- Email: [email protected]
Mortality in patients with schizophrenia
Correspondence
Jari Tiihonen and colleagues1 found lower mortality in patients on longterm treatment with antipsychotics than in patients receiving no treatment. Their database is the largest ever reported and the quality of this study is astonishing. Nevertheless, there are still some questions left to be answered. Many epidemiological studies on the risks and benefits of secondgeneration antipsychotics have focused on cardiovascular risk, especially with regard to development of metabolic syndrome and other causes such as pulmonary diseases or cancer.2–4 Tiihonen and colleagues obtained the data on ischaemic heart disease, suicide, and general mortality from a nationwide register in Finland. However, a specific description of data on general mortality with, for example, a table of the exact causes of death would have been helpful for interpretation of the results. According to Tiihonen and colleagues, the safety of clozapine with respect to suicide and mortality was not due to the intensity of monitoring. Knowledge about the exact causes of death would be interesting as more and more research focuses on primary prevention strategies. The duration of antipsychotic treatment was calculated using the purchased defined daily dose.5 The means to calculate the defined daily dose are not available in every European country—eg, Germany— owing to patient confidentiality restrictions. However, the total amount of chlorpromazine equivalents in each patient has been widely used to control dose as well as antipsychotic effects in recent psychiatric studies so far. The knowledge of chlorpromazine equivalents as well as the defined daily dose over the study period would allow direct comparison of treatment doses. We declare that we have no conflicts of interest.
Wolfgang Sperling, *Teresa Biermann [email protected]
1592
Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, 91054 Erlangen, Germany 1
2
3
4
5
Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374: 620–27. De Hert M, Schreurs V, Vancampfort D, Van Winkel R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry 2009; 8: 15–22. Patel JK, Buckley PF, Woolson S, et al. Metabolic profiles of second-generation antipsychotics in early psychosis: findings from the CAFE study. Schizophr Res 2009; 111: 9–16. Simon V, van Winkel R, De Hert M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review. J Clin Psychiatry 2009; 70: 1041–50. Mantel-Teeuwisse AK, Klungel OH, Verschuren WM, Porsius A, de Boer A. Comparison of different methods to estimate prevalence of drug use by using pharmacy records. J Clin Epidemiol 2001; 54: 1181–86.
Jari Tiihonen and colleagues1 found that clozapine seems to be associated with substantially lower mortality than any other antipsychotic in patients with schizophrenia. They suggest that monitoring of patients might not be the main reason for these good outcomes. There is a strong association between premature mortality and substance abuse, and comorbid substance abuse in schizophrenia is a major problem. In the Epidemiologic Catchment Area Study,2 the prevalence of substance abuse disorders in patients with schizophrenia was 47% in their lifetime, compared with 17% in individuals without schizophrenia. Some studies suggest that the atypical antipsychotic clozapine could decrease substance misuse in patients with schizophrenia to a greater extent than other antipsychotic agents. For instance, Green and colleagues3 found that abstinence rates were significantly higher in patients treated with clozapine than in those treated with risperidone. In their study, all the patients were offered the same substance abuse services. Drake and colleagues4 found that, among 151 schizophrenic patients with current substance use disorder, those placed on clozapine were more
than twice as likely to attain full remission of substance abuse as those on other antipsychotic medications. In a prospective 10-year followup study, Brunette and colleagues5 found that clozapine was associated with prevention of substance abuse relapses, compared with other antipsychotic medications. In conclusion, reducing substance abuse could be a link between clozapine treatment and reduced mortality in patients with schizophrenia. We declare that we have no conflicts of interest.
*Alain Dervaux, Xavier Laqueille [email protected] Service d’Addictologie, Hôpital Sainte-Anne, 75014 Paris, France 1
2
3
4
5
Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374: 620–27. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) study. JAMA 1990 ; 264: 2511–18. Green AI, Burgess ES, Dawson R, Zimmet SV, Strous RD. Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. Schizophr Res 2003; 60: 81–85. Drake RE, Xie H, McHugo GJ, Green AI. The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr Bull 2000; 26: 441–49. Brunette MF, Drake RE, Xie H, McHugo GJ, Green AI. Clozapine use and relapses of substance use disorder among patients with co-occurring schizophrenia and substance use disorders. Schizophr Bull 2006; 32: 637–43.
