Better Than Prozac: Creating the New Generation of Psychiatric Drugs

  • Samuel Barondes
Oxford University Press: 2003. 240 pp. $26, £16.99

The past 50 years have seen a transformation in the practice of psychiatry. The emphasis has moved from psychotherapy with a limited repertoire of drugs that were used only in the most severely ill patients, to the widespread use of drugs that act on the central nervous system (CNS), with psychotherapy being an expensive luxury for a minority of patients. Samuel Barondes is well placed to review the psychopharmacology revolution and to offer predictions for the future, as he has worked through this period as a practising psychiatrist and as an active researcher who has made important contributions to the field.

An early section of the book explains how the existing drugs used to treat psychiatric illnesses — antidepressants, antipsychotic drugs, tranquillizers and amphetamines — were discovered, with colourful accounts of the individuals involved. Along the way there are explanations in simple language of how the drugs affect various neurotransmitter mechanisms in the brain, and an introduction to the concepts of controlled clinical trials, the placebo effect and the mystery of why it takes many weeks of treatment before the maximum therapeutic benefits of many CNS drugs are seen.

Barondes uses individual case histories to illustrate many of these points, a device that helps to involve the reader with real people who have benefited from drug treatments, and to illustrate some of the shortcomings of the medicines that are presently available. There is a graphic description, for example, of the power of the selective serotonin re-uptake inhibitor (SSRI) Prozac to transform a patient from a state of sadness and agitation to one of calm and tranquility, albeit with a diminished intellectual passion and reduced sex drive.

A second section provides an overview of the prospect that a better Prozac will emerge from current research in this field. Like many others, the author believes that this will come from a better understanding of the nature of the biological disturbances that underlie psychiatric illnesses. There is reason for optimism: several valuable clues have already emerged from research on the genetic risk factors underlying these illnesses, and potential candidate genes have been described in the past year for schizophrenia and for manic-depressive illness. It is likely that most psychiatric illnesses are partly inherited through genetic risk factors but also depend on environmental factors. Nevertheless, identifying the genetic risk factors may provide important clues about new treatment strategies.

A case in point is Alzheimer's disease, in which mutations in several different genes are known to increase the risk of developing the disease, and in a small number of patients, mutations in the amyloid precursor protein (APP) cause the illness directly. This new genetic information has greatly strengthened the hypothesis that the abnormal formation and deposition of amyloid-β, a protein derived from APP, is a key event underlying the pathology of Alzheimer's. This in turn has triggered a large research effort directed towards the discovery of drugs that can reduce the formation or deposition of amyloid-β. Whether these will prove effective in the clinic remains to be seen, but for the first time a rational approach to the treatment of this devastating illness has become possible.

Understanding the underlying disease process and developing medicines that interrupt this process remain the ultimate goals in devising a better Prozac. In the meantime, better drugs can be developed to treat the symptoms of psychiatric illnesses, for example by the introduction of antagonists of the neuropeptide substance P to create new antidepressants that lack the adverse effects of SSRIs on sexual function. Alternatively, antagonists of the neuropeptide corticotropin-releasing factor could be used to make potential 'anti-stress' agents. New uses are also being found for existing drugs — for example, SSRIs can be used in the treatment of bulimia nervosa, obsessive–compulsive disorder, panic disorder and post-traumatic stress syndrome. The latest addition is the treatment of 'social phobia' using the SSRI paroxetine (ad line: “How shy is too shy?”).

Overall, this is a well-written and comprehensive account of a field that has developed rapidly in the past few decades. It was written for intelligent non-scientific readers, but experts will also find much entertaining material about the scientists who were involved in some of the major discoveries, and in the case histories. An extensive bibliography allows access to the basic scientific literature. The development of psychopharmacology has been well reviewed by David Healy in his two books published by Harvard University Press — The Antidepressant Era (1998) and The Creation of Psychopharmacology (2002) — but Barondes' new book provides a shorter and more personal account, and is an excellent read.