Drugs for Mental Health Treatment Flashcards
Today’s lecture
low-prevalence disorders: less common conditions such as
schizophrenia, bipolar disorder, major depressive disorder.
Ideas about ‘madness’ and how these have changed over time.
History of diagnosis and treatment of low prevalence
disorders.
The dopamine hypothesis of schizophrenia.
Some longstanding problems with this form of treatment: side
effects, Big Pharma, off-label prescription, noncompliance, consumer movements, and the limits of the
biogenetic model.
Some ways forward?
Learning outcomes
To describe how the modern
construct and classification
of ‘mental disorder’ and its
treatment has developed
since the 18th century.
To describe the development
of treatments for lowprevalence mental disorders,
up to and including antipsychotic medication.
To describe key elements of
the critique of antipsychotic
use for mental disorders.
To describe the basics of the
dopamine hypothesis of
schizophrenia.
‘Madness’
‘Madness’, ‘lunacy’, ‘insanity’ are as old as
humanity.
A ‘mad’ person’s speech / behaviour did not
conform to social norms.
This varies from culture to culture.
Multiple causes:
possession
malevolent ghosts
physical illness or injury to head
sorcery or curse
poor diet
displeasing gods
too much alcohol or recreational
substances
influence of conjunctions of planets /
stars / moon
The beginnings of modern
psychiatry
Eighteenth century in Europe – rationalism.
‘Mad’ people had ‘lost their reason’= had to
be treated like animals.
Philippe Pinel (1745-1826) – physician.
‘Madness’ was not a punishment or an
illness.
It was a moral condition affecting the
person’s spirit/soul.
The ‘mad’ must be treated as potentially
recoverable.
‘Moral treatment’
People were to be allowed to move about as much as
possible.
They were to be treated as ‘normal’.
Should be kept occupied / given work to do.
Chaining was outlawed.
The only forms of punishment that were allowed
were restraint and seclusion.
Restraint = use of straitjacket or other garments.
Seclusion = isolation in single room with no
furniture for specified periods of time.
Changing ideas of madness – the 19th
century
‘Lunacy’ was closely associated with physical illnesses.
Concerns with hereditary madness –eugenics.
Major causes of admissionto mental hospitals and asylums included:
Dementias of old age
Physical illnesses - tertiary syphilis
Neurological conditions - epilepsy
Developmental disorders and disabilities - Down syndrome,
autism, hydrocephaly, cerebral palsy
Reproductive problems: menarche, post-natal depression,
menopause
Alcoholism and drug addiction
How can you tell if
someone is ‘mad’?
No international standardised
diagnostic criteria for major mental
disorders until 1952.
Doctors would rely on their experience
and best judgement
They would also consult with the
person’s relatives, jailers, spouses,
neighbours and other doctors
How can you
tell if
someone is
‘mad’?
Mania: wild, uncontrollable behaviour or
obsessions.
Melancholia: sadness, inertia.
Confusional insanity: person appears very
confused by normal events, cannot understand
what is going on.
Delusional insanity: person experiencing
hallucinations or delusions.
Epilepsy: fitting, collapses, unconsciousness,
choking.
Senility / softening of the brain: elderly.
Idiocy / Imbecile: children with developmental
disabilities.
How can you tell if someone is
‘mad’?
1952: the American Psychiatric Association
developed the first Diagnostic and Statistical
Manual of Mental Disorders, or DSM-I.
First step towards standardised diagnosis of
mental disorders:
DSM I 1952 – 106 mental disorders
* DSM-II in 1968 – 182 mental disorders
* DSM-III in 1980 – 265 mental disorders
* DSM-IV in 1994 – 297 mental disorders
* DSM-V in 2013 – 297 mental disorders
Critiques of DSM (I -V)
- It’s not used consistently -Allsop et al (2019)
https://doi.org/10.1016/j.psychres.2019.07.005 - Evidence base lacks reliability – not much improved since the 1950s.
- Lacks validity: lack of empirical standards to distinguish ‘pathological’
states from normal human variations or other disorders. - DSM diagnoses are not correlated with outcomes or length of stays in
hospital.
DSM may be propping up an illusion of ‘science’ and clinical utility that it
can’t live up to. - Because of this, there are lots of holes in DSM as a construct.
- impact of cultural expectations, power, privilege, gender, race.
International
Classification
of Diseases
(ICD)-10/11
- Australia: ICD-10 (ICD-11) classification
system in mental health units. - May be slightly more reliable for
some disorders. - Available free online.
- Uses guidelines, not criteria.
https://icd.who.int/en
How can you
tell if
someone has
a mental
disorder?
Mental disorders are still
difficult to diagnose:
No blood test.
No genome sequencing
or DNA test.
No x-ray, MRI, fMRI.
Physical tests can diagnose specific physical
pathology(tumours, genetic problems,
brain damage, vitamin deficiencies).
But people with same mental disorder can
have different symptoms.
People with different mental disorders can
have the same symptoms.
What causes low prevalence
mental disorders?
