Antipsychotics (neuroleptics)—Breaking the Brain? In what follows I draw upon these books, but especially the excellent work of Robert Whitaker.
As I have not really discussed the effects of antipsychotic medications in the main body of this book, and because this is such an important topic, let me at the very least say a few brief words before I close. What follows can in no way do justice to the vast body of research pursuing the pros and cons of antipsychotic medication—their benefits, their side effects, and their harmful neurological effects. As I can only provide the most cursory survey here, I have placed a short list of useful books at the end of this appendix for those interested in pursuing this topic further.
While it is true that antipsychotics can help certain people some of the time, inflated claims about their ability to “cure” mental disorders are as unsubstantiated as are claims made for the “curing” powers of antidepressants. Like the claims for antidepressants, those made in favor of antipsychotics must also be weighed against the facts. And any serious reading of the research literature on antipsychotics reveals that the facts are problematic.
Antipsychotics (or neuroleptics, as they are more technically known) are administered for what are considered to be the more severe forms of mental disorder, including schizophrenia, bipolar disorder, delusional disorder, and psychotic depression. These drugs are broadly classed under first-, second-, and third-generation headings—third-generation being the newest wave of antipsychotic medications. All antipsychotics are said to work in a similar way, most purporting to block dopamine (the chemical thought responsible for psychotic experiences) receptors in different brain pathways. It is important to note, however, that just as for the antidepressants, there is no research confirming that antipsychotics fix any known brain abnormality or that they “rebalance” brain chemistry to some optimal level.211 Rather, like any mood-altering substance, they simply alter the brain’s functioning, and in ways that are still mostly opaque to researchers.
Despite the uncertainty as to how antipsychotics work neurologically, studies of their effects over the short term do reveal them to have moderately better results than placebos at reducing certain psychotic symptoms, helping people stabilize after a psychotic episode. That conclusion is now rarely disputed. What is disputed, however, is the precise value of this “stabilized” state, especially for people who may have recovered spontaneously or may have responded well to other therapeutic support. For instance, using antipsychotics over the short term does not just lead to a reduction in the intensity of psychotic symptoms. Their effects are less specific than that: they also diminish other physical and emotional functions integral to all our mental activity. Psychiatrist Peter Breggin has referred to this state of diminished activity as “deactivation.”
To give a sense of what the very common experience of deactivation looks like for people taking antipsychotics, let me quote a patient’s description of deactivation documented in the British Medical Journal. While this patient felt his psychotic symptoms had somewhat abated after antipsychotic use, he also bemoaned other disturbing changes: “My personality has been so stifled that sometimes I think the richness of my pre-injections days—even with brief outbursts of madness—is preferable to the numbed cabbage I have now become … In losing my periods of madness I have had to pay with my soul.”212
It is of course up to the individual patient to decide whether paying with one’s soul is an acceptable price for the mitigation of their symptoms, assuming first that the patient is in an able enough emotional state to make this decision for himself, and second that the patient has been provided by his doctor the information necessary for making an informed decision (which generally does not happen).
So let’s provide some of this information here, by way of assessing the long-term effects of antipsychotic treatment. First, despite many claims that neuroleptics improve the outcome of schizophrenia, the actual evidence for this is scant.213 On the contrary, research conducted over consecutive decades since the 1950s indicates that long-term usage may actually make outcomes worse for the majority of patients. A particularly pertinent suite of studies in the 1970s revealed this paradoxical conclusion.
William Carpenter and Thomas McGlashan at the National Institute for Mental Health explored whether patients fared better off drugs. Their study, published in the American Journal of Psychiatry, showed that 35 percent of the non-medicated group relapsed within a year after discharge, compared with 45 percent of the medicated group. This finding was confirmed in a later study by Jonathan Cole, published in 1977 in the American Journal of Psychiatry,which reviewed all of the long-term studies on schizophrenic outcomes. It concluded that at least 50 percent of all schizophrenia patients could fare well without drugs, and therefore requested a serious reappraisal of current prescription practices.
This was quickly followed by a study in International Pharmacopsychiatry published in 1978 by Maurice Rappaport from the University of California. He followed eighty young males diagnosed with schizophrenia over a period of three years. All had been initially hospitalized, but not all had been administered antipsychotics. He showed that those not treated with antipsychotics, again, had by far the best outcomes: of those treated with antipsychotics a full 73 percent were rehospitalized, compared with only 47 percent who were not given meds. Rappaport thus concluded that “many unmedicated-while-in-hospital patients showed greater long-term improvement, less pathology at follow-up, fewer rehospitalizations, and better overall functioning in the community than patients who were given chlorpromazine while in the hospital.”214
Studies like these gained further legitimacy in the 1980s, when two researchers from the University of Illinois, Martin Harrow and Thomas Jobe, began a long-term study of sixty-four newly diagnosed schizophrenia patients. Every few years the researchers assessed their progress. They asked whether the patients’ symptoms had decreased, whether they were recovering, how they were getting on with their lives, and whether they were still taking antipsychotics. After observing the patients for two years, they noticed that the experience of those still taking antipsychotics began to diverge from those who weren’t. By four and a half years into the study, nearly 40 percent of those who had stopped taking medication were “in recovery” and more than 60 percent were working. Whereas of those still taking medication, only 6 percent were “in recovery” and few were working.
