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History of Pharmacological Treatments for Mental Health   699
Further Readings
Centers for Disease Control and Prevention. “Hispanic
or Latino Populations.” http://www.cdc.gov/
minorityhealth/populations/REMP/hispanic.html
(Accessed May 11, 2015).
Commonwealth Fund. “Catching Up: Latino Health
Coverage Gains and Challenges Under the
Affordable Care Act” (September 25, 2014). http://
www.commonwealthfund.org/publications/issue-
briefs/2014/sep/gains-for-latino-adults (Accessed
May 11, 2015).
“Low Participation of Hispanics in Pharmaceutical
Trials.” Fox News Latino (March 13, 2013). http://
latino.foxnews.com/latino/health/2013/03/12/low-
participation-hispanics-in-pharmaceutical-trials/
(Accessed May 11, 2015).
National Center for Complementary and Alternative
Medicine. “The Use of Complementary and
Alternative Medicine in the United States.” https://
nccih.nih.gov/sites/nccam.nih.gov/files/camuse.pdf
(Accessed May 24, 2015).
National Hispanic Council on Aging. “Health Literacy.”
http://www.nhcoa.org/health-literacy/ (Accessed
May 11, 2015).
Ortiz, Bianca I., Kelly M. Shields, Kevin A. Clauson,
and Patrick G. Clay. “Complementary and
Alternative Medicine Use Among Hispanics in the
United States.” The Annals of Pharmacotherapy,
v.43/6 (2007).
U.S. Department of Health and Human Services Office
of Minority Health. “CLAS & the CLAS
Standards.” https://www.thinkculturalhealth.hhs
.gov/content/clas.asp (Accessed May 24, 2015).
History of Pharmacological
Treatments for Mental Health
The belief that the origins of psychiatric disor-
ders lay within the individual’s biomedical and
genetic malfunctions gave birth to the term
psychopharmacology. Ancient cultures like
Ancient Indians believed that substances like
rauwolfia had healing effects for spiritual
health, and the different concepts of mankind
throughout history (naturalism and spiritual-
ism) shaped the use of pharmacological treat-
ments for mental health at different times. The
prototypes of modern psychopharmaceuticals
were discovered for the first time between
1952 and 1958. This led to the development of
biological psychiatry and to efforts toward
effective treatment of psychiatric disorders like
schizophrenia, psychosis, depression, and
anxiety. Psychopharmacology is associated
­
with further developments on mental health
care during the late 20th century and the
­development of clinical psychiatry. The use of
psychopharmaceuticals is now combined with
other types of interventions like behavioral and
psychotherapeutic treatment, and long-term
hospitalized mental health patients are now
fewer than 50 years ago. The history of psycho-
pharmacology helps to understand its contri-
bution to mental health care.
Origins of Psychopharmacology
Psychopharmacology is defined as the scientific
study of drugs’ effects on psychological factors
like behavior, mood, and cognitions. The term
was first used in 1548 by German scientist
Reinhardus Lorichius of the city of Hadamar,
but with a different meaning—that of spiritual
medicine. In its contemporary meaning, psy-
chopharmacology was first described in 1824
by the German scientist P. J. Schneider, who
classified psychotropic agents into “narcotic”
and “excitants, analeptics.” Therefore, pre-
scribed medication is used in conjunction with
other methods like psychotherapy for the treat-
ment of mental health disorders, which are
defined as a medical condition where a per-
son’s mood, ability to relate with other people,
thinking ability, emotions, and daily activities
are severely disrupted. Severe mental health
disorders include acute depression, schizophre-
nia, bipolar disorder, obsessive-compulsive
 Copyright © 2015 SAGE Publications. Not for sale, reproduction, or distribution.
700   History of Pharmacological Treatments for Mental Health
disorder (OCD), post-traumatic stress disorder
(PTSD), anxiety disorders, eating disorders,
panic disorder, and borderline personality dis-
order, among others. The definition, treatment,
and classification of mental disorders vary by
time and culture.