We don’t know.
Not really, anyway:
Multiple possible causes for multiple
possible disorders.
Lots of theories.
Lots of guessing.
Lots of anecdotal evidence.
Physical treatments
for mental disorders
Moral treatment didn’t work for
everyone.
1920s: interest in trying new physical
treatments for mental disorder.
These were completely experimental.
Based on often-conflicting theories about
the origin of mental disorders.
Often cruel and unusual.
Trialled out of desperation at growing
asylum populations.
Physical
treatments
for mental
disorders,
1920s and
1930s
ECT is still standard treatment
ECT is still the standard treatment for refractory
depression in Western Australia.
Originally given unmodified (without anaesthetic or
muscle relaxants).
Since the 1980s in Australia, all ECT has been given
modified.
Given in both public and private system.
Requires informed consent under Mental Health Act
2014 (WA).
There are theories only as to how ECT works:
Singh and Kar 2017 -
https://www.ncbi.nlm.nih.gov/pmc/articles/PM
C556508/
Anderson 2021 - doi:10.1192/bja.2021.23
So what about drugs?
Lithium treatment pioneered in the late 1940s
by Australian researcher John Cade in Victoria.
Cade first tested a preparation of lithium
carbonate on himself and then people with
mania-type illnesses (bipolar disorders).
Found that it had a calming effect (but
eventually killed one patient in the trial and
made two others very ill).
Published results in 1949.
Drug did not take off until the 1960s: lithium
seemed to treat mania without increasing
depression.
How
does lithium
work?
Our knowledge of how lithium works is
incomplete.
Its ability to inhibit one enzyme, glycogen
synthase kinase 3 (GSK-3), seems especially
important.
This molecule is also implicated in epilepsy,
Alzheimer’s, and diabetes.
This enzyme participates in the regulation of
neuronal excitability.
So: Does lithium work by reducing neuronal
activity in brain regions responsible for manic
behaviours? Maybe.
The first anti-psychotics
The ‘typical’ (first generation)
antipsychotics were developed in the
early 1950s, largely by accident.
anaesthetics and antihistamines.
Chlorpromazine was first synthesised in
France in December 1950.
Antipsychotics slow responses and
apparently control agitation.
Allowed people to carry out basic daily
functions of living.
Immediately impacted on the use of
restraint and seclusion for violent and
agitated patients.
Side effects
These drugs were completely
experimental.
Based on often-conflicting theories about
the origin of mental disorders.
Often cruel and unusual doses.
Trialled out of desperation at growing
asylum populations.
No testing for long-term side effects.
Typical antipsychotics had distressing sideeffects.
long-term heavy use can produce tardive
dyskinesia, a neurological disorder:
https://www.youtube.com/watch?v=W_3b
bpFjI68
So …
If we don’t know what causes
mental disorders, then how can
we treat them effectively with
medications?
We can’t treat the causes.
We can treat the symptoms.
Schizophrenia
Example: ‘schizophrenia’.
First identified in the 18th century as dementia
praecox.
‘Schizophrenia’ coined by Eugen Bleuler in
1908.
Dis-integration of emotion, thought and action
= split up:
Positive symptoms: excess of normal
function, eg. delusions, inappropriate
affect, speech disruptions, odd
behaviour.
Negative symptoms: absence of normal
function, eg. lack of emotion, lack of
speech, lack of motivation.
What causes schizophrenia?
We don’t know.
It affects around 1% of population.
Chance of a relative with schizophrenia is around
10%.
Identical twin concordance rates of 50 - 80%.
Experience and environment are also likely to have
significant effect on developing schizophrenia.
No single gene identified.
Early epigenetic factors? parental malnutrition, birth
complications, parental stress, infection,
autoimmune reactions, toxins, traumatic injury.
Later epigenetic factors? recreational drug use,
stress, migration.
Schizophrenias? Plural?
Dopamine
theory of
schizophrenia
Developed after drug treatment for schizophrenia began in the
1950s.
Parkinson’s disease research (1960s) suggested that
antipsychotics worked by disrupting dopaminergic
transmission.
Was schizophrenia caused by ‘too much dopamine’ in the brain?
Chlorpromazine is a very effective dopamine antagonist at
receptor sites.
So perhaps it’s not high levels of dopamine, but high levels of
activity at dopamine receptors?
More holes in
the theory
These drugs block D2 within hours - but the
therapeutic effect is not seen for weeks.
These drugs only seem to help around 1 in 7
patients.
They only work against the positive symptoms of
schizophrenia.
So dopamine is a factor …
… but there are other as yet unidentified factors
Dopamine
receptors
But haloperidol had low affinity for dopamine receptors – so how
come it works?
Discovery of at least five different dopamine receptor subtypes.
Phenothiazines (like chlorpromazine) bind to D1 and D2
receptors.
Butyrophenones (like haloperidol) bind to D2 receptors.
So is schizophrenia caused by high levels of activity at D2
receptor site?
Do people with Sz have higher or lower numbers of D2
receptors?
