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The Science
INTRODUCTION
The Road Back Program and the development of the program:
1. There are basic common denominators of psychotropic drug side effects.
2. How our individual DNA affects drug metabolism.
3. The effect of psychotropic medication within the Hypothalamic-Pituitary- Adrenal Axis and
immune system.
4. Utilizing DNA clinical trials, test subject trials and psychotropic drug clinical trials to formulate
specific nutritional products to eliminate, reduce or avert withdrawal side effects, while not
creating drug/supplement interactions.
This research and development complexity has been transformed into an easy to understand,
systematic program, which allows an individual to taper off their medication while alleviating a
vast percentage of the debilitating side effects of withdrawal.
The sequence of this program and the application of each step is the key to success. Your
patient will not begin to reduce a medication until the pre- taper is complete. The pre-taper is a
7-day process.
Statements of fact: All psychoactive medications metabolize through specific pathways. All
psychoactive medications alter the Hypothalamic Pituitary-Adrenal Axis to some degree. To
some extent, you can predict the duration before drug- adverse reactions begin with most
psychoactive drugs if the patient’s P450 (CYP) enzymes have been screened. A poor metabolizer
as well as an extensive metabolizer will eventually reach the same saturation point; the poor
metabolizer much faster, of course. If one were to look at the basic structure of the human
body, the chemical structure of psychoactive drugs, and include how psychoactive drugs are
metabolized, how foods, vitamins, minerals, DNA, amino acids, hormones, glands, proteins, fatty
acids and enzymes work, in relation to psychoactive drugs, you have The Road Back Science.
The patient has been under some duress and stress before a diagnosis was given and the
prescription was written. With this in mind the patients JNK gene would have been overly
expressed for some duration. Balancing the JNK gene activation will lead to a normalization of
the patient in time.
Drug targets for most disorders will be the purinergic system, the dynorphin opioid
neuropeptide system, the cholinergic system (muscarinic and nicotinic systems), the melatonin
and serotonin system, and the HPA axis. An additional reason the supplements were selected to
be used in this program; their natural action of helping to balance the same drug targets.
DNA and Prediction of Drug Adverse Reactions
The following charts detail the P450 enzymes used to metabolize the most common
antidepressants, anti-psychotics, benzodiazepines and ADHD stimulant medications. An X in the
row denotes that the medication utilizes that specific pathway. Below each chart, you will find
