- Email: [email protected]
Psychotropics and risk of violent crime
Correspondence
On admission to Bichat–ClaudeBernard Hospital, the patient’s temperature was 38·4°C, with a blood pressure of 120/70 mm Hg, and an arterial oxygen saturation of 98%. She reported headaches, rhinorrhea, and a dry cough. Malaria diagnostic testing was negative. The white blood cell count was 4400 per mm³, lymphocyte cell count 360 per mm³, and platelet count 144 000 per mm³. The C-reactive protein concentration was 26 mg/L. Liver and renal functions were normal. She was given ceftriaxone 1 g/day and atovaquone-proguanil taken since her arrival in Guinea was continued. Two real-time reverse-transcription PCR tests, one targeting the Ebola virus nucleoprotein,2 and the other (RealStar filovirus screen kit, Altona Diagnostics, Hamburg, Germany) targeting the L gene of Filoviruses, were done on admission. Both were negative. Ebola was excluded and protective measures stopped on Oct 20, when apyrexia had been stable for 24 h without antipyretic drugs. A nasopharyngeal sample was positive for influenza B virus in a multiplex respiratory pathogen real-time PCR test (FilmArray kit; BioFire, UT, USA). The patient was discharged on Oct 21, 6 days after symptom onset. This case shows that like other infectious diseases such as malaria, influenza can mimic Ebola. Influenza virus circulates in countries neighbouring those with Ebola. To reduce the number of cases classified as possible Ebola, measures to prevent infectious diseases should more than ever be applied to travellers— particularly malaria prophylaxis and influenza vaccination. These measures are essential for health-care workers and volunteers handling suspected, possible, or confirmed cases of Ebola. Such measures could minimise unnecessary and costly hospitalisation of caregivers, especially in west Africa, where resources are limited. In countries with a high Ebola incidence, such as Liberia, Médecins 2024
Sans Frontières is considering malaria chemoprevention in areas where population density is very high to avoid occurrence of Ebola-like symptoms and their consequences on already stretched health systems.3 Influenza vaccination might also be considered in these areas to prevent an influenza epidemic. We thank the Ministère de la santé et de l’action sociale (Senegal), the Institut Pasteur in Dakar, Arnaud Fontanet (Unité d’Epidémiologie des Maladies Emergentes, Institut Pasteur) for information on influenza epidemiology in Senegal, and Alexandra Mailles (Institut National de Veille Sanitaire). We declare no competing interests.
*Sophie Matheron, Sylvain Baize, Isabelle Lerat, Nadira Houhou, Yazdan Yazdanpanah [email protected] Infectious and Tropical Diseases Department (SM, IL, YY), and Virology Department (NH), Hôpital Bichat—Claude-Bernard, Assistance Publique-Hôpitaux de Paris, 75018 Paris, France; Université Paris Diderot, Paris 7, Paris, France (SM, IL, YY); Unité mixte de recherche 1137 (Infection, Antimicrobiens, Modélisation, Evolution), Institut national de la santé et de la recherche médicale, Paris, France (SM, IL, YY); and National Reference Center for Viral Hemorrhagic Fevers, Unité de Biologie des Infections Virales Emergentes, Institut Pasteur—Centre International de Recherche en Infectiologie, Lyon, France (SB) 1
2
3
WHO Ebola Response Team. Ebola virus disease in west Africa—the first 9 months of the epidemic and forward projections. N Engl J Med, 2014; 371: 148–95. Huang Y, Wei H, Wang Y, Shi Z, Raoul H, Yuan Z. Rapid detection of filoviruses by real-time TaqMan polymerase chain reaction assays. Virol Sin 2012; 27: 273–77. Médecins Sans Frontières. MSF begins malaria program in Ebola-ravaged Monrovia, Liberia. Oct 30, 2014. http://www. doctorswithoutborders.org/article/msfbegins-malaria-program-ebola-ravagedmonrovia-liberia (accessed Nov 12, 2014).
school class, community, or country. The index case, however, is the patient in an outbreak who is first noticed by the health authorities, and who makes them aware that an outbreak might be emerging. Even outbreaks of disease that is not spread from human to human, such as Legionnaire’s disease, might have an index case. For many outbreaks, the primary case will never be known—the worldwide HIV epidemic is one example. In an outbreak that goes unnoticed, no index case is present, but for all outbreaks that are discovered, there will always be one (or more). In the present terrible outbreak of Ebola virus disease in west Africa, the child who might have had contact with an infected animal in December last year would be the primary case. The index case would be the first person (or probably group of people) diagnosed with Ebola in the following March, which led to notification to WHO on March 26. In some instances, the primary case is also the index case, but often they are not the same. The first term is linked to the basic epidemiology of the outbreak, the second rather to the surveillance system and public health action. Both are quite straightforward, and they deserve not to be mixed up. I declare no competing interests.