Author’s reply We agree with Debasish Basu and Munish Aggarwal that people with schizophrenia are more likely to have mortality-increasing risk factors such as smoking and obesity than those without schizophrenia. We also agree that long-term health-care engagement and use are important issues. However, we think that there is no conflict between our results and those of previous studies and systematic reviews.1,2 These studies did not investigate overall mortality during current or cumulative antipsychotic use compared with no use or a reference drug, but instead www.thelancet.com Vol 374 November 7, 2009
Jari Tiihonen and colleagues1 found lower mortality in patients on longterm treatment with antipsychotics than in patients receiving no treatment. Their database is the largest ever reported and the quality of this study is astonishing. Nevertheless, there are still some questions left to be answered. Many epidemiological studies on the risks and benefits of secondgeneration antipsychotics have focused on cardiovascular risk, especially with regard to development of metabolic syndrome and other causes such as pulmonary diseases or cancer.2–4 Tiihonen and colleagues obtained the data on ischaemic heart disease, suicide, and general mortality from a nationwide register in Finland. However, a specific description of data on general mortality with, for example, a table of the exact causes of death would have been helpful for interpretation of the results. According to Tiihonen and colleagues, the safety of clozapine with respect to suicide and mortality was not due to the intensity of monitoring. Knowledge about the exact causes of death would be interesting as more and more research focuses on primary prevention strategies. The duration of antipsychotic treatment was calculated using the purchased defined daily dose.5 The means to calculate the defined daily dose are not available in every European country—eg, Germany— owing to patient confidentiality restrictions. However, the total amount of chlorpromazine equivalents in each patient has been widely used to control dose as well as antipsychotic effects in recent psychiatric studies so far. The knowledge of chlorpromazine equivalents as well as the defined daily dose over the study period would allow direct comparison of treatment doses. We declare that we have no conflicts of interest.
Wolfgang Sperling, *Teresa Biermann [email protected]
1592
Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, 91054 Erlangen, Germany 1
2
3
4
5
Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374: 620–27. De Hert M, Schreurs V, Vancampfort D, Van Winkel R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry 2009; 8: 15–22. Patel JK, Buckley PF, Woolson S, et al. Metabolic profiles of second-generation antipsychotics in early psychosis: findings from the CAFE study. Schizophr Res 2009; 111: 9–16. Simon V, van Winkel R, De Hert M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review. J Clin Psychiatry 2009; 70: 1041–50. Mantel-Teeuwisse AK, Klungel OH, Verschuren WM, Porsius A, de Boer A. Comparison of different methods to estimate prevalence of drug use by using pharmacy records. J Clin Epidemiol 2001; 54: 1181–86.
Jari Tiihonen and colleagues1 found that clozapine seems to be associated with substantially lower mortality than any other antipsychotic in patients with schizophrenia. They suggest that monitoring of patients might not be the main reason for these good outcomes. There is a strong association between premature mortality and substance abuse, and comorbid substance abuse in schizophrenia is a major problem. In the Epidemiologic Catchment Area Study,2 the prevalence of substance abuse disorders in patients with schizophrenia was 47% in their lifetime, compared with 17% in individuals without schizophrenia. Some studies suggest that the atypical antipsychotic clozapine could decrease substance misuse in patients with schizophrenia to a greater extent than other antipsychotic agents. For instance, Green and colleagues3 found that abstinence rates were significantly higher in patients treated with clozapine than in those treated with risperidone. In their study, all the patients were offered the same substance abuse services. Drake and colleagues4 found that, among 151 schizophrenic patients with current substance use disorder, those placed on clozapine were more
than twice as likely to attain full remission of substance abuse as those on other antipsychotic medications. In a prospective 10-year followup study, Brunette and colleagues5 found that clozapine was associated with prevention of substance abuse relapses, compared with other antipsychotic medications. In conclusion, reducing substance abuse could be a link between clozapine treatment and reduced mortality in patients with schizophrenia. We declare that we have no conflicts of interest.
*Alain Dervaux, Xavier Laqueille [email protected] Service d’Addictologie, Hôpital Sainte-Anne, 75014 Paris, France 1
2
3
4
5
Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374: 620–27. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) study. JAMA 1990 ; 264: 2511–18. Green AI, Burgess ES, Dawson R, Zimmet SV, Strous RD. Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. Schizophr Res 2003; 60: 81–85. Drake RE, Xie H, McHugo GJ, Green AI. The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr Bull 2000; 26: 441–49. Brunette MF, Drake RE, Xie H, McHugo GJ, Green AI. Clozapine use and relapses of substance use disorder among patients with co-occurring schizophrenia and substance use disorders. Schizophr Bull 2006; 32: 637–43.
Author’s reply We agree with Debasish Basu and Munish Aggarwal that people with schizophrenia are more likely to have mortality-increasing risk factors such as smoking and obesity than those without schizophrenia. We also agree that long-term health-care engagement and use are important issues. However, we think that there is no conflict between our results and those of previous studies and systematic reviews.1,2 These studies did not investigate overall mortality during current or cumulative antipsychotic use compared with no use or a reference drug, but instead www.thelancet.com Vol 374 November 7, 2009