PRESENTED BY: LESLIE MOZULAY

THOMAS DONAHUEHEATHER PANE

CALDWELL COLLEGEABA 553

A Review ofDRUG THERAPY

What is Drug Therapy?

Drug therapy/treatment of disease with drugs is also called pharmacotherapy

Rapidly growing component of psychotherapyRelates to knowledge of the chemistry of the

nervous system as well as geneticsRemedies for “psychological problems” with

“physiological roots” Drugs don’t address the roots of all

psychological problems

Benefits of Drug Therapy

Promotes healthy functioningReduces or cures illnessMost conditions can be treated with

medicationsSymptoms of incurable conditions can be

treated with medicationsReduction of symptoms provides opportunity

to address other needs

Regulation

Food, Drugs and Cosmetics Act of 1938 came about after years of lobbying and

challenges occurrence of “Elixir Sulfanilamide tragedy”

made Congress act to tighten regulationshttp://www.youtube.com/watch?v=6-tYOdg

Mez0 Information regarding severity of the “Elixir

Sulfanilamide tragedy”

               

Regulation

Food, Drugs and Cosmetics Act of 1938 more authority given to agency through stronger

legislation to regulate patent medicine industry to start mandatory pre-market approval for new drugs to regulate therapeutic claims on labels to assure adequate directions for safe use

Regulation

1962 Drug Amendments (Kefauver-Harris Amendments) to the Food, Drugs and Cosmetics Act. occurrence of another therapeutic crisis

thalidomide – sedative to address morning sickness in pregnant women caused birth deformities

Regulation

Prior to release, drug companies to assure drugs

safe effective (not required in 1938 law)

FDA was given greater authority clinical trials for new drugs drug advertising establishing good manufacturing practices (i.e., coding

production) accessing company records to monitor practices (i.e., shipping

records)

Pre-market approval process may have caused decline in new drugs 

Regulation

U.S. Food and Drug Administration - U.S. Department of Health and Human Services “As a result (of increased FDA authority), the US

today has among the toughest drug approval regimes in the developed world.”.

Regulations may be the reason that new medicines often are first introduced in European markets.

http://eh.net/encyclopedia/article/Law.Food.and.Drug.Regulation

Regulation

Prescription Drug User Fee Act of 1992 Drug manufacturers have to pay fees to FDA

pay reviewers to assess new drug applications

Speed of drug approval relates to need for drug higher incidence of adverse drug reactions from new

pharmaceuticals

Research and Trials

Drug Approval Research and Clinical Trials: Can take years

phase 1- animal studies• determine if it is safe to test• note side effects

phase 2• see if it works• establish dosage range

phase 3- human studies• better than placebo• better than other treatments• note side effects

submit for FDA approval

Research and Trials

Very expensive

Most drugs not approved

Labeling is key to approval limited use with dangerous drugs with broader there’s more money

Generic vs. Brand Name

Generic drugs are copies of brand-name drugs

Generic drugs usually less costly savings due to not having to research, develop

and market new Brand Name drug manufacturers can apply to the FDA for

permission to make and sell generic versions of the drug when patent nears expiration on Brand Name drug,

multiple companies can start production so competition drives price

Generic Drugs

Pharmacological effects are exactly the same as the brand name drug same dosage intended use and effects route of administration side effects risks safety strength as the original drug

Labeling

Must provide all information side effects contra indications

Limited to proven efficacyPhysicians

knowledge pharmacology and therapeutics to choose drugs

concern when non-physician is allowed to prescribe drugs

Off Label Use

Treat a symptom of a conditionAny use not FDA approved

time money FDA does not regulate physicians

Examples of multiple uses of drugs Brand Name- Revia (Generic Name - Naltrexone)

to treat alcoholism or opium addictions also used to address self injurious behaviors occurring for sensation drug lowers pain threshold so reach “satisfaction” of sensation

sooner drug side effect- impact desire to eat

curbing appetite for weight reduction

Risk factors

Type of mental disorderAgeGenderBody sizePhysical illnessesUse of tobaccoUse of alcoholLiver and kidney functionWhether medications taken as prescribed

http:/www.nimh.nih.gov/health/publications/mental-health-medications/complete-index.sht

