Generic & Brand Medication Differences May Harm Certain Autistics

| by Val

What about the issue of metabolism with regard to medications tried on those within the autism spectrum?

Many drugs that are used to treat those within the autism spectrum interact with CYP2D6, so this enzyme receives a lot of attention with regard to researching how drugs metabolize in the system. Poor metabolizers of the CYP2D6 enzyme, who are tried on medications that interact with CYP2D6, might experience increased plasma concentrations that can increase the risk of serious adverse consequences. (source link)

CYP2D6 is considered a low-capacity, high-affinity enzyme and CYP2D6 will preferentially metabolize drugs at lower concentrations. As the concentration of a drug increases, the metabolism spills over to CYP3A4 and CYP1A2, which are high-capacity, low-affinity enzymes. Thus if a drug that has several metabolic pathways but relies on CYP2D6 as its major pathway is given to a patient with poor CYP2D6 activity, the other P-450 enzymes that are high capacity, low affinity will clear the drug, but clearance will be slower and less efficient, and drug levels will increase, increasing the risk for adverse drug reactions. Four phenotypes are identified: poor metabolizers (PM), ultrarapid metablizers (UM), intermediate metabolizers (IM) and normal metabolizers (NM). (source link)

The antidepressants that are metabolized by CYP2D6 are ones that are used frequently, and they include: cimetidine (Tagamet), the selective serotonin reuptake inhibitors (SSRIs) and some tricyclic antidepressants. ...Paroxetine (Paxil) appears to have the greatest ability to inhibit the metabolism of CYP2D6 substrates. This is followed by fluoxetine (Prozac) and norfluoxetine; sertraline (Zoloft) and desmethylsertraline; fluvoxamine (Luvox), nefazodone (Serzone) and venlafaxine (Effexor); clomipramine (Anafranil), and amitriptyline (Elavil)... Although sertraline appears to be less likely than the other SSRIs to inhibit CYP2D6, inhibition may still occur at doses greater than 50 mg. The clinical significance of the inhibition of tricyclics by SSRIs or cimetidine is subject to variation in enzyme activity between individuals, the degree to which the patient metabolizes and co-ingestion of other enzyme inhibitors. (source link)

Paxil is high on the list as a drug that inhibits metabolism and it did make my autistic daugther violent when she was tried on it for a very short period. A doctor insisted that we try Paxil because of her frequent trips to the bathroom. She was only on Paxil for a couple weeks.

From Hello Dr. Wells - Most important to the psychiatrist was the fact that she tried Paxil for suspected obsessive compulsive tendencies in the spring of 2003. However, her problem ended up being interstitial cystitis. The Paxil made her violent when titrated up to full dose and it did not help with the frequent trips to the bathroom. What helped was identifying that she had interstitial cystitis and then treating her for it.

A relevant article (circa 2009) has information stating that some experts believe - half of patients who take medications are not experiencing any type of benefit from them due to metabolism issues, and are being exposed to potential danger from side effects. The article expressed the idea that at some point perhaps, medical professionals will let go of the one pill fits all mindset.  Many obstacles will detour that process. There is hesitation by doctors to utilize CYP2D6 testing since there are are no clear guidelines about how they should act upon the information provided by the test.  Also, "The ability of test developers to prove that their tests are accurate and useful is one major obstacle. Other obstacles include the reluctance of drug makers to encourage or develop tests that could limit the use of their drugs and the possibility that insurers might not pay for the tests. However, drug makers are "starting to realize that their medicines might not be approved or paid for without better evidence that they work," according to the Times (Pollack, New York Times, 12/30/08)". (source link)

A CYP2D6 test at Mayo offered an explanation about why my daughter wasn't recieving benefit from initial drug trials that were begun due to worsening autism that looked like schizophrenia in winter, 2004. During her first evaluations at Mayo, test indicated her slow metabolism of the CYPD26 enzyme, and then more care was given as far as looking for side effects. In the month prior to her initial referral to Mayo she had tried some medications; ones that would be affected by the CYP2D6 metabolism issue. Perhaps if we had known of the issue to do with processing the psychotropic medications, then the titration would have been applied in a less typical and more careful manner - and the process for helping her with medication would not have been so confusing at the start. 

Before my daughter's worsening at ten years of age, we had opted for behavioral intervention and no medications, except for the abbreviated experience with Paxil. As a matter of fact I was pretty much resistant to the idea of medicating, up to the point that my daughter literally was taken over by psychosis. The fact is, many children begin using medications at a very early age and one analysis "... included 75 children enrolled in the long-term Collaborative Programs of Excellence in Autism. The study found that 52% used at least 1 psychotropic medication between the ages of 3 and 12 years and 20% had taken 4 or more." (source link)

Within the autism spectrum population there are those who experience worsening that require polypharmacy. Meaning, more than one medication might be required to alleviate the varied symptoms. Polypharmacy presents its own risk, and so it might be important to require testing with regard to metabolization of medications - for those who are in need of polypharmacy due to more severe problems with autism or psychosis.

Learning what I have about the metabolism issue from experience - I often become curious about the possibility with regard to how many children who were on a brand medication and doing well, suffered a worsening simply because they had been switched to a generic that was deemed safe and equivalent by the FDA. The families trust the rating and may never consider that the switch to generic is what caused the worsening. For those within the autism spectrum this might be a huge issue.

Generic medication and brand medication might very likely be considered neither safe or equivalent where a switch would be concerned, for those within the very sensitive autism population. The 20 percent delivery difference of active ingredients that the FDA allows in generics, is necessary because the inactive ingredients (fillers) vary as compared to the brand medication counter part. The different fillers in generics do affect how a sensitive person - such as; allergy prone, immune deficient or known atypical metabolizer - will respond to the delivery of the active ingredients in the generic. This is validated among professionals in the medical community. (See more about the complexities with regard to generic versus brand at  Generic or Brand? Differences Might Hurt Sensitive Patients)

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