Drugs for Mental Health Treatment

Question 1

Today’s lecture

Answer 1

 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?

Question 2

Learning outcomes

Answer 2

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.

Question 2

‘Madness’

Answer 2

‘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

Question 3

The beginnings of modern
psychiatry

Answer 3

 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.

Question 3

‘Moral treatment’

Answer 3

 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.

Question 4

Changing ideas of madness – the 19th
century

Answer 4

‘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

Question 5

How can you tell if
someone is ‘mad’?

Answer 5

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

Question 6

How can you
tell if
someone is
‘mad’?

Answer 6

 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.

Question 6

How can you tell if someone is
‘mad’?

Answer 6

 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

Question 7

Critiques of DSM (I -V)

Answer 7

• 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.

Question 7

International
Classification
of Diseases
(ICD)-10/11

Answer 7

• 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

Question 8

How can you
tell if
someone has
a mental
disorder?

Answer 8

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).

Answer 9

But people with same mental disorder can
have different symptoms.

People with different mental disorders can
have the same symptoms.

Question 10

What causes low prevalence
mental disorders?

Answer 10

We don’t know.
 Not really, anyway:
 Multiple possible causes for multiple
possible disorders.
 Lots of theories.
 Lots of guessing.
 Lots of anecdotal evidence.

Question 11

Physical treatments
for mental disorders

Answer 11

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.

Question 11

Physical
treatments
for mental
disorders,
1920s and
1930s

Answer 11

Question 12

ECT is still standard treatment

Answer 12

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

Question 13

So what about drugs?

Answer 13

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.

Question 14

How
does lithium
work?

Answer 14

 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.

Question 14

The first anti-psychotics

Answer 14

 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.

Question 14

Side effects

Answer 14

 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

Question 15

So …

Answer 15

 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.

Question 16

Schizophrenia

Answer 16

 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.

Question 17

What causes schizophrenia?

Answer 17

 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?

Question 17

Dopamine
theory of
schizophrenia

Answer 17

 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?

Question 17

More holes in
the theory

Answer 17

 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

Question 17

Dopamine
receptors

Answer 17

 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?

Question 18

What about Big
Pharma?

Answer 18

 Psychiatric medications
have been big business
since the 1950s.
 Driving legitimate
research.
 BUT: Ongoing problem with
selective publication and
suppression of adverse
research findings.
 Lack of access to data -
except when exposed in
court.

Question 19

Off-label prescription

Answer 19

 When a drug is prescribed for an indication, a route
of administration, or a patient group that is not
included in the approved product information
document for that drug.
 e.g. Seroquel (quetiapine; antipsychotic) = sleeping
pill.
 Semi-experimental / anecdotal process of selection.
 Little guidance for prescribers.
 Product information does not include advice about
unapproved indications.
 Best practice: everyone involved should know that
the prescription is off-label.

Question 20

A different world

Answer 20

 The community outside the
hospital changed dramatically in
the 1960s and early 1970s.
 A more articulate and educated
consumer movement made up of
ex-patients.
 Spectrum of attitudes among them
from ‘collaborative’ to ‘antipsychiatry’.
 Drawing attention to the complex
inter-relationship of hospitals,
research institutions and large drug
manufacturing companies.
 Also highlighting the substantial
gaps in psychiatry’s knowledge and
understanding of mental illnesses,
their origins and best forms of
treatment.

Question 20

The
social impact
of antipsychotic
medication

Answer 20

 Increased use of outpatient facilities (rather than
lifelong inpatient custodial care).
 Increased discharges from large psychiatric
hospitals.
 Introduction of step-down programs to help expatients readjust to living independently.
 Increased visibility of former and current
psychiatric patients in the community.

Question 21

Medication revolution -> noncompliance

Answer 21

 Unpleasant and unwanted side-effects: sleepiness,
weight gain, loss of interest in sex, dizziness, nausea.
 Serious physical health problems such as metabolic
syndrome and cardiovascular disease.
 The side effects can be more unpleasant than the
psychiatric symptoms.
 Some people hate the feeling of dependence on a
drug.
 People forget to take it.
 People believe that because they now feel well, they
no longer need the medication.