Risk Factors

GeneticsOther prescribed drugsOver the counter drugsHerbal supplementsMineral supplementsVitamin supplementsDiet

http:/www.nimh.nih.gov/health/publications/mental-health-medications/complete-index.sht

Communication and Maintenance

Inclusion of drugs with therapy program considered on case by case basis

Regularly scheduled appointmentsUnderstanding of side effectsSuddenly stopping a drugDrug dependence and drug abuse

Autism Therapy and Drug Therapy

Autism Therapy to address not only educational interventions, but

to improve quality of life and functional independence abnormal behaviors

restricted stereotyped patterns self injury interests activities

Autism and Drug Therapy

Medical management of neuropsychiatric disorders

seizures hyperactivity anxiety obsessive-compulsive Tourette’s other disturbances

sleep disturbances irritability

Autism and Drug Therapy

No known medication solves Autism’s core symptoms related to:

verbal and nonverbal communication social interaction

“When there is no cure there are 1000 treatments.”

-Donald J. Cohen

 

http://www.nytimes.com/2001/10/04/us/donald-j-cohen-61-dies-changed-field-of-child-psychiatry.html

No Decade like the 90’s

Research boom with government and drug companiesSix new atypical antipsychoticTwelve new antidepressants (SSRIs)Several new stimulants

 

ADVOCATES, BIG PHARMA MAKE PUSH FOR AUTISM DRUGS

Spring 2012 announcementLargest single autism research investment everAutism Speaks, academia, and pharmaceutical

companies$38.7 million investmentResearch data bases in Europe and the United

StatesClinical trial networks to test treatments on those

with autism

http://www.disabilityscoop.com/2012/03/20/advocates-big-pharma-drugs/15213/

Drug Therapy

Medications are used for treating the three core symptoms of autism:

1. Communication difficulties 2. Social challenges 3. Repetitive behavior

Medications for treating autism are most effective when used in conjunction with behavioral therapies (e.g., ABA)

Drug Therapy

The physician is not treating autismThe symptoms of autism are being treatedWhen the symptoms are successfully treated,

people with autism may be better able to learn, communicate and generally connect with others

Symptoms may include behavior issues, anxiety, depression, mood swings, attention issues, and hyperactivity

Drug Therapy

Medication does not “cure” any psychiatric disorder

As in the case of diabetes or hypertension are not cured by insulin or antihypertensives

Success in psychopharmacology means control of symptoms and this requires ongoing treatment

Drug Therapy

No uniform “best” medication or medication regime

Just as two children with autism are not the same

The range and severity of symptoms, presence of associated disorders (e.g., ADHD, OCD, child’s IQ)

Symptoms to be targeted determine which medications are tried and in what combinations

Drug Therapy Claims

Claims:

To help the individual function near normal in society

To decrease challenges and barriers individual, and their teachers, caretakers, and medical professionals.

To provide a safe and effective treatment

Top five drugs used to help with Autism

1. SSRIs 2. Anti-psychotics (Typical) 3. Anti-psychotics (A-Typical) 4. Anti-convulsants 5. Stimulants - Ritalin

SSRI’s

Selective serotonin reuptake inhibitors

Known as anti-depressants Drugs that treat anxiety, depression, and

obsessive-compulsive disorder (OCD)Serotonin is a neurotransmitter that has

many roles in the functioning of the brain.

SSRI’s

One of the most commonly used is fluoxetine (Prozac).

Some of the FDA approved SSRIs are used to treat symptoms of autism in children over the age of 7 include: Prozac, Luvox, Zoloft, and Anafranil

Anafranil should be avoided for individuals with seizures.