Johan Giesecke [email protected] Karolinska Institute, SE-171 77 Stockholm, Sweden 1
Last JM. A Dictionary of epidemiology. Oxford: Oxford University Press, 2008.
Primary and index cases Scientists—and journalists—are increasingly using the term index case when they actually mean primary case. Both terms are well defined for outbreaks,1 and should not be confused. The term primary case can only apply to infectious diseases that spread from human to human, and refers to the person who first brings a disease into a group of people—a
Psychotropics and risk of violent crime Seena Fazel and colleagues have done an impressive epidemiological study (Sept 27, p 1206),1 which shows that patients with schizophrenia or mania profit from individualised appropriate drugs, not only in highly aggressive outbursts, but also in less aggressive www.thelancet.com Vol 384 December 6, 2014
Correspondence
We declare no competing interests.
*Michael Dettling, Ion Anghelescu [email protected] Department of Psychiatry and Psychotherapy, University Clinic Charite, Berlin 14050, Germany (MD); and Clinic Dr Fontheim, Liebenburg, Germany (IA) 1
2
3
4
Fazel S, Zetterqvist J, Larsson H, Långström N, Lichtenstein P. Antipsychotics, mood stabilisers, and risk of violent crime. Lancet 2014; 384: 1206–14. Malhi GS, Chengappa KN, Gershon S, Ghaemi SN. Atypical mood stabilizers: a new role for neuroleptics? Bipolar Disord 2011; 13: 583–86. van der Werf M, Hanssen M, Köhler S, et al. Systematic review and collaborative recalculation of 133 693 incident cases of schizophrenia. Psychol Med 2014; 44: 9–16. Sherazi R, McKeon P, McDonough M, Daly I, Kennedy N. What’s new? The clinical epidemiology of bipolar I disorder. Harv Rev Psychiatry 2006; 14: 273–84.
risk of violence and crime rates, leading to an inherent selection bias in the study sample? 2 Moreover, type and phase of illness were not mentioned, which are both known to affect the risk of violent behaviour and subsequent crime rates.3 Sufficient evidence exists to suggest that substance misuse complicates and confounds aggressive behaviour across the range of mental disorders.4 The authors did mention rates of substance misuse, but their possible confounding effects deserve more discussion. The paradoxical issue of benzodiazepine both inducing and reducing agitation in patients was also left unaddressed. In their study, Fazel and colleagues also showed additional benefit of the use of an antipsychotic rather than a mood stabiliser for reduction of violence and crime rates. However, they did not mention whether the patients were on single or multiple antipsychotics, which could affect study outcomes and results interpretation. Finally, their claim of the study’s superiority compared with previous works should be taken with caution. We feel that the authors could have substantially increased the validity of their findings by asking a few questions from patients or their immediate caregivers related to compliance, domestic violence, effect of hospitalisation, and substance misuse. We declare no competing interests.
*Mohit Varshney, Rishab Gupta [email protected] Department of Psychiatry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, Delhi 110029, India 1
2
Seema Fazel and colleagues1 deserve credit for their epidemiological study. However, some issues merit further discussion. Were non-compliant patients excluded from withinindividual analyses, thus missing patients who might have had severe psychopathology and, hence, a high www.thelancet.com Vol 384 December 6, 2014
3
4
Fazel S, Zetterqvist J, Larsson H, Långström N, Lichtenstein P. Antipsychotics, mood stabilisers, and risk of violent crime. Lancet 2014; 384: 1206–14. Hodgins S, Riaz M. Violence and phases of illness: differential risk and predictors. Eur Psychiatry 2011; 26: 518–24. Bobes J, Fillat O, Arango C. Violence among schizophrenia out-patients compliant with medication: prevalence and associated factors. Acta Psychiatr Scand 2009; 119: 218–25. Dolan M, O’Malley K, McGregor K. The role of psychopathic traits and substance abuse in predicting violent victimization in patients with schizophrenia spectrum disorders. Personal Ment Health 2013; 7: 28–38.
