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December 2009

Cholinesterase Inhibitors Cause Syncope
Cholinesterase inhibitors, such as donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon), which are used to treat Alzheimer's disease, may cause syncope.

In Brief
Cigarettes and Coffee May Elevate Risk of Suicidal Behavior in Patients with Bipolar Disorder; Depression and Anxiety Have Different Effects on Risk of Mortality

Antipsychotics Decrease Mortality
Treatment with antipsychotics increases life expectancy for patients with schizophrenia.

On to 2010!
Dr. Alan Gelenberg reviews biological interventions approved during the past year, including new antipsychotics and a device to deliver repeated transcranial magnetic stimulation (rTMS).

2009 Index

Iloperidone (Fanapt)
Iloperidone, an antipsychotic recently approved by the U.S. Food and Drug Administration (FDA), is comparable in efficacy to other second-generation agents.

Antipsychotics Decrease Mortality

December 2009

People with chronic and serious mental illness die on average 25 years earlier than do people without psychiatric conditions. About 40% of this excess mortality can be attributed to suicide and other "unnatural causes," but the remaining 60% reflects the patients' greater propensity to develop cardiovascular, pulmonary, and other diseases. The additional mortality for the chronically mentally ill increased from the 1970s to the 1990s, which some observers blamed on adverse effects of second-generation antipsychotic drugs. Many of these agents cause weight gain and adverse changes in serum lipids, which, in turn, can increase cardiovascular disease.

Weinmann and coauthors reviewed studies of the association between antipsychotic agents and mortality in patients with schizophrenia.1 They conclude that data are insufficient to draw firm conclusions and that interpretations are confounded by the greater likelihood that the most severely mentally ill patients will have more severe medical diseases. The authors do find reasonable evidence, nonetheless, that long-term antipsychotic exposure might increase mortality risk in schizophrenia patients.

Has the mortality gap between the mentally ill and the general population continued to increase since the mid-1990s? How have antipsychotics contributed to excess mortality? These questions were investigated by Tiihonen and colleagues.2

Nationwide registers in Finland were used to compare mortality among 66,881 patients with schizophrenia against figures for the entire Finnish population between 1996 and 2006. Investigators linked data for the patients with their use of antipsychotic medications.

During the period studied, second-generation agents rose from 13% to 64% of all antipsychotics used. But contrary to expectations, the gap in life expectancy between patients with schizophrenia and the general population actually shrank (to a nonsignificant degree)—from 25 to 22.5 years. Life expectancy at age 20 among the general public rose by 2.4 years, while among patients with schizophrenia, it increased by 4.9 years. Long-term cumulative exposure to any antipsychotic was associated with lower mortality than no exposure to antipsychotics.

There were some differences among medications. Quetiapine (Seroquel), haloperidol (Haldol and others), and risperidone (Risperdal and others) were associated with increases in mortality from 34% to 41%. But clozapine (Clozaril and others) was associated with a 26% decrease in mortality.

How may these findings be explained? Beyond doubt, all antipsychotics carry risks—some serious. Among these are weight gain and metabolic changes, QT-interval prolongation, and, for clozapine, agranulocytosis. But when patients with schizophrenia and other chronic mental illnesses respond well to medicines, they may take better care of themselves and lead healthier lives. They might eat better, get more exercise, seek appropriate medical care, preserve their health, and protect their safety. The challenge for doctors and the healthcare system is to balance inevitable and individualized risks with potential benefits.

1Weinmann S, Read J, Aderhold V: Influence of antipsychotics on mortality in schizophrenia: Systematic review. Schizophr Res 2009;113:1-11.

2Tiihonen J, Lönnqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J: 11-year follow-up of mortality in patients with schizophrenia: A population-based cohort study (FIN11 study). Lancet 2009;374:620-627