{"id":47969,"date":"2014-07-07T11:56:22","date_gmt":"2014-07-07T15:56:22","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=47969"},"modified":"2014-07-07T12:11:00","modified_gmt":"2014-07-07T16:11:00","slug":"part-three-the-questions","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2014\/07\/07\/part-three-the-questions\/","title":{"rendered":"part three: the questions&#8230;"},"content":{"rendered":"\n<div align=\"justify\" class=\"small\">As for efficacy, Tyrer et al say [see <a href=\"http:\/\/1boringoldman.com\/index.php\/2014\/07\/06\/47923\/\" target=\"_blank\">part one: the bind&hellip;<\/a>]:        <\/div>\n<ul>\n<div align=\"justify\" class=\"small\"><font color=\"#200020\">What  is the evidence for the benefits of these drugs in the treatment  of  challenging behaviour? Virtually none. Almost all the evidence in  favour  comes from small trials conducted by drug companies.  Yet it  would be perverse if doctors continued to prescribe these drugs,   knowing about their adverse effects, if they were entirely without   efficacy, and many claim that they cannot care adequately for their   patients without the option of drug treatment&#8230;<\/font><\/div>\n<\/ul>\n<div align=\"justify\" class=\"small\">In 2012, a Cochrane Systematic Review [not limited to children with mental retardation] found only eight studies of a quality to include &#8211; seven with <strong><font color=\"#200020\">Risperdal&reg;<\/font><\/strong> and one with <strong><font color=\"#200020\">Seroquel&reg;<\/font><\/strong>:         <\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22972123\" target=\"_blank\">Atypical antipsychotics for disruptive behaviour disorders in children and youths.<\/a><\/div>\n<div align=\"center\" class=\"small\">by Loy JH, Merry SN, Hetrick SE, and Stasiak K.<\/div>\n<div align=\"center\" class=\"middle\"> <strong><font color=\"#200020\">Cochrane Database of Systematic Reviews<\/font><\/strong>. 2012 9:CD008559 .<\/div>\n<p>             <\/p>\n<div align=\"justify\"><u><strong><font color=\"#200020\">BACKGROUND<\/font><\/strong><\/u>: Disruptive  behaviour disorders include conduct disorder, oppositional defiant  disorder and disruptive behaviour not otherwise specified. Attention  deficit hyperactivity disorder [ADHD] is frequently associated with  disruptive behaviour disorders. The difficulties associated with  disruptive behaviour disorders are demonstrated through aggression and  severe behavioural problems. These often result in presentation to  psychiatric services and may be treated with medications such as  atypical antipsychotics. There is increasing evidence of a significant  rise in the use of atypical antipsychotics for treating disruptive  behaviour disorders in child and adolescent populations.<\/div>\n<div align=\"justify\"><u><strong><font color=\"#200020\">OBJECTIVES<\/font><\/strong><\/u>: To  evaluate the effect and safety of atypical antipsychotics, compared to  placebo, for treating disruptive behaviour disorders in children and  youths.<\/div>\n<div align=\"justify\"><u><strong><font color=\"#200020\">SEARCH METHODS<\/font><\/strong><\/u>: We searched the following  databases in August 2011: CENTRAL&#8230; MEDLINE&#8230; EMBASE&#8230; PsycINFO&#8230; CINAHL&#8230; ClinicalTrials.gov&#8230; Australian New Zealand Clinical Trials Registry&#8230; CenterWatch&#8230; and  ICTRP&#8230;<\/div>\n<div align=\"justify\"><u><strong><font color=\"#200020\">SELECTION CRITERIA<\/font><\/strong><\/u>: We  included randomised controlled trials with children and youths up to and  including the age of 18, in any setting, with a diagnosis of a  disruptive behaviour disorder. We included trials where participants had  a comorbid diagnosis of attention deficit hyperactivity disorder, major  depression or an anxiety disorder&#8230;<\/div>\n<div align=\"justify\"><u><strong><font color=\"#200020\">MAIN RESULTS<\/font><\/strong><\/u>: We  included eight randomised controlled trials, spanning 2000 to 2008.  