Benefits unclear for 1st versus 2nd generation antipsychotics

Currently, 75 percent of U.S. adults who are prescribed antipsychotic medications take these second-generation drugs, which were developed largely due to concerns about side effects with their predecessors, experts noted.

First-generation antipsychotics are also called typical antipsychotics. This class of drugs includes chlorpromazine (Thorazine), haloperidol (Haldol), perphenazine (Etrafon, Trilafon) and fluphenazine (Prolixin). Second-generation drugs, known as atypical, antipsychotics include risperidone (Risperdal), aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine Fumarate (Seroquel) and ziprasidone (Geodon). There is a major cost difference between the two classes of drugs: For example, a month's supply of olanzapine can cost $546, while a month's supply of haloperidol ranges from $18 to $27, according to Consumer Reports.

But are these newer drugs really more effective or less risky? Researchers at the U.S. Agency for Healthcare Research and Quality reviewed 114 studies involving 22 comparisons between the two classes of drugs to answer these questions. Their review appears in the Aug. 14 issue of the Annals of Internal Medicine.

The review found that the second-generation antipsychotics are not much better than the earlier incarnations at treating positive symptoms associated with schizophrenia. "Positive symptoms" is the umbrella term for symptoms of psychosis such as delusions and hallucinations. By contrast, negative symptoms reflect a decrease or loss of normal function including expression or speech.

Two second-generation drugs, olanzapine and risperidone, did seem to be more effective at treating negative symptoms when compared with the older haloperidol, the investigators said.

There was insufficient evidence to compare risk profiles between the two classes of drugs, the researchers said. Long-term risks of antipsychotics may include diabetes, major metabolic syndrome and a neurological disorder that causes involuntary, repetitive movements (tardive dyskinesia). Metabolic syndrome refers to a cluster of risk factors that increase risk for diabetes and heart disease.

"The typical antipsychotics that have been around for a long time are just as good at treating schizophrenia symptoms as the newer ones," said Dr. Dolores Malaspina, director of the Institute for Social and Psychiatric Initiatives at NYU Langone Medical Center in New York City. In the future, doctors may adopt a personalized medicine approach to better pair treatments with individual symptoms and disease manifestations, she suggested.

Until then, "my first choice would be to try one of the medications that have a longer track record, and then move on if need be," Malaspina said, adding that the main differences between the first- and second-generation medications are side effects.

Commenting on the review, Dr. David Straker, an adjunct assistant clinical professor of psychiatry at Columbia University Medical Center in New York City, said: "The newer drugs seem to be more effective with negative symptoms and, as such, they help with concentration and focus, but they cost a lot more and may have more metabolic side effects. It comes down to weighing the risks versus the benefit in each individual patient."

And, according to Dr. Roberto Estrada, a psychiatrist at Lenox Hill Hospital in New York City, the review raises an important issue that psychiatrists face in treating people with schizophrenia.

"The limitations of first-generation antipsychotics were well known prior to the introduction of second-generation antipsychotics, but now the metabolic issues and expense associated with using second-generation antipsychotics has created further challenges in the treatment of schizophrenia," Estrada said.

The new review "is unable to draw clear conclusions about differences between the two in the treatment of schizophrenia," Estrada explained. "However, in clinical practice using the second-generation drugs, we see comparable symptom management with little acute adverse effects, but different and equally long-term adverse effects."

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Journal reference: Annals of Internal Medicine

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