Although it is often possible to help depressed people through caring, enthusiastic psychotherapy (see chapters 6 and 16), biopsychiatrists typically reject psychological approaches and instead make extraordinary claims for the efficacy of drugs.
Barely Escaping the Antidepressants
The young man sitting with me in my office had a broad grin on his face as he reminded himself of how much better he now felt. A few months earlier he'd been hospitalized for severe depression with feelings of utter worthlessness and thoughts of suicide; but when antidepressants had been urged on him, he had managed to say no. Probably the doctors would have forced the drugs on him, except that his parents, advocates of more natural cures, had supported his rejection of the drugs. He'd been discharged AMA (against medical advice) and was now virtually free of depression after a relatively short time.
"I was lucky," he said, "because my friends told me the effects they saw on other students who got them. They said, 'Don't take them. They space you out, and they're hard to get off of. They're addictive.' "
The hospital doctor had said the opposite: "Antidepressants don't affect the mental processes at all, and aren't addictive."
The antidepressants also are being pushed by nonpsychiatric physicians. One of my clients, a young man, was going through a period of severe distress when he went to his family doctor for a cold. A shy person, he didn't mention he was seeing a psychiatrist. The family doctor, noticing his emotional distress, gave him a mimeographed handout stating that antidepressants have no serious side effects and that they correct a biochemical imbalance. The handout also said that depression is no longer believed to be psychological in origin. The doctor then prescribed Elavil; but the first dose so "zonked" the young man that he had thrown the bottle away by the time he came to see me again. Eventually he got over his distress without drugs.
A friend of mine whom I hadn't seen in years, a forty-year-old professional woman, stopped by one day recently to say hello. In the course of conversation, she asked me about Prozac. She was a recovering alcoholic and her psychiatrist had prescribed Prozac as a "substitute" for drinking. After taking the drug for about a year, her doctor wanted her to stay on it indefinitely. She then tried to come off it on her own 7 and a few days after stopping, she became overwhelmed with exhaustion. it was so debilitating that she started the drug again and was immediately relieved.
Although she's a bright individual, it never dawned on my friend that she had undergone a drug withdrawal reaction. She mistakenly concluded that she must need the drug to fight off depression. How these withdrawal reactions come about is not hard to understand (see ahead), but the danger is not told to patients or even mentioned in current textbooks.
Antidepressants: Widespread and Growing Usage
Antidepressants are very much in vogue, but they have been around for a long time. Elavil (amitriptyline) and Parnate (tranylcypromine), for example, have been in use for three decades. In 1984, thirty-four million prescriptions were written for antidepressants, placing them a distant second behind the minor tranquilizers; but the Prozac craze is narrowing the lead. More than two-thirds of antidepressant prescriptions are for women.
The great majority of antidepressant prescriptions are written by nonpsychiatric physicians. Psychiatrists, however, set the tone for the widespread use of these agents. Right now psychiatrists are advocating their use for a variety of disorders, from depression and anxiety to eating problems, premenstrual tension, phobias, and obsessions and compulsions. They have become a jack-of-all-trades drug. This in itself should warn us not to trust the claims being made.
Tricyclic Antidepressants: Some General Principles
The antidepressants represent a varied group of agents, and their effects on the brain and mind are little understood. We can, however, make some generalizations about one group of antidepressants, the tricyclics, which are the best studied among them. With generic names in parentheses, they include Tofranil or janimine (imipramine), Elavil or Endep (amitriptyline), Adapin or Sinequan (doxepin), Surmontil (trimipramine), Norpramin or Pertofrane (desipramine), Aventyl or Pamelor (nortriptyline), and Vivactil (protriptyline). Another, Anafranil (clomipramine), is advocated for obsessive-compulsive problems and will be discussed in chapter 11.
Closely related to the tricyclics is Asendin (amoxapine), which turns into a neuroleptic in the body and presents all of the hazards of that class of drugs, including tardive dyskinesia and tardive dementia (see chapter 4). Triavil and Etrafon combine a tricyclic and a neuroleptic, entailing the various dangers of both drugs, including tardive dyskinesia and tardive dementia from the neuroleptics, compounded by the unpredictable complexity of their interactions.
Limbitrol is a combination of the tricyclic Elavil and the minor tranquilizer Librium, a sedative or anti anxiety drug that is highly addictive (see chapter 11).(2)
Several generalizations can be made about tricyclic antidepressants. First, evidence for their usefulness is very slim indeed. Research studies generate extremely variable results and indicate that they are hardly much better than placebo.