The famous German psychiatrist Emil
­Kraepelin is believed to be the father of psy-
chopharmacology and conducted the first
psychopharmacological experiments in 1892
at the laboratory of Wilhelm Wundt in
Leipzig—the first laboratory of experimental
psychology. Kraepelin aimed to investigate the
effects of alcohol, hypnotics like paraldehyde
and chloral hydrate, and “inhalation poisons”
like chloroform and ether on mental processes.
Mental performance was measured using reac-
tion time in time-estimation and association
experiments. These methods are widely used
today in the area of experimental and cogni-
tive psychology.
Kraepelin’s experiments were the first to
assess the effects of drugs on mental processes.
He observed that biphasic action was the result
of 30 to 50 grams of alcohol consumption.
Alcohol caused improvement in simple pro-
cesses like reading and reaction time after 30 to
45 minutes (stimulation phase) and reduction
in all activities after 45 minutes (paralyzing
action). Similar results were observed after
injection of 3 to 5 grams of hypnotic paralde-
hyde with a briefer stimulation phase and
stronger paralyzing action. The consumption of
caffeine and tea improved performance in an
arithmetic test and a word associations test, but
no improvement was observed in inventiveness
of the words that individuals produced.
Even though Kraepelin’s findings were
novel, the utilization of pharmacological treat-
ments for mental health for exploring their
effect on the brain was initiated a long time
afterward, in 1951, when the effects of chlor-
promazine were confirmed. Prior to that and
during the late 1940s, J. Cade also had observed
that another drug—lithium—had antimanic
effects.
Psychopharmacology and
Other Treatments
Today, the use of prescribed medication for the
management and cure of mental disorders is
interchangeable with behavioral and psycho-
therapeutic interventions like cognitive-behav-
ioral therapy, family or systemic therapy,
psychodynamic approaches, and counseling.
These interventions are often used in the con-
text of the mental disorder; for example, there
is strong evidence of the effectiveness of
­psychoeducational and cognitive therapies for
the treatment of the manic episode of bipolar
affective disorders, while for the depressive
episode of the same disorder, family or
­interpersonal therapy is preferred. Cognitive-
behavioral therapy and family therapy together
with other interventions like social learning,
cognitive remediation and adaptation therapy,
and illness management are recommended for
schizophrenia. However, in cases of severe
mental disorders, these interventions are not
found to be effective whereas they can also be
more expensive and impractical for certain
groups of patients.
Psychopharmacology has also evolved
together with psychosurgery, which is still used
today. Psychosurgery refers to the surgical
removal of parts of the brain or other forms
of neurointerventions that are considered
as alienating mental disorders. Convulsive
­therapy was introduced by the Hungarian neu-
rologist Ladislas Meduna in 1934, who used
pentetrazol to treat depression. Pentetrazol
was substituted by electricity by Italian neu-
rologist Ugo Cerletti in a new therapy called
electroconvulsive therapy (ECT), also known
as electroshock. ECT is widely used today for
 Copyright © 2015 SAGE Publications. Not for sale, reproduction, or distribution.
History of Pharmacological Treatments for Mental Health   701
the treatment of mental disorders like major
depression, schizophrenia, and mania, together
with other therapies like transcranial electro-
magnetic therapy and bright light therapy,
which is used for the treatment of seasonal
affective disorder.
Conception of Mental Illness
in Ancient Times
For a long period of time, mental disorders
were considered a spiritual disease, attributed
either to the wrath of gods or to witchery and
evil spirits. Naturalism in conceptualizing men-
tal health and mental health disorders was used
for the first time by ancient Greeks through the
observation by the medical theorist Alcmaeon
of Croton (who lived in the 5th century b.c.e.)
of human anatomy and the pathways connect-
ing the brain with ears and eyes. This led to the
realization that the brain is the human being’s
central point of observation when it comes to
psychological or “spiritual” characteristics.
Ancient Greek physician Hippocrates devel-
oped his humoral theory, which set the basis
for the foundation of psychological science and
psychiatry. The humoral theory suggested that
the body fluids (humors) in a normal state are
equally spread across the body, and when
imbalances occur then the result is four mental
disorders: melancholy, calm insanity, mania/
insanity, and hysteria. Each mental disorder
was the result of the imbalance of different
humors (blood, phlegm, choler, and black bile).
