[HN Gopher] Dextromethorphan-Bupropion in Major Depressive Disor...
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       Dextromethorphan-Bupropion in Major Depressive Disorder: Controlled
       Trial
        
       Author : bookofjoe
       Score  : 21 points
       Date   : 2022-09-28 22:07 UTC (53 minutes ago)
        
 (HTM) web link (pubmed.ncbi.nlm.nih.gov)
 (TXT) w3m dump (pubmed.ncbi.nlm.nih.gov)
        
       | mpalczewski wrote:
       | TLDR: Have some cough syrup with your Bupropion (anti-depressant)
       | for increased efficacy.
        
         | genewitch wrote:
         | Guaifenesin, another ingredient in most cough syrups, is also
         | used in muscle relaxants.
         | 
         | Who knew that "more tussin" would be the answer?
        
           | schwartzworld wrote:
           | Guaifenesin also makes you puke if you have too much.
        
         | xen2xen1 wrote:
         | Just had a problem finding regular Nyquil last night, now I get
         | why they changed it so much.
        
         | sallystarace wrote:
         | Dextromethorphan tolerance builds so rapidly. I have found the
         | withdrawal to be hell after taking it legitimately for a cold
         | longer than I realized. I have tried SSRIs and found that they
         | also have a synergetic effect with Bupropion (good medicine).
         | SSRIs also make me drowsy, but at least they can be sustainably
         | taken daily for months.
        
       | PaulHoule wrote:
       | See https://www.erowid.org/chemicals/dxm/faq/
        
         | PragmaticPulp wrote:
         | Not the same. The Bupropion significantly changes the
         | metabolism of Dextromethorphan when administered as a combo.
         | 
         | It's nothing like taking high doses of DXM alone for
         | recreational purposes.
        
       | bergenty wrote:
       | DXM is a fantastic dissociative. There's a reason so many rappers
       | with really bad childhoods use it so much.
        
         | skyyler wrote:
         | Is this a potshot directed at someone in particular? I wasn't
         | aware that DXM was popular with rappers.
        
           | Mandatum wrote:
           | Google "lean". They made it popular in the 90s.
        
       | PragmaticPulp wrote:
       | The combination is known as AXS-05 in studies and will be
       | marketed as Auvelity.
       | 
       | Interesting combo. Buproprion is an antidepressant by itself, but
       | it also inhibits the enzymes that break Dextromethorphan down in
       | the body. Taking the two drugs together is not equivalent to
       | taking the same dose of Dextromethorphan alone because Bupropion
       | induces a very different exposure to DXM and its metabolites.
       | Ignore anyone who tries to compare this to recreational DXM
       | consumption because they're quite different.
       | 
       | Dextromethorphan gets a lot of attention for being an NMDA
       | antagonist, but fewer people know that it has quite strong
       | affinity for the serotonin transporter (the primary affinity of
       | SSRIs). It also has potentially significant affinity for the
       | sigma-1 receptor, the norepinephrine transporter, and several
       | other receptors that have been noted to be potentially useful for
       | depression modulation.
       | 
       | In other words, this feels a little bit like a shotgun approach
       | to poking a wide array of receptors that may or may not be
       | helpful in modulating depressive disorders. I'd take some of the
       | narratives about this being an "NMDA drug like ketamine" with a
       | huuuge grain of salt.
       | 
       | People have been trying this combination for several years in DIY
       | fashion (not recommended, but info is out there) since the
       | original study came out. I've seen some reports of good results,
       | other reports of weird side effects that interfered with daily
       | activities. I wouldn't rush to characterize this as a miracle
       | drug or a first-line treatment, but it does seem to help certain
       | patients who haven't seen much benefit from previous drugs.
       | 
       | Also worth noting that other studies haven't been as
       | overwhelmingly positive as this one. Axsome Therapeutics (company
       | researching the drug) stumbled a few years ago when their own
       | trial failed to show statistical significance for Bupropion+DXM
       | over Bupropion alone. Later studies seem to have been more
       | positive though.
        
         | forbiddenvoid wrote:
         | Thank you for explaining the interaction that makes this work.
         | I was very confused for a bit trying to understand how mixing a
         | cough suppressant with an anti-depressant would change the
         | chemistry to the extent highlighted in the study.
        
       | braingenious wrote:
       | I'm always happy to see this.
       | 
       | I know a therapist that's interested in ketamine/psilocybin
       | therapy and when she asked me about these types of drugs, I
       | immediately told her that DXM is hands down obviously going to
       | have clinical use.
        
       | nnlsoccer wrote:
       | Unable to access the full paper at the moment, but curious if
       | they addressed the fact that Bupropion can take 6-8wks before
       | symptoms such as depressed mood or anhedonia are affected. Were
       | these bupropion naive patients? From the abstract, this was only
       | a 6wk study - which means that the bupropion may not yet have
       | been working at maximal efficacy for those in the bupropion group
       | during the study period and therefore of course the AXS would
       | show a benefit when compared to only bupropion
        
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       (page generated 2022-09-28 23:00 UTC)