{"id":1045,"date":"2016-05-09T15:07:03","date_gmt":"2016-05-09T15:07:03","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1045"},"modified":"2017-08-21T10:54:56","modified_gmt":"2017-08-21T10:54:56","slug":"primary-care-corner-with-geoffrey-modest-md-smoking-cessation-meds-in-pts-with-psych-disorders","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/09\/primary-care-corner-with-geoffrey-modest-md-smoking-cessation-meds-in-pts-with-psych-disorders\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Smoking Cessation Meds in Pts with Psych Disorders"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>A couple of recent articles dealt with issues of smoking cessation:<\/p>\n<ol>\n<li>The lancet had a study finding no significant increase in psychiatric risk with any\u00a0of the smoking cessation\u00a0medications (see doi.org\/10.1016\/S0140-6736(16)30272-0 ).\u00a0The FDA had\u00a0issued an early warning on neuropsych concerns with varenicline, later extended to bupropion,\u00a0based on case reports, and issued a post-marketing requirement for makers of both drugs to do RCTs to assess these risks. Hence this drug-company sponsored study.<\/li>\n<\/ol>\n<p>Details:<\/p>\n<ul>\n<li>8144 smokers smoking at least 10 cigarettes\/d in\u00a0the past year, 4116 having underlying psych disorders\/4028 in the non-psych cohort. In terms of the cohorts:<\/li>\n<li>Nonpsych cohort:\u00a0mean age 46, 50% female, 83% white\/13% black, wt\u00a080 kg, 47% US\/33% Western Europe\/11% Eastern Europe\/10% Central\/South America, Fagertstrom Test for Cigarette Dependence (FTCD) score 5.5 [a score\u00a0signifying moderate dependence], 13 years\u00a0duration of smoking, 21 cigs\/day in past month, 3.3 prior quit attempts<\/li>\n<li>Psych cohort:\u00a0mean age 47, 62% female, 80% white\/16% black, wt\u00a080 kg, 58% US\/29% Western Europe\/9% Eastern Europe\/4% Central\/South America, Fagertstrom Test for Cigarette Dependence (FTCD) score 6.0, 12\u00a0years\u00a0duration of smoking, 21 cigs\/day in past month, 3.5\u00a0prior quit attempts. 70% with unipolar or bipolar depression, 20% anxiety disorder, 9% psychotic. 33% on antidepressants, 15% anxiolytics, 16% antipsychotics [of note: all had to be stable for the prior 6 months and not at risk for\u00a0self-injury]<\/li>\n<li>Randomized to nicotine patch 21 mg\/d with taper, varenicline 1mg bid, or bupropion SR\u00a0150mg bid for 12 weeks\u00a0with\u00a012 week non-treatment follow-up. Done in 14 centers in 16 countries\u00a0between 2011-2015 (this was a double-blind, triple dummy, placebo controlled trial \u2013 i.e. everyone took pills from 2 different unmarked bottles and used a patch)<\/li>\n<li>All had brief smoking\u00a0cessation\u00a0counseling (no more than 10 minutes, at each clinic visit)<\/li>\n<li>Quit date was 1 week after randomization, coinciding with end of uptitration of bupropion and varenicline\u00a0and initiation of patch<\/li>\n<li>Main outcomes: composite measure of moderate and severe neuropsych events; and biochemically confirmed continuous abstinence from smoking for weeks 9-12.<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>The same percent (78%) of each group completed the study<\/li>\n<li>In the non-psychiatric cohort: moderate-to-severe\u00a0neuropsych adverse events occurred in\n<ul>\n<li>Varenicline:\u00a013 of 990 people (1.3%)<\/li>\n<li>Bupropion:\u00a022 of 989 (2.2%)<\/li>\n<li>Patch: 25 of 1006 (2.5%)<\/li>\n<li>Placebo: 24 of 999 (2.4%)<\/li>\n<li>The only significant difference between active drug and placebo: varenicline-placebo risk difference was 1.28. Of note, there were essentially zero patients with psychosis, panic, mania, suicidal ideation or behavior, anxiety, or depression.