Taking Issue: Pharmacological Progress: Seeking Balance

The article by Dr. Jeffrey Lieberman and his colleagues beginning on page 1254 justly celebrates progress made over the past 50 years in the pharmacotherapy of mental illness. And yet, for all these advances, schizophrenia remains a disabling disorder for the majority of patients, and depression is still the fourth most important cause of disability worldwide.

The Lieberman review focuses on the last decade—the introduction of atypical antipsychotics for schizophrenia and selective serotonin reuptake inhibitors (SSRIs) for depression. But, as the authors point out, progress has not been unalloyed. The clinical benefit of atypical antipsychotics is small to modest, with little evidence of widespread dramatic gains in quality of life. The clearest advantage is reduction of extrapyramidal side effects, but adverse effects such as weight gain, diabetes, and hyperlipidemia threaten to take their place. By all accounts, SSRIs are no more effective than tricyclic antidepressants. They are easier and safer to administer and may generate better medication compliance, but they too are associated with many troublesome side effects.

Why be cautious in celebrating our progress? Partly, it's so we won't mislead the public. The lay press is far too ready to declare victory with each step forward, and the public deserves to know how serious these illnesses and their residual effects are, even after treatment. We must also weigh gains against costs. In 1999 U.S. sales of atypical antipsychotic drugs were about $2 billion, 10 percent of the total treatment costs for schizophrenia, and sales of SSRIs topped $5 billion. Savings in health services use with these medications have turned out to be more modest than early, uncontrolled reports suggested. We simply do not know what services we may have given up for this $7 billion.

In addition, we read with concern how, in other areas of medicine, studies sponsored by pharmaceutical companies consistently show more positive results than studies funded by neutral parties. One of the world's largest drug companies spends more than a third of its revenue on marketing. Virtually no professional meeting, journal, or training program is without highly visible drug company support.

While progress has been made, final victory over mental illness is not near. We must retain the highest hopes for our patients and our professions, but we must not be swayed by hype, glitz, or flawed research. It is difficult to make balanced judgments, but it is our responsibility to find and maintain that balance.