OVERVIEW OF THE

DEPRESSIVE DISORDERS
Professor Gordon Parker, Scientia Professor of Psychiatry, UNSW.
 Defining Depression?

How to define depression, and is ‘depression’

synonymous with:
• anxiety?
• grief?
 Definition: ‘Depression.’
Central features of ‘depression’ per se (+):
• Lowered self-esteem
• Self-criticism
• Depressed mood

Associated features (+/-): Non-specific features (+/-):

• Anhedonia • Insomnia
• Non-reactive mood • Libido changes
• Hopelessness and • Fatigue
helplessness • Appetite and weight
• Amotivation changes
• Suicidality. • Somatic Symptoms
 …and Anxiety?

• Sense of uncertainty
• Apprehension
• Insecurity or fear
• Hyperarousal (so can affect appetite,
sleep)
• Sense of ‘going mad’ during acute
anxiety attacks
 ...and Grief?

• Sense of loss (e.g. of other,

or ideal, etc) – generally
following break in social
bond - and no primary drop
in self-esteem.
 ‘Normal depression’

• “Do you feel depressed, have lost

your sense of self-worth and self-
value, feel hopeless and helpless,
self-critical and tough on yourself,
and feel like giving up?”.
Defining Clinical Depression
(i) A duration of 2 weeks or more.

(ii) Disability or social impairment.

(iii) Certain ‘more pathological’ or more

severe features’, with common non-specific
features including: sleep and appetite disturbance
(up as well as down), insomnia, anhedonia, libido
decrease, fatigue, pain.
Impact of Clinical Depression

• Clinical depression has high

disability and associated costs
(economic; personal – work,
relationships, secondary D&A,
suicide).
• Impairment.........
 Developed a single measure of DISEASE BURDEN - the DALY -
measuring years of life lost to premature death and years lived with
disability.

One DALY = one lost year of healthy life.

YLL YLD
DALY = Mortality + Disability
Burden Years life lost Years of life lived
with disability

DISABILITY was measured after factoring in incidence, average age of

onset, average duration and severity.
Ten Leading Causes of Burden of
Disease, World, 2004 and 2030

World Health Organization, The Global Burden of Disease: 2004 Update, WHO press: Geneva, 2008,
page 44.
 Epidemiological Data
Australian ABS (2008) data indicate that – over
any one year – 4.1% of people will experience a
depressive episode; rates being higher in
women (5.1%) compared to men (3.1%).
Lifetime prevalence is 11.6%; again rates are
higher in women (14.5%) than men (8.8%).
The sex difference is seemingly limited to the ‘non-
biological’ depressive disorders, reflecting both
(i) artefactual and (ii) true differences.

Australian Bureau of Statistics, National Survey of Mental Health and Wellbeing: Summary of Results, 2008.
Artefactual Factors
§ Women admit, report, help seek and
remember more.
§ Depression measures weighted to sex
dimorphic items (eg crying, hyperphagia).

Real Factors
§ Sex hormone effects
§ Sex role effects
§ Sex dimorphic effects
 DEADLY
Suicide

Every year, almost

one million people
die from suicide; a
"global" mortality
rate of 16 per
100,000, or one
death every 40
seconds.
In the last 45 years suicide rates have increased by 60% worldwide. Suicide is
among the three leading causes of death among those aged 15-44 years
in some countries, and the second leading cause of death in the 10-24
years age group; these figures do not include suicide attempts which are
up to 20 times more frequent than completed suicide.

WHO, Mental Health: Suicide Preventrion (SUPRE), accessed 11.12.12

http://www.who.int/mental_health/prevention/suicide/suicideprevent/en/index.html
Australian Suicide Data

