If the amphetamine [Adderall, Dextrostat, dextroamphetamine] is poorly metabolized because the pipe is plugged by drug like Prozac or Paxil, or because of genetic variants [meaning you didn't get that particular pipe in the first place - more later], -if is not metabolized at all – big problems drift downstream, down our own inside stream.

You or your loved ones can become relatively toxic, either slowly in the first week or so, or can have a big ongoing problem months down the road. The drug slowly builds up because it isn’t being burned properly.

It sneaks up on you, you start cycling, and what does everyone say… she’s bipolar! How many have heard that one before? Most characteristic is the feeling of great overfocus for short periods, getting almost too much done, and then it’s as if the lights go out.

Can’t think, can’t complete sentences. Cognitive abilities are worse! Let’s see, what should we do? Use more amphetamines? No, just change the antidepressant.

Yes the drugs are wrong, but not absolutely. They are the wrong mix. A different antidepressant will not block that path, the amphetamine product works perfectly, and no accumulation occurs.

Basic applied science, works almost every time. As you know nothing in medicine is 100%, because the complexities can turn the day. So why not master the complexities? Stay tuned.

ADD ADHD Medications: SSRI + Amphetamine Interactions Cause Serious Problems

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ADD ADHD Medications: SSRI + Amphetamine Interactions Cause Serious Problems

by Dr Charles Parker on November 25, 2006 · 10 comments

Kenneth Zaleski

Dr. Parker, I find your work to be very interesting and very informative. I have a question for you regarding amphetamines and their metabolism that would be right up your alley. I am a 41yr old male and I was taking 20mg of Pexeva and 300mg of Wellbutrin. The psychiatrist added 20 mg of Dexedrine Spansules per day. I have never used amphetamines before. I seemed to get no positive effects from the medicine and discontinued after 1 week. There was no increased focus, motivation, or energy. It was befuddling. The only thing I did get was horrendous side effects in the form of extremely high BP and very high heart rate. I have been on Ritalin before and had some decent results. Could the lack of therapeutic effects be due to the medicine combo I was on. Also, I noticed you said that Zoloft does not have a negative effect on the 2d6 pipe. The drug information on various web sites says it does. I have seen various drug info web sites and Wikipedia say that it does have an effect. Any reason why they would say that?

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Dr Charles Parker

Kenneth, You must be from out of the USA as Pexeva is not a brand here, so look it up and tell me the generic. It could be the med combo, just look it up or call your pharmacy, drop me a note and I will get back. Regarding other interactions: I frequently get calls from pharmacies because other SSRIs are on the list in their computers, but show no real evidence in the drug interaction books. Zoloft and Effexor are often sited, but those two have been clean on 2D6 as far as I can see from my perch. Actually I am glad that people are talking about these reactions, even if they aren't a major problem... Prozac and Paxil are major problems and Wellbutrin, by the way, is often a problem with moderate inhibition at the 300mg range. The feeling on interaction is usually [with an AMP like Dex] one of irritation and mind racing. cp

Laura

Is this a problem with Zoloft (sertraline) as well? I take Zoloft and Vyvanse daily and have never heard of this possibility before. Laura

Laura, No prob with Zoloft, clean on 2D6. cp

Karen Maloney

I don't get it. "these drugs are not "broken down" by these liver pathways, but are built up so they can be used, metabolized and excreted. The amphetamines all come up through this one pipe, the 2D6 pipe [the CYP450 2D6 pipe]" How are they built up? This idea is new to me. What is amphetamine built up to? Or is it adminstered in a form that is not active amphetamine.

Karen, They are 'broken down' in the sense that they can be metabolized and excreted. The process of metabolism, the breaking down process, actually involves a biotransformation process that adds to the molecule making it more hydrophilic, less lipophilic. In a water solution it can be excreted more easily than when bonded with fat. I'm using the 2D6 liver and pipe line metaphor to help picture the plugged and unplugged phenomenon that can prevent the biotransformation and will, over time encourage an accumulation taking the person out the top of the therapeutic window. The CYP 450 is like the size of the drain, big drain = fast drainage, small or no drain with drug still coming on board = overflow. Size in 2D6 is often genetically determined, all of which makes this subject so much more interesting! Just to confuse matters: new research does indicate that 'neurotransmitters' [Dopamine, Norepinephrine] are both broken down and actually created in the proximal tubule of the kidney - an entirely different matter relating to a different set of variables regarding neurotransmitter precursors. Hope this helps! cp

Dr. Charles Parker

Thanks for your kind words! Multiple places to read about brain and gut, and will be posting several blogs and podcasts on this subject in the near future. In my offices my colleagues call me the poopmeister with these dramatic stories, and when I give a presentation I try to get the poop out of the way before dinner even tho it's often a medical audience. Book: The Second Brain by Mike Gershon, MD. More in the very next post.

Dennis Dilday

It was the colon - brain connection that hooked me... can you tell me where you discuss that? This is a great example of a really juiced up blog with gobbs of features, well-written and easy to read stories and resources all over. Very well done!! DD Oh, yeah, and I'll be back to see what else you have share. The people I know need to see this.