<\/li>\n<\/ul>\n<\/li>\n<li>In the psychiatric cohort:\n<ul>\n<li>Varenicline: 67\u00a0of 1026\u00a0people (6.5%)<\/li>\n<li>Bupropion 68\u00a0of 1017\u00a0(6.7%)<\/li>\n<li>Patch: 53 of\u00a01016 (5.2%)<\/li>\n<li>Placebo: 50 of 1015 (4.9%)<\/li>\n<li>No significant risk differences between active drug and placebo, though there were 14 of patients (2%) in the psych group who developed suicidal ideation<\/li>\n<\/ul>\n<\/li>\n<li>Quit rates at 9-12 weeks, vs placebo (documented by exhaled carbon monoxide measurements):\n<ul>\n<li>Varenicline (statistically significantly\u00a0better than the other 2 active treatments), with OR 3.61 (3.07-4.24); most frequent adverse effect: 25% nausea<\/li>\n<li>Bupropion: OR 2.07\u00a0(1.75-2.45);\u00a0most frequent adverse effect: insomnia 12%<\/li>\n<li>Patch: OR 2.15 (1.82-2.54);\u00a0most frequent adverse effect: abnormal dreams 12%<\/li>\n<li>Placebo: headache in 10%<\/li>\n<li>Quit rates looking at weeks 9-24 showed some deterioration over those from weeks 9-12, but the order and significance of efficacy remained as above<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>So, this study adds a few things to the literature:<\/p>\n<ul>\n<li>As a large study, it showed that neither varenicline nor bupropion posed a significant risk to smokers with or without a psych history.<\/li>\n<li>The odds ratios for efficacy in smoking cessation did not vary by initial psych status: those with underlying psych issues had similar abstinence rates to those without<\/li>\n<li>And, this is pretty important since the likelihood of smoking is 2-3x\u00a0higher in those with underlying psych disorders (perhaps as self-medication with nicotine, a pretty potent psychoactive drug\/anxiolytic: evidence shows improved vigilance, attention and cognition;\u00a0decreased perceived stress, embarrassment, irritability, or\u00a0depression; nicotine\u00a0can be both a\u00a0stimulant\u00a0and relaxant, with\u00a0initial epinephrine release causing stimulation but\u00a0increasing dosages causing sedation)<\/li>\n<li>A few caveats:\n<ul>\n<li>As per prior blog (<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/03\/28\/primary-care-corner-with-geoffrey-modest-md-abrupt-vs-gradual-smoking-cessation\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/03\/28\/primary-care-corner-with-geoffrey-modest-md-abrupt-vs-gradual-smoking-cessation\/<\/a>) there might have been more success if the patch had been started earlier than 1 week before the quit date<\/li>\n<li>I would still\u00a0be concerned about using varenicline in those with psychotic disorders, since these were pretty underrepresented in the psych cohort (as were those with personality disorders, &lt;1% of the cohort). But importantly, a large % (34%) had a history of suicidal ideation and 13% had a history of suicidal behavior. Also of importance, this study did not include patients with underlying with substance use disorders, including alcohol, in the past 12 months.<\/li>\n<li>Although varenicline outshined the others, this trial only looked at monotherapy, and there are many studies showing the superior efficacy of multi-therapies<\/li>\n<li>The evaluation of smoking cessation at 12 weeks should be viewed with some caution, since this may not reflect long-term abstinence<\/li>\n<\/ul>\n<\/li>\n<li>So, bottom line, varenicline, as a single agent, seemed to be the most effective in smoking cessation and did not seem to have any real increased neuropsych risk, even in those with underlying psych disorders (i.e.: assessing the confidence intervals above, it did not appear that there could be more than a 1.5\u00a0percentage point increase in neuropsych events by either varenicline or bupropion in\u00a0those without psych disorders, or more than 4 percentage points in those with psych disorder). For patients with underlying psych disorders\u00a0who meet the above criteria\u00a0(including being stable psychiatrically and non-other-substance using), any of these methods seemed to work well and be well-tolerated, though I would really follow them more closely.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Smoking Cessation Meds in Pts With Psych Disorders  [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/09\/primary-care-corner-with-geoffrey-modest-md-smoking-cessation-meds-in-pts-with-psych-disorders\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1045","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1045","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1045"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1045\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1045"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1045"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1045"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}