Authors’ reply We are grateful to Michael Dettling and Ion Anghelescu for raising clinically relevant questions about the drugs that we investigated in our study.1 We selected antipsychotics and mood stabilisers, but not hypnotics (including benzodiazepines) because we focused on long-term outcomes associated with widely prescribed psychiatric drugs, whereas hypnotics are typically prescribed for short periods. We studied antipsychotics and mood stabilisers together for the primary analyses because their coadministration is common, at least in schizophrenia-spectrum disorders. Additionally, we investigated drugs separately according to standard drug classes, rather than to their potential effects. Thus, second-generation antipsychotics with possible mood-stabilising effects were investigated as antipsychotics. As shown in table 3 of our study,1 both first-generation and second-generation antipsychotics were associated with substantial reductions in violent crime in bipolar disorder (hazard ratio 0·52, 95% CI 0·39–0·92). The sex ratio of our sample shows that we used a national patient register with full coverage for outpatients and inpatients. Nevertheless, although the authors of the epidemiological investigation2 cited by Michael Dettling and Ion Anghelescu do not report prevalence ratios for schizophrenia, the female to male incidence rate ratios for the age groups <20 years (0·53, 95% CI 0·41–0·69) and 20–29 years (0·47, 0·41–0·54) are similar to the female to male prevalence ratios in our sample (0·51, 0·49–0·53), which consisted mostly of those aged 20–29 years. In bipolar disorder, the prevalence ratio in our sample was 1·74 (1·68–1·80), an over-representation of women consistent with register-based studies in other countries, such as Denmark.3 Regarding Mohit Varshney and Rishab Gupta’s question about non-compliant patients exclusion—
Robert Brook/Science Photo Library
outbursts. We would like to expand the discussion with some clinical and drug-based remarks. First, to group drugs into antipsychotics and mood stabilisers, or hypnotics, seems uncommon for clinicians because hypnotics represent normal comedication for both antipsychotics and mood stabilisers, at least for acute psychotic and aggressive states. Do any data derived from this study exclude this context? Second, some atypical antipsychotics have mood-stabilising effects.2 Were any data collected from bipolar patients using only atypical antipsychotics as mood stabilisers? Third, the sex distribution in the study for both schizophrenia and bipolar disorders differs obviously from established sex distributions known for these diseases.3,4 Do Fazel and colleagues have an explanation for this finding? To better understand this difference, could this sex discrepancy be seen in the type of violent crime patients diagnosed with schizophrenia and bipolar disorder have been arrested for?
2025
On admission to Bichat–ClaudeBernard Hospital, the patient’s temperature was 38·4°C, with a blood pressure of 120/70 mm Hg, and an arterial oxygen saturation of 98%. She reported headaches, rhinorrhea, and a dry cough. Malaria diagnostic testing was negative. The white blood cell count was 4400 per mm³, lymphocyte cell count 360 per mm³, and platelet count 144 000 per mm³. The C-reactive protein concentration was 26 mg/L. Liver and renal functions were normal. She was given ceftriaxone 1 g/day and atovaquone-proguanil taken since her arrival in Guinea was continued. Two real-time reverse-transcription PCR tests, one targeting the Ebola virus nucleoprotein,2 and the other (RealStar filovirus screen kit, Altona Diagnostics, Hamburg, Germany) targeting the L gene of Filoviruses, were done on admission. Both were negative. Ebola was excluded and protective measures stopped on Oct 20, when apyrexia had been stable for 24 h without antipyretic drugs. A nasopharyngeal sample was positive for influenza B virus in a multiplex respiratory pathogen real-time PCR test (FilmArray kit; BioFire, UT, USA). The patient was discharged on Oct 21, 6 days after symptom onset. This case shows that like other infectious diseases such as malaria, influenza can mimic Ebola. Influenza virus circulates in countries neighbouring those with Ebola. To reduce the number of cases classified as possible Ebola, measures to prevent infectious diseases should more than ever be applied to travellers— particularly malaria prophylaxis and influenza vaccination. These measures are essential for health-care workers and volunteers handling suspected, possible, or confirmed cases of Ebola. Such measures could minimise unnecessary and costly hospitalisation of caregivers, especially in west Africa, where resources are limited. In countries with a high Ebola incidence, such as Liberia, Médecins 2024
Sans Frontières is considering malaria chemoprevention in areas where population density is very high to avoid occurrence of Ebola-like symptoms and their consequences on already stretched health systems.3 Influenza vaccination might also be considered in these areas to prevent an influenza epidemic. We thank the Ministère de la santé et de l’action sociale (Senegal), the Institut Pasteur in Dakar, Arnaud Fontanet (Unité d’Epidémiologie des Maladies Emergentes, Institut Pasteur) for information on influenza epidemiology in Senegal, and Alexandra Mailles (Institut National de Veille Sanitaire). We declare no competing interests.
