- Email: [email protected]
AIDS
Comment
achieve and maintain therapeutic anticoagulation is a goal that will be accomplished one polymorphism at a time.
7
8
Mark J Alberts UTSW Medical Center, Dallas, TX 75390–8897, USA [email protected]
9
I have been a paid consultant and speaker for Boehringer Ingelheim, Janssen Pharmaceuticals, Bristol-Myers Squibb, Pfizer, and Merck.
10
1
2 3 4
5
6
Newman DH, Zhitomirsky I. The prevalence of nontherapeutic and dangerous international normalized ratios among patients receiving warfarin in the emergency department. Ann Emerg Med 2006; 48: 182–89. Tan GM, Wu E, Lam YY, Yan BP. Role of warfarin pharmacogenetic testing in clinical practice. Pharmacogenomics 2010; 11: 439–48. Loebstein R, Yonath H, Peleg D, et al. Interindividual variability in sensitivity to warfarin—nature or nurture? Clin Pharm Therapeut 2001; 70: 159–64. Rieder MJ, Reiner AP, Gage BF, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. New Engl J Med 2005; 352: 2285–93. Mlynarsky L, Bejarano-Achache I, Muszkat M, Caraco Y. Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers. Eur J Clin Pharm 2012; 68: 617–27. Nakamura K, Obayashi K, Araki T, et al. CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects. J Pharm Therapeut 2012; 37: 481–85.
11
12 13 14 15
Lane S, Al-Zubiedi S, Hatch E, et al. The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors. Brit J Clin Pharm 2012; 73: 66–76. Limdi NA, Beasley TM, Crowley MR, et al. VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans. Pharmacogenomics 2008; 9: 1445–58. Yang L, Ge W, Yu F, Zhu H. Impact of VKORC1 gene polymorphism on interindividual and interethnic warfarin dosage requirement—a systematic review and meta analysis. Thromb Res 2010; 125: e159–66. Voora D, Koboldt DC, King CR, et al. A polymorphism in the VKORC1 regulator calumenin predicts higher warfarin dose requirements in African Americans. Clin Pharm Therapeut 2010; 87: 445–51. Perera MA, Cavallari LH, Limdi NA, et al. Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study. Lancet 2013; published online June 5. http://dx.doi.org/10.1016/ S0140-6736(13)60681-9. Ott J. Association of genetic loci: replication or not, that is the question. Neurology 2004; 63: 955–58. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet 2001; 29: 306–09. Thompson CA. FDA encourages genetics-aided warfarin dosing. Am J Health Syst Pharm 2007; 64: 1994–96. Steffel J, Braunwald E. Novel oral anticoagulants: focus on stroke prevention and treatment of venous thrombo-embolism. Eur Heart J 2011; 32: 1968–76.
A decade ago the world faced the devastating consequences of an HIV pandemic that to many seemed unstoppable. But when the US Government committed support to the response to HIV in 2003 by creating the largest bilateral global health programme in history, it set bold goals. Thanks to its investments in HIV programmes and its health diplomacy efforts in partner countries around the globe, especially in those most affected by HIV, the US initiative known as the President’s Emergency Plan for AIDS Relief (PEPFAR) met or even surpassed most of those goals: saving the lives of millions of people; supporting the scale-up of HIV prevention, care, and treatment; and strengthening systems and policies for the HIV response.1 For example, according to the most recent results reported by PEPFAR, as of September, 2012, the US Government has supported life-saving antiretroviral treatment for nearly 5·1 million men, women, and children worldwide.2 In fiscal year 2012, PEPFAR supported antiretroviral drugs for the prevention of mother-to-child transmission for nearly 750 000 pregnant women who were HIV positive.2 With this success, PEPFAR restored hope to many and changed people’s ideas for what can be accomplished in global health with ambitious aims and ample funding. www.thelancet.com Vol 382 August 31, 2013
PEPFAR’s Congressional reauthorisation in 2008 asked the US Institute of Medicine to assess the effectiveness of the US Government’s response to global HIV/AIDS.3 The assessment, done over 4 years, examines PEPFAR since its inception. It drew on a variety of data sources, including financial data, programme monitoring indicators and clinical data, extensive document review, and primary data collection through more than 400 semi-structured interviews with a range of stakeholders in 13 PEPFAR partner countries, at PEPFAR headquarters, and from other institutions and multilateral agencies involved in the global HIV response. This assessment’s painstaking analysis through rigorous mixed quantitative and qualitative methods provided the assessment committee at the Institute of Medicine with an unprecedented depth of knowledge to speak in a strong voice about how to improve the federal government’s support for the global response to HIV/AIDS. The resulting report, Evaluation of PEPFAR, was released on Feb 20, 2013.1 The report outlines key challenges for the future. Despite a decade of investment from the US Government, other international donors, and countries themselves, many challenges remain. Even with PEPFAR’s contribution to the substantial scale-up of HIV services in countries with restricted resources and
Institute of Medicine of the National Academies
The future of the US response to global HIV/AIDS
Published Online February 20, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)60184-1
For the report, Evaluation of PEPFAR, see http://www.iom. edu
751
Comment