Question 22

Grassroots
movements

Answer 22

 ‘Anti-psychiatry’ movement
 ‘Consumer’ movement
 ‘Recovery’ movement
 ‘Neurodiversity’ movement
 ‘Psychiatric survivor’/’peer’/’ex-patient’
movements
 All work from similar principles but have
different emphases
 All identify similar abuses and concerns about
human rights issues in mental health care

Question 23

Drug-free or adjuvant ways
forward

Answer 23

 Neuroplasticity: brain architecture is constantly
changing, and can be measurably changed by human
activity and input through physical and talk therapy.
 Trauma-informed diagnosis: tracing the cause of
some serious mental disorders back to trauma; using
somatic treatments and psychodynamic therapies.
 A 2021 meta-analysis found “robust benefits
in reducing the risk of relapse for family
interventions, family psychoeducation, and
cognitive behavioural therapy.”
 https://www.thelancet.com/journals/lanpsy/article/PII
S2215-0366(21)00243-1/fulltext

Question 24

What we currently know - and don’t know

Answer 24

 Mental disorders may be the result of both genetic and environmental factors
(not just ‘biogenetic’ factors).
 Structural changes in certain brain areas are not necessarily the cause of mental
disorders.
 There is often a huge gap between the mental health evidence base and what
the media reports about it.
 Our evidence base has not really translated into better treatments yet.
 Antipsychotics do alleviate psychiatric symptoms in many cases.
 However, the idea that psychiatric drugs ‘correct chemical imbalances’ is now
discredited by researchers.
 https://journals.lww.com/hrpjournal/fulltext/2020/11000/messaging_in_biologica
l_psychiatry_.4.aspx

Question 25

Maybe we need
to think
differently

Answer 25

 Should we change our thinking about mental
disorders?
 Transdiagnostic approach sees mental health as a
continuum:
 we all share the psychological processes that
underlie ‘disorders’.
 we all exhibit ‘disorders’ to varying degrees.
 helps to account for the apparent overlap between
traditional classification of disorders.
 makes more sense of broad spectrum of mental
health experiences.
 could clarify the common factors that underlie poor
mental health.
 https://aeon.co/essays/common-mental-processesoften-underlie-different-diagnoses

Question 26

To summarise

Answer 26

 Psychiatry transitioned from ‘moral’ treatment to ‘medical’
treatment in 19th century.
 Early ‘medical’ treatments were very drastic and not very
effective.
 Origins of most mental disorders still unknown.
 Drugs control behaviour, but do not ‘cure’ any ‘illnesses’.
 Very few long-term studies of drug effects.
 Major challenges to biogenetic psychiatry from 1960s onwards.
 Should we change how we think about mental disorders?

Question 27

Today’s lecture

Answer 27

 What are anti-anxiety medications?
 What are antidepressants?
 Where did they come from?
 Where are they going?
 Why are we taking them by the millions?
 High-prevalence disorders: very common in the general population

Question 28

Learning outcomes

Answer 28

To correctly describe anxiolytic drug development:
bromides, barbiturates, benzodiazepines.
To correctly describe antidepressant drug development: tricyclics,
MAOIs, SSRIs.
To describe current theories about the causes and classification of
both anxiety and depression.
To critique the current high rate of drug-based treatment for anxiety
and depression with reference to disease origins and side-effects

Question 29

Anxiety, stress
and depression

Answer 29

 These three conditions all overlap in their presentation.
 They very often co-exist.
 An ‘anxiolytic’ is an anti-anxiety medication.
 What is anxiety? And why does it need medication?

Question 30

The
beginnings of
modern
anxiety

Answer 30

 Jean-Martin Charcot (1825-1893) – neurologist.
 Dubious experiments with female ‘hysterics’ opened
the way to explore ‘neuroses’.
 Mysterious conditions that had behavioural
manifestations, but seemed to have no clear physical
origin.
 The first ‘mental illness’?
 1866: Bénédict-Augustin Morel – is severe anxiety due
to a dysfunction in nervous system?
 Neurasthenia: late 19th century catch-all diagnosis for
a wide range of symptoms – tiredness, panic, inability
to cope, restlessness, morbid fears.