Therefore, treatment should seek to restore this
imbalance. Hippocrates’s theory shifted the
movement from mysticism to an approach
where mental illness could be regarded as a
dysfunction of the human brain rather than
spiritual possessions.
During the 1st century c.e., the heritage
of Hippocrates’s writings were brought to
Roman encyclopedist Aulus Cornelius Celsus.
This heritage created the need in society to
focus and care for people with mental disorders
or people who were acting abnormally. For
example, people with mania were chained and
people were told to avoid those who were
considered mad. Substances like opium and
­
henbane were used for treatment. Galen of
­Pergamum also adopted the humoral theory of
Hippocrates in the 2nd century c.e., as did
­doctors in the Arabic world. Galen classified
mental health disorders and recommended
­several treatments, which included a substance
called soporifics that are today used as psycho-
active drug for the treatment of insomnia. In his
work “Opus,” Galen examined the impact of
opium use for sleep disturbance. Furthermore,
based on the humoral theory, the Arab physi-
cians differentiated between physically and
mentally ill patients, and as a result separate
psychiatric wards were built for the first time in
Baghdad (750 c.e.) and Cairo (873 c.e.).
The Middle Ages and Age
of Enlightenment
The circular nature of the transition between
naturalism and spiritualism is evident through-
out history. For example, for various theologi-
cal, sociological, and historical reasons, people
during the Middle Ages (from the 5th century
to the 15th century c.e.) returned to a spiritu-
alistic perception of health and mental health.
Those who were mentally unstable were burned
or considered possessed by evil spirits. As a
consequence, unlike in the Arab world, medi-
cine was not further developed in Europe even
though there were physicians like the Swiss-
German Paracelsus, the Dutch Johann Weyer,
and the Swiss Felix Plater, who maintained the
focus of medical treatment of mental health,
toward interventions to restore physical imbal-
ance rather than spiritual or witchcraft
practices.
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702   History of Pharmacological Treatments for Mental Health
The development of psychiatry and psycho-
pharmacology was benefited by the social and
scientific developments of the Age of Enlight-
enment in the 17th century. During this period,
the major contradictions of modern psychiatry
were born: Mentally ill patients were sepa-
rated from the general populations by living
outside the cities and towns, but at the same
time they were provided with tasks and work
in order to return to a “socially normal life.”
The spiritual practices were brought to an end
in France, when the term alienation was
replaced by “maladie mentale” in an 1838
textbook written by Jean Étienne Esquirol.
Similar reforms were initiated in Germany by
­Wilhelm Griesinger, who introduced the treat-
ment effects of opium, ether, prussic acid, and
chloroform narcosis. The medical model of
mental health care was introduced.
In France, during the early 19th century,
Philippe Pinel and Jean Étienne Esquirol classi-
fied mental disorders based on clinical observa-
tions and statistical methods. During this period,
psychiatry in France was further developed
away from nonscientific treatments, and Esqui-
rol’s 1818 expert report signaled the reform of
mental health care. Kraepelin, in his 1899 text-
book of psychiatry, listed a number of pharma-
ceuticals that were in practice at the time:
narcotics (opium, morphine, hyoscine, and
hashish), hypnotics (chloral hydrate, sulfonal,
trional, alcohol, chloroform), and bromine salts.
Seventeen years later, another textbook of psy-
chiatry by Swiss psychiatrist Paul Eugen Bleuler
provided a similar taxonomy of psychotropic
drugs: hypnotics (sulfonal, trional, chloral
hydrate, veronal, paraldehyde, and alcohol),
bromine, opiates, and hyoscine (scopolamine).
Substances Used Through the Evolvement
of Psychopharmacology
In ancient times and the Middle Ages, there
were several substances used for mental health
treatment and maintenance and that were asso-
ciated with mental health stability. Opium,
together with other substances like rauwolfia
and hellebore, are considered the ancient psy-
chotropic s­ubstances. The foundations of
opium use lay within the Stone Age. The Sume-
rians in 3 ­ 000  B.C.E. called opium “happy” and
“lucky,” and ancient civilizations in Cyprus,
Egypt, and elsewhere were using opium as a
healing substance for many disorders including
sleeping disorders. Black hellebore was used as
a laxative and white hellebore as an emetic
during ancient times in order to remove patho-
logic substances from the body and treat
mental i­llness like melancholy and mania.