SSRI’s Claims

Reduce repetitive behaviorsImprove resistance to change Improve perseverative talkingImprove ritualistic or compulsive behaviorImprove moodReduce tantrumsReduce aggressionAnd to some degree, improve attention and

eye contact

SSRI’s

6–8 weeks for drug to begin to reach full potential slow onset is considered a downside to treatment

Many side effects disappear after the adaptation phase when the antidepressant effects begin to come to prominence

Despite being called general, the side effects and their durations are highly individual and drug-specific

Common side effects are: nausea, dry mouth, headache, diarrhea, nervousness, agitation

or restlessness, reduced sexual desire or difficulty reaching orgasm, inability to maintain an erection (erectile dysfunction), rash, increased sweating, weight gain, drowsiness, and insomnia

Antipsychotics Claims

Antipsychotics are broadly divided into two groups: Typical or first-generation antipsychotics Atypical or second-generation antipsychotics

Help in the treatment of behavioral disorders

Typical Antipsychotics Claims

Referred to as major tranquilizers, because some of them can tranquilize and sedate

Common conditions with which they might be used include schizophrenia, mania and delusional disorder. They might be used to counter psychosis associated with a

wide range of other diagnoses

They are used to help to manage symptoms of Autism Spectrum Disorders

Typical Antipsychotics

Some of these medications are Haldol®, Moban®, Navane®, Mellaril® and Orap®

Haldol® is a common drug used in emergency rooms for extremely aggressive individuals

Concern about side effects impact widespread usage

Typical Antipsychotics

Range of side-effects

Many people (around two thirds in controlled drug trials) discontinue antipsychotics, partly due to adverse effects

Extra pyramidal reactions include acute dystonias, akathisia, parkinsonism (rigidity and tremor), tardive dyskinesia, tachycardia, hypotension, impotence, lethargy, seizures, and hyperprolactinaemia

Anti-psychotics (Atypical)

Newer antipsychotic medication – Risperdal®, Zyprexa®, Seroquel®, Abilify®, and Geodon®

The newer atypical antipsychotics are supposedly rationally designed drugs in which a theoretical understanding of both the condition to be treated and the effect of certain molecules on the body

Continued off-label use of the newer drugs indicates that old-fashioned empirical drug discovery is still important in evaluating this class of medication.

Atypical Antipsychotics Claims

Fewer side-effects

Atypical antipsychotics (especially Olanzapine®) seem to cause weight gain more commonly than the typical antipsychotics

Metabolic side effects associated with weight gain include diabetes that, frequently, can be life threatening.

Proven effective in treatment of aggression and self-injury among children

Only Risperdal® and Abilify® are FDA approved for treatment of irritability associated with autism

Anti- Convulsants

Anti-convulsants : antiepileptics or AEDs, are a group of drugs which aim to prevent or reduce the severity of fits (convulsions) in various types of epilepsy

They work by acting on the brain and central nervous system

Examples - Tegretol, Lamictal, Topomax, and Depakote

One of every four individuals with autism have seizures

Anti- Convulsants Claims

Used to reduce some of the core symptoms of autism: social and communication difficulties repetitive, compulsive behavior

Potential side effects Cause abnormalities of blood or platelet counts and

liver function Dizziness, drowsiness, unsteadiness, nausea, and

vomitingSkin rashes may occur Confusion as well as nervousness, headaches, and

constipation

Stimulants Claims

Used to treat inattention and hyperactivity in children with ASD

Examples of stimulants are: Ritalin, Adderall, Concerta, and Metadate ER

Side effects : insomnia, irritability, decreased appetite and anxiety (National Resource Center on ADHD)

Additional risk of developing tics; however, this frequently stops when medication is changed or stopped.

Drug Therapy Video

Drugging kids. (2010). CCHRINT. Available from http://www.youtube.com/watch?v=MR4EWSbXLWA&feature=relmfu 

Literature Review on Antipsychotics

Risperidone= Risperdal® Approved in 2006 for treating “irritability” in people with autism,

5 to 17 yrs old.