Question 31

Anxiety as neurosis - Freud

Answer 31

 Regarded as product of sexual dysfunction or guilt.
 Treated with psychotherapy.
 Wartime experiences with ‘neurasthenics’ and shell-shock
victims helped shift belief that environmental stress was
critical factor.
 “The name anxiety—angustial (“narrowness”), emphasizes
the characteristic tightening of the breath, which was at the
time a consequence of an actual situation and is henceforth
repeated almost regularly in the emotion.” - Freud

Question 32

Treating anxiety with drugs

Answer 32

Alcohol was an early anxiolytic – self-prescribed or prescribed by
doctors.
 Paraldehyde (hypnotic) first synthesised 1829.
 Bromides (chemical compound with a bromide ion).
 Bromide of potassium produced as a salt – 1850s.
 These were found to have calming effect and anti-convulsive effect in
epilepsy.
 Gamma-amino butyric acid (GABA) - endogenous chemical with antiseizure and anti-anxiety effects.
 Bromides act via GABA potentiation? (hypothesised only)

Question 32

Treating anxiety with drugs -
barbiturates

Answer 32

First synthesised 1864 from animal urea.
 1903: barbital (the first barbiturate) used for euthanising
animals.
 barbital/barbitone then marketed as Veronal (sleeping drug).
 pentobarbital = Nembutal
 secobarbital = Seconal
 Barbiturates enhance action of GABA: bind to a site on the
GABAA receptor/chloride channel.

Question 33

Treating anxiety with drugs -
meprobamate

Answer 33

1950: meprobamate synthesised.
 The first non-barbiturate used extensively in the
treatment of anxiety.
 Turned out (like barbiturates) to be highly addicting and
fatal in overdose.
 Not sure yet about the mechanism of action? Similar to
barbiturates?

Question 34

Treating anxiety
with drugs -
benzodiazepines

Answer 34

 The first benzodiazepine, chlordiazepoxide,
discovered accidentally in 1955.
 Marketed in 1960 by drug company HoffmannLaRoche as Librium.
 Librium was marketed to medical professionals as a
means to an end – getting the patient to engage
with and benefit from psychotherapy.
 Binds to benzodiazepine binding sites on GABA (A)
receptor complexes in CNS.
 It helps GABA to bind to the GABA(A) receptor.

Question 35

Treating anxiety
with drugs -
benzodiazepines

Answer 35

 diazepam developed 1963.
 3 to 10 times the potency of chlordiazepoxide (Librium).
 Best-known brand name: Valium.
 Competing in a market with already-established sedatives and
anxiolytics.
 Seems to work the same way as chlordiazepoxide, but better.

Question 36

Valium takes off

Answer 36

By 1974, Hoffman-LaRoche had
cornered 81% of the US tranquiliser
market.
 By 1976 in the US, women Valium users
over 30 outnumbered male users two to
one.
 Valium became top-selling
pharmaceutical in the United States
from 1969 to 1982, with peak sales in
1978 of 2.3 billion tablets.
 Jan-Sept 2009 - global financial crisis:
over 3.6 million prescriptions in England
(11% increase on 2006).
 Australian anxiolytic prescriptions
increased by about 15% in Jan-June
2020 (COVID19).

Question 37

The other side
of the story

Answer 37

 Benzodiazepines have toxicity and dependence
issues.
 Psychological and physical dependence may occur.
 Withdrawal symptoms: anxiety, agitation,
restlessness, and tension.
 Can be dangerous when combined with alcohol.
 Currently the most common drug involved in
accidental poisonings in Australia.
 Other side effects include:
 Sedation, anxiety, psychomotor impairment,
drowsiness, dizziness, tiredness, weakness, dry
mouth, diarrhea, nausea, changes in appetite

Question 38

A mysterious
transition

Answer 38

 1980: US Food and Drug
Administration forced HoffmanLaRoche to state in
medical journal advertising
that”anxiety or tension associated
with the stress of everyday life
usually does not require treatment
with an anxiolytic drug.”
 The backlash about anxiolytic
consumption led to another
phenomenon.
 The number of people diagnosed and
treated for anxiety FELL in the US.
 But this was matched by a
corresponding rise in the number of
people diagnosed and treated for
depression.
 1961 advertisement for early
antidepressant.

Question 39

Depression

Answer 39

 Robert Burton, The Anatomy of Melancholy (1621)
 Melancholy could be either transitory or habitual.
 No one could expect to escape it completely in their life.
 When it becomes habitual: ‘a serious ailment, a settled humour …
not errant, but fixed: and as it was long increasing, so, now being
(pleasant or painful) grown to a habit, it will hardly be removed.’
 Humoral theory: caused by an excess of black bile in the person’s
system (melan chole).
 Reasonably common cause of admission to mental hospitals in
19th century.

Question 40

Depression –
from neurosis
to medical
condition

Answer 40

 Over the 19th century, melancholia became
progressively medicalised.
 During 1850s and 1860s, the term
‘depression’ was introduced to psychiatry.
 Borrowed from cardiac medicine.
 Assumed psychological connotations such
as the decrease in “psychic nerve force” and
eventually a “sinking in spirits”.
 Was melancholia an illness in itself - or just a
symptom of other mental or physical
illnesses?
 1904: Adolf Meyer suggested discarding
‘melancholia’ and instead using the term
‘depression’.

