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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ESome of the results from the Systematic Enhancement Treatment Program for Bipolar Disorder [STEP-BD] trial are presented in this article. The primary focus of STEP-BD was to determine whether or not standard antidepressants are effective treatment for bipolar disorder [\u003Cem\u003EN Engl J Med\u003C\/em\u003E 2007].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Emood disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Epsychopharmacology\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003ESome of the results from the Systematic Enhancement Treatment Program for Bipolar Disorder (STEP-BD) were presented by Gary Sachs, MD, Harvard Medical School, Boston, MA. The primary focus of STEP-BD was to determine whether or not standard antidepressants are effective treatment for bipolar disorder [\u003Cem\u003EN Engl J Med\u003C\/em\u003E 2007], and as the study was being designed, Dr. Sachs had expectations regarding the outcome. \u201cI had gone my entire career believing that these drugs were not so effective and, in fact, that they often caused worsening. And here I was putting together a study to convince myself I might be wrong.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EIn this double-blind, placebo-controlled study, Dr. Sachs randomized 366 patients with bipolar depression to receive up to 26 weeks of treatment with mood stabilizers and either adjunctive antidepressant or matching placebo. Choice of mood stabilizer (MS) was lithium or valproate; the antidepressants (AD) that were used were paroxetine or bupropion. Study endpoints were durable recovery, defined as \u22658 consecutive weeks euthymic; transient remission, being euthymic 1 to 7 weeks; effectiveness response, a 50% improvement from baseline depression scores; or nonresponder.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EDurable recovery was 23.5% with antidepressant adjunctive treatment, as compared with 27.3% recovery for patients who received no additional medication (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Effectiveness response was 32.4% versus 38.0%, and transient remission was 41% versus 49% for MS\/AD versus MS, respectively (for all results, p\u0026gt;0.23).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/24\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Proportion Achieving Durable Remission.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-255938289\u0022 data-figure-caption=\u0022Proportion Achieving Durable Remission.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/24\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/24\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/24\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10905\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EProportion Achieving Durable Remission.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EDr. Sachs then went on to analyze results for treatment-emergent affective switch, mindful that he often had seen patients switch when antidepressants were added to the mix. However, results contradicted his expectations. \u201cNow, this is something I\u0027ve believed my entire career, and we actually selected paroxetine and bupropion because they are historically less associated with switch.\u201d No difference was noted between the treatment arms (10.1% vs 10.7%).\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAnother pilot study to emerge from STEP-BD looked at the addition of lamotrigine, inositol, or risperidone to antidepressants (n=66; Nierenberg. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2006). All patients were in a current major depressive episode that was nonresponsive to a combination of adequate doses of established mood stabilizers plus at least one antidepressant. Results for durable recovery in this setting were: risperidone 5%; inositol 17%; and lamotrigine 24%. \u201cSo, maybe we have something here with inositol or lamotrigine,\u201d said Dr. Sachs, \u201cbut risperidone does not look like something to further explore.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EWhat about psychiatric interventions? Dr. Sachs reviewed one study\u2014an extension of the investigation described above\u2014that used psychosocial intervention in addition to protocol pharmacotherapy (n=293; Miklowitz D. \u003Cem\u003EArch Gen Psychiatry\u003C\/em\u003E 2007). Patients were randomly assigned to intensive psychotherapy or collaborative care (a brief psycho-educational intervention). Results showed that patients who received intensive psychotherapy had significantly higher year-end recovery rates (64.4% vs 51.5%) and shorter times to recovery than patients in collaborative care (p=0.01). \u201cThe big news is, when they got better, they got better on average 110 days sooner. For most of our patients, that is a clinically meaningful difference.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EDr. Sachs did point out a caveat to this presumed good news. In a similar trial of 253 depressed bipolar patients who were treated with medication and cognitive behavioral therapy (CBT), it was determined that overall there was no benefit of adding CBT to treatment as usual. Adjunctive psychotherapy was beneficial in patients who had 1 to 6 prior episodes but was inferior to medication alone for those patients who had had more than 30 previous episodes. \u201cEarlier in the course of disease appears to be when these interventions are most likely to be the most beneficial.\u201d Dr. Sachs considered these results to be analogous to the rehabilitation of a heart patient\u2014those who had one or few cardiac events might be expected to fully recover, but those patients who had repeated events might be best advised to avoid intensive exercise.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EMark Frye, MD, Mayo Clinic Mood and Research Program, Rochester, MN, presented more encouraging results for the treatment of bipolar depression with antidepressants [Post RM. \u003Cem\u003EBr J Psychiatry\u003C\/em\u003E 2006]. \u201cWe use these medicines all the time and we need to know if they work, and if they do, for what patient population. Secondly, we need to know that they are safe.\u201d The study was a 10-week, multicenter, randomized double-blind investigation of adjunctive treatment with either sertraline (50\u2013200 mg\/day), bupropion (75\u2013450 mg\/day) venlafaxine (37.5\u2013375 mg\/day), or matching placebo. All patients received mood stabilizers (n=174). Patients had inventory depression symptomatology (IDS) \u226516 and CGI \u22653. Patients who had a YMRS \u226514 or a CGI-BP mania severity of \u22653 at baseline were excluded. Endpoints for response were \u226550% improvement in IDS, \u22652 point decrease in CGI-BP depression score; remission was defined as IDS \u0026lt;12 or CGI-BP score of 1; and switch, a 2-point increase at any point on the CGI-BP mania severity scale.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EResults showed that all 3 antidepressants were associated with a similar range of acute response (49% to 53%), which answered Dr. Frye\u0027s first question regarding whether or not antidepressants work in this setting. \u201cIn contrast to the STEP data, we found that almost half of our cohort bipolar patients who were on mood stabilizers responded to adjuvant antidepressant therapy. We saw no difference by drug in regard to response or remission rate.\u201d Recall that his second question addressed safety: In fact, differences did emerge for incidence of switching. \u201cWhen we looked at destabilizing elements, we did see a difference, suggesting that switch rates were higher with venlafaxine,\u201d defined by either YMRS or CGI-BP scales (p\u0026lt;0.05; \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/24\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Antidepressant Response and Remission.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-255938289\u0022 data-figure-caption=\u0022Antidepressant Response and Remission.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/24\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/24\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/24\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10907\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-12\u0022 class=\u0022first-child\u0022\u003EAntidepressant Response and Remission.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EIn a sub-analysis of the switch data, non-rapid cycling patients were found to have equivalent switch rates between treatment arms; amongst rapid cyclers, however, those who were treated with bupropion had significantly lower rates for switching as compared with those patients who were treated with venlafaxine (p\u0026lt;0.01). There were no differences that were observed in this analysis for bupropion versus sertraline, or sertraline versus venlafaxine. The majority of those patients who switched was bipolar I. \u201cThat struck us as odd because the bipolar I\u0027s were the most aggressively controlled with mood stabilizers.\u201d Upon further examination, switching subjects were found to have minimal manic symptoms in syndromal depression at baseline\u2014minimal, as in YMRS scores \u0026lt;4\u2014yet higher symptoms than those patients who didn\u0027t switch.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/8\/3\/24.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmdxq\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmdxq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}