Seven assessed risperidone and one assessed quetiapine. Three of the  studies were multicentre. Seven trials assessed acute efficacy and one  assessed time to symptom recurrence over a six-month maintenance  period.We performed meta-analyses for the primary outcomes of  aggression, conduct problems and weight changes but these were limited  by the available data as different trials reported either mean change  scores [average difference] or final\/post-intervention raw scores and  used different outcome measures. We also evaluated each individual  trial&#8217;s treatment effect size where possible, using Hedges&#8217; g.For  aggression, we conducted two meta-analyses. The first included three  trials [combined n = 238] using mean difference [MD] on the Aberrant  Behaviour Checklist [ABC] Irritability subscale. Results yielded a final  mean score with treatment that was 6.49 points lower than the  post-intervention mean score with placebo [95% confidence interval [CI]  -8.79 to -4.19]. The second meta-analysis on aggression included two  trials [combined n = 57] that employed two different outcome measures  [Overt Aggression Scale [modified] [OAS-M] and OAS, respectively] and  thus we used a standardised mean difference. Results yielded an effect  estimate of -0.18 [95% CI -0.70 to 0.34], which was statistically  non-significant.We also performed two meta-analyses for conduct  problems. The first included two trials [combined n = 225], both of  which employed the Nisonger Child Behaviour Rating Form &#8211; Conduct  Problem subscale [NCBRF-CP]. The results yielded a final mean score with  treatment that was 8.61 points lower than that with placebo [95% CI  -11.49 to -5.74]. The second meta-analysis on conduct problems included  two trials [combined n = 36], which used the Conners&#8217; Parent Rating  Scale &#8211; Conduct Problem subscale [CPRS-CP]. Results yielded a mean score  with treatment of 12.67 lower than with placebo [95% CI -37.45 to  12.11], which was a statistically non-significant result.With respect to  the side effect of weight gain, a meta-analysis of two studies  [combined n = 138] showed that participants on risperidone gained on  average 2.37 kilograms more than those in the placebo group over the  treatment period [MD 2.37; 95% CI 0.26 to 4.49].For individual trials,  there was a range of effect sizes [ranging from small to large] for  risperidone reducing aggression and conduct problems. The precision of  the estimate of the effect size varied between trials.<\/div>\n<div align=\"justify\"><u><strong><font color=\"#200020\">AUTHORS&#8217; CONCLUSIONS<\/font><\/strong><\/u>: There  is some limited evidence of efficacy of risperidone reducing aggression  and conduct problems in children aged 5 to 18 with disruptive behaviour  disorders in the short term. For aggression, the difference in scores of  6.49 points on the ABC Irritability subscale [range 0 to 45] may be  clinically significant. For conduct problems, the difference in scores  of 8.61 points on the NCBRF-CP [range 0 to 48] is likely to be  clinically significant. Caution is required due to the limitations of the  evidence and the small number of relevant high-quality studies. The  findings from the one study assessing impact in the longer term suggest  that the effects are maintained to some extent [small effect size] for  up to six months. Inadequately powered studies produced non-significant  results. The evidence is restricted by heterogeneity of the population  [including below average and borderline IQ], and methodological issues  in some studies, such as use of enriched designs and risk of selection  bias&#8230; Further high-quality  research is required with large samples of clinically representative  youths and long-term follow-up to replicate current findings.<\/div>\n<\/blockquote>\n<div align=\"justify\" class=\"small\">Nothing much to write home about there &#8211; confirming Tyrer et al&#8217;s point that although the use of antipsychotics in intellectually impaired kids with challenging\/disruptive behavior is near &quot;<em>Dogma<\/em>,&quot; it&#8217;s not &quot;<em>evidence-based Dogma<\/em>.&quot; It&#8217;s just what &quot;<em>doctors-habitually-think-Dogma.<\/em>&quot; So all the questions remain unanswered:<\/div>\n<ul>\n<li>\n<div align=\"justify\" class=\"small\"><font color=\"#200020\">Are [Atypical] Antipsychotics effective in managing challenging\/disruptive behavior in intellectually impaired children? or for that matter, children with other non-psychotic diagnoses? Short term? Long term?<\/font><\/div>\n<\/li>\n<li>\n<div align=\"justify\" class=\"small\"><font color=\"#200020\">What is the incidence of various Adverse Effects using [Atypical] Antipsychotics in intellectually impaired children? or again, children with other non-psychotic diagnoses? Short term? Long term? Are these drugs actually harmful?<\/font><\/div>\n<\/li>\n<li>\n<div align=\"justify\" class=\"small\"><font color=\"#200020\">What are alternative recommendations for managing challenging\/disruptive behavior in retarded children? or children with other non-psychotic diagnoses? Short term? Long term? <\/font>      <\/div>\n<\/li>\n<\/ul>\n<div align=\"justify\" class=\"small\">The ubiquitous influence of the pharmaceutical industry and the cost-cutting restrictions of managed care have had an enormous influence on the way we approach issues like this over the last fifty years.