When the so-called “atypical antipsychotic” drugs became available for the treatment of schizophrenia, physicians began prescribing them like crazy because they did not cause debilitating extrapyramidal side effects like their predecessors. As we described previously, relentless and occasionally unscrupulous marketing campaigns by drug makers also drove utilization of the newer agents.
Unfortunately, the atypical agents turned out to have a nasty side-effect profile of their own. They promote obesity and diabetes, increase the risk of cardiovascular events, precipitate tics and increase mortality in elderly patients with dementia, among other things.
The weight gain/diabetes problem is particularly severe in children—a demographic in which these agents are rarely indicated. In one study for example, the drugs caused youths between the ages of 4 and 19 to gain between 10 and 19 pounds on average in just 11 weeks.
Recently, G. Caleb Alexander and colleagues at the University of Chicago reviewed historical trends in the use of atypical antipsychotics and published their findings in Pharmacoepidemiology and Drug Safety. It’s a largely confirmatory study, and the picture they paint is not pretty.
Caleb’s team queried nationally representative data from IMS Health’s National Disease and Therapeutic Index to characterize prescribing behavior for antipsychotic drugs in outpatient settings.
They found that overall, antipsychotic use (including atypical antipsychotic and first-generation agents) nearly tripled from 6.2 million treatment visits in 1995 to 16.7 million visits in 2008. For children, the number of treatment visits involving an antipsychotic increased 8-fold, from 0.3 million in 1995 to 2.4 million in 2005. And as expected, the scientists documented a tectonic shift in prescribing patterns: in 1995, 84% of the prescriptions for antipsychotic agents were for first-generation agents, whereas by 2008, 93% of them were for atypical agents.
As physicians prescribed fewer first-generation agents, they tended to use them more specifically for schizophrenia, the indication for which they were initially approved by the FDA (30% in 1995 vs 48% 2008). On the other hand, the prescribing tsunami for atypical agents was accompanied by a three-fold increase in prescriptions for bipolar disease (10 to 34%) and a marked cut in their use for schizophrenia (56 to 23%). the now infrequently used typical agents.
On the cost side, the total cost of typical antipsychotics—which are now available in generic form–was $0.6 billion in the US in 2008, whereas that for atypical drugs was $9.9 billion.
Overall, antipsychotic use for non-FDA approved indications rose from 4.4 million visits in 1995 to 9.0 million in 2008. The scientists estimated the cost associated with off-label use of these drugs to be $6.0 billion in 2008, alone.
These trends occurred even though scientists have yet to prove that the atypical agents offer a clear advantage over their older congeners, when both efficacy and side-effects are considered, Caleb’s group said.
“Recent trials failing to demonstrate clinically significant differences in the effectiveness of these two classes in schizophrenia raise the question of whether typical antipsychotics should be reconsidered as a first line therapy, given that the superiority of atypical agents has yet to be established,” they wrote.
“Our results…suggest a substantial exposure to therapies for clinical indications that have not received regulatory scrutiny and where the evidence base is uncertain.”