Polypharmacy in Psychiatry

We are all aware that polypharmacy is a common practice—eminently rational when we engage in it but blatantly irrational in the hands of others. Dr. Ghaemi assembled a cast of mainly Boston-area authors (12 of 14 chapters) to tackle the daunting topic of polypharmacy in psychiatry. The first chapter, providing conceptual and historical background, is a dandy, replete with pithy aphorisms from such luminaries as Oliver Wendell Holmes (“If the whole materia medica, as now used, could be sunk to the bottom of the sea, it would be all the better for mankind—and all the worse for the fishes”) and William Osler (“The true polypharmacy is the skillful combination of remedies”). It becomes readily apparent that even the word “polypharmacy” has numerous meanings with several implications. Combining an antidepressant and an antipsychotic for delusional depression is considered first-line treatment, but combining two or three atypical antipsychotics for treatment-resistant schizophrenia is controversial.

The book goes on to deal with the polypharmacy of specific disorders (bipolar disorder, depression, schizophrenia, anxiety disorders, and posttraumatic stress disorder [PTSD]), polypharmacy across the ages (the old and the young) and in the medically ill, the psychology and psychosocial aspects of polypharmacy, and even herbal and cultural polypharmacy. The chapters run hot and cold: those on bipolar disorder and schizophrenia are particularly well done but that on anxiety disorders is quite the opposite (generalizations without substance).

The chapter on polypharmacy in the medically ill strays from the topic of psychiatric polypharmacy and provides a more general overview of drug-drug interactions. The numerous tables address selected interactions between psychiatric and other medical drugs, but they are incomplete and not derived from original data but, rather, adapted from earlier (1995, 2000) publications. Under such circumstances, it is always difficult to know if fact, fiction, or combinations thereof are being passed on to current readers. Perhaps even more troublesome are unsubstantiated, unreferenced statements (e.g., blood-brain barrier changes with age allow adequate CSF lithium levels to be attained at lower serum levels). The chapter on PTSD has a considerable amount on neurochemistry, perhaps because, as the authors point out, “there have been no clinical studies of polypharmacy in PTSD.”

When dealing with herbal medications, one is always confronting polypharmacy, even when only one product is used, given the complex chemical makeup of the herbals. Mix a few of them together, and the chemical permutations become almost infinite. The combination of herbals with more conventional psychotropics is virtually unstudied with regard to efficacy and greatly underappreciated with regard to risk (St. John’s wort inducing CYP3A4 and P-glycoprotein, ginkgo biloba interfering with platelet function, kava inducing hepatotoxicity, fluvoxamine increasing melatonin levels 17-fold, and so on down the line).

All in all, the editor and authors have done their best in dealing with a rather murky, understudied, ill-defined topic. Many of the chapters conclude with suggestions, guidelines, and recommendations for clinicians. The book itself concludes with recommendations from Ghaemi: Base combination treatment on empirical evidence (unfortunately, there isn’t much), reserve polypharmacy for treatment resistance, focus treatment on syndromes rather than symptoms, eliminate unnecessary polypharmacy, and encourage more and better research in the area.

Overall, this is a book well worth reading (you won’t find anything else like it), but be prepared to accept some unevenness among the chapters.