­
­Indians used rauwolfia as a remedy for mental
illnesses and, since the 1950s, it was used in
Europe as a psychotropic agent for schizo-
phrenic psychoses.
One of the first evidences on the effects of
psychotropic medicine was found in the late
1940s and early 1950s. Lithium was discov-
ered as a pharmacological treatment of mania
by Australian psychiatrist John F. Cade in
1949. At the same time, researchers high-
lighted the use of chlorpromazine (neurolep-
tic) for the treatment of psychosis, the tricyclic
antidepressants (TCAs) for the treatment of
depression, and the antidepressant and psy-
chostimulant effects of nonselective mono-
amine oxidase inhibitors (MAOIs). Until that
time, mental illness was considered untreatable,
and other interventions like psychotherapy
and psychosurgery were not as effective.
In the late 1950s, another substance called
chlordiazepoxide was found to cause a level of
equilibrium. Diazepam belongs to the family
of benzodiazepines and was introduced in the
pharmacological treatment of mental disor-
ders in 1963 in a drug widely known as
Valium, which is the most prescribed drug of
all time. Valium and other diazepam drugs
replaced barbiturates for the treatment of
insomnia and anxiety.
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History of Pharmacological Treatments for Mental Health   703
Modern psychopharmaceuticals are classi-
fied as antipsychotics (or neuroleptics and
major tranquilizers), which are used for the
treatment and/or management of schizophre-
nia and the agitation of other psychiatric dis-
orders; antidepressants (or thymoleptics and
thymeretics) for the treatment and/or manage-
ment of depression; mood stabilizers for the
treatment and/or management of mania and
hypomania and variations of bipolar disorder;
anxiolytics (or minor tranquilizers) for the
treatment and/or management of anxiety
­disorders; psychostimulants (or stimulants and
analeptics) for the treatment and/or manage-
ment of attention deficit hyperactivity disorder
(ADHD) and narcolepsy; and nootropics (or
their most recently developed form of antide-
mentia drugs) for the treatment and/or man-
agement of cognitive functions.
The history of each psychopharmaceutical
shares similarities and differences. The first
antipsychotic drug (chlorpromazine) was dis-
covered in 1953 by French psychiatrists Jean
Delay and Pierre Deniker. Later on, in 1967,
the sedative actions of antipsychotic drugs were
distinguished in three phases where the patient
feels drowsiness and sleepiness with detachment
and no initiative (the first phase lasting one
week), then the antipsychotic effect is held
constant and the sedative effect is receded (the
second phase lasting one week), and finally,
emotional responses are reduced but with
minimum loss of drive with the antipsychotic
effect held constant (the third phase).
The origins of antidepressants lay within the
use of opioids, amphetamines, and metham-
phetamines prior to the 1950s. The term anti-
depressant was coined by American psychiatrists
Max Lurie and Harry Salzer in 1953. The first
generation of antidepressants were established:
(1) isoniazid, whose stimulating effect was
described by French psychiatrists Jean Delay
and Jean-Francois Buisson and established by
Max Lurie in 1952; (2) iproniazid, which was
also found to have stimulant effects by U.S.
medical researchers Irving Selikoff and Edward
Robitzek in 1951; and (3) imipramine, which
was found to benefit mental and motor retar-
dation of patients with depression by Swiss
psychiatrist Ronald Kuhn in 1957. These
research discoveries led to antidepressants
being prescribed for the treatment of depres-
sion since the 1950s. The second generation of
antidepressants include the MAOIs, tricyclics,
SSRIs (i.e., zimelidine, indalpine), and fluox-
etine. Lithium and anticonvulsants are used as
mood stabilizers. The U.S. Food and Drug
Administration (FDA) approved lithium as a
mood stabilizer for mania at first and bipolar
disorder later in the 1970s. During the same
period, the Anticonvulsant Screening Program
was established in the United States to promote
the use of anticonvulsant medications.