other routes of metabolism if applicable. These medications inhibit metabolism via listed CYP
pathways.
Chapter 22
Marked medications (*) will also use other routes for metabolism.
Adapin – ABCB1-P-pg, UGT1A3, UGT1A4
Anafranil – UGT2B10, CYP3A4, UGT1A4, UGT1A4, UGT2B7, ABCB1-P-gp,
CYP3A4
Amitriptyline – 3A4, UGT2B10, UGT1A4, SLC22A1- OCT1, ABCB1-P-gp, UGT2B7,
CYP3A4, CYP2C8, CYP2D6
Celexa – ABCB1-P-gp, CYP3A4
Clomipramine – UGT2B10, CYP3A4, UGT1A4, UGT2B7, UGT1A4, UGT1A3
Doxepin – ABCB1-P-gp, UGT1A3, UGT1A4
Desyrel – CYP3A4, ABCB1-P-gp, P-pg
Effexor – CYP3A4, ABCB1-P-gp, P-gp
Effexor XR – CYP3A4, ABCB1-P-gp, P-gp
Elavil – UGT1A4, UGT1A3, P-gp
Imipramine – UGT2B10, ABCB1-P-gp, UGT1A4, CYP3A4, SLC22A2-OCT2,
UGT1A3, UGT2B7, SLC22A1-OCT1, SLC22A3-OCT3, CYP3A4
Luvox – 2B6, P-gp, intestinal 3A, ABCB1-P-gp, CYP2B6, CYP3A4
Norpramin – SLCC22A1-OCT1, SLC22A2-OCT2, SLC22A3- OCT3, CYP3A4
Pamelor – CYP3A4, ABCB1-P-gp, CYP2C8 Paxil – 2B6, P-gp, CYP3A4, CYP2B6,
ABCB1-P-gp
Paxil CR – CYP3A4, CYP2B6,ABCR1-P-gp
Pristiq – Assorted UGT isoforms
Prozac – 2B6, P-gp, ABCG2-BCRP, SLC22A3-OCT3, CYP3A4, SLC22A1- OCT1,
ABCB1-P-gp
Sarafem – 2B6, P-gp, ABCG2-BCRP, SLC22A3-OCT3, CYP3A4, SLC22A1- OCT1,
ABCB1-P-gp
Serzone -- U
Sinequan – UBCB1-P-gp, UGT1A3, UGT1A4
Tofranil – UGT1A4, UGT1A3, P-gp,
Triptil – ABCB1-P-gp
Wellbutrin – 2E1, 2A6, 2B6, CYP2B6
Wellbutrin SR – CYP2B6
Zoloft – UGT2B7, UGT1A4, P-gp, 2B6, CYP2B6, MAO, CYP3A4, ABCB1-P-gp
Marked medications (*) will also use other routes for metabolism:
Chlorprom – UGT1A4, UGT1A3, P-gp
Chlorpromanyl – UGT1A4, ABCB1-P-gp
Clozaril – FMO, UGT1A4, UGT1A3, ABCB1-P-gp, FMO3, ABCG2-BCRP Geodon –
Aldehyde oxidase substrate
Haldol – Glucuronidation, P-gp, UGT2B7, CYP3A4, CYP3A5, UGT1A9, ABCB1-P-
gp
Mellaril – CYP3A4, CES1, P-gp
Ridazine – UGT1A4, ABCB1-P-gp
Risperdal – P-gp, renal extraction, CYP3A4, ABCB1-P-gp, ABCG2-BCRP
Saphris – Various UGT
Seroquel – Glucuronidation, P-gp, intestinal 3A, epoxide by quetiapine, CYP3A4,
ABG2-BCRP, ABCB1-P-gp
Zyprexa – Glucuronidation, FMO, UGT1A4
Marked medications (*) will also use other routes for metabolism.
Ativan – UGT2B15, UGT2B7
BuSpar – Intestinal 3A, 3a4
Carbatrol – 3A4, CYP2C8, SLC22A5-OCT2N, UGT2B7, CES1, CYP2B6, ABCB7-
ASAT, SULT1A1, ABCC2-MRP2, ABCG2- BCRP, SLCO1A2- DATP1A2
Depakene – CYP2B6, UGT1A6, CYP2A6, UGT2B15, UGT2B7, UGT1A9, ABCB1-P-
gp
Depakote – UGT2B7, UGT1A6, UGT1A9, UGT2B15, UGT1A4, UGT1A3
Dilantin – UGT1A4, UGT1A6, UGT1A9, ABCB1-P-gp, CYP2C9, CYP2C8, UGT1A1,
CYP3A5, UGT2B7, CYP3A4, CYP2B6, UGT2B15
Halcion – CYP3A4, CYP3A5
Klonopin – NAT2, CYP3A4
Lamictal – UGT1A3, UGT2B7, UGT1A4
Librium – CYP3A4
Neurontin – SLC22A4-OCTN1
Valium – CYP3A4, CYP2B6, CYP3A5, UGT2B7
Xanax – Hepatic 3A, CYP3A5, CYP3A4
Marked medications (*) will also use other routes for metabolism:
Concerta – Glucuronidation, CES1A1.
Medate – CES1A1.
Methylin – CES1A1.
Ritalin – Glucuronidation, CES1A1.
Ritalin – CES1A1.
