The story of antidepressants is a bit subtler, and yet it leads to the same conclusion that these drugs increase chronic illness over time. Even their short-term efficacy, in terms of a benefit greater than placebo, is of a questionable sort.
In the early 1960s, there were two types of antidepressants, monoamine oxidase inhibitors (MOAIs) and tricyclics. However, MOAIs soon fell out of the favor because of dangerous side effects and a 1965 finding by the Medical Research Council in the United Kingdom that they were no more effective than placebo (Medical Research Council, 1965). Four years later, the NIMH concluded that there was also reason to doubt the merits of tricyclics. After reviewing the medical literature, NIMH investigators determined that in “well-designed studies, the differences between the effectiveness of antidepressant drugs and placebo are not impressive.” About 61% of the drug-treated patients improved, versus 46% of the placebo patients, producing a net drug benefit of only 15% (Smith, 1969).
This finding led some investigators to wonder whether the placebo response was the mechanism that was helping people feel better. What the drugs did, several speculated, was amplify the placebo response, and they did so because they produced physical side effects, which helped convince patients that they were getting a “magic pill” for depression. To test this hypothesis, investigators conducted at least eight studies in which they compared a tricyclic to an “active” placebo, rather than an inert one. (An active placebo is a chemical that produces an unpleasant side effect of some kind, like dry mouth.) In seven of the eight, there was no difference in outcomes, leading investigators at New York Medical College to conclude “there is practical value in viewing (psychotropics) as mere amplifiers or inhibitors of the placebo effects” (Thompson, 1982).
With such confusion over the efficacy of tricyclics hanging in the air, the NIMH launched an ambitious long-term study of depression treatments in the early 1980s. Two hundred thirty-nine patients were randomized into four treatment groupscognitive behavior therapy, interpersonal therapy, the tricyclic imipramine, and placebo. The results were startling. At the end of 16 weeks, “there were no significant differences among treatments, including placebo plus clinical management, for the less severely depressed and functionally impaired patients.” Only the severely depressed patients fared better on a tricyclic than on placebo. However, at the end of 18 months, even this minimal benefit disappeared. Stay-well rates were best for the cognitive behavior group (30%) and poorest for the imipramine group (19%) (Elkin, 1990). Moreover, two pharmacology researchers at the State University of New York, Seymour Fisher and Roger Greenberg, concluded that if study dropouts were included in the analysis, then the “results look even worse.” Patients treated with an antidepressant were the most likely group to seek treatment following termination of the initial treatment period, they had the highest incidence of relapse, and they “exhibited the fewest weeks of reduced or minimal symptoms during the follow-up period” (Greenberg and Fisher, 1997, pp. 147).
Once again, the results led to an unnerving conclusion. Antidepressants were making people chronically ill, just like the antipsychotics were. Other studies deepened this suspicion. In 1985, a U.K. group reported that in a two-year study comparing drug therapy to cognitive therapy, relapse “was significantly higher in the pharmacotherapy group”(Blackburn, 1986). In 1994, Italian researcher Giovanni Fava reviewed the outcomes literature and concluded that “long-term use of antidepressants may increase the (patient’s) biochemical vulnerability to depression,” and thus “worsen the course of affective disorders” (Fava, 1994). Fava revisited the issue in 2003. An analysis of 27 studies, he wrote, showed that “whether one treats a depressed patient for 3 months or 3 years, it does not matter when one stops the drugs. A statistical trend suggested that the longer the drug treatment, the higher the likelihood of relapse” (Fava, 2003, pp. 124).
Manufacturing Mental Illness
It is well known that all of the major classes of psychiatric drugsantipsychotics, antidepressants, benzodiazepines, and stimulants for ADHDcan trigger new and more severe psychiatric symptoms in a significant percentage of patients. This is the second factor causing a rapid rise in the number of disabled mentally ill in the United States. Moreover, it is easy to see this epidemic-creating factor at work with Prozac and the other SSRIs.
Although serotonin has been publicly touted as the brain’s mood molecule, in truth it is a very common chemical in the body, found in the walls of the blood vessels, the gut, blood platelets, and the brain. The serotonin system is also one that could be said to be primitive in kind. Serotonergic neurons are found in the nervous systems of all vertebrates and most invertebrates, and in humans their cell bodies are localized along the midline of the brain stem. From their, their axons spread up into the brain and down into the spinal cord. The first purpose of this neuronal network is thought to be control of respiratory, cardiac, and repetitive motor activity, as opposed to higher cognitive functions.