Second, they have a dulling effect on the mind. In effective doses they can produce lethargy and disinterest, that feeling of being "zonked." They also tend to produce generalized mental dysfunction and, as we shall see, sometimes relieve depression by rendering the brain and mind unable to generate higher psychospiritual responses. But often they are given in smaller doses, which may have a lesser impact or a placebo effect.
As a third general principle, many of the tricyclics have a sedative effect that aids sleep, for a time, much as does any sedative.
Fourth, they can cause severe withdrawal symptoms and can therefore become very difficult to stop taking. The tricyclics are extremely lethal in overdose and have numerous side effects.
Antidepressant Side Effects
The tricyclic antidepressants originally were tested as neuroleptics because chemically they are very similar to Thorazine (chlorpromazine). They are, in many ways, neuroleptics in disguise. Their side effects stem mainly from suppression of the cholinergic nerves of the autonomic nervous system and the brain, and when the individual tries to stop taking them, the cholinergic system rebounds with great force, making it hard to get off them.
Nearly all of the antidepressants commonly produce the following side effects: various autonomic nervous system signs, such as blurred vision, dry mouth, and suppressed function of gut, bladder, and sexual organs, as well as low blood pressure on standing, weight gain, sleep disturbances, seizures, and impaired cardiac function. They can bring about anxiety, produce or exacerbate psychotic symptoms, and cause delirium.
They frequently produce sedation, lethargy, and a blunting of emotional responsiveness, although this often goes unacknowledged by psychiatrists.
The antidepressants can cause death when only a few doses are taken at once. In combination with other depressants of the central nervous system - such as alcohol, neuroleptics, lithium, sleeping pills, painkillers, and minor tranquilizers - the antidepressants become increasingly dangerous. They suppress central nervous system function, thereby impairing respiration, and they cause cardiac arrhythmias, leading to heart failure. Caution must be taken in regard to their use by the elderly.
A number of years ago antidepressants replaced sedatives as the prescription medications most frequently involved in successful suicide attempts. Obviously, there is a built-in danger to giving such lethal drugs to depressed patients who have a high and unpredictable suicidal potential.
Withdrawal from Tricyclic Antidepressants
In an article with an extensive bibliography entitled "Antidepressant Withdrawal Symptoms" in the 1987 International Clinical Psychopharmacology, DiSalva and his colleagues estimate that 55 percent of adults will undergo withdrawal symptoms when stopping these medications. In addition to the flu-like symptoms, withdrawal symptoms from antidepressants often make the person seem irrational and even crazy, with high levels of anxiety and disturbing dreams that awaken the individual in a state of panic or dread. Often there is jitteriness or irritability. There are reports of patients becoming high or manic on withdrawal. Patients also can become depressed, perhaps in response to the fatigue and lethargy associated with withdrawal.
In the May 1981 American Journal of Psychiatry, William Law III and his colleagues report on their review of the charts of twenty-two children who had been removed from high doses of a tricyclic antidepressant, Tofranil (imipramine). Each of the children suffered from two or more of the following categories of withdrawal symptoms: (1) gastrointestinal complaints, including epigastric pain, abdominal pain, nausea, vomiting; (2) drowsiness and fatigue; (3) decreased appetite; (4) tearfulness; (5) apathy and withdrawal; (6) headaches; and (7) agitation. Tapering didn't seem to help.
The mental health professionals working with these children often incorrectly attributed their withdrawal symptoms to "mental illness," to specific stresses, such as "changing visits from family, visiting home, dealing with 'loaded issues,' " allergies, or viral illnesses. Unfortunately, antidepressants were reinstituted for some of these children, who were mistakenly diagnosed as relapsing during the withdrawal period.
Anyone being started on an antidepressant should be informed in advance that withdrawal symptoms are very common and that they can be both confusing and distressing. For the same reasons discussed in regard to the neuroleptics, the antidepressants should be considered addictive.
As in withdrawing from the neuroleptics (chapter 4), patients trying to stop taking antidepressants may need emotional support and patience. The patient and the doctor, and members of the patient's inner circle of friends and family, may have to put up with troublesome symptoms and behavior during the withdrawal period.
Permanent Mental and Neurological Damage?
