Researchers from Italy and the United Kingdom also found that three antipsychotic drugs — first-generation haloperidol (Haldol) along with later formulations of risperidone (Risperdal) and olanzapine (Zyprexa) — outperformed 11 other drugs. The scientists analyzed results from 68 randomized, controlled trials with more than 16,000 participants over a 30-year period.
Mania typically alternates with depression in those with bipolar disorder, which tends to run in families and begin between the ages of 15 and 25, according to the U.S. National Institutes of Health. Acute manic episodes — characterized by hyperactivity, racing thoughts and reckless behavior — are not experienced by all bipolar patients, but severe symptoms often require hospitalization, health officials said.
Broadly defined as an “excessively raised mood,” mania affects about 1 percent of the population, according to the study authors.
“The most important point is that this is a study about acute treatment of manic episodes, not long-term management or prevention,” said Dr. Gregory Simon, a psychiatrist and mental health researcher at Group Health Cooperative in Seattle, who was not involved in the study. “The idea that antipsychotic treatments are good for manic episodes is well-known, but the finding that one of the older ones is better is newsworthy here.”
Antipsychotics and other drugs commonly used to treat mania are known to have many significant side effects, which can sometimes disrupt treatment. Study co-author Dr. Andrea Cipriani, a lecturer in psychiatry at the University of Verona in Italy, said haloperidol and risperidone are more likely than olanzapine to cause movement problems such as tremors and rigidity, while olanzapine is linked to higher rates of weight gain, metabolic syndrome and diabetes. Some antipsychotic medications may cause irregular heartbeat as well.
Cipriani said the new research was the first of its type to compare anti-manic drugs — including antipsychotics, anticonvulsants and lithium — and rank them according to their effectiveness and ability to be tolerated. She and her colleagues completed a similar study on antidepressants several years ago.
In head-to-head comparisons among drugs, the study authors found that haloperidol was more effective than aripiprazole, asenapine, carbamazepine, valproate, gabapentin, lamotrigine, lithium, quetiapine, topiramate and ziprasidone. Risperidone, olanzapine and quetiapine were most likely to be tolerated by patients and outperformed lithium, lamotrigine, topiramate and gabapentin.
The new research, which was not funded by the pharmaceutical industry, appears in the Aug. 17 online edition of The Lancet.
“Psychiatrists now have an evidence-based hierarchy when they are to prescribe an anti-manic agent for acute mania,” Cipriani said. “These findings are in line with what psychiatrists usually prescribe in their daily practice. There are new treatments that have been recently marketed for acute mania, but this study shows that clinicians should be aware these new compounds are not better — and may be worse — than older ones, and these [new] drugs are much more expensive.”
Long-term management of bipolar disorder usually requires a combination of medications, Cipriani and Simon said, and antipsychotics typically are used for extreme manic episodes for only several weeks at a time.
In a commentary accompanying the study, Australian researchers Dr. Michael Berk, chair of psychiatry at the Deakin University School of Medicine, and Gin S. Malhi, with the department of psychiatry at Royal North Shore Hospital in Sydney, said it’s useful to know that haloperidol seems to be a top-line treatment for the treatment of acute mania.
But, they added, haloperidol “lacks maintenance efficacy for depression — the predominant clinical state [of patients with bipolar disorder] — and indeed carries an inherent risk of incident depression.”