Antidepressive drugs reduce the mortality rate of schizophrenic patients, while treatment with bensodiazepines greatly increases it, especially as regards suicide. Giving several antipsychotics simultaneously, however, seems to have no effect at all. This according to a new study examining different drug combinations administered to patients with schizophrenia.

“We weren’t aware that the beneficial effects of antidepressives were so powerful,” says Jari Tiihonen, professor of clinical psychiatry at Karolinska Institutet’s Department of Clinical Neuroscience.

The study followed 2,588 Finns who had recently developed schizophrenia from the time of their initial admission to hospital for an average of four years. By accessing the Finnish registers, the researchers were then able to ascertain the effects of different drug combinations on the mortality risk within the group.

A total of 160 people died in the study, most commonly from external causes such as drowning, poisoning or violent crime, something that affected 57 people. Thirty-five of these cases were suicide, which made it and cardiovascular disease the two main causes of death.

The researchers found that when taking bensodiazepines, the participants ran a 91 per cent higher risk of early death than at times when these drugs were not used. By far the most common cause of death was suicide, and most deaths occurred with patients who had been taking their bensodiazepines for longer than four weeks.

“The increased suicide risk for patients with long-standing benzodiazepine use may be partly attributable to the possible development of withdrawal symptoms when the drugs run out,” says Professor Tiihonen. “These symptoms, which can be severe severe anxiety and insomnia, might have affected some of the patients’ decisions to commit suicide. It’s therefore extremely important that bensodiazepines are discontinued gradually rather than abruptly over a period of weeks or months and in consultation with a doctor.”

“The temporary acute use of benzodiazepines is justifiable if the patient is suffering a great deal of anxiety,” he continues. “But benzodiazepines should be discontinued within a month according to psychiatric recommendations, which doctors must start following and respecting.”

During the periods the participants took antidepressive drugs, they ran a 43 per cent lower mortality risk than during the periods when these drugs were not used. The decrease in suicide risk was 85 percent, a result that also was statistically significant. Antipsychotics had no effect on mortality if the patients were on multiple prescriptions simultaneously.

“People think that it’s dangerous to treat patients with schizophrenia with more than one antipsychotic drug, but there is nothing to back that up, says Professor Tiihonen. “I believe that most doctors prescribe several antipsychotics if their patients are not helped by just one kind, and our study finds no link between this and increased mortality during a four year follow-up. But it does mean more adverse effects, such as the risk of weight-gain, which also impacts the health in the long run, so the recommended attitude is still one of restraint.”

The study was financed by EVO funding from the Finnish Ministry of Social Affairs and Health and pharmaceutical company Janssen-Cilag.

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Jari Tiihonen, Jaana T. Suokas, Jaana M. Suvisaari, Jari Haukka, Pasi Korhonen
Polypharmacy with antipsychotics, antidepressants or benzodiazepines and mortality in schizophrenia

Archives of General Pschiatry, online first 7 May 2012