There is an ominous aspect to these withdrawal symptoms, most of which are produced by rebound hyper-reactivity of the suppressed cholinergic nerves. Cholinergic nerves of the autonomic nervous system activate the so-called vegetative or digestive processes of the body,(3) and when they rebound, flu-like symptoms develop. However, the cholinergic nerves in the brain play a major role in mental processes, and when they rebound, they cause mental disturbances, such as anxiety, depression, or mania.
We have seen how a similar rebound hyperactivity of a different neurotransmitter produces permanent mental and neurological disorders after long-term exposure to the neuroleptics (chapter 4). The questions must be asked, Are we producing permanent symptoms of mental dysfunction, including anxiety, depression, or mania, by giving patients antidepressants? How often do we induce a vicious circle in which patients attempt to come off the medications and then experience withdrawal symptoms that are mistaken for a recurrence of depression or other mental dysfunction - leading to further treatment with the offending medication?
Innumerable animal studies have documented that chronic exposure to antidepressants produces hyperreactivity of the neurotransmitter systems of the brain. It also can produce chronic subsensitivity or reduced reactivity. These findings sound a serious - but almost wholly ignored - warning about the danger of permanent negative effects on the human mind as a result of antidepressant treatment. If the lessons of neurophysiology hold true, the brain frequently does not fully revert to normal functioning after prolonged exposure to toxic medications.
Many clinicians continue to believe that only the neuroleptics, and not the antidepressants, cause tardive dyskinesia, with its permanent, untreatable tics and spasms of the voluntary muscles. However, some studies suggest that the tricyclic antidepressants also produce tardive dyskinesia, but much less frequently. These findings are not surprising in light of the similarity between the chemical structures of the tricyclics and the phenothiazine neuroleptics. One report found a relatively high incidence of 6 percent.
Since the tricyclic antidepressants closely resemble neuroleptics, and since all antidepressants powerfully affect the brain and mind, I am very concerned about the largely unexplored danger of permanent cognitive dysfunction and brain atrophy similar to that found during prolonged neuroleptic treatment. Patients diagnosed with "affective disorders" (depression, manic-depression, and schizoaffective disorder) are showing up with atrophy on brain scan, suggesting that antidepressants may play a role in causing brain damage. However, the studies done thus far do not rule out electroshock, neuroleptics, and other drugs as possible culprits. Many patients with diagnoses of affective disorders have received a broad spectrum of brain-disabling treatments. Of course, the biopsychiatrists who perform the studies assume that the brain pathology is due to mental illness.
Depression Caused by the Antidepressants?
There are reports that administration of the antidepressants can cause depression, especially early in the treatment. Namir Damluji and James Ferguson discuss "Paradoxical Worsening of Depressive Symptomatology Caused by Antidepressants" in the October 1988 Journal of Clinical Psychopharmacology. They describe four cases of major depression that were exacerbated to the point of suicidal behavior. Improvement followed immediately on stopping the medication.
Any drug that disrupts mental function can make people feel more helpless and despairing. Drugs that cause mental confusion, sluggishness, and physical fatigue are especially prone to precipitate or worsen depression. Harvey Greenberg and H. Robert Blank report a series of cases who felt dazed, fatigued, and confused in the June 15, 1973, issue of the New York State Journal of Medicine; but little attention is paid to these problems in the literature or clinical practice.
Meanwhile, some psychiatrists persist in telling patients and the public that these drugs have no "psychoactive" or mental effects at all.(4) When uninformed patients then feel numbed or "zonked" from the medication, they are very likely to think their condition is worsening, thereby encouraging suicidal feelings. Dr. Caligari's Psychiatric Drugs puts it bluntly:
Antidepressants and Suicide
In helping seriously depressed people, reducing the suicide rate is one of the first concerns. Do antidepressants have a beneficial impact on suicide? Despite the relative ease of conducting objective studies of suicide rates - the criterion of death is an indisputable one - there is no published evidence that the antidepressants are helpful in reducing suicide. In the PDR, the manufacturers of the various antidepressants warn practitioners not to rely on the medications to prevent suicide.
One study, "Mortality in Depressed Patients Treated with Electroconvulsive Therapy and Antidepressants," by David Avery and George Winokur in the September 1976 Archives of General Psychiatry, shows an increased suicide rate among patients receiving antidepressant therapy.
