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Biological and Somatic Treatment
of Severe Mental Illness
Before Modern Times
Zachary Lane, MD
September 8, 2015
Some Early Treatments
• Trepanation
• Bloodletting
• Surgical Bacteriology
Some Early Treatments
• Tranquilizer Chair
• Sensory Deprivation Chair
Some Early Treatments
• Restraints
Asylum Reformation Movement
• 18th and 19th Centuries
• Moral therapy
– Philippe Pinel
– Benjamin Rush
– Dorothea Dix
Early Drug Therapies
Used for behavioral control and sedation
Decrease the use of restraints
Many nonspecific indications
– Natural remedies
• Plant based (Alkaloids)
– Synthesized in the lab
• Strengthened the link between medical research and
psychiatric treatment
• Legitimized psychiatric conditions
Early Drug Therapies
• Natural remedies:
– Opium, Morphine
• Treat aggression, melancholy, and delusions
• The addictive nature, toxicity, and side effects later
became evident
Early Drug Therapies
• Synthesized in the lab (19th Century):
– Mercury – treatment for mania
– Bromides - treatment for seizures, stress,
psychosis, mania, morphine addiction, alcoholism
– Chloral Hydrate – hypnotic, “knockout drug”
– Paraldehyde - hypnotic
Early Drug Therapies
• Synthesized in the lab:
– Barbiturates (20th Century):
• Barbital, Phenobarbital
– Hypnotic, anxiolytic, anti-epileptic
– Addictive, overdose potential
Early Drug Therapies
• Synthesized in the lab:
– Amphetamines (20th Century):
• Antidepressant, weight loss
• “Pep pill” or inhalers
• Addictive, led to anxiety/psychosis
Prolonged Sleep Therapy
(Continuous Narcosis)
• 1910’s - 1930’s
• Continuous administration of bromides or
• Sleep for 6-8 days
• Briefly awaken to eat and toilet
• Believed to give rest to an overactive nervous
Prolonged Sleep Therapy
(Continuous Narcosis)
• Treatment for psychosis, mania, agitated depression, &
• Effective for “shellshock” (PTSD) in World War I
• Required intensive monitoring
• Replaced by Insulin Coma Therapy in 1930’s
• Later scandals – CIA’s MKULTRA (mind control) experiments,
Australian Chelmsford Scandal
• 1800’s to mid-1900’s
• Using water to relieve “cerebral congestion”
– Bring blood away from the brain and to the skin
• Wet Sheet Pack
– Sheet dipped in water and wrapped snuggly
around patient for hours
– Cold – agitated patient
– Warm – frail patient
• Continuous Bathing
– Patient placed in tub with replenishing warm
water and fastened in hammock for hours to days
• Jet Streams and Steam Cabinets
Malaria Fever Therapy
• Neurosyphilis (General Paresis of the Insane)
– Around 20% of patients institutionalized in early
20th Century
– Physical and psychiatric problems, high mortality
– Immoral patients seen as deserving of their fate
– No cure (Penicillin not discovered until 1928)
Malaria Fever Therapy
• Hippocrates and Galen noted improvements
in some patients after malaria
• Julius Wagner-Jauregg – injected malaria into
patients with Neurosyphilis to induce fever
– Later would cure their malaria with Quinine
• First full cure for a specific mental illness
– Mental illness seen as having a biological cause
Malaria Fever Therapy
• Why it worked?