*Sophie Matheron, Sylvain Baize, Isabelle Lerat, Nadira Houhou, Yazdan Yazdanpanah [email protected] Infectious and Tropical Diseases Department (SM, IL, YY), and Virology Department (NH), Hôpital Bichat—Claude-Bernard, Assistance Publique-Hôpitaux de Paris, 75018 Paris, France; Université Paris Diderot, Paris 7, Paris, France (SM, IL, YY); Unité mixte de recherche 1137 (Infection, Antimicrobiens, Modélisation, Evolution), Institut national de la santé et de la recherche médicale, Paris, France (SM, IL, YY); and National Reference Center for Viral Hemorrhagic Fevers, Unité de Biologie des Infections Virales Emergentes, Institut Pasteur—Centre International de Recherche en Infectiologie, Lyon, France (SB) 1
2
3
WHO Ebola Response Team. Ebola virus disease in west Africa—the first 9 months of the epidemic and forward projections. N Engl J Med, 2014; 371: 148–95. Huang Y, Wei H, Wang Y, Shi Z, Raoul H, Yuan Z. Rapid detection of filoviruses by real-time TaqMan polymerase chain reaction assays. Virol Sin 2012; 27: 273–77. Médecins Sans Frontières. MSF begins malaria program in Ebola-ravaged Monrovia, Liberia. Oct 30, 2014. http://www. doctorswithoutborders.org/article/msfbegins-malaria-program-ebola-ravagedmonrovia-liberia (accessed Nov 12, 2014).
school class, community, or country. The index case, however, is the patient in an outbreak who is first noticed by the health authorities, and who makes them aware that an outbreak might be emerging. Even outbreaks of disease that is not spread from human to human, such as Legionnaire’s disease, might have an index case. For many outbreaks, the primary case will never be known—the worldwide HIV epidemic is one example. In an outbreak that goes unnoticed, no index case is present, but for all outbreaks that are discovered, there will always be one (or more). In the present terrible outbreak of Ebola virus disease in west Africa, the child who might have had contact with an infected animal in December last year would be the primary case. The index case would be the first person (or probably group of people) diagnosed with Ebola in the following March, which led to notification to WHO on March 26. In some instances, the primary case is also the index case, but often they are not the same. The first term is linked to the basic epidemiology of the outbreak, the second rather to the surveillance system and public health action. Both are quite straightforward, and they deserve not to be mixed up. I declare no competing interests.
Johan Giesecke [email protected] Karolinska Institute, SE-171 77 Stockholm, Sweden 1
Last JM. A Dictionary of epidemiology. Oxford: Oxford University Press, 2008.
Primary and index cases Scientists—and journalists—are increasingly using the term index case when they actually mean primary case. Both terms are well defined for outbreaks,1 and should not be confused. The term primary case can only apply to infectious diseases that spread from human to human, and refers to the person who first brings a disease into a group of people—a
Psychotropics and risk of violent crime Seena Fazel and colleagues have done an impressive epidemiological study (Sept 27, p 1206),1 which shows that patients with schizophrenia or mania profit from individualised appropriate drugs, not only in highly aggressive outbursts, but also in less aggressive www.thelancet.com Vol 384 December 6, 2014
Correspondence
We declare no competing interests.
*Michael Dettling, Ion Anghelescu [email protected] Department of Psychiatry and Psychotherapy, University Clinic Charite, Berlin 14050, Germany (MD); and Clinic Dr Fontheim, Liebenburg, Germany (IA) 1
2
3
4
Fazel S, Zetterqvist J, Larsson H, Långström N, Lichtenstein P. Antipsychotics, mood stabilisers, and risk of violent crime. Lancet 2014; 384: 1206–14. Malhi GS, Chengappa KN, Gershon S, Ghaemi SN. Atypical mood stabilizers: a new role for neuroleptics? Bipolar Disord 2011; 13: 583–86. van der Werf M, Hanssen M, Köhler S, et al. Systematic review and collaborative recalculation of 133 693 incident cases of schizophrenia. Psychol Med 2014; 44: 9–16. Sherazi R, McKeon P, McDonough M, Daly I, Kennedy N. What’s new? The clinical epidemiology of bipolar I disorder. Harv Rev Psychiatry 2006; 14: 273–84.
