Chapter Nineteen

THE SCIENCE BEHIND THE ROAD BACK

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 Hypothalamus-Pituitary-Adrenal Axis.
    
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 even begin to reduce a medication until all or nearly all-existing medication-induced side effects are eliminated. This gives the physician, as well as the patient, prediction, as well as a structured step-by-step standard approach for tapering off psychoactive medication.

Statements of fact: All psychoactive medications metabolize through specific pathways. All psychoactive medications alter the Hypothalamus 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 patients’ 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 psychiatric drugs, and include with this how psychiatric drugs are metabolized, how foods, vitamins, minerals, DNA, amino acids, hormones, glands, proteins, fatty acids, and enzymes work, in relation to psychiatric drugs, you have The Road Back Science.

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.

These marked medications (*) will also use other routes for metabolism:

Elavil – UGT1A4, UGT1A3, P-gp
Luvox – 2B6, P-gp, intestinal 3A
Paxil – 2B6, P-gp
Prozac – 2B6, P-gp
Tofranil – UGT1A4, UGT1A3, P-gp
Wellbutrin – 2E1, 2A6, 2B6
Zoloft – UGT2B7, UGT1A4, P-gp, 2B6

These marked medications (*) will also use other routes for metabolism:

Clozaril – FMO, UGT1A4, UGT1A3
Geodon – Aldehyde oxidase substrate
Haldol – Glucuronidation, P-gp
Risperdal – P-gp, renal extraction
Seroquel – Glucuronidation, P-gp, intestinal 3A, epoxide by quetiapine
Zyprexa – Glucuronidation, FMO, UGT1A4.

These marked medications (*) will also use other routes for metabolism:

BuSpar – Intestinal 3A
Depakote – UGT2B7, UGT1A6, UGT1A9, UGT2B15, UGT1A4, UGT1A3
Valium – 2B6, UGT2B7, intestinal 3A
Xanax – Hepatic 3A.

These marked medications (*) will also use other routes for metabolism:

Concerta – Glucuronidation.
Ritalin – Glucuronidation.

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 shared pathways first.

Example: Ambien being used concurrently with Luvox, Paxil, Prozac, Wellbutrin or Zoloft. You should reduce the Ambien first.

If you were to reduce any of the antidepressants listed first, the Ambien would be reduced 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)

If your patient is 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 your patient is taking two antidepressants or one antidepressant and one antipsychotic, and the CYP pathways match, evaluate the patient’s current side effects, when each side effect started, when each medication was introduced, and determine from those side effects which taper schedule to follow.

From time to time, you will have a patient also taking a drug as an inducer of the CYP pathways.

Determine if this “inducer” was prescribed to help offset the inhibitor drugs effect or is the inducer drug prescribed for other health reasons not related.

You will generally find that your patients 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 a patient is taking 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 insert to determine metabolism route or the Physicians’ Desk Reference.

Example 1: If your patient is taking multiple medications and each medication uses the same metabolic route, each of the medications is competing for clearance. If you reduce one of the medications, 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 Lexapro for two years and has 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 dependant.

• 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.

Supplements, Herbs and Foods

Using supplements, herbs or eating certain foods can have a direct impact on the success of the taper.

Datum: If a patient 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 your patient is taking Depakote and starts or stops smoking, the impact on the medication will be dramatic.

Coffee or caffeine inhibits the CYP1A2, 2E1 and the 3A. A high percentage of these medications metabolize through these pathways and the result of caffeine usage will be to dramatically increase the medication, or if the patient 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.

What time a patient takes their medication and when they drink two cups of coffee can have an impact as well. If your patient 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.

Green tea, with its current popularity is the most problematic at this time. I am not saying green tea is not a benefit to the body. I am saying there is a time and place for supplements, herbs and some specific foods once a person is off all medication for 45-days.

The daily routine your patient currently is on should not be changed. If they were on a poor diet before starting this program, do not change their diet drastically. If they do not exercise before starting this program, do not advise the patient 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.

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.

