Bill’s world was a dangerous one. He believed that people could control his mind using devices similar to a TV remote. He was not sure who was his friend and who was his foe. I found him curled up in a hospital bed, afraid to step out of his room. As a young man with schizophrenia, he had previously taken a common antipsychotic medication called haloperidol, which was no longer effective. We could have prescribed newer medications, but we wanted to avoid the weight gain that is often associated with these medications. An older, senior doctor on our team suggested we try the medication molindone.
“Molindone? Is that a new medication?” I asked.
“No, quite old,” he said.
Within a week of starting molindone, Bill went from isolated and paranoid to pleasant and cooperative, and he went home soon afterwards.
I marveled at this miraculous transformation. Like many young doctors, I tend to prescribe medications with which I am familiar. For patients with psychosis, I was most comfortable with the so-called second-generation antipsychotics. In medical school we learned about the dreaded side effects of first-generation antipsychotics such as molindone. Most concerning was tardive dyskinesia, a potentially irreversible reaction characterized by involuntary lip-smacking and puckering movements. In clinical practice I rarely see these older medications used, other than for sedation when a patient is agitated, so my default was to prescribe second-generation antipsychotics.
In addition to fewer side effects, psychiatrists were hopeful that second-generation antipsychotics would be more effective for psychotic symptoms than the older ones were. At one point I was taught that these newer medications were more effective for specific psychotic symptoms, such as lack of motivation and decreased sociality. When I began residency I was excited to hear about even newer medications called third-generation antipsychotics. My assumption was that newer was better.
But in fact, newer is not necessarily better, as Bill’s story illustrates. Studies have found little to no difference in efficacy between first- and second-generation antipsychotics in treating the symptoms of schizophrenia. It is true that tardive dyskinesia is less likely to occur with second-generation medications, but the difference is not as much as was previously suggested. Second-generation drugs can also cause weight gain, which is difficult to reverse and increases risk for cardiovascular disease and diabetes. In addition, newer medications are more expensive. As one doctor told me, “With the cost of a 30-day supply of a newer antipsychotic, you could fill a whole room with an old antipsychotic.” These concerns are not unique to psychiatry. There are similar debates in other fields of medicine about the under-prescription of effective older medications for diabetes and hypertension. Personally, I support pharmaceutical innovation, but new medications should add benefit, not just profit.
The trend toward using newer medications often develops during residency training. Pharmaceutical firms market their products to young doctors in all specialties. Whether with free meals, medical tools or travel scholarships, pharmaceutical companies find ways to influence doctors’ prescribing practices. Because most physicians continue recommending the medications they learned in residency, these companies strategically expose residents to newer medications that are still under patent and thus far more profitable for the manufacturers.
Bucking this this trend is not always easy. A month after Bill left the hospital, we learned that the manufacturer of molindone had stopped producing the medication. As mentioned before, the side effects of some older medications can be scary. Side effects loom large because our minds are more sensitive to these adverse events than to benefits. In addition, patients may seek newer medications from their physicians for a variety of reasons—including pharmaceutical ads on TV that tell them to “ask your doctor.”
Although we cannot necessarily force a pharmaceutical company to continue manufacturing a medication, we can urge physicians—particularly younger ones—to be open to prescribing older medications. Working with senior doctors has made me a lot more comfortable with prescribing them. Working overseas, where older medications are the only ones available, has also broadened my knowledge and appreciation of them. Also, if possible, we can track our prescribing practices to increase our awareness of possible bias in favor of new drugs. Electronic health records make this more feasible. My institution recently presented us with our individual and group prescribing patterns, which has made me more conscious of which medications I tend to favor.
As doctors, if we do not learn to prescribe older medications, we miss out on effective alternatives, and our patients and their insurance companies spend more than they need to.
Therefore, if the situation is appropriate, don’t be afraid to try something old.