Aripiprazole= Abilify® Approved in 2009 for patients aged 6 to 17 for symptoms of

aggression toward others, deliberate self injury, temper tantrums and quickly changing moods.

Literature Review on Risperidone/Risperdal®

PsycINFO and MEDLINE Peer-reviewed English language

Risperidone and autism= 189Risperidone and autism and irritability= 37

Methodology

Article review Retrospective studyRandomized double-blind studyDouble-blind ,placebo controlled trial

Multi site

Mouse model of autism Case studyOpen label, titrated

Dependent Variable

IrritabilityAggressionSelf injurious behavior (SIB)

Approval of Risperidone®

Two 8-week, placebo-controlled trials156 patients- 5 to 16 years90 percent were 5-12 years oldMeasurement: Aberrant Behavior Checklist (ABC)

Clinical Global Impression - Change (CGI-C) scale Primary outcome measure: The change from baseline to

endpoint in the ABC (ABC-I). Results: Children achieved significantly improved

scores for certain behavioral symptoms of autism compared to children on placebo.

Side Effects: Drowsiness, constipation, fatigue and weight gain.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108759.htm

Research Units on Pediatric Psychopharmacology Autism Network

Purpose: to evaluate the efficacy and safety of Risperidone in children with autism with serious behavioral disturbances

Participants: 101 Diagnosed with autism, age 5-17 Tantrum, aggression, SIB, or a combination of these

problems No report of medication success in the past Drug free interval of 7-28 days

McCracken, J. T., McGough, J., Shan, B., Cronin, P., Hong, D., Aman, M. G., et al. (2002). Risperidone in children with autism and serious behavior problems. The New England Journal of Medicine, 347, 314-321.

Method

Phase 1: Eight-week, double-blind, randomized, placebo-controlled trial Those with no improvement in the placebo group were

offered open label treatment Those with positive response in the treatment group

were offered open label treatment

Phase 2: Open- Label Treatment for 4 months

2 month placebo controlled period

Baseline Assessment

Autism Diagnostic Interview — RevisedIntelligence testingVineland Adaptive Behavior Scales Physical, laboratory testsIrritability subscale of the Aberrant Behavior

ChecklistClinical Global Impressions — Improvement

(CGI-I) scale

Reassessment conducted 7-14 days after initial assessment

Measurement

The Aberrant Behavior Checklist-Irritability (ABC-I) Subscale: contains 15 items

care giver rated assessment tool measure symptoms of irritability:

including aggression towards others deliberate self-injuriousness temper tantrums and quickly changing moods

Aman MG, Singh NN: Aberrant Behavior Checklist—Community: Supplementary Manual. East Aurora, NY, Slosson Educational Publications, 1994

ABC-Irritability(ABC-I) subscale

Measurement

Clinical Global Impressions — Improvement (CGI-I) scale 7 point scale clinician assess how much the patient's illness has

improved or worsened relative to a baseline rated as: 1, very much improved; 2, much improved;

3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.

Guy W: ECDEU Assessment Manual for Psychopharmacology —Revised (DHEW Publ No ADM 76-338). Rockville, MD, U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs, 1976, pp 218–222

Procedure

Randomly assigned : Risperidone (49 children) Medication Schedule or placebo (52 children)

Children seen weeklyTwo professionals unaware of treatment

assignment

Outcome Measures

Irritability subscale of the Aberrant Behavior Checklist 8 weeks Parent's or primary caretaker's rating

Clinical Global Impressions — Improvement (CGI-I) scale clinical evaluator

Statistical Analysis

Results

Children who had at least a 25 percent reduction in the Irritability score and a rating of “much improved” or “very much improved” on the CGI-I scale were considered to have a positive response.