Question 41

Treating depression with drugs -
tricyclics

Answer 41

Tricyclic antidepressants:
 1950: accidental discovery of imipramine.
 Imipramine inhibits the reuptake of norepinephrine and
serotonin (antagonist).
 Marketed as Tofranil in 1958.
 Provided relief to 60% to 80% of patients.
 Side effects: sluggishness, weight gain, overdose.
 Half-life of about 24 hours in body = daily dosing.

Question 42

Treating
depression with
drugs - MAOIs

Answer 42

 MonoAmine Oxidase Inhibitors.
 Developed early 1950s – iproniazid – originally for tuberculosis.
 Monoamine oxidase is an enzyme.
 Two isoenzymes, MAOA and MAOB
 MAOA helps to break down serotonin, melatonin,
noradrenaline, and adrenaline.
 MAOB helps to break down phenethylamine and benzylamine.
 Inhibiting MAO’s action allows the ‘happy’ neurotransmitters to slosh
around the brain in greater quantities.
 MAOIs found to be effective in those who did not respond to tricyclics.
 More dangerous: risky dietary and drug interactions.
 Stroke risk if consuming foods high in tyramine (cheese, wine,
pickles).

Question 43

Treating
depression
with drugs –
other

Answer 43

 Nardil (phenelzine – an MAOI).
 Like early anxiolytics, these were
advertised as a means to get
patients to accept and benefit from
psychotherapy.
 They were not seen as a ‘cure’ in
themselves.

Question 44

1987 – what
else happened?

Answer 44

 Selective Serotonin Reuptake Inhibitors.
 Act directly upon serotonin reuptake by brain.
 Theory: slowing reutake allows serotonin to slosh
around for longer in the brain.
 Easier to prescribe without risking overdose.
 Fewer side effects:
 1987: Prozac (fluoxetine)
 1991: Zoloft (sertraline)
 1992: Aropax (paroxetine)
 Selective Norepinephrine Reuptake Inhibitors
(SNRIs).

Question 44

Depression takes over from anxiety

Answer 44

 In 1975, depression overtook anxiety in the US as a major mental health
condition.
 18 million diagnoses that year, compared to only 13 million diagnoses for anxiety.
 From then onwards, diagnosis rates for depression steadily increased.
 Between 1987 and 1997, the number of people in the US receiving outpatient
treatment for depression rose by more than 300 per cent.

Question 45

What causes
anxiety?

Answer 45

 Today anxiety is the most prevalent mental
disorder in Western countries.
 Commonly associated with stress.
 Some genetic or epigenetic component?
 Low levels of GABA, a neurotransmitter that
reduces activity in the central nervous
system?
 Dysfunctional amygdala processing?
 Social and cultural issues around resilience –
growing inability to cope with normal
stresses of living?
 Individualised living and loneliness?
 Alcohol, caffeine, benzodiazepines all
aggravate anxiety.

Question 46

Diagnosing anxiety

Answer 46

How we treat anxiety will depend on what we think causes it.
 Anxiety disorders were not categorised systematically until around 1980:
 In DSM-II (1968) they were classed as ‘neuroses’.
 DSM-III (1980) gave them their own grouping.
 Argument continues:
 Is OCD an ‘anxiety disorder’ or an ‘impulse control disorder’?
 Are simple phobias really an ‘anxiety disorder’?
 Is there such a thing as a ‘pure’ anxiety disorder?
 Or is anxiety always a symptom of another illness, like depression?

Question 46

What causes depression?

Answer 46

We don’t know – polymorphous and highly individual.
 “Chemical imbalance” hypothesis of depression is not supported -
insufficient evidence that depression is caused by a simple imbalance of
any neurotransmitter or biochemical (Moncrieff et al,
2022; Kendler, 2008; Lacasse & Leo, 2015).
 Genetic factors? No solid proof yet that anxiety, depression or posttraumatic stress disorder (PTSD) are inherited conditions.
 Epigenetic factors are more likely contributor?
 Psychological factors = maladaptive coping mechanism? Stress? Grief?
Anger? Fear?
 Normal adaptive response to an inflammatory illness somewhere in the
body?
 Normal adaptive response to adversity?
 Lack of sufficient sunlight?

