{"id":12577,"date":"2011-08-28T11:09:37","date_gmt":"2011-08-28T15:09:37","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=12577"},"modified":"2011-08-28T11:09:37","modified_gmt":"2011-08-28T15:09:37","slug":"2-when-na-few","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2011\/08\/28\/2-when-na-few\/","title":{"rendered":"2. <em>when n=a few<\/em>&#8230;"},"content":{"rendered":"\n<div align=\"justify\">This post takes a look at what others have found using the idea of an &quot;ultra high risk&quot; group of people that may develop ouvert Schizophrenia. The first study is from The University of Manchester, UK. They looked at the effect of Cognitive Therapy in the high risk group [four articles]:<\/div>\n<blockquote>\n<div align=\"center\"><u><strong><a target=\"_blank\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12271805\"><font color=\"#200020\">Randomised  controlled trial of early detection and cognitive therapy for  preventing transition to psychosis in high-risk individuals. Study  design and interim analysis of transition rate and psychological risk  factors.<\/font><\/a><\/strong><\/u><br \/>                        <sup>by Morrison AP, Bentall RP, French P, Walford L, Kilcommons A, Knight A, Kreutz M, and Lewis SW.<\/sup><br \/>                        <strong><font color=\"#200020\">British Journal of Psychiatry<\/font><\/strong> Supplement 2002 43:s78-84.<\/div>\n<p>                        <\/p>\n<div align=\"justify\"><sup><u><strong><font color=\"#200020\">BACKGROUND<\/font><\/strong><\/u>: There  is interest in the possibility of indicated prevention of psychosis.  There is a strong case for using psychological approaches to prevent  transition to psychosis in high-risk patients.<br \/>                         <u><strong><font color=\"#200020\">AIMS<\/font><\/strong><\/u>: To  identify individuals at high risk of transition to psychosis, and  psychological characteristics relevant to the development of psychosis  in this group.<br \/>                         <u><strong><font color=\"#200020\">METHOD<\/font><\/strong><\/u>: The design of a randomised  controlled trial of cognitive therapy for the prevention of psychosis in  people at high risk (meeting operational criteria of brief or  attenuated psychotic symptoms, or first-degree family history with  functional decline) is outlined. The first patients recruited are  compared with non-patient samples on cognitive and personality factors;  an interim analysis of transition rate is reported.<br \/>                         <u><strong><font color=\"#200020\">RESULTS<\/font><\/strong><\/u>: Cases  (n = 31) were recruited mainly from primary care. Of the 23 high-risk  patients monitored for 6-12 months, 5 (22%) made the transition to  psychosis. The high-risk group scored significantly higher than  non-patients on measures of schizotypy, metacognitive beliefs and  dysfunctional self-schemas (sociotropy).<br \/>                         <u><strong><font color=\"#200020\">CONCLUSIONS<\/font><\/strong><\/u>: The  findings validate the methods of identifying individuals at high risk  of experiencing a psychotic episode. Compared with non-patient controls,  the cases showed dysfunctional metacognitive beliefs and self-schemas. <\/sup><\/div>\n<p>                  <\/p>\n<div align=\"center\"><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15458988\" target=\"_blank\"><u><strong><font color=\"#200020\">Cognitive therapy for the prevention of psychosis in people at ultra-high risk: randomised controlled trial.<\/font><\/strong><\/u><\/a><br \/>                       <sup>by Morrison AP, French P, Walford L, Lewis SW, Kilcommons A, Green J, Parker S, and Bentall RP.<\/sup><br \/>                       <strong><font color=\"#200020\">British Journal of Psychiatry<\/font><\/strong> . 2004 185:291-7.<\/div>\n<div align=\"center\">[<a target=\"_blank\" href=\"http:\/\/bjp.rcpsych.org\/content\/185\/4\/291.long\"><u><strong><font color=\"#200020\">full text online<\/font><\/strong><\/u><\/a>]                       <\/div>\n<p>                      <\/p>\n<div align=\"justify\"><sup><u><strong><font color=\"#200020\">BACKGROUND<\/font><\/strong><\/u>: Advances  in the ability to identify people at high risk of developing psychosis  have generated interest in the possibility of preventing psychosis.<br \/>                        <u><strong><font color=\"#200020\">AIMS<\/font><\/strong><\/u>: To evaluate the efficacy of cognitive therapy for the prevention of transition to psychosis.<br \/>                        <u><strong><font color=\"#200020\">METHOD<\/font><\/strong><\/u>: A  randomised controlled trial compared cognitive therapy with treatment  as usual in 58 patients at ultra-high risk of developing a first episode  of psychosis. Therapy was provided over 6 months, and all patients were  monitored on a monthly basis for 12 months.