infrastructure, the most profound challenge is simply the unmet need. In the future, it will be crucial for PEPFAR to work effectively with partner countries and global stakeholders to ensure that hard-fought gains are sustained and to continue to make progress against the HIV pandemic in the face of a weak global economy and many competing demands for resources for health and development. In addition to achieving adequate coverage of services, fundamentally altering the course of the HIV epidemic will hinge on a renewed and strengthened emphasis on HIV prevention. Developing and implementing appropriately comprehensive prevention programme portfolios is an important challenge. Even as it maintains its support for interventions that target all modes of HIV transmission, PEPFAR should prioritise reduction of sexual transmission. The unequivocal epidemiological evidence that sexual transmission, with underlying behavioural drivers, is responsible for most new infections is in stark contrast with the mixed availability of evidence that lends support to effective behavioural interventions for prevention. As the largest available platform for testing innovative interventions and methods, and for implementation of research to understand effectiveness at scale, it is incumbent on PEPFAR to contribute to filling this knowledge gap. Without better knowledge, investment will tip towards an unbalanced implementation of biomedical approaches. Although these measures are profoundly important and should also be supported, they will be insufficient to address the multiple, complex factors that underlie HIV transmission. As PEPFAR matures, it has been moving away from the emergency response that defined its early existence towards embedding a country’s ability to respond within its existing health system. This evolution brings new challenges and inherent tensions among different aims of the initiative. This transition was among the key topics for which robust evidence emerged from the committee’s interviews. Over time, there has been a growing expectation from the global community that partner countries assume greater ownership of HIV programmes in response to their epidemics by defining goals, increasing service provision, and providing more funding. PEPFAR increasingly is supporting partner countries’ planning and development of national frameworks, policies, and strategic plans, which are 752
crucial for a sustained HIV response that is nationally led. This will shift PEPFAR’s efforts and investments away from providing services directly in favour of providing technical assistance and capacity building. This new era will require an adjustment in assessing PEPFAR’s performance and progress to focus on its contribution to the improved effectiveness of national efforts rather than direct attribution of results. While transitioning to new models of PEPFAR support will be part of a necessary strategy for fostering sustainable management and enhancing country ownership, it also carries inherent risks that the same rate of progress toward targets and the same access to services for populations in need will not be achievable, and that the quality of services, programmes, and information might diminish. At the same time, greater embedding of HIV services in national health systems might offer opportunities for better integration of care, greater efficiencies, and broader health benefits. In the transition to increasing country ownership, PEPFAR’s influence will lessen and gradually cede control as partner countries adopt more dominant roles in strategic priority setting for any investment in their HIV response and accountability for their results. In the evaluation report, this process of transition was described by one interviewee from the US Government: “The transition has to occur with trust, they shouldn’t be afraid to let go but at the same time they need to have systems in place to make sure the quality of the care provided is ensured. There is anxiety about readiness… It’s time to change the relationship with the countries, changing the role of PEPFAR staff from the person who manages the program to the person who is with the person who manages the program.”1 Comprehensive plans for future US Government support should focus on long-term systems strengthening and capacity building in partner countries. The essential pillars will be components of health systems that support service delivery and leadership capacity for financial management, programme management, and knowledge management. Important elements must be strengthening processes and capacity for evidenceinformed decision making and for establishing mutually agreed principles for priority setting and making difficult choices about the best use of limited resources. The pace of the transition to this new era and the necessary steps to achieve it will vary by country. The www.thelancet.com Vol 382 August 31, 2013
Comment
resulting progress will take time, but the evolution is vital to ensure the sustainability and completeness of the response to HIV. Robert E Black Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA [email protected]
I was Chair for the Institute of Medicine Committee on the Outcome and Impact Evaluation of the Global HIV/AIDS Programs Implemented Under the Lantos-Hyde Act. I have no financial conflicts of interest. 1 2
3
Institute of Medicine. Evaluation of PEPFAR. Washington, DC: National Academies Press, 2013. Office of the Global AIDS Coordinator. PEPFAR blueprint: creating an AIDS-free generation. Washington, DC: Office of the Global AIDS Coordinator, 2012. Tom Lantos and Henry J Hyde United States Global Leadership Against HIV/AIDS, Tuberculosis, and Malaria Reauthorization Act of 2008 (P.L. 110-293) at §101(c), 22 U.S.C. 7611(c).