Risperidone group had a 56.9% decrease in the mean Irritability score

As compared with a 14.1% decrease in the placebo group

Results

Adverse Effects and Limitations

Adverse Effects: Weight gain, fatigue, no serious side effects

Limitations: Only 8 weeks Only diagnoses of ASD Did not identify the minimal effective dose Focused on specific behavioral problems rather than

on the core symptoms of autism

• Less attention on cognitive skills and skill performance• Environmental influences of drug effects on behavior are

rarely considered• Method: Effects of two doses of risperidone on the

performance of a matching task under tangible reinforcement and nonreinforcement conditions

• Woman with mental retardation, autism

Yoo, J. H. , Williams, D. C., Napolitano, D. A., Peyton, R. T., Baer, D. M., Schroeder, S. R. (2003). Rate-decreasing effects of the atypical neuoroleptic risperidone attenuated by conditions of reinforcement in a woman with mental retardation, Journal of Applied Behavior Analysis, 36, 245-248.

• ABCA design drug trial• A: placebo• B: 2.0 mg/day• C: 2.9 mg/day

• Phases 4 weeks each, double-blind• Perfection®: 5 trials with reinforcement, 5 withoutResults:

Risperidone caused a decrease in response rate and an increase in response time when compared with placebo

Changes were much smaller when tangible reinforcement was added Added reinforcement had a protective effect on the rate decreasing effects of

risperidone

Yoo, J. H. , Williams, D. C., Napolitano, D. A., Peyton, R. T., Baer, D. M., Schroeder, S. R. (2003). Rate-decreasing effects of the atypical neuoroleptic risperidone attenuated by conditions of reinforcement in a woman with mental retardation, Journal of Applied Behavior Analysis, 36, 245-248.

Literature Review on Abilify

PsycINFO: and MEDLINE Peer-reviewed English language

Abilify= 17 Schizophrenia and Bipolar

Abilify and autism= 0Aripiprazole and autism= 39

Methodology

Retrospective review Article review Case study Pilot Study Open label multicenter study Placebo controlled, fixed dose trial Post-hoc analysis

Approval of Abilify

Two eight week, randomized, double blind, placebo controlled multi center studies:

1- Flexible-dose study 98 patients

2-Fixed-dose study 218 patients

6-17 years old (autism and irritability), 75% under 13 years oldMeasurement: Aberrant Behavior Checklist, Clinical Global

Impression Primary efficacy: Mean change from baseline to week 8 in both

scalesResults: Each dose demonstrated significantly greater

improvements compared to placeboSide effects: weight gain, sedation, fatigue, vomiting

Conclusion: Drug Therapy for Autism

Does not treat core symptoms of ASDTreats behaviors associated with ASD (e.g.,

irritability)Should be combined with educational treatment

(e.g., ABA)There is strong evidence from large, well-designed

randomized clinical trials supporting the use of medications (Risperdal)® for those with ASD with persistent tantrums, aggression, and SIB.

Must be prescribed and monitored by qualified physicians.

Suggested References

Association for Science in Autism Treatmenthttp://www.asatonline.org/treatment/treatments/medications.htm

Weeden, M., Ehrhardt, K., & Poling, A. P. (2010). Psychotropic drug treatment for people with autism and other developmental disorders: A primer for practicing behavior analysts, Behavior Analysis in Practice, 3, 4-12.

Questions/Comments

References

Aman MG, Singh NN: Aberrant Behavior Checklist—Community: Supplementary Manual. East Aurora, NY, Slosson Educational Publications, 1994

Department of Health and Human Services (2007). FDA approves risperedal for two psychiatric conditions in children and adolescents. Retrieved June 5, 2012 from http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108969.htm

 

Department of Health and Human Services (2009). U.S. food and drug administration approves abilify for the treatment of irritability associated with autistic disorder ain pediatric patients (ages 6 to 17). Retrieved June 5, 2012 from www.business wire.com/news/home/2009/U.S.-food-drug-administration