Psychopharmacology Today
The 1990s were described by the U.S. Library
of Congress and the U.S. National Institute of
Mental Health as the “decade of the brain” in
order to shift the public’s awareness toward
the benefits of neuroscience research. Before
the  1990s, psychopharmacology was limited
­
in the use of TCAs, MAOIs, conventional
­antipsychotics (mainly haloperidol and chlor-
promazine), benzodiazepines (anxiolytics),
­barbiturates, and lithium. Because of this land-
scape, major developments occurred in the area
of psychopharmacology, especially in the treat-
ment of major depression, anxiety disorders,
bipolar affective disorder, and substance abuse.
A new generation of atypical antipsychotics
and antidepressants was introduced, including
selective serotonin reuptake inhibitors (SSRIs).
During this period, a major research focus
was shifted toward patterns of drug interac-
tions and adverse drug reactions and the role
of physicians in managing and preventing
drug-related harm. The complexity of the
 Copyright © 2015 SAGE Publications. Not for sale, reproduction, or distribution.
704   History of Pharmacology: Ancient China
drugs’ pharmacokinetic profiles and clinical
pharmacology was revisited. On the other
hand, the expansion of psychotropic drugs cre-
ated more needs for mental health clinicians
because they had to choose from a larger
“pool” of substances with various and com-
plex drug reactions and effects. Many authors
support that, until today, mental health clini-
cians are facing difficulties in overcoming this
prescription problem.
Today, prescribed pharmacological therapy
is used together with other forms of therapies
(like psychotherapy) for the treatment and
management of mental disorders. Psychoactive
drugs are usually prescribed by either a psy-
chiatrist or another clinician according to the
national or local mental health system (family
doctors, general practitioners, etc.). There are
today a number of different groups of drugs
for the treatment and management of mental
disorders. Antipsychotics (both typical like
phenothiazines and atypical like clozapine) are
prescribed for treating psychotic disorders like
schizophrenia and anxiety. Antidepressants
known as MAOIs are prescribed for treating
clinical (or acute) depression and sometimes
for anxiety and other disorders. Anxiolytics
are used short term for treating anxiety disor-
ders and related symptoms like insomnia.
Stimulants are prescribed for treating ADHD.
Finally, mood stabilizers are prescribed for
treating bipolar disorder.
Angelos P. Kassianos
University of Cambridge
See Also: Antianxiety Drugs; Antidepressants;
Antipsychiatry Movement; Antipsychotics;
Geographic Variation in Prescribing Practices;
History of Pharmacology: Ancient China; History of
Pharmacology: Ancient Egypt; History of
Pharmacology: Europe; History of Pharmacology:
Europe, Middle Ages; History of Pharmacology:
U.S., Colonial Period to 1865; History of
Pharmacology: U.S., 1865 to 1900; History of
Pharmacology: U.S., 1900 to 1945; History of
Pharmacology: U.S., 1945 to Present; Mental
Health Parity; Opium (Herbal Medicine);
Psychopharmacology.
Further Readings
Barchas, J. D. Psychopharmacology: From Theory to
Practice. New York: Oxford University Press,
1977.
Edward, K. L. and C. Alderman. Psychopharmacology:
Practice and Contexts. Melbourne, Victoria: Oxford
University Press, 2013.
Meyer, J. S. and L. F. Quenzer. Psychopharmacology:
Drugs, the Brain, and Behavior. Sunderland, MA:
Sinauer Associates, 2013.
Spiegel, R. Psychopharmacology: An Introduction.
Chichester: Wiley & Sons, 2003.
History of Pharmacology:
Ancient China
The Chinese for centuries have developed
herbal and other remedies as part of their phar-
macological practices, which include the use of
minerals, animals such as insects and dried
earthworms, and various fungi. Traditional
Chinese medicine consists not only of herbal
cures and remedies but also medical activities
such as moxibustion, in which the smoke of
burning mugwort is used to treat various
­ailments, acupuncture along the body’s energy
meridians, meditation such as qigong and tai
chi, massage (tui na), and diet to support phar-
macological practices. Although modern
science has questioned the effectiveness of
­
some aspects of Chinese medicine, such as acu-
puncture and moxibustion, maintaining that
these practices are not useful in modern medi-
cine, some herbal remedies are now becoming
part of modern pharmacological investigation
through new understanding and clinical evalu-
ation of folk medicine. It is a transformation