Let’s talk therapy: treatments for children with autism The biological causes of autism spectrum disorders remain poorly understood, thus limiting treatment and prevention strategies. Neuropharmacological treatments are widely used to treat symptoms of autism, such as risperidone for repetitive behaviour and haloperidol for hyperactivity. Multiple pharmacological agents might be prescribed together to treat different symptoms, and adverse events can include weight gain, fatigue, extrapyramidal symptoms, and seizures, among others.1 It might seem surprising that there is a growing trend to prescribe antipsychotics to children with autism.2 Antipsychotics were not developed to treat people with autism spectrum disorders. Published studies of antipsychotics in autism can be plagued by limitations of design, such as short follow up, and reported substantial adverse events.3 There is, therefore, a need for more double-blind, randomised controlled trials of medication to treat symptoms in people with autism. Moreover, publication bias could lead to unrealistic expectations of the effectiveness of antipsychotic drugs.4 The sedative effects of antipsychotics might reduce the incidence of challenging behaviour in some children with autism, but this is not a permanent, condition-specific, or, some would argue, acceptable solution. Some psychosocial treatments, such as cognitive behavioural therapy, are known to improve symptoms of autism.5 A treatment strategy for children with autism that incorporates occupational therapy, for example, would improve developmental skills, such as joint attention, memory, problem solving, and decision making.6 Further research is needed to explore the efficacy of psychosocial therapies, because such treatment strategies might not only be beneficial for children with autism spectrum disorders, but also lack harmful side-effects. www.thelancet.com Vol 382 August 31, 2013
Given that the risk–benefit ratio for behavioural and psychosocial therapies seems to be lower than that for pharmacological interventions in children with autism, health-care professionals should make families aware of non-pharmaceutical treatment options where resources permit. Managing the hyperactive behaviour of a child with autism can be a challenge for families,7 and medication might seem to be a simple solution. But until there is a more thorough understanding of the biological mechanisms that underlie autism spectrum disorders, which would allow targeted interventions, clinicians should put their prescription pads aside and instead inform families of productive alternatives, such as support groups and respite care programmes, in addition to referrals to speech, occupational, and behavioural therapy. Michael Granovetter Princeton University, Princeton, NJ 08544, USA [email protected] I declare that I have no conflicts of interest. 1
2
3
4 5
6
7
Dove D, Warren Z, McPheeters ML, Taylor JL, Sathe NA, Veenstra-VanderWeele J. Medications for adolescents and young adults with autism spectrum disorders: a systematic review. Pediatrics 2012; 130: 717–26. Murray ML, Hsia Y, Glaser K, et al. Pharmacological treatments prescribed to people with autism spectrum disorder (ASD) in primary health care. Psychopharmacology (Berl) 2013; published online May 17. http://dx.doi. org/10.1007/s00213-013-3140-7. Dua V. Commentary on: “review of the pharmacotherapy of irritability of autism”: a skeptic’s view on second generation antipsychotics in autism. J Can Acad Child Adolesc Psychiatry 2012; 21: 165–66. Turner EH. Publication bias, with a focus on psychiatry: causes and solutions. CNS Drugs 2013; 27: 456–68. Storch EA, Arnold EB, Lewin AB, et al. The effect of cognitive-behavioral therapy versus treatment as usual for anxiety in children with autism spectrum disorders: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry 2013; 52: 132–42. Frolek Clark GJ, Schlabach TL. Systematic review of occupational therapy interventions to improve cognitive development in children ages birth–5 years. Am J Occup Ther 2013; 67: 425–30. Harper A, Dyches TT, Harper J, Roper SO, South M. Respite care, marital quality, and stress in parents of children with autism spectrum disorders. J Autism Dev Disord 2013; published online March 26. http://dx.doi.org/ 10.1007/s10803-013-1812-0.