risk of violence and crime rates, leading to an inherent selection bias in the study sample? 2 Moreover, type and phase of illness were not mentioned, which are both known to affect the risk of violent behaviour and subsequent crime rates.3 Sufficient evidence exists to suggest that substance misuse complicates and confounds aggressive behaviour across the range of mental disorders.4 The authors did mention rates of substance misuse, but their possible confounding effects deserve more discussion. The paradoxical issue of benzodiazepine both inducing and reducing agitation in patients was also left unaddressed. In their study, Fazel and colleagues also showed additional benefit of the use of an antipsychotic rather than a mood stabiliser for reduction of violence and crime rates. However, they did not mention whether the patients were on single or multiple antipsychotics, which could affect study outcomes and results interpretation. Finally, their claim of the study’s superiority compared with previous works should be taken with caution. We feel that the authors could have substantially increased the validity of their findings by asking a few questions from patients or their immediate caregivers related to compliance, domestic violence, effect of hospitalisation, and substance misuse. We declare no competing interests.
*Mohit Varshney, Rishab Gupta [email protected] Department of Psychiatry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, Delhi 110029, India 1
2
Seema Fazel and colleagues1 deserve credit for their epidemiological study. However, some issues merit further discussion. Were non-compliant patients excluded from withinindividual analyses, thus missing patients who might have had severe psychopathology and, hence, a high www.thelancet.com Vol 384 December 6, 2014
3
4
Fazel S, Zetterqvist J, Larsson H, Långström N, Lichtenstein P. Antipsychotics, mood stabilisers, and risk of violent crime. Lancet 2014; 384: 1206–14. Hodgins S, Riaz M. Violence and phases of illness: differential risk and predictors. Eur Psychiatry 2011; 26: 518–24. Bobes J, Fillat O, Arango C. Violence among schizophrenia out-patients compliant with medication: prevalence and associated factors. Acta Psychiatr Scand 2009; 119: 218–25. Dolan M, O’Malley K, McGregor K. The role of psychopathic traits and substance abuse in predicting violent victimization in patients with schizophrenia spectrum disorders. Personal Ment Health 2013; 7: 28–38.
Authors’ reply We are grateful to Michael Dettling and Ion Anghelescu for raising clinically relevant questions about the drugs that we investigated in our study.1 We selected antipsychotics and mood stabilisers, but not hypnotics (including benzodiazepines) because we focused on long-term outcomes associated with widely prescribed psychiatric drugs, whereas hypnotics are typically prescribed for short periods. We studied antipsychotics and mood stabilisers together for the primary analyses because their coadministration is common, at least in schizophrenia-spectrum disorders. Additionally, we investigated drugs separately according to standard drug classes, rather than to their potential effects. Thus, second-generation antipsychotics with possible mood-stabilising effects were investigated as antipsychotics. As shown in table 3 of our study,1 both first-generation and second-generation antipsychotics were associated with substantial reductions in violent crime in bipolar disorder (hazard ratio 0·52, 95% CI 0·39–0·92). The sex ratio of our sample shows that we used a national patient register with full coverage for outpatients and inpatients. Nevertheless, although the authors of the epidemiological investigation2 cited by Michael Dettling and Ion Anghelescu do not report prevalence ratios for schizophrenia, the female to male incidence rate ratios for the age groups <20 years (0·53, 95% CI 0·41–0·69) and 20–29 years (0·47, 0·41–0·54) are similar to the female to male prevalence ratios in our sample (0·51, 0·49–0·53), which consisted mostly of those aged 20–29 years. In bipolar disorder, the prevalence ratio in our sample was 1·74 (1·68–1·80), an over-representation of women consistent with register-based studies in other countries, such as Denmark.3 Regarding Mohit Varshney and Rishab Gupta’s question about non-compliant patients exclusion—
Robert Brook/Science Photo Library
outbursts. We would like to expand the discussion with some clinical and drug-based remarks. First, to group drugs into antipsychotics and mood stabilisers, or hypnotics, seems uncommon for clinicians because hypnotics represent normal comedication for both antipsychotics and mood stabilisers, at least for acute psychotic and aggressive states. Do any data derived from this study exclude this context? Second, some atypical antipsychotics have mood-stabilising effects.2 Were any data collected from bipolar patients using only atypical antipsychotics as mood stabilisers? Third, the sex distribution in the study for both schizophrenia and bipolar disorders differs obviously from established sex distributions known for these diseases.3,4 Do Fazel and colleagues have an explanation for this finding? To better understand this difference, could this sex discrepancy be seen in the type of violent crime patients diagnosed with schizophrenia and bipolar disorder have been arrested for?
2025