Talk given to psychiatrists that explores three questions about vortioxetine:
And the way that i structure the sending email you all that the handout that i’m using to guide the talk is just asking three basic questions about each medication why should it work does it work and should we use it the first drug bordey occitane or burnt elects the question of why should we use it no that’s not the first question first question is why should it
Work so it actually has a cool pharmacodynamic profile there is this snow new class called the serotonin modulators and vilasa doan is in that class so lightful acetone it’s able to bind to the serotonin reuptake transporters but not to saturate all of them so most ssris will saturate at about 80% and it’s thought that that kind of massive serotonergic effect is
Correlated with a lot of the side effects the sexual side effects and other side effects that can afflict many people who take ssris so what’s kind of cool about the mechanism for gordy occitane even though it’s not truly the novel mechanism or a novel drug is that at about 40% of saturation of those serotonin serotonin transporters you’re actually able to derive an
Antidepressant effect in both animal and human models in addition to blocking the serotonin transporter and having partial agonist activity at five ht1 like buspar and like vlado it also antagonizes us v ht 7 receptor bio att reset 587 is like pretty cool right now in the literature i actually found more compelling explanation or justification of the 587 hype when
I was looking at this third drug ‘la to des and for laputa to work as an antidepressant in animal models v ht 7 has to be intact so when they do knockout mice by 57 knockout mice with latina or la rasa don’t you you don’t replicate the depressing effects in animal models i thought that was like pretty legit because you know there are like 12-14 serotonin receptors
And roams busting them out 553 five or six back to the eleven and we don’t really know what they do and we don’t really understand the serotonin system so i was skeptical of 587 right now i’m kind of liking it so in addition to those pharmacodynamic properties it has some elements of dirtiness so it does enhance serotonin norepinephrine dopamine acetylcholine and
Histamine models at least an animal it levels at least in animal models and then jumping to this next question of does it work i think it does so it was approved by the fda based on six large studies it’s been approved at a dose range of five to twenty milligrams and its record is not bad so it’s it’s three three and three three wins and three losses that may seem
Like not that great but you know in clinical trials given the historic and astronomic rise of the placebo effect it’s not that to defeat placebo and three trials the other cool thing about these trials that in the three positive studies there were robust separations between drug and placebo on the madra so you’re getting like four to six point separations and also
On the hamilton and you know the critical study in 2011 i think by kirsch when he claimed that all and depressants don’t really do much that was based on the fda’s general approval level which if you look at it for all the other antidepressants the separation on the health at than two points so for six points is something it means something and also we’re talking
About separation in rates of response in remission of 15 to 20 percent versus placebo so it seemed to be working in those three positive studies the other cool thing about the literature around this drug is that the pharmaceutical company had the fortitude to test it against active comparators so they tested it against cymbalta and they tested effexor they did
Not have the fortitude to do a formal statistical comparison of how it did compared to those agents relative to placebo you know was it actually better than effexor was it actually better than cymbalta if you look at the trends it does seem that the snris are slightly superior particularly cymbalta looked like it did a little better but i thought it was cool that
They threw those drugs in there and that they showed that both the cymbalta or the venom of vaccine and this new drug poor deoxy team work third question should you use it so i’ll just go through awesome attributes and attributes that aren’t goals and then you can decide if you want this is really a breakthrough for the drug it is super well tolerated so the rate
Of sexual dysfunction in these large studies we’re talking like ends of 500 wasn’t 1% or less it’s like the sibo so maybe better than it was just well tolerated so the most common side effects reported were not rat headache and dizziness another very cool feature of this drug the graphs look beautiful in the studies i mean they look so good that you’re like really
Could this be an actual study when they do to make it look so good but they set this drug separates from placebo at two weeks in one study and at one week in another study so it there’s evidence that it works faster than our other antidepressants and then the other thing that convinces me that this is worthy drug is that if you look at the breakdown by subscale
So you know the ma dress is composed of these ten items that measure different dimensions of mood and it can be easy sometimes to manipulate a study you know if you have sirocco for example in an antidepressant study considerable knocks everyone out and that’s that’s a heavily weighted item on a on a you know depression rating it can look like it’s having a really
Awesome antidepressant effect but really you’re just knocking people out so if you look at the distribution of effects among subscales it’s nine out of ten yeah nine out of ten items on the mod rooms separated from placebo so the ma dress is very cool for those of you who haven’t used it it has these sort of poetic items like lassitude sadness inner tension but um
You know it does seem to be working across domains um and then it’s got a nice pharmacokinetics it’s kind of like lexapro no drug drug interactions it’s got a lovely half-life of sixty to seven hours so probably unlikely to cause really acute withdrawal syndromes if people stopped it it might be easy to taper and then there’s this idea that it may be more effective
From mixed anxiety depression that just like use juice bar it has that 5ht one partial agonist alright what’s a bummer about this drug so multi-centered studies in europe asia and africa these things were not done in the united states and i think a lot of us in the clinical trials world believe that the studies that are done in other countries may have lower quality
So that’s kind of a bummer also you always kind of worried when i think one of the studies had like involved 68 countries how do you do how do you coordinate a study across 68 countries there’s just so much potential for mishap and error another thing that’s not so cool is that it did not seem to omit mention this ready but did not seem to be as effective as the
Snr i’ve again they didn’t do a formal analysis and then like most antidepressant studies these are not our patients so the you know these were patients that didn’t have comorbidities substance abuse dated suicidality that was really concerning
Transcribed from video
Vortioxetine (Brintellix) By OpenSourcePsychiatry