753
achieve and maintain therapeutic anticoagulation is a goal that will be accomplished one polymorphism at a time.
7
8
Mark J Alberts UTSW Medical Center, Dallas, TX 75390–8897, USA [email protected]
9
I have been a paid consultant and speaker for Boehringer Ingelheim, Janssen Pharmaceuticals, Bristol-Myers Squibb, Pfizer, and Merck.
10
1
2 3 4
5
6
Newman DH, Zhitomirsky I. The prevalence of nontherapeutic and dangerous international normalized ratios among patients receiving warfarin in the emergency department. Ann Emerg Med 2006; 48: 182–89. Tan GM, Wu E, Lam YY, Yan BP. Role of warfarin pharmacogenetic testing in clinical practice. Pharmacogenomics 2010; 11: 439–48. Loebstein R, Yonath H, Peleg D, et al. Interindividual variability in sensitivity to warfarin—nature or nurture? Clin Pharm Therapeut 2001; 70: 159–64. Rieder MJ, Reiner AP, Gage BF, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. New Engl J Med 2005; 352: 2285–93. Mlynarsky L, Bejarano-Achache I, Muszkat M, Caraco Y. Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers. Eur J Clin Pharm 2012; 68: 617–27. Nakamura K, Obayashi K, Araki T, et al. CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects. J Pharm Therapeut 2012; 37: 481–85.
11
12 13 14 15
Lane S, Al-Zubiedi S, Hatch E, et al. The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors. Brit J Clin Pharm 2012; 73: 66–76. Limdi NA, Beasley TM, Crowley MR, et al. VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans. Pharmacogenomics 2008; 9: 1445–58. Yang L, Ge W, Yu F, Zhu H. Impact of VKORC1 gene polymorphism on interindividual and interethnic warfarin dosage requirement—a systematic review and meta analysis. Thromb Res 2010; 125: e159–66. Voora D, Koboldt DC, King CR, et al. A polymorphism in the VKORC1 regulator calumenin predicts higher warfarin dose requirements in African Americans. Clin Pharm Therapeut 2010; 87: 445–51. Perera MA, Cavallari LH, Limdi NA, et al. Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study. Lancet 2013; published online June 5. http://dx.doi.org/10.1016/ S0140-6736(13)60681-9. Ott J. Association of genetic loci: replication or not, that is the question. Neurology 2004; 63: 955–58. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet 2001; 29: 306–09. Thompson CA. FDA encourages genetics-aided warfarin dosing. Am J Health Syst Pharm 2007; 64: 1994–96. Steffel J, Braunwald E. Novel oral anticoagulants: focus on stroke prevention and treatment of venous thrombo-embolism. Eur Heart J 2011; 32: 1968–76.
A decade ago the world faced the devastating consequences of an HIV pandemic that to many seemed unstoppable. But when the US Government committed support to the response to HIV in 2003 by creating the largest bilateral global health programme in history, it set bold goals. Thanks to its investments in HIV programmes and its health diplomacy efforts in partner countries around the globe, especially in those most affected by HIV, the US initiative known as the President’s Emergency Plan for AIDS Relief (PEPFAR) met or even surpassed most of those goals: saving the lives of millions of people; supporting the scale-up of HIV prevention, care, and treatment; and strengthening systems and policies for the HIV response.1 For example, according to the most recent results reported by PEPFAR, as of September, 2012, the US Government has supported life-saving antiretroviral treatment for nearly 5·1 million men, women, and children worldwide.2 In fiscal year 2012, PEPFAR supported antiretroviral drugs for the prevention of mother-to-child transmission for nearly 750 000 pregnant women who were HIV positive.2 With this success, PEPFAR restored hope to many and changed people’s ideas for what can be accomplished in global health with ambitious aims and ample funding. www.thelancet.com Vol 382 August 31, 2013
PEPFAR’s Congressional reauthorisation in 2008 asked the US Institute of Medicine to assess the effectiveness of the US Government’s response to global HIV/AIDS.3 The assessment, done over 4 years, examines PEPFAR since its inception. It drew on a variety of data sources, including financial data, programme monitoring indicators and clinical data, extensive document review, and primary data collection through more than 400 semi-structured interviews with a range of stakeholders in 13 PEPFAR partner countries, at PEPFAR headquarters, and from other institutions and multilateral agencies involved in the global HIV response. This assessment’s painstaking analysis through rigorous mixed quantitative and qualitative methods provided the assessment committee at the Institute of Medicine with an unprecedented depth of knowledge to speak in a strong voice about how to improve the federal government’s support for the global response to HIV/AIDS. The resulting report, Evaluation of PEPFAR, was released on Feb 20, 2013.1 The report outlines key challenges for the future. Despite a decade of investment from the US Government, other international donors, and countries themselves, many challenges remain. Even with PEPFAR’s contribution to the substantial scale-up of HIV services in countries with restricted resources and
Institute of Medicine of the National Academies
The future of the US response to global HIV/AIDS
Published Online February 20, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)60184-1
For the report, Evaluation of PEPFAR, see http://www.iom. edu
751
Comment