– High fevers destroyed spirochetes
– Stimulated the body’s immune response
• Wagner-Jauregg won 1927 Nobel Prize in
Malaria Fever Therapy
• Malaria later replaced by other fever inducers
into the 1950’s: inject foreign
protein/chemicals, immerse in hot bath,
electromagnetic currents, full body fever
Shock Therapies
• Shock Therapies:
– Insulin Shock Therapy
– Metrazol Convulsive Therapy
– Electroconvulsive Therapy (ECT)
• Initially used for treating psychosis based on
erroneous belief that people with epilepsy
cannot have comorbid psychosis
• All found to be more effective for depression
Shock Therapies:
Insulin Shock Therapy
• 1930’s - 1940’s
• Daily injections of high doses of Insulin until
coma induced
• Treatments lasted hours and were terminated
with glucose via IV or NG Tube
• Courses lasted for ~60 days and required close
• Replaced in 1940’s by ECT due to Insulin
shortage during World War II
Shock Therapies:
Insulin Shock Therapy
Shock Therapies:
Metrazol Convulsive Therapy
• 1930’s - 1940’s
• Metrazol (Pentylenetetrazol) – circulatory and
respiratory stimulant
• Given via injection 2-3 times/week for several
• Caused “explosive seizure” one minute after
administration that could cause fractures
– Dread after administration
• No antidote to reverse
• Replaced in 1940’s by ECT
Shock Therapies:
Electroconvulsive Therapy (ECT)
• 1930’s - Present Day
• Electrically induced convulsions
• Thought convulsions produced vitalizing
compounds that had defense properties
(“acro amines”)
Shock Therapies:
Electroconvulsive Therapy (ECT)
• Easier to use, lower cost, fewer complications
• Curare used in late 1940’s as muscle relaxant to
decrease fractures
• Amnesia viewed positively – “forget your
• ECT declined due to public opinion and the
antipsychiatry movement in the 1960’s and
1970’s – more recent resurgence and still in use
today as one of the most effective treatments in
Shock Therapies:
Electroconvulsive Therapy (ECT)
The video on the following slide shows graphic
medical procedures. Viewer discretion is
Shock Therapies:
Electroconvulsive Therapy (ECT)
The video on the following slide shows graphic
medical procedures. Viewer discretion is
Prefrontal Lobotomy
• 1930’s – Egas Moniz
• Some patients more docile after accidental
frontal lobe damage
• Cut strands connecting prefrontal cortex and
– Rationale: neuronal pathways became “fixed” and
needed to be disrupted
• Initially used as “last resort” in severe cases
• Moniz won 1949 Nobel Prize in Medicine
Transorbital Lobotomy
• 1940’s – Walter Freeman & James
• Exploded in popularity
– Attempt to relieve state hospital burden
– Expanding indications – no longer “last resort”
– Took just minutes, no anesthesia, done in clinic
– Children and adolescents as well
• Initially thought to be a permanent cure but
results turned out to be poor
• Side effects: personality changes (childlike,
disinhibited, apathetic), apraxia, cognitive
problems, “lost the sparkle”
• Waned in popularity in 1950’s with
introduction of antipsychotic medication
• Other types of psychosurgery still performed
today in select cases
Beginning of Modern Era
of Psychiatric Treatment
Early Modern
Antipsychotic Medications
• Chlorpromazine (Thorazine)
– Synthesized in 1951 for use in general anesthesia
– Also found to produce “euphoric quietude” where patients lost
interest in their surroundings
– First drug effective for psychotic symptoms (and not just sedation)
• Dopamine antagonist -> led to dopamine excess theory of Schizophrenia
Early Modern
Antipsychotic Medications
• Chlorpromazine (Thorazine)
– Adopted by psychiatrists worldwide by mid-1950’s
– Led to further development of 1st generation
antipsychotics (neuropleptics)
– Began deinstitutionalization movement
Early Modern
Antidepressant Medications
• Iproniazid (1951)
– Medication for Tuberculosis
– Improved mood in depressed patients
– Weak monoamine oxidase inhibitor
• Led to monoamine theory of depression
Early Modern
Antidepressant Medications
• Imipramine (1956)
– Found serendipitously while trying to manufacture
an antipsychotic medication
– Improved mood in depressed patients
– First Tricyclic Antidepressant (TCA)
• Led to creation of other TCA’s and later SSRI’s
Concluding Thoughts