Biomedical Therapies

Brian J. Piper, Ph.D.

Goals

• Psychopharmacology– Antipsychotics– Antianxiety– Antidepressants

• Brain Stimulation– Transcranial Magnetic Stimulation– Electroconvulsive Therapy

• Psychosurgery

Prevalence of Psychopharmacology

http://online.wsj.com/article/SB10001424052970203503204577040431792673066.html?mod=WSJ_WSJ_US_News_5

Decreases in child antidepressants &anti-anxiety meds in elderly

Overall: 22% increase

Psychopharmacology

• Most psychological drugs target neurotransmitters – Dopamine– Norepinephrine– 5-hydroxytryptamine (5-HT or serotonin)– Gamma Aminobutyric Acid (GABA)

• It is not known if these mechanisms are responsible for the therapeutic effects

History of Antipsychotics (aka Neuroleptics/Major Tranquilizers)

• 1950s: Typical (D2 antagonist) antipsychotic chlorpromazine developed as a anesthetic but helps against hallucinations & delusions

• 1950s (late): tardive dyskinesia identified• 1970s: Atypical (D2/5-HT2A antagonist)

clozapine antipsychotic introduced.• 2000s: substantial weight gain recognized

Psychological Disorders & Reduced Lifespan (N = 5,036,662)!

Male Life Expectancy

MaleYears Lost

FemaleLifeExpectancy

FemaleYears Lost

All (Psychiatric History - )

76.5 NA 80.9 NA

Schizophrenia 57.8 18.7 64.6 16.3

Bipolar 62.9 13.6 68.8 12.1

Laursen (2011). Schizophrenia Research, 131, 101-104.

Reduced Lifespan

Male Life Expectancy

MaleYears Lost

FemaleLifeExpectancy

FemaleYears Lost

All (Psychiatric History - )

76.5 NA 80.9 NA

Schizophrenia 57.8 18.7 64.6 16.3

Bipolar 62.9 13.6 68.8 12.1

Laursen (2011). Schizophrenia Research, 131, 101-104.

Contributing Factorssuicide, accident, homicides, self-care, metabolic (?)

Antidepressants

• Monoamine Oxidase (MAO) is an enzyme that breaks down 5-HT, NE, & DA

MAO-Is

• Monoamine Oxidase (MAO) is an enzyme that breaks down 5-HT, NE, & DA; peak use in 1970s

• Food Interactions: Tyramine rich foods (aged cheese, beer, wine) + MAO-I results in increased blood pressure & headaches (“cheese effect”)

• Moderate effectiveness but moderate side-effects

Antidepressants: Serotonin Reuptake Inhibitors

• Prozac (fluoxetine) was the original SRI• Greater affinity for SERT than NET• Not Selective (sigma receptors)• Anorgasmia• Low effectiveness but low side-effects

Cognitive Behavioral Therapy

• Short, evidence based, therapy• Developed by Aaron T. Beck• Instruction in how thoughts & feelings

influence behavior

1921-

CBT + Medication• Patients randomized to receive Nefazodone (5-

HT2A/1 antagonist), CBT, or both for 3 months

Nef CBT Nef +CBTCompleters 69.5% 72.2% 76.5%

No Response 44% 48% 15%Remission 22% 24% 42%

Keller et al (2000). New England J of Medicine, 342, 1462-1470.

Electroconvulsive Therapy

• Brief seizure is induced• Peak use in 1940s-1950s, resurgence• Conditions: Major Depressive Disorder,

schizophrenia, bipolar• Very effective for MDD but memory loss

1940s Present

Wave sinusoidal pulse

Anesthetic no yes

Consent ? yes

Biomedical Therapies & Neurogenesis

• New neurons are produced in the hippocampus in adults

ECS: electroconvulsive therapy; TCP: trancyclpromine (MAO-I), or Reboxetine (SNRI)

Mahlberg (2000). J Neurosciece, 20, 9104-9110.

Electroconvulsive Therapy Video

• Caitlin & Meghan Davies• Season 1: Episode 2

– 1:05:00-1:08:00– 1:29:30-1:50:00

Zofran (Ondansetron): 5-HT3 antagonist

Transcranial Magnetic Stimulation

• pulse of electromagnetic field• very low risk of seizures & syncope• Control condition?• Repeated TMS shows moderate utility for

MDD• Mechanism unknown

Psychosurgery

• 1949: Antonio Egas Moniz received Nobel prize for frontal leucotomy

• 1940s-1967: Walter Freeman develops frontal lobotomy (transorbital)

• Current: lesioning & deep brain stimulation is a last resort

1874-1955

Who prescribes?

• Mostly MDs– Psychiatrists– Pediatricians– General Practitioners

• Some clinical psychologists– New Mexico (2002)– Louisiana (2004)

Tanya Tompkins