Jerry Avorn - Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs

Expressive [and] well-documented. Dr. Jerry Avorn brings convincing data and sharp analysis to Powerful Medicines, his timely, challenging appraisal of health policy.

The Boston Globe

This is an authoritative, stunningly comprehensive, and beautifully written work about a subject that ought to interest every American. At last: a smart Harvard doctor who knows drugs, understands FDA and regulatory policy, and has a sense of humor. Unbelievable!

Donald Kennedy, Ph.D., Editor in chief, Science; President Emeritus, Stanford University; Former Commissioner of the FDA

Deepens a reader's understanding of the complex cost-benefit analysis involved with prescription drugs.

New York Post

Powerful Medicines is a must-read for anyone interested in the use, abuse, and economics of prescription drugs. The issues it addresses are central to the ongoing debate about how to reduce the cost and improve the quality of health care in America.

Senator Edward M. Kennedy

Provides insight into one of the central medical debates of our time: how to ensure that prescription drugs are affordable, effective and safe.

American Scientist

Passionate and well-informed. [Avorn] goes beyond articulating the problems and makes many creative suggestions about how we can do better.

Annals of Internal Medicine

In Powerful Medicines, Dr. Avorn brilliantly demonstrates the corrosive effects of commercial influence over medical research, education, and clinical care. This impressive book demonstrates the adverse effects such privatization can have on the health care system and ultimately on patients.

Bernard Lown, M.D., Winner of the Nobel Peace Prize, Professor Emeritus, Harvard School of Public Health

Through a striking set of coincidences, the original hardcover edition of Powerful Medicines appeared at the same time as a string of dramatic drug-related events that instantly brought its subject matter to the center of public awareness and debate. Throughout 2004, the media and medical journals spotlighted revelations and questions about medication risks, benefits, and costs that illustrated most of the issues raised in the book. I have revised the text in light of these developments and will continue to update its website, www.powerfulmedicines.org, to cover new issues, insights, and references as they emerge in this fast-moving field.

In the spring, clinical trials yielded the disturbing news that popular SSRI antidepressants (such as Prozac, Paxil, and Zoloft) could actually increase suicidal thoughts and attempts in adolescents and children. When the drugs were first introduced in the late 1980s, there had been anecdotal reports of such problems, but they were based on the clinical impressions of a few psychiatrists who were caring for severely ill people, or the observations of patients treated in routine practice, in whom a host of confounding factors could have explained away the findings ( people. In these new studies, the subjects randomly allocated to take the drug were more likely to develop suicidal thoughts than those given a dummy pill, a difference that could not be blamed on doctors drug preferences or patients underlying illnesses. Other controlled trials found that suicide risk also rose in young subjects given the SSRIs for problems such as obsessive-compulsive disorder and anxietyconditions not normally associated with high rates of self-destructive behavior.

What explained this influx of new clinical trial data for a drug class that had been on the market for well over a decade? Like many medications, the newer antidepressants were widely used in children and adolescents but had never been well studied in age groups at either end of the life cycle another by-product of the nation's quick-as-possible drug approval process (). The companies were not willing to conduct new pediatric studies without an economic incentive. They received an offer from Congress that promised a very lucrative result: if a company tested one of its drugs in young people, the government would extend its patent by six monthsa windfall for products whose annual sales approximated Si billion or more. It wasn't necessary for the new studies to show that the drug actually worked in young people; conducting the trial alone was enough to win the valuable patent extension. The new findings about increased suicide risk in teenagers taking SSRIs emerged accidentally from a series of clinical trials that wasn't even done to study side effects.

The pediatric antidepressant revelations raised new questions about how drugs could remain on the U.S. market for up to fifteen years and suddenly turn out to have severe and potentially lethal risksa theme that recurred several times in Powerful Medicines first year on the shelves. Those of us who study drug side effects had long been aware that the U.S. drug safety surveillance system was not working well (), and that the FDA was having great difficulty in dealing with hazards that were discovered in products it had approved. The antidepressant crisis and those that followed brought these defects to national prominence.

The problem turned out to have multiple layers, each more worrisome than the last. By law, drug companies must inform the FDA about adverse effects that arise during their clinical trials. But in this case, the agency had failed to aggregate, analyze, and inform the public about the very reports it had in its own files. At first, its efforts were hampered by an astonishing flaw in the data. In many of their antidepressant studies, the companies hadn't used a uniform method to record suicidal thoughts, gestures, or attempts. (The manufacturers may not have anticipated an increase in suicidal symptoms, but you'd expect them to track these problems systematically anyway, to look for a reduction.)

A researcher familiar with the FDA's investigation told me about some of the problems caused by the chaotic systems used to record adverse events. To describe medicated patients who reported intolerable feelings like "wanting to jump out of my skin," some companies used the term "activation" in reporting the results to the FDAa benign-sounding term that could have positive connotations. One young study subject became agitated during a school exam and stabbed himself in the neck with a pencil; the episode was reported to the FDA as an "accidental injury" rather than as an attempt at self-harm.