{"id":61461,"date":"2015-11-14T21:55:34","date_gmt":"2015-11-15T02:55:34","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=61461"},"modified":"2015-11-14T22:02:33","modified_gmt":"2015-11-15T03:02:33","slug":"a-simple-truth","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2015\/11\/14\/a-simple-truth\/","title":{"rendered":"a simple truth…"},"content":{"rendered":"\n
In psychiatry, we’re rarely afforded the definitive data enjoyed in a lot of science. It’s just the way things are. But that doesn’t mean we can’t be glad when some definitive graphs come along – particularly when they support clinical experience. The data in this 2004 paper is an example. I received this link from multiple directions when I wrote about the recent article claiming increased efficacy with increasing dose [an inconvenient truth…<\/a>]. The graphs are of 5-HTT transporter occupancy at varying doses of five different SSRI\/SNRIs [the minimal effective dose marked with the dotted vertical lines]: <\/div>\n
\n
Serotonin Transporter Occupancy of Five Selective Serotonin Reuptake Inhibitors at Different Doses:<\/a><\/div>\n
An [11<\/sup> C] DASB Positron Emission Tomography Study<\/a><\/div>\n
by Jeffrey H. Meyer, Alan A. Wilson, Sandra Sagrati, Doug Hussey, Anna Carella, William Z. Potter, Nathalie Ginovart, Edgar P. Spencer, Andy Cheok, and Sylvain Houle<\/div>\n
American Journal of Psychiatry<\/font><\/strong> 2004 161:826–835.<\/div>\n
[full text on-line<\/a>]<\/div>\n

<\/p>\n

Objective<\/font><\/strong>: Minimum therapeutic doses of paroxetine and citalopram produce 80% occupancy for the serotonin [5-HT] transporter [5-HTT]. The authors used [11 C] DASB positron emission tomography to measure occupancies of three other selective serotonin reuptake inhibitors [SSRIs] at minimum therapeutic doses. The relationship between dose and occupancy was also investigated.<\/div>\n
Method<\/font><\/strong>: Striatal 5-HTT binding potential was measured in 77 subjects before and after 4 weeks of medication administration. Binding potential is proportional to the density of receptors not blocked by medication. Subjects received citalopram, fluoxetine, sertraline, paroxetine, or extended-release venlafaxine. Healthy subjects received subtherapeutic doses; subjects with mood and anxiety disorders received therapeutic doses. Percent reduction in 5-HTT binding potential for each medication and dose was calculated. To obtain test-retest data, binding potential was measured before and after 4 weeks in six additional healthy subjects.<\/div>\n
Results<\/font><\/strong>: Substantial occupancy occurred at subtherapeutic doses for all SSRIs. Compared to test-retest data, each drug at the minimum therapeutic dose had a significant effect on striatal 5-HTT binding potential. Mean occupancy at this dose was 76%–85%. At higher plasma SSRI concentrations, 5-HTT occupancy tended to in- crease above 80%. For each drug, as the dose [or plasma level] increased, occupancy increased nonlinearly, with a plateau for higher doses.<\/div>\n
Conclusions<\/font><\/strong>: At tolerable doses, SSRIs have increasing occupancy with increasing plasma concentration or dose. Occupancy of 80% across five SSRIs occurs at minimum therapeutic doses. This suggests that 80% 5-HTT blockade is important for therapeutic effect. Occupancy should be measured during development of antidepressant compounds targeting the 5-HTT.<\/div>\n

<\/p>\n

<\/div>\n
hat tip to alto et al…<\/font><\/strong> <\/div>\n<\/blockquote>\n
In spite of 25 years of dreams and schemes, if these drugs don’t help on the first shot, they’re unlikely to do much better with prestidigitation<\/span>. Because of the escalating side effects with increased dose, these drugs, like many in clinical medicine, have a therapeutic window<\/font><\/em>. I’m awed with the number of patient dosed well beyond the window<\/font>. Getting them to come down slowly is often a major undertaking, though there’s rarely a complaint once on a more rational dose. More doesn’t seem to be better, at least in my hands…<\/div>\n","protected":false},"excerpt":{"rendered":"

In psychiatry, we’re rarely afforded the definitive data enjoyed in a lot of science. It’s just the way things are. But that doesn’t mean we can’t be glad when some definitive graphs come along – particularly when they support clinical experience. The data in this 2004 paper is an example. I received this link from […]<\/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_forum_subforum_count":0,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-61461","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/61461","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=61461"}],"version-history":[{"count":16,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/61461\/revisions"}],"predecessor-version":[{"id":61477,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/61461\/revisions\/61477"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=61461"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=61461"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=61461"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}