The author has conducted over 200 drug reaction tests. The objective was to determine how well you could predict drug-adverse reactions, and if there was 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 would experience drug-adverse reactions faster than normal or intermediate metabolizers.

However, the normal or intermediate metabolizers would still experience 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.

Using 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 would be able to be in 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 gave this program substantial information to work with. The author tested over 100 subjects’ ability to metabolize B vitamins, folate, calcium, Omega 3, phase II liver detox genes, and an assortment of other genetic differences that ultimately determine overall health and the well-being of the body.

The Road Back Program and all suggested nutritionals used for medication tapering address the most common genetic variations the population has at large. DNA science is not precise at this date, but enough evidence is available to formulate part of a program to address the highest percentage of the population.

Hypothalamus-Pituitary-Adrenal Axis (HPA)

Psychoactive medications will 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 hypothalamus as: “Hypothalamus is 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 will directly alter specific areas within the HPA. Examine any patient using 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. The intent here 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 when you have a male patient with extremely high estrogen levels, a female with high testosterone or any other problem that can be associated within the HPA.

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 other 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 decisions made within one system will induce response in the other. The supplements used in this program are designed to also influence the immune response.

Interleukin-2 (IL-2) can be increased and anxiety, psychotic behavior, insomnia and other assorted manifestations associated with these symptoms may very well vanish. Our beta 1, 3-D Glucan is clinically proven to increase IL-2 levels in humans.

When using the IL-2 reference range of 223-710 as a guideline, keep in mind any result with IL-2 lower than 466 needs to be increased if the patient is still showing signs of anxiety, psychosis or insomnia. It is advantageous to test the IL-6 along with the IL-2 for a complete understanding of the patient’s current immune response and inflammation factors.

IL-6 reference range will be from 0.0 – 14.0. If the IL-6 is greater than 3, it is advantageous to gradually lower the inflammation. Patients with a low IL-2 and high IL-6 will fall in the category of highly anxious and fatigued or depression symptoms.

Titrating Medication

The Road Back has tried titrating the medication gradually without the use of nutritionals and the results were: 50% of the people could taper off their medication but they suffered extreme withdrawal side effects.

Using a gradual titration, while using 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 the standard 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. Setting the body up nutritionally and getting rid of all, or the vast majority of existing side effects, needs to be accomplished so the patient knows they can make it off the medication this time and allow them to reduce the medication without causing additional trauma.

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 day of taking medication.

Additional Items

When you have a patient taking a vast array of vitamins and they are not doing well, the other vitamins the patient is taking might be the problem.

Start the patient on one-half the normal amount of each suggested nutritional used with this program and only increase every fourth day if they are doing well. The nutritionals used with The Road Back Program will make the other vitamins begin to work and the patient may experience a rapid detox due to the other vitamins. If the patient reacts to the lower introduction amount of the nutritionals used with this program, the only thing left to do is taper the patient off their existing vitamins over a one-month period. Then you can restart the pre-taper.

I do understand that there are very good and essential vitamins an individual may take, but if the intent is to help the patient off the psychotropic medication, the other vitamins need to wait until the patient is off the medication 45-days.

Titrating Psychoactive Medication:

Have your patient compound his/her medication whenever possible. An exact reduction of the medication each week gives a 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 discontinuing.

There seems to be a consensus within the medical community 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 to the patient. 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 will cause an 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 and your patient eliminating nearly all, or all, side effects before reducing the medication, you can rest assured the side effect starting during the taper is only due to one of the following:

• The patient changed something.
• The reduction of the medication is too large.

Locating a change a patient might have made 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 this point. While trying to taper off Paxil in the past, the individual would have extreme withdrawal side effects after the first reduction attempt and would then need to go back to a full dosage again.

With no valid explanation, this person began to suffer withdrawal side effect symptoms like in the past. 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. He or she started this 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 very well need to dig.

If a patient is keeping a complete Daily Journal these changes can be spotted quicker and trouble tapering can be avoided.

Use the Suggested Supplements