Confessions of an Rx Drug Pusher Read online

  Shortly into the study, Dr. Healy noticed an unusual number of side effects not listed for either drug. After breaking the blind, Healy noted:

  2/3 of the group felt significantly worse on one of the two drugs—not simply by virtue of inconvenient side effects, such as difficulties in passing water [urination], but in terms of being depressed or disturbed or in some other way realizing this was not a drug for them. The implication was there was a very high chance, perhaps approaching fifty-fifty, that primary-care physi cians could put their patients on a pill unsuitable for them (Healy, Let Them Eat Prozac, 180-181).

  Two of the patients in the study group became suicidal. Healy recounts this startling development of events with one participant named Joanna:

  …she looked almost shrunken, worried, and nervous. She withdrew from interactions with others. She began impulsively spending money and doing other things she was reluctant to tell. She might begin to cry for no reason. Her moods swung from gloom to doom in a matter of minutes, so much that a number of people described her as almost manic. She had repeated dreams of slitting her throat and bleeding to death in bed beside her mate (Healy, Let Them Eat Prozac, 182-183).

  Joanna’s nightmare would culminate one night as she struggled with her sanity and the overwhelming impulse to throw herself in front of a car or a train. She was on her way out the door to kill herself when the phone rang, disrupting her hypnotic state and saving her life (Healy, Let Them Eat Prozac, 183-184).

  Dr. Healy was alarmed that his trial had picked up an effect like suicide in such a small group of totally normal people. The second participant that became suicidal was haunted by the theme of hanging. This theme is common to many SSRI-related suicides. Both participants were females who had shown “lower than average traces of any kind of depressive thinking” prior to drug treatment. It was later discovered that both were taking Zoloft.

  According to Dr. Healy, the women remained “greatly disturbed several months later; seriously questioning the stability of their own personalities.” This struck him as “ludicrous.” However, he said he had great difficulty persuading them it had been the drug and only the drug. Their view of themselves had been shaken. The experience had “at least a medium-term impact on both women’s self-esteem” (Healy, Let Them Eat Prozac, 185-187).

  By 1999, the FDA had received 2,000 reports of suicide by Prozac users. Of which, about twenty-five percent could be linked to akathisia and agitation reactions. According to the FDA’s own estimates, it only receives reports on approximately one to ten percent of all adverse reactions. That would imply that as many as 50,000 akathisia-related suicides could be attributed to Prozac alone. The total estimate for the entire SSRI class of drugs would, of course, be much higher (DeGrandpre).

  So, if there is so much information available about these life-threatening, adverse reactions and if it has been in the literature since the introduction of the SSRIs, why are so many doctors uninformed about it? In defense of private practicing physicians who often work twelve-to fourteen-hour days, are required to do ever-increasing amounts of administrative work, and see large patient loads, there really is little leisure time for reading. I often saw desktops laden with journals and other unopened mail. If it suits their cause, pharmaceutical reps may point out the latest studies about a drug. If it does not, they may go undiscovered by the doctor for some time.

  Unfortunately, doctors still frequently mistake akathisia symptoms for agitated depression. In which case, the common rationale is to increase the blood levels more rapidly by upping the dose. So, instead of discontinuing the drug, the dosage is increased. The agitation is then magnified, which is a combination for disaster.

  Part of the problem that exists here is embedded in the highly dynamic patient-doctor relationship. The doctor assumes an authoritative position, making it more difficult for the patient to stop taking a drug in the case of adverse reactions. When things go wrong in the case of SSRIs, the situation can escalate very rapidly. The dynamics of this crisis are comparable to a hostage situation. The doctor, who has probably unwittingly trapped the patient, becomes the only way out. The patient may be too frightened to even question—much less go against—what the doctor has advised. When the doctor instructs the patient to continue taking the medication or increase the dose when the patient is going mad, it takes an extremely brave person to do the opposite (Healy, Let Them Eat Prozac, 274).