Since antidepressants are now the drugs most commonly implicated in successful suicides, it would seem far more appropriate to designate them as "suicide drugs" rather than antisuicide drugs. Yet psychiatrists persist in giving them to depressed patients who are suicidal.
Do They Work?
The antidepressants have many drawbacks, but do they work? Is there convincing evidence for efficacy to balance against the costs and risks of taking these toxic agents?
It is difficult to evaluate the effectiveness of drugs for depression. Spontaneous improvement of depression (that is, with no psychiatric treatment whatsoever) takes place in at least one-quarter of patients within the first month or so of becoming depressed and in one-half or more over a few months. Even people with severe depression have a high rate of recovery 'without psychiatric treatment. Since it takes most antidepressants a month or more to have their presumed beneficial effect, it easily overlaps with spontaneous recovery. In addition, placebo has a potent effect on depressed patients; most experts indicate that 40 percent or more will improve during the first month or two of taking a "sugar pill."
The slightly higher rates of improvement for antidepressants over inert placebos, such as a sugar pill, may itself be a special kind of placebo effect. I call this the enhanced placebo effect. Consciously or not, when taking an inert placebo the patient realizes that his mind and body are not being impinged upon strongly by the medication. In sharp contrast, the antidepressants have many obvious physical side effects, so the patient receiving them is likely to believe that he or she is taking a powerful medicine. The concept of the enhanced placebo reflects the wisdom that led hucksters to make patent medicines taste awful.
Ironically, enthusiasm for the use of antidepressants has been skyrocketing among practicing psychiatrists at the same time that research has cast more and more doubt on their efficacy. In The Limits of Biological Treatments for Psychological Distress (1989), Seymour Fisher and Roger Greenberg conclude that years of research have failed to provide justification for their use. Here are some highlights from their thoroughly documented review:
Psychotherapy Versus Antidepressants at NIMH
NIMH coordinated a large-scale, highly publicized study at several medical centers, comparing cognitive behavior therapy, interpersonal psychotherapy, antidepressants, and placebo over a sixteen-week period. A recent publication, by senior author Irene Elkin in the November 1989 Archives of General Psychiatry, confirms how difficult it is to find any differences under these conditions between brief psychotherapy, drug therapy, and placebo. When the treatments - including placebo - were compared for the entire sample of 250 patients, no difference was found among them.
For more severely impaired patients there was a relatively greater benefit from interpersonal psychotherapy and the antidepressant. In these cases the drug performed slightly better than psychotherapy, according to the investigators; but the data show no meaningful difference. To find the drugs slightly superior required fancy statistical footwork based on a limited number of criteria. This did not prevent biopsychiatrists from making much ado about nothing in the press.
Most experienced psychotherapists would probably do far better than those working within the strictures of the NIMH comparative study. First, sixteen weeks for psychotherapy is very short and the time limit is very arbitrary. Depressed patients want to know that their therapist will be much more available than that. Second, the therapy methods used were stilted and routinized to conform to distinctions between cognitive behavioral and relationship models. Most therapists would never limit themselves to one orthodoxy, and they rarely list either one of the NIMH techniques among their repertoire. For example, hardly anyone in the membership directory of the American Academy of Psychotherapists includes either one among the many and varied approaches. Considering such handicaps, psychotherapy performed surprisingly well.
Monoamine Oxidase Inhibitors
The monoamine oxidase inhibitors are among the most dangerous agents used in medicine. They include Marplan (isocarboxazid), Nardil (phenelzine), Parnate (tranylcypromine), and Eutonyl (pargyline). Another, Eldepryl (selegiline), is recommended only for the treatment of parkinsonism and is considered very useful.
Careful adherence to a special diet is required to avoid very severe and life-threatening cardiovascular reactions. The list of foods to avoid is too wide for discussion here (see textbooks and the PDR), but includes all those containing tyramine, such as beer and wine, aged cheese, chocolate, fermented foods, yeast, yogurt, chocolate, raisins, and many others. MAOIs also interact dangerously with many other medications, increasing the risk of cardiovascular crises, including hypertension and stroke, as well as brain dysfunction and mental distress. Headaches are frequent and can be a warning sign. They often cause restlessness and insomnia and can produce confusion, disorientation, and a euphoric or manic reaction. They are very lethal in overdose, a special hazard in potentially suicidal depressed patients. Withdrawal from an MAOI can produce depression or its opposite, euphoria.