Vyvanse – CYP3A4, MAO
How to Use Charts to Decide Sequence of Medication Reduction
If you have two or more medications sharing the same CYP pathway to metabolize,
reduce the medication that uses the fewest pathways first. Example: Ambien used
concurrently with Luvox, Paxil, Prozac, Wellbutrin or Zoloft. Reduce the Ambien first.
If you were to reduce any of the antidepressants listed first, the Ambien would begin
to clear the body faster and the patient would experience Ambien withdrawal without
the current Ambien dosage being reduced. Ambien would be reduced by as much as
43% if the antidepressant were reduced first. (See Ambien product insert.) The best
approach is to always taper the anticonvulsant, antianxiety, benzodiazepine or sleep
medication first and then tackle the antipsychotic and antidepressant.
If taking two antidepressants concurrently, or taking an antidepressant and an
antipsychotic, selecting which one to reduce first would also follow the format
outlined earlier in this section. The drug using fewer common CYP pathways should
be reduced first.
If taking two antidepressants or one antidepressant and one antipsychotic, and the
CYP pathways match, evaluate the current side effects, when each side effect
started, when each medication was introduced, and determine from those side
effects which taper schedule to follow and which drug to taper first. From time to
time, a person will also be taking a drug as an inducer of the CYP pathways.
Determine if this “inducer” was prescribed to help offset the inhibitor drug’s effect or
is the inducer drug prescribed for other health reasons not related. You will generally
find that those who are also taking the inducer medication will be suffering from a
wide variety of adverse side effects. When reducing any medication attached to the
same pathway as an inducer medication, reduce the normal taper speed by one-half
for at least the first 2 months.
You may need to alternate reduction of the inducer drug and the inhibitor drug every
other reduction in order to maintain a balance.
Other medications must be closely evaluated. Lipitor, as an example, is an inhibitor
of the CYP 2C19, 2D6, and 3A, along with inhibiting the UGT1A3, UGT1A1, P-gp,
and intestinal 3A.
Use drug product inserts to determine metabolism route or the Physicians’ Desk
Reference.
Example 1: If taking multiple medications and each medication uses the same
metabolic route, each of the medications is competing for clearance. If one
medication is reduced, the other medications will also be reduced or clear the body
faster.
Decide which medication to taper off first based on:
CYP charts.
Full evaluation of side effects.
When side effects started with which medication.
If patient has used Viibryd for two years and used Risperdal for 2 months and side
effects increased dramatically once Risperdal was introduced, taper the Risperdal
first.
Example 2: If multiple medications are being taken and all medications can
metabolize through several routes, the impact will be lessened, and selecting which
medication to taper first would not be pathway dependent.
Avoid all supplements that compete with the same pathways, and eliminate as much
as possible all foods that compete with the medication by inducing or inhibiting the
metabolism routes of the medications.
With the advancements of The Road Back Program, as described in this book,
patients can now taper off antidepressants, antipsychotics and ADHD medications
and stimulants simultaneously. Reduce the medications as slowly as possible, as
close to 10% reduction as possible, and only increase the rate of reduction once the
patient has shown tapering success at lower reductions.
Supplements, Herbs and Foods
Supplements, herbs or certain foods can have a direct impact on the success of the
taper.
Datum: If a person smokes or drinks coffee before starting the pre- taper, do not
suggest they quit. Cigarette smoke induces the CYP1A2, 2E1, 3A and UGT2B7.
Nicotine inhibits UGT1A1, UGT1A4, UGT2A6, and UGT1A9. If taking Depakote and
starting or stopping smoking, the impact on the medication will be dramatic. If a
patient starts to smoke or quits smoking while taking Cymbalta, the drug will be
altered by as much as 15%. In theory, this should apply as well to any other drugs
sharing the same metabolism routes.
Coffee or caffeine inhibits the CYP1A2, 2E1 and the 3A.
A high percentage of these medications metabolize through these pathways and
caffeine usage will dramatically increase the medication, or if the person were to quit
drinking caffeine, they would begin to go into withdrawal to some degree because
the pathways will begin to metabolize the medication faster.