<br \/>                        <u><strong><font color=\"#200020\">RESULTS<\/font><\/strong><\/u>: Logistic  regression demonstrated that cognitive therapy significantly reduced  the likelihood of making progression to psychosis as defined on the  Positive and Negative Syndrome Scale over 12 months. In addition, it  significantly reduced the likelihood of being prescribed antipsychotic  medication and of meeting criteria for a DSM-IV diagnosis of a psychotic  disorder. Analysis of covariance showed that the intervention also  significantly improved positive symptoms of psychosis in this population  over the 12-month period<br \/>                        <u><strong><font color=\"#200020\">CONCLUSIONS<\/font><\/strong><\/u>: Cognitive therapy appears to be an acceptable and efficacious intervention for people at high risk of developing psychosis.<\/sup><\/div>\n<p>                  <\/p>\n<div align=\"center\"><a target=\"_blank\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16973786\"><u><strong><font color=\"#200020\">Three-year  follow-up of a randomized controlled trial of cognitive therapy for the  prevention of psychosis in people at ultrahigh risk<\/font><\/strong><\/u><\/a>.<br \/>                     <sup>by Morrison AP, French P, Parker S, Roberts M, Stevens H, Bentall RP, and Lewis SW.<\/sup><br \/>                     <strong><font color=\"#200020\">Schizophrenia Bulletin<\/font><\/strong>. 2007 33(3):682-7.<\/div>\n<div align=\"center\">[<a target=\"_blank\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2526150\/?tool=pubmed\"><u><strong><font color=\"#200020\">full text online<\/font><\/strong><\/u><\/a>]                      <\/div>\n<p>                     <\/p>\n<div align=\"justify\"><sup>There  have been recent advances in the ability to identify people at high  risk of developing psychosis. This has led to interest in the  possibility of preventing the development of psychosis. A randomized  controlled trial compared cognitive therapy (CT) over 6 months with  monthly monitoring in 58 patients meeting criteria for ultrahigh risk of  developing a first episode of psychosis. Participants were followed up  over a 3-year period. Logistic regression demonstrated that CT  significantly reduced likelihood of being prescribed antipsychotic  medication over a 3-year period, but it did not affect transition to  psychosis defined using the Positive and Negative Syndrome Scale (PANSS)  or probable Diagnostic and Statistical Manual of Mental Disorders,  Fourth Edition diagnosis. However, exploratory analyses revealed that CT  significantly reduced the likelihood of making progression to psychosis  as defined on the PANSS over 3 years after controlling for baseline  cognitive factors. Follow-up rate at 3 years was 47%. There appear to be  enduring benefits of CT over the long term, suggesting that it is an  efficacious intervention for people at high risk of developing  psychosis.<\/sup><\/div>\n<p>                  <\/p>\n<div align=\"center\"><a target=\"_blank\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18055943\"><u><strong><font color=\"#200020\">Effects of cognitive therapy on the longitudinal development of psychotic experiences in people at high risk of developing psychosis.<\/font><\/strong><\/u><\/a><br \/>                   <sup>by French P, Shryane N, Bentall RP, Lewis SW, and Morrison AP.<br \/>                    <strong><font color=\"#200020\">British Journal of Psychiatry<\/font><\/strong> Supplement&nbsp; 2007 51:s82-7.<\/sup><\/div>\n<p>                   <\/p>\n<div align=\"justify\"><sup><u><strong><font color=\"#200020\">BACKGROUND<\/font><\/strong><\/u>: There  have been recent advances in the identification of people at high risk  of psychosis and psychological treatments have shown promise for  prevention.<br \/>                     <u><strong><font color=\"#200020\">AIMS<\/font><\/strong><\/u>: To compare the longitudinal course of  psychotic experiences and emotional dysfunction in high-risk  participants receiving cognitive therapy with those receiving treatment  as usual.<br \/>                     <u><strong><font color=\"#200020\">METHOD<\/font><\/strong><\/u>: Data from a recent randomised  controlled trial of cognitive therapy for people at risk of developing  psychosis were utilised to examine three different statistical models  that were based on 432 measurements of psychotic experiences and 421 of  emotional dysfunction (anxiety-depression) contributed by 57  participants across the 13 measurement occasions (monthly monitoring for  a year).<br \/>                     <u><strong><font color=\"#200020\">RESULTS<\/font><\/strong><\/u>: Psychotic experiences and emotional  dysfunction were correlated and decreased significantly over the course  of the study, with most improvement in the early months. The reduction  in positive symptoms, but not emotional dysfunction, was enhanced by  allocation to cognitive therapy.<br \/>                     <u><strong><font color=\"#200020\">CONCLUSIONS<\/font><\/strong><\/u>: Psychotic  experiences and emotional dysfunction appear to interact in people at  risk of developing psychosis. There appears to be a specific benefit of  cognitive therapy.<\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">The focus of the Manchester Group seems to be to use Cognitive Therapy as an alternative to medication in this high risk population.Their study confirmed the ability of the &quot;ultra high risk&quot; criteria predictiong coming Schizophrenia, though at a lower transition rate that McGorry [22%]. Their intervention had a statistically significant and clinically relevant effect on the transition rate. For anyone interested, their full text papers have a lot more information of interest than I mention here. The links are included above.                 <\/div>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"400\" vspace=\"5\" height=\"141\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/mcgorry-3.gif\" \/>&nbsp;<\/div>\n<div align=\"justify\">The next study is a collaborative North American clinical trial funded by <strong><font color=\"#990000\">Eli Lilly<\/font><\/strong>, maker of Olanzapine &#8211; the study drug. This study addressed only the drug intervention &#8211; Olanzapine vs Placebo:<\/div>\n<div align=\"center\">\n<blockquote>\n<div align=\"center\"><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16648318\" target=\"_blank\"><u><strong><font color=\"#200020\">Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis<\/font><\/strong><\/u><\/a>.<br \/>                <sup>by by McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller T, Woods SW, Hawkins KA, Hoffman RE, Preda A, Epstein I, Addington D, Lindborg S, Trzaskoma Q, Tohen M, and Breier A.<\/sup><br \/>                <strong><font color=\"#200020\">American Journal of Psychiatry<\/font><\/strong>. 2006 163(5):790-9.<br \/>             [<a target=\"_blank\" href=\"http:\/\/ajp.psychiatryonline.org\/cgi\/content\/full\/163\/5\/790\"><u><strong><font color=\"#200020\">full text online<\/font><\/strong><\/u><\/a>]<\/div>\n<p>        <\/p>\n<div align=\"justify\"><sup><u><strong><font color=\"#200020\">OBJECTIVE<\/font><\/strong><\/u>: This  study assessed the efficacy of olanzapine in delaying or preventing  conversion to psychosis and reducing symptoms in people with prodromal  symptoms of schizophrenia.<br \/>                 <u><strong><font color=\"#200020\">METHOD<\/font><\/strong><\/u>: This randomized trial  occurred at four North American clinics in the Prevention Through Risk  Identification, Management, and Education project. Outpatients received  olanzapine (5-15 mg\/day, N=31) or placebo (N=29) during a 1-year  double-blind treatment period and no treatment during a 1-year follow-up  period. Efficacy measures included the conversion-to-psychosis rate and  Scale of Prodromal Symptoms scores.<br \/>                 <u><strong><font color=\"#200020\">RESULTS<\/font><\/strong><\/u>: During the  treatment year, 16.1% of olanzapine patients and 37.9% of placebo  patients experienced a conversion to psychosis, a nearly significant  difference. The hazard of conversion among placebo patients was about  2.5 times that among olanzapine-treated patients, which also approached  significance. In the follow-up year, the conversion rate did not differ  significantly between groups. During treatment, the mean score for  prodromal positive symptoms improved more in the olanzapine group than  in the placebo group, and the mixed-model repeated-measures  least-squares mean score showed significantly greater improvement  between weeks 8 and 28 with olanzapine. The olanzapine patients gained  significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg,  SD=4.24).<br \/>                 <u><strong><font color=\"#200020\">CONCLUSIONS<\/font><\/strong><\/u>: A significant treatment difference  in the conversion-to-psychosis rate was not demonstrated. However,  these results may be influenced by low power. The nearly significant  differences suggest that olanzapine might reduce the conversion rate and  delay onset of psychosis. Olanzapine was efficacious for positive  prodromal symptoms but induced weight gain. Further treatment research  in this phase of illness is warranted.<\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">This study had many of the characteristics of industry-funded studies of the era. There were no conflict of interest declarations and it&#8217;s unknown if any of the authors were <strong><font color=\"#990000\">Eli Lilly<\/font><\/strong> employees. There were high drop-out rates in both groups and the correction methodology was opaque.<\/div>\n<div align=\"center\"><a href=\"http:\/\/ajp.psychiatryonline.org\/cgi\/content-nw\/full\/163\/5\/790\/T2\" target=\"_blank\"><img loading=\"lazy\" decoding=\"async\" width=\"500\" vspace=\"5\" height=\"145\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/mcgorry-4.gif\" \/><\/a><\/div>\n<div align=\"justify\">A greater proportion of placebo treated subjects developed ouvert psychosis, but the differences were not significant, though the authors suggested the &quot;nearly significant&quot; values might be meaningful.<\/div>\n<div align=\"center\"><a target=\"_blank\" href=\"http:\/\/ajp.psychiatryonline.org\/cgi\/content\/full\/163\/5\/790\/F1\"><img decoding=\"async\" width=\"300\" vspace=\"5\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/mcgorry-5.gif\" \/><\/a><\/div>\n<div align=\"justify\">One useful take-away from the study was that 21\/60 developed psychosis, seeming to validate the reported criteria and transition rate [35%].<\/div>\n<p>    <\/p>\n<div align=\"justify\">The final study is from Copenhagen:<\/div>\n<blockquote>\n<div align=\"center\"><strong><font color=\"#200020\">Transition rates from schizotypal disorder to psychotic disorder for first-contact patients included in the OPUS trial.