For many years these drugs were viewed as too dangerous for routine use, and some experts rejected them entirely. With the resurgence of radical biopsychiatry they are becoming more commonly prescribed.
Another group, seldom used as antidepressants today, includes the highly addictive stimulants, such as Ritalin and Dexedrine. They pump up the sympathetic nervous system. We will discuss them in regard to the treatment of children with behavior problems. Until their addictive qualities were fully appreciated they were liberally prescribed for weight reduction. Most physicians no longer recommend them as a treatment for obesity or depression.
Newer Types of Antidepressants
Newer antidepressants of mixed types are sometimes called the atypical antidepressants. They include Asendin (amoxapine; whose extreme hazards are described earlier in this chapter), Ludiomil (maprotiline), Desyrel (trazodone), and Wellbutrin (buproplon). Most textbooks of psychiatry, as well as Fisher and Greenberg's The Limits of Biological Treatments for Psychological Distress, confirm that these drugs have not proven themselves more effective than the old standbys, the tricyclics, whose efficacy itself is highly in doubt. We are dealing with a more questionable subclass of a very questionable class of drugs.
Ludiomil carries most of the risks of the tricyclics, including sedation, hypotension on standing, skin rashes, and disturbed mental reactions. A special danger is the increased rate of seizures.
Desyrel also carries many of the risks of tricyclics, including heart problems, a special threat among the elderly. All tricyclics can produce sexual dysfunction, but Desyrel carries a particular risk for priapism - uncontrolled, permanent penile erection - sometimes requiring surgical intervention.
Wellbutrin is a very new drug and in a class of its own, which means that anyone taking it in the next several years will be contributing to research on its side effects. It has a fourfold greater tendency to cause seizures than have the tricyclics. Many patients became agitated and unable to sleep while taking it, so sedatives are often required. It also has many other side effects similar to those of the tricyclics.
1. If it turns out that Prozac received especially favorable treatment from the FDA, or that it had an extraordinary boost from certain media leaders, political influence may be at work. Eli Lilly, based in Indianapolis, was a large contributor to the senatorial campaigns of Dan Quayle. In addition, according to the October 2, 1988, Washington Post, "Quayle's uncle, William C. Murphy, opened Lilly's government relations office in Washington in 1964 and his 1980 campaign manager, Mark D. Miles, went to work for the company in 1982 as director of communications" (p. A25). Quayle was instrumental in passing legislation described by a Lilly spokesman as the most important drug measure before Congress at that time.
2. In general it is best to avoid combining psychoactive drugs, since their effects when mixed become even more unpredictable and are poorly understood.
3. The cholinergic (or parasympathetic) nerves of the autonomic nervous system cause the smooth muscles of the stomach, intestine, and bladder to contract. They tend to increase digestive processes, promote salivation, slow the heart, lower the blood pressure, and narrow the pupils. In general, they act in opposition to the energizing adrenergic (sympathetic) nerves.
4. This is so remarkable that I may need to be more specific. When debating psychiatrists about the impact of antidepressants, a few have literally argued that the drugs have no effect on the mind. How they reconcile this with an alleged antidepressant impact is difficult to understand.
5. Even placebo is not wholly harmless, since many people taking them believe that they are having side effects and actually develop symptoms. Furthermore, an active or enhanced placebo will of necessity have some side effects.
Peter Breggin's Home Site - Peter R. Breggin, M.D. founded The International Center for the Study of Psychiatry and Psychology (ICSPP) as a nonprofit research and educational network concerned with the impact of mental health theory and practices upon individual well-being, personal freedom, and family and community values. For 25 years ICSPP has been informing the professions, media and the public about the potential dangers of drugs, electroshock, psychosurgery, and the biological theories of psychiatry.
Brain-Disabling Treatments in Psychiatry : Drugs, Electroshock, and the Role of the FDA Today! by Peter R. Breggin, M.D.
The Manufacture of Madness : A Comparative Study of the Inquisition and the Mental Health Movements by Thomas S. Szasz, M.D., Professor
Law, Liberty, and Psychiatry : An Inquiry into the Social Uses of Mental Health Practices by Thomas S. Szasz, M.D., Professor
The Limits of Biological Treatments for Psychological Distress by Seymour Fisher and Roger P. Greenberg
Psychiatric Drugs: Hazards to the Brain by Peter R. Breggin, M.D.
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