  Discontinuation Syndrome: A Nice Name for Withdrawal

  Patients using antidepressants are at risk for suicidal ideation and behavior both while using the drug as well as in the months following discontinuation of the drug. The new FDA warnings specifically address the need to monitor this risk while increasing or decreasing the dose. Therefore, it is imperative that patients wanting to discontinue or taper off the dose of their medication do so under a doctor’s supervision. The first couple of months are generally the riskiest; however, depending on the length of time the antidepressant has been used, it can take several months to successfully discontinue treatment (“Dr. Glenmullen’s Q & A: Antidepressant Side Effects”).

  Effexor, the drug Meg took for more than eight months and stopped abruptly, is cited as one of the worst antidepressants in terms of causing severe withdrawal reactions, especially the increased risk for suicide. In fact, in August 2003, Wyeth, the drug’s manufacturer, issued a warning letter to doctors because it was concerned about clinical trial evidence linking Effexor to suicidal thoughts in young patients. In that letter, the company announced to practitioners that it would be adding the following statement to the precautions section of the Effexor label: “In pediatric clinical trials, there were increased reports of hostility and, especially in Major Depressive Disorder, suicide-related adverse events such as suicidal ideation and self-harm.” Subsequently, the FDA asked Wyeth to remove its precaution and replace it with the more generic class labeling. An FDA spokesperson said the agency had asked Wyeth to change the precaution because the statement represented a discrepancy with the FDA-approved warning required on all antidepressants in March 2004. That warning states that “it has not been concluded that these drugs cause worsening depression or suicidality.”

  Now, almost a year later, a new FDA analysis appears to validate Wyeth’s original concern. Of the six drugs that were compared in the analysis, the results of the three Wyeth clinical trials for Effexor showed that young patients on the drug were nearly five times as likely to have suicidal thoughts or behavior as those on placebo. When just the data of the two trials on depression were analyzed, suicidal tendencies were 8.8 times as likely in the young patients taking Effexor (Wilde Mathews).

  Some statistics from studies of patients affected by withdrawal when they stopped taking their antidepressants cold turkey include seventy-eight percent of Effexor patients, sixty-six percent of Paxil patients, sixty percent of Zoloft patients, and fourteen percent of Prozac patients. Depending on how quickly the drug washes out of the body, withdrawal reactions can range from mild to severe (“Dr. Glenmullen’s Q& A: Antidepressant Side Effects”). Meg had complained of debilitating depression, social phobia, and electrical shock waves that ran through her brain, which her mother thought was a psychotic delusion.

  Symptoms of SSRI and SNRI antidepressant withdrawal can include, but are not limited to, suicide, impulsivity, aggression, anxiety, depression, crying spells, insomnia, dizziness, vertigo, nausea, vomiting, headaches, tremors, and electric “zap” sensations in the brain. Symptoms can be so severe that patients cannot get out of bed or work. In these cases, the dosage should be tapered off more slowly. The patient should also allow additional time before completely discontinuing the drug (Dr. Glenmullen’s Q & A: Antidepressant Side Effects”).

  Typical Concerns Raised by the Atypical Antidepressants

  One atypical antidepressant that has become fairly popular for treating depression as well as smoking cessation is Wellbutrin (buproprion). In fact, Well- butrin’s twin, Zyban, was introduced specifically to captu
re the market for the latter indication and extend the patent on buproprion. Wellbutrin blocks theneurotransmitter dopamine as well as serotonin. The risk of seizure with Wellbutrin has been found to be four times greater than with other antidepressants. The danger increases to tenfold at twice the normal daily dose of 300 milligrams. People who have had head injury, brain and spinal tumors, or previous seizures are at the greatest risk. Seizures may also be precipitated by an abrupt increase in the dosage.

  Some patients experience central nervous system effects that produce a very unpleasant hypersensitivity. Agitation, anxiety, and insomnia are often reported at the beginning of Wellbutrin therapy. The simultaneous use of a tricyclic antidepressant can further increase the risk of seizure.

