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The Dangers of Anti-Depressants:

A Review of Prozac Backlash by Joseph Glenmullen, M.D.

by Lynn Mollick & Milton Spett

In September, 1989, Joseph Wesbecker, a disgruntled employee, walked into the Standard Gravure Printing Company with an AK-47 and opened fire. He killed eight employees, wounded twelve, and then killed himself. He had been on Prozac for a month.

The survivors and the relatives of the dead filed suit against Eli Lilly, the manufacturer of Prozac. Oddly, in the middle of the trial, the plaintiffs suddenly declined to present some of their most compelling evidence. The jury found for Lilly, and awarded no damages to the plaintiffs. And there the matter rested. Or did it?

Four months later the trial judge ordered an investigation. The state attorney general's office found that during the trial a secret deal had been made between Lilly and the plaintiffs. Lilly would pay a "tremendous" amount of money to the plaintiffs, but the plaintiffs would deny this arrangement. The deal was structured so that it was in the plaintiffs' interest to lose the case. The judge directed that the outcome of the trial be changed from "jury verdict in favor of the defendant" to "settled out of court." But it was too late. The original verdict had been highly publicized, and both physicians and the general public believed that Prozac had been exonerated.

In Prozac Backlash (Simon and Schuster, 2000), Joseph Glenmullen argues that serotonin boosters are indeed dangerous and should only be given to patients who are at least moderately depressed. He believes that the problems are not limited to Prozac, or even to the SSRIs; he argues that any drug which boosts serotonin levels causes the following side effects:

Agitation, suicidality, and homicidality. Inexplicably, suicidal patients were excluded from the initial studies which purported to demonstrate the safety and effectiveness of the drug. Glenmullen also asserts that during the initial research on Prozac, many patients were given sedatives to control their agitation, and Lilly hid this from the FDA. He backs up his allegations against Lilly with quotes from the public record, but there is no controlled research on the prevalence of these side effects. Prior to the Wesbecker verdict, 150 lawsuits had been filed against Prozac. Lilly settled many of these cases with the stipulation that the settlement remain secret. Lilly then claimed they had never lost a Prozac lawsuit.

Brain damage and movement disorders. Glenmullen asserts that long-term exposure to high levels of serotonin kills brain cells, causes memory loss and dementia, increases the probability of developing Alzheimer's disease, and, like the neuroleptics, causes movement disorders including tics, twitches, Parkinsonism, and eventually tardive dyskinesia. Glenmullen points out that neuroleptics such as Thorazine were on the market for about ten years before tardive dyskinesia was recognized. Unfortunately, both neuroleptics and serotonin boosters suppress the symptoms of movement disorders, so these symptoms may not appear until the patient goes off the drug. Once again, no controlled research exists on the prevalence of these side effects.

Sexual dysfunctions. Glenmullen cites uncontrolled research that 60% of patients taking serotonin boosters experience a wide variety of sexual dysfunctions. (But he does not report the prevalence of sexual dysfunctions on placebos.) So how can Lilly and the other drug manufacturers claim that these side effects only occur in 2 - 5% of patients? The initial studies never asked patients if they experienced any sexual dysfunctions on these drugs. The 2 - 5% of patients who reported these effects are those who volunteered the information.

Tolerance. Glenmullen asserts that the anti-depressant effect of these drugs "wears off" for 30 - 40% of patients. Other than anecdotes, the only evidence Glenmullen presents for this assertion is an article by Fava, et al. in the February, 1995 issue of the Journal of Clinical Psychiatry. Fava et al. report that 26 patients initially responded to 20 mg. Prozac, then relapsed. Glenmullen erroneously assumes that these 26 depressed patients relapsed because their Prozac "wore off." But neither Glenmullen nor Fava, et al. report any data on the placebo control group, so there are at least two other explanations of why the 26 patients relapsed:

1. The original benefit may not have been due to the Prozac, but at least partially due to a placebo effect. It might have been the placebo effect that wore off, not the biochemical effect of the Prozac.

2. Additional stresses, losses, or setbacks may have occurred in these patients' lives. It is possible that the 20 mg. of Prozac was enough to overcome their initial depression, but subsequent negative events increased the intensity of their depression to the point where a higher dose of Prozac was necessary.

Most, if not all drugs are either physically addictive or not physically addictive. It would be very strange if Prozac and the other serotonin boosters were physically addictive to one third of the people who took them, but not to the other two thirds.

Alternatives to Drugs.

Glenmullen advocates non-drug treatment for mild to moderate depressions. Unfortunately, he makes a number of errors in arguing for non-drug treatments of depression. One example is his statement that research has found psychotherapy plus drugs no better than psychotherapy alone. Some research does support this position, but other research finds therapy plus drugs superior to therapy alone (while the patient is taking the drugs). A second example is his blithe statement that depression is caused by "stifled anger and sadness." Even psychoanalysts don't believe that anymore. On the positive side, he reports that exercise is an effective treatment for depression. Controlled research does support the anti-depressant effects of strenuous aerobic exercise and weight training.

Glenmullen correctly asserts that there is no evidence to support the "chemical imbalance" theory that depression is caused by a serotonin deficiency. We would add that there is much evidence to the contrary: 1. Some drugs which do not increase serotonin are effective anti-depressants; 2. Drugs that increase serotonin do so immediately, yet their anti-depressant effect builds up over weeks or months; and 3. Many depressed individuals do not respond to drugs that are known to increase serotonin levels.

Conclusions

1. Glenmullen mentions but does not emphasize the most important conclusion: anti-depressants cannot cure anyone of depression. Research has found that after a course of anti-depressants, patients are just as likely to become depressed as they were before taking the drug. Only psychological treatment can make changes that will endure after the treatment is completed.

2. Agitation and sexual dysfunctions occur more frequently than is generally recognized.

3. Controlled research is needed to determine if the long term use of serotonin boosters causes permanent brain damage and movement disorders.

4. Eli Lilly has systematically hidden some evidence and distorted other evidence on the negative effects of Prozac.

5. There is no evidence of physical habituation to these drugs.

6. The most dangerous side effect of anti-depressants is their tendency to divert patients from psychotherapy, the only cure for depression.

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