Psychopharmacology 101

For Non-prescribing

Mental Health Professionals -

A Training Resource

1. Medical errors in the United States are the 3rd Leading cause of death.

Makary, M.A., & Daniel, M. (2016). Medical error – The third leading cause of death

in the US. The BMJ, 353, doi: 10.1136/bmj.i2139.

2. Medication errors, among Medicare beneficiaries, cause an estimated 530 million

Adverse Drug Reactions (ADRs) yearly.

(1) Neal, A. & Hogan, B. (2012). Are your prescriptions killing you? New York: Simon and Schuster.

(2)Field, T.S., Gilman, B.H., Subramanian, S., et al. (2005). The costs associated with
adverse drug events among older adults in the ambulatory setting. Medical Care, 42, 1171-1176.

3. 1 out of every 15 children will experience “medical accidents” during their stay in hospitals

Children’s adverse events. (April 7, 2008). Reported on ABC “Good Morning America.”

4. The extent of faulty provider-patient communication is related to the fact that up to one-third

cannot repeat their diagnosis and up to one-half do not understand important details of treatment.

Taylor, S.E. (2009). Health Psychology. New York: McGraw-Hill.

5, 2% of medications identified in a “brown bag review” as appropriate for elimination

(no longer needed) are re-started. This finding came from a study of polypharmacy

targeted on if anti-psychotic polypharmacy could be reversed. There was a large trial

N=127 over a 12-month period. All these patients were stable on polypharmacy and

2/3rd were successfully moved to monotherapy without “any significant worsening.”

(1) Essock, S.M. et al. (2011). Effectiveness of moving from antipsychotic polypharmacy to monotherapy. American Journal of Psychiatry, 168, 702-708.

(2) Too Much Medication, Consumer Reports, March, 2012.

6. The FDA received 141,829 reports of serious, disabling, or fatal ADR’s in 2010.

This represents an increase of 31% percent since 2009.

2009 Year Reported in 2010 31%

2010 Year Reported in 2011 ↑11% Over Previous Year

2011 Year Reported in 2012 ↑16% Over Previous Year

2012 Year Reported in 2013 ↑16% Over Previous Year

2014 Year Reported in 2013 ↑12.7% (Net increase of 4.1% from 2012)

2015 Year Reported in 2014 ↑32.9%

From 2005 – 2015 ↑500%

Institute for Safe Medication Practices www.ismp.org/QuarterWatch/

7. If an individual is taking seven or more medications, there is 99.9% risk of interaction.

(1) Interview with Merla Arnold. (September, 2008). The Tablet, Newsletter of Division 55
of the American Psychological Association, 9(3), 8-10.
(2) Hilts, P.J. (2004). Protecting America’s Health. Chapel Hill, N.C.: The University of
North Carolina Press.

8. Assuming no substitute has be discovered and approved, the Health Research Group

recommends waiting 7 years before taking a new drug.

9. Americans spend more on medicines than do all the people of any country in the world.:

Petersen. M. (2008). Our daily meds. New York: Sarah Crichton Books.

10. The story of Thalidomide

In 1954 Thalidomide was used in the Chemie Grünenthal Haven for labor-camp.

The scientists and doctors prescribed thalidomide as non-toxic OTC antidote

to morning sickness and sleeplessness. This resulted in thousands of babies

born with deformities.

Finally after a long legal battle in 2009 a voluntary endowment of €50 million was given to German Thalidomide Foundation to compensate these families whose children were impaired.

But is thalidomide used today?

Yes it is. It is now known as Thalomid® and is used for HIV Wasting; Multiple Myeloma

& Hansen’s Disease (Leprosy).

Science behind this fact: In 1954 Thalidomide was used to address morning sickness and

sleeplessness of pregnant womren, but children were born with birth defects. At that time

Germany field tests of meds for USA .An important fact of pharmacology was discovered that

One side of a drug does what we want it to do and the other side did not. In the case of

Thalidomide, the Stereoisomer Left side resulted in Birth Defects and the Right Side had

Therapeutic Effect. Thuse the role out of Thalomid.