Diament, Michelle. Disability Scoop, LLC. Advocates, big pharma make push for autism drugs. Retrieved June 10, 2012 from http://www.disabilityscoop.com/2012/03/20/advocates-big-pharma-drugs/15213/

Elixer of death. Retrieved June 5, 2012 from http://www.youtube.com/watch?v=6-tYOdgMez0

Goode, E. Donald J. Cohen, 61, Dies; Changed Field of Child Psychiatry. New York Times. October 4, 2011. Retrieved from http://www.nytimes.com/2001/10/04/us/donald-j-cohen-61-dies-changed-field-of-child-psychiatry.html

Goodman W.K, Price L.H, Rasmussen S.A, et al. The Yale–Brown Obsessive–Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 1989;46:1006–1011. PMID 2684084

Guy W: ECDEU Assessment Manual for Psychopharmacology —Revised (DHEW Publ No ADM 76-338). Rockville, MD, U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs, 1976, pp 218–222

References

Handen, B. L. ,and Lubetsky, M. (2005). Pharmacotherapy in autism and related Ddisorders. School Psychology Quarterly., 20(2), 155-171

Law, Marc. History of food and drug regulations in the united states. EH.Net Encyclopedia, edited by Robert Whaples. October 11, 2004. URL http://eh.net/encyclopedia/article/Law, Food, and Drug Regulation

McCracken, J. T., McGough, J., Shan, B., Cronin, P., Hong, D., Aman, M. G., et al. (2002). Risperidone in children with autism and serious behavior problems. The New England Journal of Medicine, 347, 314-321.

National Institute of Mental Health. Introduction: mental health medications. Retrieved June 2, 2012 from http:/www.nimh.nih.gov/health/publications/mental-health-medications/complete-index.sh

Stoppler, Melissa, M.D. Generic drugs, are they as good as brand names? MedicineNet.com. Retrieved June 5, 2012 from http://www.medicinenet.com/script/main/art.asp?articlekey=46204

Tsai, L.Y. (1998). Psychopharmacology in Autism. Psychosomatic Medicine. 61, 651-655.

Weeden, M., Ehrhardt, K., Poling, A. (2009). Psychotropic drug treatments for people with autism and other developmental disorders: a primer for practicing behavior analysts. Behavior Analysis in Practice, 3(1), 4-12. 

Yoo, J. H. , Williams, D. C., Napolitano, D. A., Peyton, R. T., Baer, D. M., Schroeder, S. R. (2003). Rate-decreasing effects of the atypical neuoroleptic risperidone attenuated by conditions of reinforcement in a woman with mental retardation, Journal of Applied Behavior Analysis, 36, 245-248.

References

Anticonvulsants and Autism. (n.d.) Research Autism, Improving the Quality of Life. Retrieved from http://www.researchautism.net/autism_treatments_therapies_intervention.ikml?print&ra=74&infolevel=4

 

Autism drugs and autism. (n.d.) A Better Future for Children with Autism, Aspergers Syndrome. Retrieved from http://autism-help.org/points-medication-antipsychotics.htm

Autism medication side effects. (August 14, 2010). Livestrong.com. Retrieved from http://www.livestrong.com/article/204678-autism-medication-side-effects/

Drugging kids. (2010). CCHRINT. Available from http://www.youtube.com/watch?v=MR4EWSbXLWA&feature=relmfu

 

Inattention, overactivity, and impulsiveness in autism spectrum disorder. (n.d.) Special Learning. Retrieved from http://www.special-learning.com/article/inattention_overactivity_and_impulsiveness_in_autism_spectrum_disorder

 

Medications that treat autism symptoms (n.d.) Everyday Health. Retrieved from http://www.everydayhealth.com/autism/medications-that-treat.aspx

 

SSRI side effects (June 9, 2012) News Medical. Retrieved from http://www.news-medical.net/health/SSRI-Side-Effects.aspx

 

Treating depression by adding Abilify aripiprazole to antidepressants. Available from http://www.youtube.com/watch?v=Uv2hS_NulHU&feature=related