infrastructure, the most profound challenge is simply the unmet need. In the future, it will be crucial for PEPFAR to work effectively with partner countries and global stakeholders to ensure that hard-fought gains are sustained and to continue to make progress against the HIV pandemic in the face of a weak global economy and many competing demands for resources for health and development. In addition to achieving adequate coverage of services, fundamentally altering the course of the HIV epidemic will hinge on a renewed and strengthened emphasis on HIV prevention. Developing and implementing appropriately comprehensive prevention programme portfolios is an important challenge. Even as it maintains its support for interventions that target all modes of HIV transmission, PEPFAR should prioritise reduction of sexual transmission. The unequivocal epidemiological evidence that sexual transmission, with underlying behavioural drivers, is responsible for most new infections is in stark contrast with the mixed availability of evidence that lends support to effective behavioural interventions for prevention. As the largest available platform for testing innovative interventions and methods, and for implementation of research to understand effectiveness at scale, it is incumbent on PEPFAR to contribute to filling this knowledge gap. Without better knowledge, investment will tip towards an unbalanced implementation of biomedical approaches. Although these measures are profoundly important and should also be supported, they will be insufficient to address the multiple, complex factors that underlie HIV transmission. As PEPFAR matures, it has been moving away from the emergency response that defined its early existence towards embedding a country’s ability to respond within its existing health system. This evolution brings new challenges and inherent tensions among different aims of the initiative. This transition was among the key topics for which robust evidence emerged from the committee’s interviews. Over time, there has been a growing expectation from the global community that partner countries assume greater ownership of HIV programmes in response to their epidemics by defining goals, increasing service provision, and providing more funding. PEPFAR increasingly is supporting partner countries’ planning and development of national frameworks, policies, and strategic plans, which are 752
crucial for a sustained HIV response that is nationally led. This will shift PEPFAR’s efforts and investments away from providing services directly in favour of providing technical assistance and capacity building. This new era will require an adjustment in assessing PEPFAR’s performance and progress to focus on its contribution to the improved effectiveness of national efforts rather than direct attribution of results. While transitioning to new models of PEPFAR support will be part of a necessary strategy for fostering sustainable management and enhancing country ownership, it also carries inherent risks that the same rate of progress toward targets and the same access to services for populations in need will not be achievable, and that the quality of services, programmes, and information might diminish. At the same time, greater embedding of HIV services in national health systems might offer opportunities for better integration of care, greater efficiencies, and broader health benefits. In the transition to increasing country ownership, PEPFAR’s influence will lessen and gradually cede control as partner countries adopt more dominant roles in strategic priority setting for any investment in their HIV response and accountability for their results. In the evaluation report, this process of transition was described by one interviewee from the US Government: “The transition has to occur with trust, they shouldn’t be afraid to let go but at the same time they need to have systems in place to make sure the quality of the care provided is ensured. There is anxiety about readiness… It’s time to change the relationship with the countries, changing the role of PEPFAR staff from the person who manages the program to the person who is with the person who manages the program.”1 Comprehensive plans for future US Government support should focus on long-term systems strengthening and capacity building in partner countries. The essential pillars will be components of health systems that support service delivery and leadership capacity for financial management, programme management, and knowledge management. Important elements must be strengthening processes and capacity for evidenceinformed decision making and for establishing mutually agreed principles for priority setting and making difficult choices about the best use of limited resources. The pace of the transition to this new era and the necessary steps to achieve it will vary by country. The www.thelancet.com Vol 382 August 31, 2013
Comment
resulting progress will take time, but the evolution is vital to ensure the sustainability and completeness of the response to HIV. Robert E Black Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA [email protected]
I was Chair for the Institute of Medicine Committee on the Outcome and Impact Evaluation of the Global HIV/AIDS Programs Implemented Under the Lantos-Hyde Act. I have no financial conflicts of interest. 1 2
3
Institute of Medicine. Evaluation of PEPFAR. Washington, DC: National Academies Press, 2013. Office of the Global AIDS Coordinator. PEPFAR blueprint: creating an AIDS-free generation. Washington, DC: Office of the Global AIDS Coordinator, 2012. Tom Lantos and Henry J Hyde United States Global Leadership Against HIV/AIDS, Tuberculosis, and Malaria Reauthorization Act of 2008 (P.L. 110-293) at §101(c), 22 U.S.C. 7611(c).