Because of the nature of our interactions, therapists have a much better opportunity to observe and discuss the effects of medications than do physicians and psychiatrists (Symptoms are more apparent)

Common concerns can be addressed and clients informed:

1. Describing how long it takes a specific medication to work
2. Preparing and supporting clients for delay in effects of SSRIs, SNRIs, and tricyclics
3. Identifying and explaining side effects
4. Help client recognize side effects.E.g.“spacey” feelings interpreted as “losing my mind” when taking SSRIs or increased anxiety due to withdrawal between dosages
5. Identifying and explaining side effects
6. Describing various effects and explaining why medications lead to certain effects
7. Helping clients to weigh relative costs and benefits
8. Distinguishing between temporary or lasting side effects— E.g. temporary initial
   increase in anxiety associated with SSRIs, SNRIs, tricyclics & clients can ask doctor about dosage and can start gradually

1. Helping clients prepare for conversations with their doctors
2. Identify questions and concerns to address, perhaps prepare list
3. Help clients recognize potential problems with medications E.g.:Benzodiazepines can cause problems with increased anxiety/panic between dosages that can be mistaken as a worsening of symptoms
4. Long term use of medications can lead to problems such as rebound anxiety, insomnia and memory difficulties for benzodiazepines, or “poop out” for SSRIs and SNRIs
5. Noncompliance with medications should be addressed
6. Clients who are not taking medications as a result of side effects or concerns
7. Clients who are taking more medication or taking meds more frequently than prescribed in order to cope with anxiety
8. Recognize clients’ attitudes toward the medication
9. Clients “waiting for the medicine” to do the work and not committed to therapy
10. Clients attributing changes to the medication and not developing self efficacy, especially with benzodiazepines, it is easy to rely on the sedative effects and not use exposure strategies
11. Help clients recognize danger of changing medications without medical assistance
12. Discontinuing medications without medical supervision can be potentially dangerous, especially for benzodiazepines (Seizures)

Monitor Clients Attitudes About Medications - They Matter

• Attitudes and beliefs about medications are as important as side effects in determining whether a client stays in treatment
• Attribution of change to medications can negatively influence outcome and reduce changes in self efficacy
  
• Clients with panic disorder who attributed their improvement to medication had 60% relapse rates vs 0% for those with internal attributions

DRUGS AND ALLERGIES

Shellfish: Glucosamine &  Cod Liver Oil

Peanuts: Laxatives; Sustanon® ;Prometrium®; Earex® Ear Drops; Derma-Smoothe® – for psoriasis; Combivent®/ipratropium, Albuterol, Beta-2 Agonist Inhalers

Gluten: Pre-gelatinized starch – look for “starch” in list of ingredients; Filler in IV drops; Coating on meds so pills won’t stick together in bottle; Pristiq®; Lorazepam (manufactures by Geneva);  Paroxetine (manufactured by Apotex)  www.glutenfreedrugs.com

BLACK BOX WARNINGS Some examples due to complaints to the FDA

• Antidepressants - Suicidality
• Stimulants - Drug Dependence
• Atypical Antipsychotics (SDAs) - Increased mortality in elderly; Dementia related psychosis; Suicidality (Quetiapine plus above)
• Carbamazepine: (The 4 “A’s”) Agranulocytosis: Acute condition involving a severe/dangerous; leukopenia (lowered white blood cell count); Aplastic Anemia; Appropriate Use
• Valporate: Hepatotoxicity & Pancreatitis
• Lamotrigine (Lamictal®):  Rash
• Naltrexone (ReVia®, Vivitrol®): Hepatotoxicity
• Nefazondone(Serzone®): Hepatic Failure; Suicidality

For more information: Index to Drug-Specific Information

https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111085.htm

FDA Pregnancy and Lactation Labeling

Changes to Drug Labels and Categories made by the FDA

Categories Old & Revised

Five (A, B, C, D & X) categories to indicate the potential of a systemically absorbed drug for causing birth defects

Key differentiation among categories rest upon the degree (reliability) of documentation and the risk vs. benefit ratio

Old drug LABELS must REMOVE pregnancy letter rating by 2020

Drugs approved after June 30, 2015, new format

Drugs approved before June 30, 2015, will only remove pregnancy “letter” category

Medicated Americans

• One out of every EIGHT pregnant women in the United States takes SSRIs to treat depression and mood disorders--Scientific American Mind, March/April 2010, 21, 8.
• Special Note: Croen, L.A., et al. (2011). Antidepressant use during pregnancy and childhood autism spectrum disorder. Archives of General Psychiatry, 68, 1101-1112.