The times a person takes medication and when they drink two cups of coffee can
have an impact as well. If the person drinks two cups of coffee every morning about
one hour after their medication, and they change the time of the morning they drink
the coffee, expect a slight to above average side effect from the medication.
The person’s current daily routine should not be changed. If they were on a poor diet
before starting this program, do not change their diet drastically. If they did not
exercise before starting this program, do not advise them to do more than a casual
walk.
Once off all medication for 45 days, a healthy diet can be implemented, an exercise
program that matches their current physical condition can be started, the patient can
stop smoking, etc.
A trace amount of an herb or supplement will not create an adverse reaction or alter
the metabolism speed.
DNA Drug Reaction Testing and Taper Prediction
For the past several years, DNA drug reaction testing has been available to
determine the patient’s ability to metabolize medication through the CYP450
enzymes.
We have conducted over 200 drug reaction tests with the objective of determining
how well drug-adverse reactions could be predicted, and if there were clinical use of
this DNA data for tapering.
Prediction of a drug-adverse reaction: The individuals who were slow or poor
metabolizers or hyper metabolizers experienced drug-adverse reactions faster than
normal or intermediate metabolizers.
However, the normal or intermediate metabolizers still experienced adverse drug
reactions, but after longer usage of the medication. The metabolism type of the
individual was not indicative of the severity of adverse reactions or duration. Once
the drug had saturated the CYP enzyme used for metabolism, all the individuals
experienced the same side effect profile regardless of their metabolism speed noted
from the DNA drug reaction test.
The test results from the DNA drug-reaction test did not lead to a worthwhile taper
guide. It was postulated; if you were to induce the enzymes or inhibit an enzyme to
match a specific test result and medication, you would be better able to adjust the
metabolism and avoid withdrawal, or predict the withdrawal sequence. Again, this
did not assist in tapering or eliminating withdrawal side effects in the slightest. This
seems to parallel the results using an inducer drug to counteract the inhibition of the
main drug.
If a DNA drug-reaction test has any use to a physician, it would be for predicting the
dosage of the medication Coumadin. The initial prescription could be limited to a
narrow band, and the correct therapeutic dosage would be found in a few weeks,
instead of several months.
Nutritional DNA Test
Nutritional DNA testing provided this program substantial information to work with.
We tested the ability of over 100 subjects to metabolize B vitamins, folate, calcium,
Omega 3, phase II liver detox genes, Interleukin-6, and an assortment of other
genetic differences that ultimately determine overall health and physical well-being.
The Road Back Program and all suggested nutritionals used for medication tapering
address the most common genetic variations of the population at large. Though DNA
science is not precise at this date, enough evidence is available to formulate part of
a program to address the highest percentage of the population. Hypothalamic-
Pituitary-Adrenal Axis (HPA).
Psychoactive medications play havoc with the HPA. While benzodiazepines usually
help with anxiety for a certain time period, the feedback loop sending incorrect data
will eventually cause cortisol levels to increase, and the result will be increased
anxiety in the morning and mid-afternoon. Insomnia will usually follow the cortisol
level increase. Other psychoactive medications have their own unique side effect
profile and ultimate effect upon the HPA.
First year medical school textbooks describe the hypothalamus as: “Hypothalamus/
homeostasis or maintaining the body’s status quo.” As an example, blood pressure,
body temperature, fluid, the electrolyte balance and body weight are held in a
precise value labeled the “set-point.” The body’s set-point may change over time, but
from day to day, the set-point will remain nearly fixed. With the HPA receiving
continual input about the state of the body and the ability of the HPA to initiate
changes, as anything might sporadically fall out of balance, it is vital for the HPA to
have at hand all necessary nutrients to assist with the compensation. When the HPA
is out of balance, you will have a problem with insulin, stress, anxiety, weight gain,
thyroid problems, fatigue, unbalanced sexual hormones and countless other body
difficulties.