  Serzone, another atypical antidepressant that was launched in 1994 and is manufactured by Bristol-Myers Squibb (BMS), was voluntarily withdrawn from the Canadian market because of reports of liver injury late in 2003. Earlier in 2003, BMS had also voluntarily pulled the drug from markets in Europe, Spain, and Turkey. Finally, citing commercial reasons, BMS stopped shipment of Serzone in the United States on June 14, 2004. Currently, there is a class action suit for Serzone injuries in the United States. Litigants in the case cite severe side effects including liver impairment, liver failure, and death resulting from Serzone use. (Fortunately, I was never required to sell Serzone when I worked for BMS because I was in the cardiovascular division.)

  The Depression Epidemic

  The World Health Organization has projected that depression will be the second-leading cause of disability in the world by 2020, following heart disease. Depression impacts millions of Americans annually, specifically an estimated ten percent of the population at any given time. Women experience depression twice as often as men do. Many circumstances can predispose an individual to depression, including loss of a parent, emotional neglect, or trauma experienced in childhood or stressful life experiences in general, for example, death, divorce, job loss, or other financial stress. A genetic link is also suggested because depression frequently runs in families.

  Depression and anxiety can manifest simultaneously in some people, and these disorders share many common symptoms (for example, irritability, fatigue, sleep disturbance, ruminating thoughts, appetite disruption, cognitive difficulties, and guilt feelings). Although some depression can be attributed to medical conditions such as thyroid disease or cancer, the majority of mild to moderate depression is primarily thought to have a psychological origin. Depression is defined by some psychologists as “anger turned inward.” These mild to moderate depressions are the main diagnoses for which antidepressant drugs are most frequently prescribed and the conditions for which the SSRIs have proven to be least effective.

  However, the DSMIV lists several types of depression such as major clinical depression. This depression runs a definite course of time (that is, it has a beginning, middle, and an end to each episode), whereas, dysthymia is a chronic type of depression that generally lasts more than two years. Manic-depressive (bipolar) disorder, on the other hand, is a little more difficult to define. Mild to extreme euphoria and grandiosity can alternate with moderate to radically low depressive states. Their course and severity are both completely unpredictable. There are three major types of bipolar disorders: bipolar I, bipolar II, and cyclothymia. (Refer to the glossary for definitions.)

  The Biogenic Amine Deficiency Theory of Depression

  Nearly all of the antidepressants currently being marketed or in various stages of development in pharmaceutical pipelines are based on the biogenic amine deficiency theory. This theory assumes depression is caused by some deficiency in either the neurotransmitter serotonin or norepinephrine activity in the brain. Translated loosely, this means there is a chemical imbalance in the brain.

  I love the current Zoloft commercial with the little, bouncing, happy face explaining depression may be attributed to a chemical imbalance in the brain and Zoloft corrects that imbalance. That simply is not so! The biochemical imbalance speculation is just that, speculation presented by industry as a scientific truth.

  Most of our biochemical research on emotional states addresses only three or four of the more than 100 neurotransmitters now estimated to be present in the brain. The newest antidepressant drugs still only act on two or three neurotransmitters, even though they are touted as having more specific receptor targets than the older drugs (Valenstein 109-110).

  The fact is there is absolutely no convincing evidence that most depressed people have low levels of biogenic amine activity. Reputable researchers working in the psychopharmacology field recognize the inadequacy of this theory and are trying to come up with alternative theories. Moreover, there is no reason to assume any biochemical deficiency is the cause of any mental disorder. Low serotonin levels are associated with a variety of psychological disorders and cannot be used to predict or identify any specific problem. Because we know stress can affect brain chemistry, it is entirely plausible that emotions are responsible for the low serotonin and norepinephrine levels, rather than the other way around (WORLD Magazine). The irony of all this is that the only known biochemical imbalance found in the brains of nearly all mental patients has been caused by the patient’s psychiatric treatments (Breggin, Talking Back to Prozac, 39).

  A less popular but more accurate theory is the biopsychosocial model. This model suggests that three areas of life interact to create psychological problems, including depression: 1) Our biology as determined by our genes, brain chemistry, medical conditions and drugs; 2) the individual collection of feelings, desires, thoughts, and behaviors that comprise our own unique psychology; and 3) the events and people in our social experience that shape our life (Drummond 16).