Category “A”

Adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.

Example: Synthroid® (levothyroxine)

Category “B”

Animal studies have not demonstrated a risk to the fetus, but there are no adequate studies in pregnant women, or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus during the first trimester of pregnancy, and there is no evidence of risk in later trimesters

Example: Tylenol®, Ambien®, Benadryl®, Ibuprofen Tylenol®/acetaminophen  Zeyan, L., et al. (2014). Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatrics, 168, 313-320.

Category “C”

Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; the benefits from the use of the drug in pregnant women may

be acceptable despite its potential risks, or there are no animal reproduction studies and no adequate studies in humans.

Examples: Prozac®, Celexa®, Thorazine®, Haldol®, Risperdal®, Bactrim®, Sonata®, Cipro®, et al.

Category “D”

There is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.

Examples: Lithium, Phenytoin (Dilantin®), doxycycline, tetracyclines, daytime benzodiazepines, amitriptyline, aspirin (in 3^rd trimester), et al.

Category “X”

Studies in animals or humans demonstrate fetal abnormalities, or adverse reaction reports indicate evidence of fetal risk.

The risk of use in a pregnant woman clearly outweighs any possible benefit.

Examples: Accutane ®, methotrexate, estrogens, Coumadin®, “statin products” (Lipitor ®, Prava- chol®, Mevacor®, Lescol®, Zocor ®, Crestor ®), Evista® (raloxifene), Halcion ® (triazolam), Restoril® (temazepam)

• New section 8.1 will include a risk summary, clinical considerations, data, and information previously included in the “Labor and Delivery” subsection
• New section 8.2 will include information about drug use when breastfeeding, including the amount of drug in the breast milk and the potential effects on the breastfeeding infant
• New section 8.3 will include information about need for pregnancy testing, contraception recommendations, and infertility as it relates to the drug

Labeling changes effective June 30, 2015.

Drugs manufactured after this date will use the new labeling method, while drugs approved on or after June 30, 2015 will be phased in gradually. Only affects prescription drugs; OTC drugs will not be affected. Risk Summary subheadings are always required, while any others can be omitted if not applicable

Genetic Polymorphisms

Frequency of CYP 2D6 Genetic Polymorphism (ethnicity missing allele on a gene)

Example 1: Niccolo Paganini (1782-1840)  “The Devil’s Violinist” -  Could extend little finger 45 degrees due to  Ehers-Danlos Syndrome, decreased collagen = increased flexibility

Example 2: Usain Bolt, Jamaican Sprinter  ACTN 3 - 70% of US athletes &  75% of all Jamaicans have Muscle contractions which affects fast twitch muscles. Due to 2D6 Genetic Polymorphisms resulting from 2D6 Poor Metabolizers in Caucasians 3%-10%, Asians .5%-2.4%, Hispanic 4.5%,US Blacks 1.9% - 6.0%. 2D6 Rapid Metabolizers (Gene Duplication) in Saudi Arabians 10.4%, Ethiopians 16.0%, Spaniards 3.5%. 50% of all people >60 years old don’t produce enough 2D6 to metabolize drugs properly

The Aging Population

Pharmacological relationship between the Newly Bred & Nearly Dead

Elder Changes Need for Concern

Decrease Monoamines

Decrease Dopamine

Decrease Norepinephrine

Decrease Serotonin

Increase in Enzymes

Increase MAO & COMT

Decrease in liver’s ability to metabolize and kidney’s ability to clear

More side effects

Beers Criteria for Potentially Inappropriate Medication Use in Older Adults: “Beers List” iGeriatrics (Beers Criteria App)  www.guideline.gov

Dementia Treatment

Early “Not Your Usual” Signs of Dementia: Missing Sarcasm, Frequent Falling, Disregard for the law, Staring, Eating objects,Losing knowledge of objects (e.g., Hair conditioner: “I don’t know what that is.”), Losing empathy,,Ignoring Embarrassment, Compulsive ritualistic behavior, Money Troubles & Difficulty Speaking

Acetylcholine (ACh)

Memory & Cognition

The Parasympathetic System

Muscarinic/Cholinergic System

“Rest, Digest, Take Out the Trash”

Agonist ADRs = “SLUDG” Salivation Lacrimation Urination Defecation GI Distress

Donepezil (Aricept ®)

FDA approved for Alzheimer Disease

Mechanism of Action: Cholinesterase inhibitor, Stop if no benefit in 3 to 6 months  Taper over 4 weeks to avoid discontinuation syndrome  1 in 12 Significant Side Effects (“SLUD”), Others: Galantamine (Razadyne® ) DO NOT use with renal, hepatic, cardiac impairment, Rivastigmine (Exelon®) - AChE in Brain & BuChE in Glial Cells (glial cells are more nourished)

Dementia Treatment

To date, no one has been healed from Alzheimer Disease.

