Why do doctors prescribe the antidepressants they prescribe? Or more
specifically, asked Mark Zimmerman, M.D., and colleagues, "If bupropion
is as effective as other antidepressants, and it does not cause the side
effects that are the most frequent causes of long-term noncompliance, why
isn't it the most frequently prescribed antidepressant medication?"
Missing evidence, marketing pressures, and hard-to-break prescribing habits
mark the gaps in translating the findings from drug efficacy studies to
real-world clinical practice, they wrote in the May Journal of Clinical
The team focused on bupropion because a comparison of side-effect rates of
nine new-generation medicines suggested that bupropion had the most favorable
side-effect profile, said Zimmerman, an associate professor of psychiatry and
human behavior at Brown University School of Medicine, Rhode Island Hospital,
in Providence. The drug is considered less likely to cause weight gain or
sexual dysfunction—side effects that loom large in the minds of patients
and may reduce their adherence.
The researchers surveyed 10 psychiatrists affiliated with the outpatient
practice in the Rhode Island Hospital Department of Psychiatry, asking them to
fill out a 43-item questionnaire for each patient prescribed a first or new
antidepressant. They got back 1,137 completed questionnaires between August
2001 and February 2002 recording factors influencing their choice of a newly
prescribed antidepressant. Over half the prescriptions (669, or 58.8 percent)
initiated antidepressant treatment, 26.6 percent reflected switches from one
drug to another, and 9 percent covered augmentation of prior
No funding from pharmaceutical companies was sought or received to support
the study or the resulting article, said the authors.
The most commonly prescribed antidepressant was citalopram (23.3 percent),
with bupropion in second place (17.4 percent). Sertraline and venlaflaxine
each accounted for 12.3 percent of prescriptions (see table on page 20).
Bupropion's bridesmaid status was confirmed when it was prescribed
significantly more often than other drugs to augment existing regimens. Since
the reasons for choosing a medication for augmentation might be different from
those for initial monotherapy, the researchers excluded augmentation
prescriptions. That left 965 patients for analysis.
"Overall, the most common influences on antidepressant choice were
the avoidance of side effects, the presence of comorbid psychiatric disorders,
and the presence of specific clinical symptoms," wrote Zimmerman and
colleagues. Prior positive or failed treatment response was the next factor
most often cited.
Avoiding specific side effects and targeting specific symptoms were the
most frequent reasons given for using bupropion, while the presence of a
comorbid condition was cited less often. Comorbid
attention-deficit/hyperactivity disorder, eating or sleeping too much, and
fatigue were given more often as reasons in favor of prescribing bupropion.
Doctors less often cited generalized anxiety disorder, panic disorder,
obsessive-compulsive disorder, social phobia, poor sleep or appetite,
irritability, or high anxiety levels as justifying bupropion.
"The DSM-IV's approach toward identifying phenomenologically
homogenous subtypes of major depressive disorder, based on the presence of
atypical or melancholic features, rarely influenced the choice of
medication," they said.
"They've detected a real phenomenon," said psychiatrist Greg
Simon, M.D., M.P.H., an investigator at Group Health Cooperative in Seattle,
in an interview. "But where does that perception come from? Evidence is
only a small part of it."
Doctors develop brand loyalty, some of it justified by their experience
with a drug, said Simon. Some doctors always use one drug, while others always
"A lot of money is spent to develop those allegiances, but physicians
may also just recall the words of a venerated med school professor when they
prescribe," he said.
The key to when bupropion is prescribed may lie in anxiety, at both the
symptom and disorder level, suggested Zimmerman. Bupropion has been shown
effective for the treatment of depression alone or in combination with
anxiety, but there are few published data on the efficacy of using it for
anxiety in the absence of depression. However, nervousness, anxiety, or
agitation are no more common among patients using bupropion than SSRIs and
other newer drugs.
The FDA has approved many of those new drugs—but not
bupropion—for treating anxiety disorders.
"Clinicians may infer greater efficacy because of the literature
demonstrating efficacy of these medications in anxiety disorders and the
approval of these medications for the treatment of these disorders,"
wrote the researchers, even though no studies demonstrate superiority of other
new-generation antidepressants for depressed anxious patients. There might
also be a difference between clinical-trial findings and the reality of
clinical practice, if efficacy trials excluded highly anxious patients.
Pharmaceutical companies' marketing practices might also influence drug
selection, they said.
Future studies, open to patients with varied comorbidities and closer
examination of physicians' prescribing patterns, may offer insight into the
best ways to use these drugs.
An abstract of "Why Isn't Bupropion the Most Frequently
Prescribed Antidepressant?" is posted online at<www.psychiatrist.com/abstracts/200505/050509.htm>▪