As one would expect, perturbing this systemand to a degree that could be considered pathologic, as Jacobs saidcauses a wide range of problems. In Prozac’s first two years on the market, the FDA’s Medwatch program received more adverse-event reports about this new “wonder drug” than it had received for the leading tricyclic in the previous 20 years. Prozac quickly took up the top position as America’s most complained about drug, and by 1997, 39,000 adverse-event reports about it had been sent to Medwatch. These reports are thought to represent only one percent of the actual number of such events, suggesting that nearly four million people in the U.S. had suffered such problems, which included mania, psychotic depression, nervousness, anxiety, agitation, hostility, hallucinations, memory loss, tremors, impotence, convulsions, insomnia, and nausea. The other SSRIs brought to market caused a similar range of problems, and by 1994, four SSRIs were among the top 20 most-complained-about drugs on the FDA’s Medwatch list (Moore, 1997).
In terms of helping fuel a rapid rise in the number of disabled mentally ill, the propensity of Prozac and other SSRIs to trigger mania or psychosis is undoubtedly the biggest problem with these drugs. In clinical trials, slightly more than one percent of the P
rozac patients developed mania, which was three times higher than the rate for patients given a tricyclic (Breggin, 2003). Other studies have found much higher rates of SSRI-induced mania. In 1996, Howland reported that 6% of 184 depressed patients treated with an SSRI suffered manic episodes that were “generally quite severe.” A year later, Ebert reported that 8.5% of patients had a severe psychological reaction to Luvox (fluvoxamine) (Breggin, 2003). Robert Bourguignon, after surveying doctors in Belgium, estimated that Prozac induced psychotic episodes in 5% to 7% of patients (Bourguignon, 1997). All of this led the American Psychiatric Association to warn that manic or hypomanic episodes are “estimated to occur in 5% to 20% of patients treated with antidepressants” (Breggin, 2003)
As Italy’s Giovanni Favi has noted, “Antidepressant-induced mania is not simply a temporary and reversible phenomenon, but a complex biochemical mechanism of illness deterioration” (Fava, 2003, pp. 126). The best available evidence suggests that this is now happening to well more than 500,000 Americans a year. In 2001, Preda and other Yale researchers reported that 8.1 percent of all admissions to a psychiatric hospital they studied were due to SSRI-induced mania or psychosis (Preda, MacLean et al., 2001). The federal government reported that there were 10.741 million “patient care episodes” in 2000; if 8% percent were SSRI-induced manic or psychotic episodes, that would mean that 860,000 people suffered this type of adverse reaction in 2000.
Thus, the SSRI path to a disabling mental illness can be easily seen. A depressed patient treated with an antidepressant suffers a manic or psychotic episode, at which time his or her diagnosis is changed to bipolar disorder. At that point, the person is prescribed an antipsychotic to go along with the antidepressant, and once on a drug cocktail, the person is well along on the road to permanent disability. Since Prozac was introduced in 1987, the number of disabled mentally ill in the U.S. has risen by 2.4 million people, and given the risk of mania and psychosis with the SSRIs, that increase was to be expected.
A century ago, fewer than two people per 1,000 were considered to be “disabled” by mental illness and in need of hospitalization. By 1955, that number had jumped to 3.38 people per 1,000, and during the past 50 years, a period when psychiatric drugs have been the cornerstone of care, the disability rate has climbed steadily, and has now reached around 20 people per 1,000. (Table 2). As with any epidemic, one would suspect that an outside agent of some typea virus, a bacterial infection, or an environmental toxinwas causing this rise in illness. That is indeed the case here. There is an outside agent fueling this epidemic of mental illness, only it is to be found in the medicine cabinet. Psychiatric drugs perturb normal neurotransmitter function, and while that perturbation may curb symptoms over a short term, over the long run it increases the likelihood that a person will become chronically ill, or ill with new and more severe symptoms. A review of the scientific literature shows quite clearly that it is our drug-based paradigm of care that is fueling this modern-day plague.
(for references see the link to the article)