Question 46

Diagnosing depression

Answer 46

Diagnosing depression
 1952: DSM-I - depressive reaction
 1968: DSM-II - depressive neurosis (an excessive reaction to internal
conflict or an identifiable event)
 1980: DSM-III – major depressive disorder
 Ongoing conflict by researchers over ‘endogenous’ (inherent) and
‘exogenous’ (reactive) depression
 Depression as continuum?
 “depression is the inability to construct a future”

Question 46

Two theories of
depression’s
aetiology

Answer 46

 Like the dopamine theory of schizophrenia - both theories have
emerged FROM drug treatment of depression.
 Monoamine theory of depression: Underactivity at serotonergic and
noradrenergic sites, BUT:
1. Just because drugs increase monoamines doesn’t mean that
depression is caused by a deficiency of monoamines.
2. Antidepressant drugs increase monoamine concentrations
almost immediately, but their antidepressant effects only
appear after a few weeks.
3. Other drugs increase monoamines but are not effective
antidepressants.
4. Some antidepressant drugs decrease monoamines.
5. Depletion of monoamines does not induce depression in
non‐depressed individuals.
 Neuroplasticity theory of depression: Decrease of neuroplastic
processes in the prefrontal cortex, hippocampus, amygdala = loss of
neurons

Question 46

Criticisms
ofthe
antidepressant
industry

Answer 46

 Systematic review shows that providing biogenetic
explanations of mental disorders does not reduce the
stigma experienced by people with a diagnosis.
 Might even increase stigmatising attitudes (Larkings
& Brown 2018).
 Cosmetic psychopharmacology = using drugs to
enhance normal personalities.
 The medicalisation of normal human mood changes,
eg. shyness, grief, transient sadness.
 The role of Big Pharma in driving medical research
agenda, concealing data around failures, and colonising
minds for profit = funding journals, conferences.
 Early 2000s: Link between SSRIs and increased suicide
risk?
 Targeting women as lifelong users.

Question 47

The balance
sheet

Answer 47

 1989: Prozac earned Eli Lilly $350 million in one year.
 1990: Prozac was most prescribed antidepressant in the US.
 Annual sales soon topped $1 billion.
 The antidepressant prescription rate per 1,000 people in Australia
has tripled in 30 years:
 223/1000 in 1992-93
 674/1000 in 2020-21
 Over 17 million antidepressant prescriptions were issued in
Australia in 2020-21.
 In 2019, the annual prevalence of antidepressant use was 170.4
per 1000 women and 101.8 per 1000 men.

Question 48

Antidepressant
discontinuation
and withdrawal

Answer 48

 ‘Prozac Poop Out’ -
‘antidepressant treatment
tachyphylaxis’.
 Abrupt discontinuation can
lead to anxiety, depression,
psychosis, nausea, vomiting,
dizziness, panic attacks.
 Not ‘addictive’ but do create
chemical changes that cause
withdrawal when not
continued:
 1990s: Marketed as ‘drugs
for life’ (diabetes concept)
 2000s: Discontinuation
seen as a cautious possibility
 Present: Short-term use is
optimal (6-24 months)

Question 48

New metaanalyses and
reviews

Answer 48

 Placebo effect studies for antidepressants began appearing in 2008.
 Evidence that up to 25% of patients became worse on an SSRI.
 Role of individual genetic profile in metabolising drugs?
 Cipriani et al 2018 showed antidepressants outperformed placebo for
moderate to severe depression, but not mild depression:
 very limited scope
 heavily critiqued

Question 49

Beyond drugs for depression

Answer 49

 ECT (electro-convulsive therapy): still the standard treatment for
refractory depression.
 New therapies using repetitive transcranial magnetic stimulation
(rTMS).
 Electromagnetic stimulation causes neurons to fire.
 Safe, painless, non-invasive, no anaesthetic, few side-effects

Question 50

To summarise

Answer 50

 Beliefs about anxiety and depression transitioned from ‘moral’ to
‘medical’ in 19th century.
 New drug discoveries in early 20th century seemed effective, but
had unwanted side effects (highly addictive, caused anxiety and
depression).
 Originally marketed as aid to psychotherapy.
 Then marketed as ‘chemical imbalance correctors’.
 Drugs control behaviour, but do not ‘cure’ any ‘illnesses’.
 Origins and mechanisms of anxiety and depression still unknown.
 Some long-term studies of drug effects show dangers of shortand long-term use.
 Maybe our way of thinking about mental disorders is wrong?