Psychopharmacology (Basics and History)

陳鴻儀
May 29 2007

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A Brief History of Psychopharmacology
Historical Perspectives

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A Brief History of Psychopharmacology –
Ancient World

Alcohol has been nearly universal in use,

and was already presenting itself as a
problem among ancient Greeks and
Romans. There are records of cannabis
use in the ancient Middle East and India.
Opium was known to the ancients, but
seems to have been restricted to
medicinal use.

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A Brief History of Psychopharmacology –
Ancient World

• An extract of the nightshade or

belladonna plant called atropine
(Anticholinergic) was used everywhere
from Rome to India as a poison -- and as
a cosmetic device: In Rome, women
sometimes used to put a drop of weak
solution in their eyes to dilate their pupils !

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 1800s
• In 1874, heroin was synthesized from
opium, and was touted as a less
dangerous form than opium or morphine.
Amphetamines, the first major synthetic
drug, was discovered in 1887. Its use as
a stimulant quickly became widespread. It
was used in World War II to help energize
soldiers and industrial workers alike.

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Drug Development Treatment for
Psychiatric Issues
• 1845 Hashish
• 1875 Cocaine
• 1892 Morphine, alcohol, ether
• 1903 Barbiturates
• 1927 Insulin Shock
• 1936 Frontal Lobotomies
• 1938 ECT
• 1949 Lithium Introduced
• 1950 Chlorpromazine (Thorazine)
• 1955 Tricyclics & MAOs
• 1990s SSRIs & SNRIs and Atypical
Antipsychotics 6
Treatment of Schizophrenia
At the dawn of 18th Century

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 Period of Trial and Errors
1920-30s

Physiopathology of Schizophrenia not understood..

Some of the treatments were:
– Rx of Cocaine
– Castor Oil
– Manganese
– Injections of Sulfur and even Turpentine
Some had partial remission with injections

Ref: Croce.G.Pyretotherapy of Schizophrenia in initial stages by injection-Schizophrenie, March1932:1:31-40

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 1930s
• Fever and Mental
Disease in 1917
• The Insulin Shock
Therapy in 1927
• Chemical
Convulsions and
Schizophrenia in
1934
• The
Electroconvulsive
Shock Therapy in
1937
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 Antipsychotic
Psychopharmacology
• First time elimination of psychotic
symptoms rather than alteration of body
status was targeted
• Chloropromazine was introduced on Jan
19, 1952. Within a period of 10 years 20
phenothiazines were in development,
ranging from chlorpromazine to
trifluoperazine to fluphenazine

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Rauwolfia Serpentina
(Reserpine)

• First paper on the use of

Rauwolfia in 1954 by
Nathan Kline, based on
an Indian Physician’s
report in New York Times
about its use in psychosis
in Indian system of
medicine. Then it fell from
favor quickly. Eventhough
still it is used in refractory
psychosis.

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 Butyrophenones
• Haloperidol, the parent substance of the
butyrophenone antipsychotics , was
synthesized on February 15, 1958.
• Based on its similarity of action with CPZ,
Psychopharmacological research
proceeded rapidly resulting by 1990 the
development of 13 products, of which 2,
haloperidol and droperidol, are clinically
useful.

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2nd Generation or Atypical
Antipsychotics
◆ Clozapine (Clozaril)-80s in USA
◆ Risperidone (Risperdal)-early 90s

◆ Olanzapine (Zyprexa) late 90s

◆ Quetiapine (Seroquel)-late 90s

◆ Ziprasidone (Geodon)-2001

◆ Aripiprazole (Abilify) in 2002

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History of Antidepressant
Development-Early 1950s

Reserpine causes “depression”?

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 Clinical Psychopharmacology

• Pharmacokinetics (quantitative)
– Movement of drugs through the body
• Pharmacodynamics
– Study of qualitative effects of drugs
– Actions
• Agonism: facilitates normal functioning of
synapse
• Antagonism: hinder

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 Effective” Treatments
• Efficacy:
– How good is the drug in diminishing the
manifestations of the disorder
• Percent of patients responding to a medication in a
controlled study
–Double-blind placebo controlled
–Relative efficacy:
• One treatment vs. another
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 “Effective” Pharmacological
Treatments
• Effectiveness:
– How in the real world is this treatment
effective
• Ease of administration
• Side effects
• Patient compliance
• Usefulness with real patients

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 “Effective” Pharmacological
Treatments
• Clinical Response
– Pharmacologic effect
– Placebo response
– Spontaneous remission

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 Goals of Pharmacotherapy
• Acute Treatment
– Used to alleviate the symptoms of an actively
occurring disorder
• Continuation Treatment
– Goal: To prevent a relapse into the same
episode for which treatment began
• Maintenance Treatment
– Goal: To prevent recurrences by the ongoing
maintenance use of a medication

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 Compliance
• Defined as: Adherence to the
recommended treatment plan of a health
care professional

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 Strategies to Increase
Compliance
• Encourage active patient participation
• Adequate communication
• Empathetic approach/Trusting relationship
• Family and community involvement and
support
• Emphasis on positive effects of medication
• Use the most simplified drug regimen

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 Various Reasons for
Noncompliance
• Stigma of disorder
• Denial of illness
• Disruption of cognitive process
• Side effects of medication
• Slow onset of beneficial effects
• Cost

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 Clinical Characteristics to
Suggest Pharmacological
Treatment
• Psychiatric Symptoms
– Sleep or Appetite Disturbance
– Fatigue
– Panic Attacks
– Ritualistic Behavior
– Cognitive Symptoms
– Psychosis such as Delusions or
Hallucinations

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 Clinical Characteristics to
Suggest Psychiatric Referral
• Prominent Physical Symptoms or Significant
Medical Disorder Resulting in Significant
Behavioral Changes
• Significant Suicidality
• Family History of Major Psychiatric Disorder
• Marked Mood Lability
• Intense Rage or Depressive Symptoms
• Nonresponse to Psychotherapy

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