Let’s talk therapy: treatments for children with autism The biological causes of autism spectrum disorders remain poorly understood, thus limiting treatment and prevention strategies. Neuropharmacological treatments are widely used to treat symptoms of autism, such as risperidone for repetitive behaviour and haloperidol for hyperactivity. Multiple pharmacological agents might be prescribed together to treat different symptoms, and adverse events can include weight gain, fatigue, extrapyramidal symptoms, and seizures, among others.1 It might seem surprising that there is a growing trend to prescribe antipsychotics to children with autism.2 Antipsychotics were not developed to treat people with autism spectrum disorders. Published studies of antipsychotics in autism can be plagued by limitations of design, such as short follow up, and reported substantial adverse events.3 There is, therefore, a need for more double-blind, randomised controlled trials of medication to treat symptoms in people with autism. Moreover, publication bias could lead to unrealistic expectations of the effectiveness of antipsychotic drugs.4 The sedative effects of antipsychotics might reduce the incidence of challenging behaviour in some children with autism, but this is not a permanent, condition-specific, or, some would argue, acceptable solution. Some psychosocial treatments, such as cognitive behavioural therapy, are known to improve symptoms of autism.5 A treatment strategy for children with autism that incorporates occupational therapy, for example, would improve developmental skills, such as joint attention, memory, problem solving, and decision making.6 Further research is needed to explore the efficacy of psychosocial therapies, because such treatment strategies might not only be beneficial for children with autism spectrum disorders, but also lack harmful side-effects. www.thelancet.com Vol 382 August 31, 2013
Given that the risk–benefit ratio for behavioural and psychosocial therapies seems to be lower than that for pharmacological interventions in children with autism, health-care professionals should make families aware of non-pharmaceutical treatment options where resources permit. Managing the hyperactive behaviour of a child with autism can be a challenge for families,7 and medication might seem to be a simple solution. But until there is a more thorough understanding of the biological mechanisms that underlie autism spectrum disorders, which would allow targeted interventions, clinicians should put their prescription pads aside and instead inform families of productive alternatives, such as support groups and respite care programmes, in addition to referrals to speech, occupational, and behavioural therapy. Michael Granovetter Princeton University, Princeton, NJ 08544, USA [email protected] I declare that I have no conflicts of interest. 1
2
3
4 5
6
7
Dove D, Warren Z, McPheeters ML, Taylor JL, Sathe NA, Veenstra-VanderWeele J. Medications for adolescents and young adults with autism spectrum disorders: a systematic review. Pediatrics 2012; 130: 717–26. Murray ML, Hsia Y, Glaser K, et al. Pharmacological treatments prescribed to people with autism spectrum disorder (ASD) in primary health care. Psychopharmacology (Berl) 2013; published online May 17. http://dx.doi. org/10.1007/s00213-013-3140-7. Dua V. Commentary on: “review of the pharmacotherapy of irritability of autism”: a skeptic’s view on second generation antipsychotics in autism. J Can Acad Child Adolesc Psychiatry 2012; 21: 165–66. Turner EH. Publication bias, with a focus on psychiatry: causes and solutions. CNS Drugs 2013; 27: 456–68. Storch EA, Arnold EB, Lewin AB, et al. The effect of cognitive-behavioral therapy versus treatment as usual for anxiety in children with autism spectrum disorders: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry 2013; 52: 132–42. Frolek Clark GJ, Schlabach TL. Systematic review of occupational therapy interventions to improve cognitive development in children ages birth–5 years. Am J Occup Ther 2013; 67: 425–30. Harper A, Dyches TT, Harper J, Roper SO, South M. Respite care, marital quality, and stress in parents of children with autism spectrum disorders. J Autism Dev Disord 2013; published online March 26. http://dx.doi.org/ 10.1007/s10803-013-1812-0.
753