Pharmacogenetics of Psychotropic Drugs. Edited by Bernard Lerer. Cambridge: Cambridge University Press. 2002. 446 pp. £95 (hb). ISBN 0 521 80617 8

Students and teachers of psychopharmacology have a sense that the most difficult topic to teach and to remember is that of pharmacokinetics. Since many aspects of pharmacokinetics are genetically determined, I approached this book with hope of enlightenment. New discoveries and techniques in molecular genetics should eventually cast light on such questions as why individual patients respond (or do not respond) to drugs, and why some experience more side-effects than others.

The editor's introduction gives a compelling account of the potential importance of pharmacogenetics, but also sounds an ominous note of caution about the complexity of the subject. More than a million single-nucleotide polymorphisms have been discovered that might be relevant. Many of the claimed associations of allelic variations with drug responses have failed attempts at replication. Psychopharmacology is likely to be more difficult than other branches of therapeutics to disentangle through molecular genetics because of the difficulty in identifying drug responders from placebo responders and the lack of biological markers of illness.

Some of the suggested links with drug side-effects are between 5-hydroxytryptamine (serotonin) 5-HT_2C receptor alleles and weight gain with antipsychotic medication, and between dopamine D₂ receptor gene alleles and side-effects such as hyperprolactinaemia. A possible algorithm for clozapine response is also suggested, as well as possible linkages with responsiveness to lithium and valproate in bipolar disorder. Alleles for the serotonin and dopamine transporters are under intense investigation, as are alleles for neurotransmitter receptors and for numerous intracellular second messengers.

One sobering fact is that although it has long been known that individual variations in the cytochrome enzyme CYP2D6 are linked to variations in the metabolism of drugs, including tricyclic antidepressants, and to adverse effects and non-responsiveness to these drugs, this fact has not been thought to merit routine clinical monitoring of 2D6 status.

This book provides a fairly comprehensive account of pharmacogenetic exploration in different areas of psychotropic drug action. Many intelligent people are working on the subject; one hopes that their labours will be rewarded, and that patients will eventually gain from a more scientific selection of treatments for individual conditions.