In this excellent volume, the author invites a renewed dialogue on a subject of medical and social importance: the dogma that mental events, mental disorders, mood, behavior, and personality are explained by neurochemistry. Although widely and uncritically accepted by researchers, practitioners, and the public, and despite contradictory evidence, most of the theory and the resulting dogma, the author asserts, are unconvincing and probably wrong.

Eliot Valenstein, PhD, emeritus professor of psychology and neuroscience at the University of Michigan, is also the author of Great and Desperate Cures: The Rise and Decline of Psychosurgery and Other Radical Treatments of Mental Illness (Basic Books, 1986). His new book begins with a historical review of the discovery of each of the psychotropic drugs, their biochemical evaluation, and their enthusiastic clinical application. These compounds seemed, at first, to provide not only a simple solution to pressing medical and political needs but also an immediate and profitable therapeutic modality. Their study produced an impressive body of knowledge about neuropharmacology, but the leap from molecular biology across a chasm of speculation to an understanding of mental functioning bypassed inconsistent data. Belief in the neurochemical hypotheses was genuine but clouded by substantial career and economic self-interest on the part of psychiatrists, researchers, insurers, and pharmaceutical companies.

Valenstein writes, "In pursuing the biochemical approach to mental disorders an enormous amount has been learned, but it is questionable how much has been learned about mental illness. We do not really know if a biochemical imbalance is the cause of any mental disorder, and we do not know how even the hypothesized biochemical imbalances could produce the emotional, cognitive, and behavioral symptoms that characterize any mental disorder." After describing research on dopamine receptor types, patient subgroups, and "atypical antipsychotics" that don't bind to dopamine receptors, he concludes, "At present the evidence fails to implicate any dopamine receptor as either the cause of schizophrenia or the critical site where an antipsychotic must act in order to be effective" and says, "There is no agreement that schizophrenics have a dopamine abnormality other than that caused by neuroleptic drug treatment." He similarly considers depression, concluding, "There is no convincing evidence that most depressed people have low levels of biogenic amine activity," and he develops a case that adherence to such reductionist hypotheses has narrowed the scope of meaningful research.

The dopamine theory of schizophrenia and the serotonin-norepinephrine theory of depression are far from conclusively proven, and the pharmacodynamics of the tricyclic compounds, benzodiazepines, Prozac, and lithium remain obscure. Fifty years after chlorpromazine was introduced from the dye-chemical industry (more than 100 versions of the drug have since been marketed) it has not been established that chemical imbalance is a major cause of any mental disorder. The author emphasizes that it is easy to forget that the correlation of some biological marker in the brain with a mental disorder does not prove causation. The origin of these disorders is unknown (the Diagnostic and Statistical Manual of Mental Disorders avoids controversy by not considering etiology), and there is no clear understanding of how drugs may alleviate them. Research homes in on receptor subtypes, ostensibly producing ever-more specific drugs, yet selective serotonin reuptake inhibitors are prescribed for a wider variety of conditions. While recognizing that psychotropic drugs are helpful, Valenstein writes, "It is unrealistic to believe that the cause of any behavior or mental disorder will ever be explained by concentrating only on the activity of a few neurotransmitters."

Do the drugs work? Pharmacodynamic theory aside, the empirical uses of psychoactive drugs have given ambivalent results. For example, the author cites reports that about half of schizophrenic patients given "antipsychotic" drugs show no alleviation of symptoms after four weeks, and there is a 25% to 40% risk of disabling tardive dyskinesia. The prestigious National Institute of Mental Health study of phenothiazines in 1961 reported improvement in 95% of patients but also noted 50% improvement in the controls. All of the antipsychotics fail to help a significant number of schizophrenic patients. Antidepressant drugs produce their maximum elevation of serotonin and norepinephrine within hours, while mood changes follow weeks later, during which time changes not involving biogenic amines confuse both the chemical and clinical picture.

The pressing need for answers and cures in psychiatry has more than a few times displaced careful evaluation of evidence. (My auto repairman posts this advice for hurried and exigent patrons: "If you want it bad you get it bad. The badder you want it the badder you get it.") The heavily promoted careers of some theorists have produced fame, Nobel prizes, and such destructive innovations as leucotomy, metrazol shock, shaking helmets, and the like. It might be argued that none of this compares with the massive promotions of pharmaceutical corporations and their enormous profits from pushing medicaments. It has never been a secret that promotional literature influences the prescribing habits of physicians and that market pressures such as managed care have restructured the practice of psychiatry. Chemical theories of mental disorders have been particularly seductive because they suggest simple explanations and solutions. Other biological and psychosocial factors are trivialized or forgotten.

The author recognizes the help done by psychotherapeutic drugs and "certainly would not discourage anyone from trying them." He simply hopes "that this book can help to start a dialogue about whether any chemical imbalance has really been shown to be the cause of mental disorders and whether we really know how drugs sometimes help to alleviate these disorders." Neurochemistry should not be pushed at the expense of "those psychological factors, interpersonal relationships, and environmental contingencies that often play a major role in the development and exacerbation of mental disorders."