The hormone, ACTH, will eventually become out of balance, as will the other
hormones and adrenals.
Psychoactive medication directly alters specific areas within the HPA. Examine any
patient using a psychoactive medication for more than three months and you will
probably find a problem with hormones, thyroid, adrenals, cortisol and immune
system or other areas within the HPA.
However, it will be equally important to move beyond the normal view of the HPA.
Psychoactive medication side effects are quite varied and diverse. This is not to
rehash data from medical school, but to tie in the knowledge gained in the
educational process with psychoactive medication.
Some fibers from the optic nerve go directly to a small nucleus within the
hypothalamus (suprachiasmatic nucleus). This nucleus regulates circadian rhythms,
and couples the rhythms to the light/dark cycles.
The nucleus of the solitary tract will collect sensory data from the vagus and relay
the data to the hypothalamus. This data will include blood pressure and gut
enlargement.
The reticular formation receives a vast supply of inputs from the spinal cord and
relays that data to the hypothalamus. Part of that data will be skin temperature.
Nuclei, circumventricular organs, are unique in their own right as they lack a blood-
brain barrier. They monitor substances in the blood and have the ability to monitor
substances normally shielded by the neural tissue. Here you will find regulation of
fluid and electrolyte balance, by controlling thirst, sodium excretion, blood volume
regulation and vasopressin secretion. Include in this the area postrema, and you
have the detection of blood toxins and the vomit-inducing center. The OVLT and
area postrema project to the hypothalamus.
The limbic and olfactory systems project to the hypothalamus. Psychoactive
medication side effects, such as eating problems and reproduction difficulty, will
probably be traced to this area.
Ionic balance and temperature will be subject to the hypothalamus via the receptors,
thermoreceptor and osmorecepter.
When the hypothalamus is aware of a problem, it will assert repair mechanisms.
Neural signals to the autonomic system will attempt to regulate heart rate,
vasoconstriction, digestion, sweating etc., and the endocrine signals to and or
through the pituitary.
The pituitary side effects will include one or all six hormones, to include ACTH and
the thyroid-stimulating hormone (TSH). The repair output attempt, and the
psychoactive medication side effect profile, seem to run near a 50 percent
occurrence. Furthermore, you can directly trace psychoactive medication side effects
to the autonomic nervous system in both the sympathetic and parasympathetic
systems.
The hypothalamus can alter blood pressure; control every endocrine gland in the
body, body temperature, adrenal levels via ACTH, and metabolism. The repetition of
HPA information in this Chapter has been intentional. Do not be surprised to find a
male patient with extremely high estrogen levels, a female with high testosterone or
any other problems that can be associated within the HPA axis.
Taper the medication first, wait 45 days after the last dosage of the medication,
reevaluate the patient, and then gradually bring all parts of the HPA back into
balance. The nutritionals used with The Road Back Program were developed to help
the body overcome this imbalance gradually. Gradually is italicized because this is
where most problems occur with psychoactive drug-taper programs. Either they do
not address the HPA or the program is really a detoxification or heavy metal
chelating program.
The Road Back Program utilizes specific nutritionals to address the drug side effects
and to begin the process of balancing the HPA. Specifics on each nutritional, what
each nutritional is addressing within the HPA or the body in relation to psychoactive
medications, can be found in The Road Back Program patent when published by the
U.S. Patent Office.
Immune System
The immune system and the HPA are in constant communication and actions within
one system will induce response in the other. The supplements used in this program
are designed to also influence the immune response.
Reducing oxidative stress has been shown to balance Interleukin-2 (IL-2) as well as
Interleukin-6. If you were to test your bipolar patients IL-2 levels, you will find they
will be too high during the manic phase and IL-6 levels will have shot up high during
the depressive phase. A schizophrenic will have either too high or too low IL-2 levels
and will usually exhibit high IL-6 levels constantly.