  Minimal Efficacy—Mega Risk

  Not only does a tremendous amount of evidence suggest these drugs are harmful to large numbers of people, there is also inadequate scientific evidence to support they are any more effective than the older, less expensive antidepressants.

  A vigilant research group in the United States utilized the Freedom of Information Act (FOIA) to obtain all of the studies (both published and unpublished) the FDA had used in their determination to approve seven of the newer antidepressants between 1987 and 1997. They included studies done on Prozac, Zoloft, Paxil, Effexor, Serzone, Remeron, and Wellbutrin SR. After reviewing all of the results from the individual manufacturers’ pivotal studies, the researchers concluded the newer antidepressants were “no more effective than the older tricyclic antidepressants.” In fact, the newer drugs were not found to be even ten percent more effective than placebos:

  Symptoms of depression improved by 30.9 percent in the people who took the placebos; by 40.7 percent in the people who took the newer antidepressants; and by 41.7 percent in people who took the older antidepressants.

  For people with mild to moderate depression, “nine out of ten studies showed that the new drugs were no more effective than placebos” (Abramson 116).

  However, because of the great marketing hype surrounding the SSRIs, one of them, Prozac, now has the distinguished honor of having more adverse effects submitted to the FDA than any other drug in history. More than 40,000 adverse reactions were reported in its first ten years on the market. No other drug even comes close (Breggin and Cohen 67).

  There have been multiple reports of fraudulent clinical testing, forgery, bribery, racketeering, and endangering patients in the testing of psychiatric drugs. Two big scandals rocked clinical research in 1993, which was the same year Warner Brothers released its mega hit, The Fugitive, starring Harrison Ford. One scandal involved the National Institutes of Health (NIH) and Eli Lilly’s clinical trials of an anti-hepatitis drug named Fialuridine. Test subjects suddenly started to drop dead of liver failure (just like the story in The Fugitive). The study was halted.

  Immediately following that scandal, a renowned child psychiatrist and teen suicide expert, Dr. Barry Garfinkel, was found guilty of two counts of mail fraud and three counts of filing false sta
tements. He would later serve six months in a halfway house and six months under house arrest and pay $210,000 in fines and restitution. Why? In 1989, while conducting a study of the antidepressant Anaf- ranil (clomipramine) at the University of Minnesota, Dr. Garfinkel had instructed a study coordinator to “invent data on patient visits that had never taken place—eye examinations and physicals that were supposed to be done to make sure the drug wasn’t harming the test subjects.” It had taken the case four years to come to court (Fried 77-78).

  In 1997, another case hit the news involving the chairman of the department of psychiatry at the Medical College of Georgia and one of its professors. Richard Borison and Bruce Diamond were convicted on 172 counts and were each fined $125,000. However, the crime for which they would serve time was not to be fraudulent clinical testing. It would be for stealing from the college. Borison and Diamond were ordered by the court to pay $4.26 million and $1.1 million respectively to the college. Borison was sentenced to fifteen years in prison. Diamond was sentenced to five years. These two psychopharmacologists were connected with the clinical testing of psychiatric drugs with twenty different companies for more than a decade. The companies included Eli Lilly, Janssen, Zeneca, Sandoz, Glaxo, Abbott, Pfizer, and Hoechst Marion Roussel. Borison and Diamond were reported to have secured 160 contracts from drug companies and made over $10 million on drug research during that time (Whitaker 269).

  In 1998, the Minnesota Board of Medical Practice suspended the license of another prominent psychiatric researcher, Dr. Frank Abuzzahab, the past president of the Minnesota Psychiatric Society and the chairman of its ethics committee, who was found “guilty of recklessly entering patients into psychiatric drug studies, falsifying their records, and fabricating positive drug responses.” Dr. Abuzzahab was one of the lead investigators in a clinical trial Eli Lilly submitted to the FDA for its approval of Prozac (Glenmullen, Prozac Backlash, 209).