<\/font><\/strong><br \/>      <sup><em><strong><font color=\"#200020\">A randomized clinical trial of integrated treatment and standard treatment.<\/font><\/strong><\/em><\/sup><br \/>       <sup>by Nordentoft M, Thorup A, Petersen L, Ohlenschlaeger J, Melau M, Christensen T&Oslash;, Krarup G, J&oslash;rgensen P, and Jeppesen P.<\/sup><br \/>       <strong><font color=\"#200020\">Schizophrenia Research<\/font><\/strong>. 2006 83(1):29-40.<\/div>\n<p>        <\/p>\n<div align=\"justify\"><sup><u><strong><font color=\"#200020\">BACKGROUND<\/font><\/strong><\/u>: Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms.<br \/>       <u><strong><font color=\"#200020\">AIM<\/font><\/strong><\/u>: To examine whether integrated treatment reduced transition to psychosis for first-contact patients diagnosed with schizotypal disorder.<br \/>       <u><strong><font color=\"#200020\">METHODS<\/font><\/strong><\/u>: Seventy-nine patients were randomized to integrated treatment or standard treatment. Survival analysis with multivariate Cox-regression was used to identify factors determinant for transition to psychotic disorder.<br \/>       <u><strong><font color=\"#200020\">RESULTS<\/font><\/strong><\/u>: In the multivariate model, male gender increased risk for transition to psychotic disorder (relative risk=4.47, (confidence interval 1.30-15.33)), while integrated treatment reduced the risk (relative risk=0.36 (confidence interval 0.16-0.85)). At two-year follow-up, the proportion diagnosed with a psychotic disorder was 25.0% for patients randomized to integrated treatment compared to 48.3% for patients randomized to standard treatment.<br \/>       <u><strong><font color=\"#200020\">CONCLUSION<\/font><\/strong><\/u>: Integrated treatment postponed or inhibited onset of psychosis in significantly more cases than standard treatment.<\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">While the abstract is terse, this is a solid study with thoughtful comments on the other studies reviewed above. Their intervention&nbsp; did not control all variables in that all subjects had treating physicians delivering treatment as usual including medications. Their integrated treatment was &quot;borrowed&quot; from their approach to first episode Schizophrenic patients rather than a specific CBT therapy. It involved the intensive application of more traditional methodologies:<\/div>\n<blockquote>\n<div align=\"justify\"><sup><u><strong><font color=\"#200020\">Integrated treatment<\/font><\/strong><\/u><br \/>   The intervention period was two years. Elements in integrated treatment were:<br \/>   (a) A modified Assertive Community Treatment model (Stein and Test, 1980) focusing on young, first-episode psychotic patients, and provided by a multidisciplinary team (psychiatrist, psychologist, psychiatric nurse, occupational therapist and social worker). Case load was 1: 10; home visits were an integrated part of the treatment model. The team member with primary responsibility for the patient provided regular assessment of symptoms (weekly) and, for patients with comorbid drug abuse, focused on helping the patient to reduce abuse of drugs.<br \/>   (b) Social skills training either in groups or individually (Liberman et al., 1986).<br \/>   (c) Psycho-education in multiple-family groups was offered to patients and their family members or friends (McFarlane et al., 1995; Jeppesen et al., 2005).<\/sup><\/div>\n<\/blockquote>\n<div align=\"justify\">This table summarizes their findings:  <\/div>\n<p align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"400\" height=\"169\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/mcgorry-7.gif\" \/><br \/> <sup>[abbreviated for readability]<br \/> <\/sup><\/p>\n<div align=\"justify\">They provide a useful tabulation of most of the studies to date reproduced below:  <\/div>\n<p align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"520\" height=\"340\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/mcgorry-6.gif\" \/><\/p>\n<div align=\"justify\">I was going to end this with a table comparing the different studies, but the Danish paper already did that for us. I&#8217;ll save my comments for the next post&#8230;<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>This post takes a look at what others have found using the idea of an &quot;ultra high risk&quot; group of people that may develop ouvert Schizophrenia. The first study is from The University of Manchester, UK. They looked at the effect of Cognitive Therapy in the high risk group [four articles]: Randomised controlled trial of [&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-12577","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/12577","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=12577"}],"version-history":[{"count":48,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/12577\/revisions"}],"predecessor-version":[{"id":12627,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/12577\/revisions\/12627"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=12577"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=12577"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=12577"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}