The JNK supplement will reduce oxidative stress and lower IL-2 levels as well as IL-
6 levels. The specific cascading effect is; JNK gene over expression leads to
increase of Interleukin-2 levels which create an imbalance of Th1 and Th2. CD4 will
usually show dysfunction after prolonged Th1 and Th2 alteration.
Titrating Medication
The Road Back has tried titrating medication gradually without the use of nutritionals
with limited success. About 50% of the people could taper off their medication
without using these nutritionals but they still suffered extreme withdrawal side
effects.
Using a gradual titration combined with a basic detoxification approach had lower
than 50% success.
The normal supplements used to remove heavy metal or for a liver detox produced
undesirable results.
A gradual titration with the use of the suggested nutritionals gives our standard
successful results.
The Key to a Successful Taper With The Road Back Program
Following the pre-taper exactly as described is critical. The pre-taper is the make or
break point for every successful taper.
Most problems occur when:
The pre-taper is done too quickly.
Patient does not stop increasing a nutritional once a positive change occurs.
Patient changes the time of day they take medication.
Patient changes the time of day they take nutritionals.
Medication is reduced too quickly.
A new medication is prescribed in addition to existing medication.
Patient is switched to a new medication.
Doctor has patient use additional supplements or vitamins not in this program.
Patient begins taking other supplements.
Patient makes a major change to their daily routine.
Patient skips days of taking medication.
Titrating Psychoactive Medication:
Have the patient compound his/her medication whenever possible. An exact
reduction of the medication each week provides prediction, no guessing, and the
highest chance of success.
In the early days of psychoactive drugs, psychiatry did not titrate psychoactive drugs
up slowly on patients and the results were catastrophic. Many drugs, other than
psychoactive drugs, must be titrated up as well as down before complete
discontinuing.
There seems to be a medical community consensus that psychoactive drugs can be
reduced quickly, or patients can abruptly be taken off one psychoactive drug and
prescribed another psychoactive drug without an adverse consequence. This is not
the case. Even switching a patient from a tablet form of a psychoactive drug to the
liquid form of the same psychoactive drug can cause extreme adverse drug
reactions.
Dr. Donald E. McAlpine, psychiatrists at the Mayo Clinic states: “It’s important to
taper off slowly, extending the taper over several weeks under your physician’s
direction. When you stop too quickly, you may experience so-called discontinuation
symptoms, which can masquerade as relapse.”
The discontinuation process and side effects therein can be confusing to both the
patient and physician. Which side effect is coming from the medication, or is it a
return of the original symptom?
With a full pre-taper completed before reducing the medication, rest assured the side
effect starting during the taper is due to one of the following: The patient changed
something.
The reduction of the medication is too large.
A change made by the patient can be the most difficult to find. It might be something
the patient does not feel is a change.
Years ago, I had a person nearly halfway off Paxil. This person experienced no
withdrawal side effects tapering the Paxil to that point. When trying to taper off Paxil
in the past, the individual had extreme withdrawal side effects after the first reduction
attempt and would then need to return to a full dosage.
With no valid explanation, this person began to suffer withdrawal side effect
symptoms similar to those earlier. Two weeks passed and I could not find anything
the person had changed. Finally, it was mentioned to me by the individual he or she
had started an all-protein diet and began the diet 3 days before the side effects
started.
For this person doing this diet was not a change. He or she would go on this all-
protein diet every six months. I give you this example to point out that the change a
patient makes may not be so obvious. You may need to dig.
If a patient is keeping a complete Daily Journal these changes can be spotted more
quickly and trouble tapering can be avoided.
Use the Suggested Supplements
If you want the standard results with The Road Back Program, use the exact
supplements suggested. Read through Chapter 3, “Nutritionals” Used on The Road
Back Program for a list of all supplements, basic description of each and where they
are available. Most, if not all of the manufacturers of these supplements offer a
healthcare provider distributor program, if you wish to carry them in your practice.