<em> The editorial by Tyrer points out that the use of antipsychotics [I would add particularly Atypical Antipsychotics, particularly <strong><font color=\"#200020\">Risperdal&reg;<\/font><\/strong>] is based on a belief that has achieved the level of <\/em><em>Dogma<\/em>, but the basis for that belief is hardly confirmed by the available scientific record. The problem their editorial addresses &#8211; the use of antipsychotics in mentally retarded children &#8211; seems to me to encompass an even greater domain than they mention i.e. Autism, primary behavioral problems, <em>whatever-the-Biederman-Bipolar-kids<\/em> represented, other non-psychotic conditions. And the answer to the question &quot;<em>What is the best practice response, if any, to challenging\/disruptive behavior in children with intellectual impairment?<\/em>&quot; is actually unknown, as is specifically &quot;<em>What is the place of antipsychotics, if any?<\/em>&quot;<\/div>\n<p align=\"justify\" class=\"small\">Parenthetically, I marvel at how a study like Aman et al&#8217;s [<em><strong><font color=\"#200020\">Risperidone Disruptive Behavior Study Group<\/font><\/strong><\/em>] <a href=\"http:\/\/ajp.psychiatryonline.org.proxy.library.emory.edu\/cgi\/content\/full\/159\/8\/1337\" target=\"_blank\">Double-Blind,     Placebo-Controlled Study of Risperidone for the Treatment of    Disruptive  Behaviors in Children With Subaverage Intelligence<\/a> can have such a large effect over the years. It was a small industry run study that was part of a failed attempt early on get approval for the behavioral management of mentally retarded children. It was reincarnated as a justification for using antipsychotics in kids with  &quot;<strong><font color=\"#000000\">super angry\/grouchy\/cranky irritability<\/font><\/strong>&quot; that came to be called Bipolar, at least for a time. And here fifteen years later, it remains as 1\/7th of the literature suitable for the Cochrane meta-analysis.<\/p>\n<div align=\"justify\" class=\"small\">I&#8217;m aware that I put more emphasis on the impact of PHARMA on this prescribing practice than Tyrer et al. I don&#8217;t think that&#8217;s because I&#8217;m some kind of wild-eyed activist. I think it&#8217;s because I heard it in person with my own ears when I went to the J&amp;J\/TMAP trial in Austin in January 2012 [<a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/the-trial\/\">State of Texas and Allen Jones v. Janssen et al<\/a>]. If you find yourself doubting that influence, I&#8217;ve posted the <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/the-trial\/\">transcripts<\/a> of that trial. I would recommend reading the testimony of sales rep <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/texas-transcripts\/2012-01-17%20State%20v.%20Janssen%20Vol%206.pdf#page=11\">Tiffany Moake<\/a> and particularly sales manager <strong><font color=\"#200020\">Tone Jones<\/font><\/strong> [<a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/texas-transcripts\/2012-01-17%20State%20v.%20Janssen%20Vol%206.pdf#page=207\">here<\/a> and <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/texas-transcripts\/2012-01-18%20State%20v.%20Janssen%20Vol%207-1.pdf#page=5\">here<\/a>]. I can pretty much guarantee that you will come around to my view before you are halfway through.   <\/div>\n","protected":false},"excerpt":{"rendered":"<p>As for efficacy, Tyrer et al say [see part one: the bind&hellip;]: What is the evidence for the benefits of these drugs in the treatment of challenging behaviour? Virtually none. Almost all the evidence in favour comes from small trials conducted by drug companies. Yet it would be perverse if doctors continued to prescribe these [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-47969","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/47969","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=47969"}],"version-history":[{"count":15,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/47969\/revisions"}],"predecessor-version":[{"id":47985,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/47969\/revisions\/47985"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=47969"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=47969"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=47969"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}