As the years unfolded these dramatic differences remained: at the fifteen-year follow-up assessment, 40 percent of those off drugs were in recovery, versus 5 percent of the medicated group. These results were published in 2007 in The Journal of Nervous and Mental Disease and led the authors to conclude that patients who had remained on medication did far worse than patients who had stopped their medication—this latter group were more successful in their lives and at work.215
Research like this has raised many serious concerns that have often been sidelined by many working within psychiatry. One of particular importance pertains to the precise long-term damage that antipsychotics can cause the brain. This is to say, can the neurological changes antipsychotics induce explain the worse outcomes of medicated patients?
Writer Robert Whitaker has closely investigated this question in his book The Anatomy of an Epidemic. He builds upon the research by two physicians, Guy Chouinard and Barry Jones from McGill University, which provides a neurological explanation for why patients taking antipsychotic medication long-term regularly fare worse than non-medicated groups. They start from the accepted position that antipsychotics work by blocking dopamine receptors in the brain, for which, they theorize, the brain then compensates by increasing the number of dopamine receptors (by up to 30 percent). This then leaves the brain hypersensitive to dopamine once the medication is stopped—a hypersensitivity believed responsible for further psychotic experiences and thus further “relapses.” Whitaker summarizes the problem thus:
Neuroleptics [antipsychotics] put a brake on dopamine transmission, and in response the brain puts down the dopamine accelerator (the extra D2 receptors). If the drug is abruptly withdrawn, the brake on dopamine is suddenly released while the accelerator is still pressed to the floor. The system is now wildly out of balance, and just as a car might careen out of control, so too the dopaminergic pathways in the brain. The dopaminergic neurons in the basal ganglia may fire so rapidly that the patient withdrawing from the drugs suffers weird tics, agitation, and other motor abnormalities; the same out-of-control firing is happening with the dopaminergic pathway to the limbic region, and that may lead to “psychotic relapse or deterioration.”216
What Whitaker argues is that Chouinard and Jones’s work had in theory ascertained why the outcomes of people taking antipsychotics were so comparatively low: medication escalates the likelihood of relapse by increasing dopamine activity once the person has ceased taking medication. As such relapses are then treated with yet more medication, which in turn raises the likelihood of yet another relapse, a vicious spiral of worsening mental health ensues.
It is not just the dopamine system that Whitaker has argued was being damaged by long-term antipsychotic use. Recent studies on macaque monkeys, for instance, have shown that after two years on either haloperidol or olanzapine, there was an observable shrinkage in their brain tissue.217 And similar structural changes in the brain have also been discerned in humans. One study showed that antipsychotics could increase the basal ganglia and, as with monkeys, reduce gray matter in certain brain regions.218
Furthermore, there is no definitive research indicating that these brain changes are indeed in any way positive. Just like the brain changes sustained by long-term drug or alcohol abuse, these changes may well be both deleterious and irreversible. For example, some patients who take antipsychotics long-term develop what is called “tardive dyskinesia” (TD), a gross motor dysfunction characterized by sudden, uncontrollable movements of voluntary muscle groups (e.g., constant movements of the mouth, tongue, jaw, and cheeks; constant tongue protrusion or squirming and twisting). The problem with this condition is that it remains after the drugs are withdrawn, which has been taken as evidence for their causing permanent brain damage. Whitaker argues that antipsychotic usage may not therefore be curing the brain but rather damaging the brain. This leads him to offer the following reflections:
This does not mean that antipsychotics don’t have a place in psychiatry’s toolbox. But it does mean that psychiatry’s use of these drugs needs to be rethought, and fortunately a model of care pioneered by a Finnish group in western Lapland provides us with an example of the benefit that can come from doing so. Twenty years ago, they began using antipsychotics in a selective, cautious manner, and today the long-term outcomes of their first-episode psychotic patients are astonishingly good. At the end of five years, 85% of their patients are either working or back in school, and only 20% are taking antipsychotics.219
Outcomes for serious mental illness are disheartening, despite increasing use of antipsychotics. Many psychiatrists often blame these poor results on the nature of the disorder itself. As one senior psychiatrist put it to me, “Schizophrenia and bipolar disorder are chronic, life-long conditions, so relapses are to be expected.” This psychiatrist did not ask whether such chronicity could be partly or entirely drug-related, an interpretation supported by studies showing that schizophrenia often has much better outcomes in places where antipsychotics are less aggressively and frequently prescribed.
As I have hardly been able to do full justice to the controversial and counter-intuitive points discussed above, fortunately there are many sources that can help you explore these important matters further. Here are some particularly well-researched and trustworthy books:
Breggin, P. R., and Cohen, D. (1999) Your Drug May Be Your Problem: How and Why to Stop Taking Psychiatric Drugs. Massachusetts: Perseus Books.
Healy, D. (2008) Psychiatric Drugs Explained. London: Churchill Livingston.
Moncrieff, J. (2009) The Myth of the Chemical Cure: a critique of psychiatric drug treatment. London: Palgrave Macmillan.
Whitaker, R. (2010) The Anatomy of an Epidemic. New York: Broadway.