SSRIs vs. Psychotherapy

To put the effectiveness of SSRIs into perspective, it’s also helpful to compare research on SSRIs with studies of psychotherapy as a treatment for depression. Several forms of brief therapy have been shown to have impacts comparable to the SSRIs. The best-established treatment is Cognitive Therapy for Depression, a therapy developed by psychiatrist Aaron Beck of the University of Pennsylvania, which focuses on challenging the accuracy of depressive thoughts and building a more optimistic worldview. Considerable evidence also supports the success of Interpersonal Therapy for Depression, a form of psychodynamic therapy developed by psychiatrist Gerald Klerman and psychologist Myrna Weissman. Behavioral approaches, centered on helping clients become more activated through self-monitoring, scheduling, and self-reward, like the approach developed by University of Oregon psychologist Peter Lewinsohn, have also proven effective. Research indicates that approximately 80 percent of depressed clients are typically helped by each of these therapies, without the side effects and increased risks that accompany medication.

Few studies have directly compared medication and psychotherapy. Such research is expensive and risky for both sides of the controversy. The best known comparative study is the NIMH Treatment of Depression Collaborative Research Program (TSCRP), conducted in the 1980s by psychologist Irene Elkin, now a professor at the University of Chicago. This study compared short-term cognitive therapy, interpersonal therapy, and tricyclic medication. The research found all the treatments had comparable impact and concluded that medication and short-term psychotherapy worked equally well in treating dysthymia and depression.

However, the study used many measures and many ways of analyzing the sample of clients, leaving a wide range of possible interpretations of the results. Some prominent psychopharmacologists, including psychiatrist Donald Klein, argue the study supports the superiority of medication, particularly in those with more severe depression. Proponents of psychotherapy, among them Robert DeRubeis of the University of Pennsylvania, rebut that conclusion. What’s most striking in the TDCRP is that the treatments were comparable in their effectiveness, and even the placebo group improved. Another factor to consider is that the time frame for treatment in these research studies–16 sessions–is more conducive to medication trials than to psychotherapy. The impact of psychotherapy is all the more impressive then, given that clients might still be in early stages of therapy treatment at the study’s conclusion.

Chronic Depression

Another research finding not generally publicized is the fact that a substantial number of depressed clients in these studies (20 to 30 percent) don’t improve, no matter what treatment they receive. And among those who do improve, there are high rates of recurrence. The risk of repeated episodes of depression exceeds 85 percent over a period of 10 to 15 years. Individuals who have one episode of major depressive disorder typically experience four major episodes of approximately 20 weeks’ duration during their lifetime, in addition to other symptoms of depression, such as intense sadness and low energy, during the periods of remission

Although some therapists and researchers think these findings about treatment failure suggest a need for better medications and more effective short-term psychotherapies, this ignores the data on the nature of depression itself. Others argue that high incidents of recurrence may simply be a risk of depression and that no treatment may fully eradicate the problem. In a landmark research study examining depressive symptoms over time, James Coyne and his colleagues Michael Klinkman and Thomas Schwenck found the patterns in depression to be more like chronic disorders, such as asthma, than like acute disorders that are amenable to targeted interventions, such as appendicitis. Coyne and colleagues suggest depression is a chronic condition and that effective intervention should focus on the factors that bring on and intensify depression, much like the lifelong treatment of diabetes. However, the acute-disorder model is the one driving most psychopharmacological intervention for depression today.

Based on the recent research on the treatment of depression, it’s clear that the health care establishment, the general population, and mental health providers need to broaden their view of depression and its treatment. This won’t be easy, because short-term decisions provide immediate gratification. To the depressed client, taking a pill to feel better soon is easier than engaging in therapy. To the health care system, dispensing pills is cheaper, faster, and more profitable than therapy. What’s missing from these approaches is the recognition of the long-term psychological and economical consequences of these short-term solutions. From a financial standpoint, the cost of taking an antidepressant over a lifetime is much greater than the cost of psychotherapy offered as needed to fit the ecology of depression. And when the psychological benefits that result only from therapy, such as increased emotional maturity, improved relationships, and greater life skills, are added to the equation, the value of medication to the depressed patient and to society pales in comparison with the efficacy of psychotherapy.


Beck, Aaron T. et al. Cognitive Therapy of Depression. New York: Guilford, 1979.

Elkin, I., T. Shea, J. T. Watkins, S. D. Imber, S. M. Sotsky, J. F. Collins, D. R. Glass, P. A. Pilkonis, W. R. Leber, J. P. Docherty, S. J. Fiester, and M. B. Parloff. “National Institute of Mental Health Treatment of Depression Collaborative Research Program: General Effectiveness of Treatments.” Archives of General Psychiatry 46 (1989): 971-82.

Healy, David. Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression . New York: New York University Press, 2004.





Jay Lebow

Jay Lebow, PhD, is a former contributing editor to the Psychotherapy Networker and clinical professor at Northwestern University. He’s also senior therapist and research consultant at the Family Institute at Northwestern University.