That person is still out there. . .

Proactive Ethical Mental Health Professionals’ Goals

1. Clients are Well educated on psychopharmacological risks
2. Clients are then better able to make a well-informed judgment concerning their treatment choices.
   
3. The clients Mental and Physical Health is protected and healed
   

“It is an art of no little importance to administer medicines properly, but it is an art of much greater and more difficult acquisition to know when to suspend or altogether to omit them.”

WELCOME TO THE REAL WORLD!
In a continuing education program on the Ethics in Psychopharmacology, the participants were asked to get involved in the following Role Play and then vote on an option they would choose if the there the executive in the role play.

Role Play: You’re an executive, director of a pharmaceutical company.

Decision: Drug X brings in $20 million a year – significant to the company’s bottom line.

Problem: It causes the deaths of 20 people a year.

Legal: Regulators ask you to take the drug off market. There are less expensive alternatives

Bottom Line: That’s $1 million for each person who dies

What to do?

• Immediately recall the drug.
• Promote it aggressively
• Or something in-between

What Happened?

79% of participants chose to continue drug promotion and to try and stop the FDA from removing it from pharmacies

Real Example: in 1969 “Panalba” (anti-inflammatory) cost $1 a pill and Upjohn used its money and power in DC to stop FDA from removing this dangerous drug. Upjohn fought for years before it stopped selling the drug.

Justification given in these cases is: Risk Benefit Ratio knowing it has negative side affects but still wanting to help clients

Social Psychology’s Attribution Theory

It attributes an internal reason for a problem that a person has. Judging a person’s behavior on something inside of self. So proceed and give a pill, convinced the pill will work, but it was a wrong diagnosis and wrong prescription:

• Diagnosis assigns cause of distress to individual rather than situational factors
• “Patient failed to respond.”

ETHICAL PRINCIPLES

Autonomy - Right of clients to make decisions for themselves.

Beneficence - Demands prescribers achieve the best possible outcome through treatment.

Confidentiality - Privacy of clients’ medical condition and health information.

Nonmaleficence - First, do no harm! “Primum non nocere.”

Fidelity - Provide what’s promised to another.

Justice - Give Justice unto Others: Allocate products and services to clients fairly, regardless of race, gender, religion, or other factors.

Veracity/Honesty- Be honest and always tell the clients the truth.

1. High-Risk Psychopharmacology

2. Long-Term Psychopharmacology

3. “Clinical Innovation”

4. Enhancement Psychopharmacology (Hsin, 2014)

High-Risk Psychopharmacology

High Risk Conditions & Risk Extenders

Long-Term Psychopharmacology can be a risk for:

1. Creative Non-Adherence
2. Long-Acting Medications
3. Polypharmacy

Clinical Innovation, which can be a risk due to:

1. Off-Label Use of Medications
2. Role of Placebo
3. Enhancement Psychopharmacology

Elective Psychopharmacology which can be a risk due to:

1. Marketing of Mental Illness
2. Iatrogenic Intoxication

Drug Associated with High-Risk Psychopharmacology

(Not a complete list)

1. Tricyclic Antidepressants

2. Benzodiazepines/hypnotics

3. Antipsychotics

4. Sedating Antihistamines – Benadryl due to side affects

5. Anticholinergics -

    a) Paroxetine (Paxil®)

    b) Chlorpromazine (Thorazine®)

    c) Clozapine (Clozaril®)

    d) Hydroxyzine (Vistaril®)

6. NSAID + (Anti-Fungals, Warfarin, Heart Meds)

The practice of psychopharmacology involving situations where patients are at high risk of adverse events or creation or new diseases as a result of treatments.

Examples:

• Pregnancy