• In 2017, 3128 Australians died by suicide

(9% increase on 2016). Leading cause of
death in those aged 14-44. Male rate 3
times higher than female rate. 20% of
deaths in young people are from suicide.
Mood disorders highest ranking cause.
• Some 65,000 suicide attempts/year.
How to Model the Depressive
Disorders?
• Most current models – and
classificatory systems -
position depression as a
single condition, merely
varying by severity.
Unitary (or Dimensional)
Model
The Binary Model.
Historical Binary Model of Depression
• Binary view (ie 2 types of depression) has a long history [e.g. St Paul in
Corinthians distinguished between depressions “from God” and others “of the
world”]. In essence, endogenous vs neurotic (now ‘melancholic’ vs ‘non-
melancholic’) depressions.
• Binany view challenged in 1920s and increasing emergence of a unitary view
(ie one type of depression that merely varies dimensionally – in essence, in
terms of severity).
• Failure to identify ‘true’ depressive sub-type (or at least a clear-cut
melancholic type) s probably reflected (i) limited multivariate statistical
analyses, (ii) inclusion of too many non-discriminating items, (iii) failure to
include truly discriminating items), (iv) melancholia phenotype being broad (like
Parkinson’s Disease), and (v) testing in inappropriate samples.
Historical Classification of Depression
• In 1980, DSM-III emerged, a criterion-based, non-aetiological, ‘reliable’
classification. Its committee favoured a unitary model (‘major depression’ vs
‘minor depressions’), but with major depression able to be sub-classed to
include melancholic and psychotic sub-groups - preserved in DSM-IV.
• The International Classification of Diseases (WHO) have (in ICD-10) an even
more dimensional system, with ‘mild’, ‘moderate’ and ‘severe’ depressions.
• More recently, ‘caseness’ boundary further redrawn to include ‘sub-syndromal’
and ‘sub-clinical’ depressions. (DSM-5 proposing an even milder MAD
condition). The expanded groupings increase lifetime risk of clinical depression
to a near universal experience – and strain credibility .
Findings lead to public and many professionals viewing
psychiatry as pathologising human misery, while wide inappropriate use
of antidepressants in such ‘normal’ states of depression leads to
challenges about them being effective ‘at all’.
Current DSM/ICD Approaches.

• Creates pseudo-categories along a

severity dimension, such as ‘major
depression’ and ‘minor depression’
which are not true categories – but
more domains capturing multiple
heterogenous conditions, and which
ignore aetiology or cause; and which
leads to a non-specific treatment
logic…..which is failing us.
Efficacy Studies for Major
Depression
• All ‘old’ and ‘new’ antidepressants show equal
efficacy, and equal to:
• Psychotherapies, such as cognitive behaviour
therapy
• Counselling
• St John’s Wort
• Bibliotherapy (or reading books)
All have efficacies of 50 –60% - when tested as UNIVERSAL
TREATMENTS
Equipotency of Treatments Leads
to….
All therapists (whether using drugs, CBT,
etc) claiming that their treatment is
effective – so that ‘everyone is a
winner’.
Failure to respect the reality that differing
depressive disorders may benefit from
quite differing treatments.
An Alternate Sub-typing Model.

Weighting
phenomenology and
cause........
DEPRESSIVE CLINICAL
SUB-TYPE FEATURE

Psychotic Psychotic
depression features

Melancholia Psychomotor
disturbance

Non-melancholic Depressed
depression mood
DEPRESSIVE CLINICAL NEUROTRANSMITTER
SUB-TYPE FEATURE

Psychotic Psychotic
depression features DA

Psychomotor NA
Melancholia
disturbance

Non-melancholic Depressed 5-HT

depression mood
Melancholic Depression held
to be more “Biological”
§ Greater chance of family history.
§ More evidence of perturbed neurobiological processes
(eg HPA axis, DST non-suppresion).
§ Low placebo and spontaneous remission rates.
§ Low response rate to psychotherapies.
§ Preferential response to physical treatments (eg ECT
and antidepressant drugs).
Melancholic Depression

Social impairment
Psychomotor disturbance
Symptoms of Melancholic
Depression
Anhedonia
Cognitive impairment
Non-reactive mood
Mood and energy worse in A.M.
Profound and uncharacteristic anergia
Many symptoms can be grouped under
‘PSYCHOMOTOR DISTURBANCE.’
[Not particularly differentiating: insomnia, appetite and weight
loss, suicidal thoughts, libido, fatigue].
Psychomotor Disturbance

– Truncal cognitive processing problems

(poor concentration; inattention)
– Retardation
– Agitation

[Assess observationally is of key benefit – otherwise rely

on symptoms listed earlier]
Melancholia as a Fronto-subcortical
Network Disruption Disorder

Disruption of circuits linking

basal ganglia and pre-
frontal cortex leads to a
triad of: (i) Depression;(ii)
Cognitive Impairment,
and (iii) Psychomotor
Disturbance
Functional Melancholia

Increased Family History of

affective disorder; generally
smooth response to treatment
Structural Melancholia

Usually older at first onset;

increased chance of of
cerebrovascular and
cardiovascular Family History;
ApoE risk factor more relevant;
increased chance of
hyperintensities and decreased
basal ganglia volume. Standard
doses of antidepressants and
frequencies of ECT may induce
delirium. NOTE: relevance of
hypertension in management.
Psychotic Melancholia

Social impairment

Psychomotor disturbance

Psychosis
How to Diagnose Psychotic
Depression
Psychotic features – delusions in >90%, hallucinations in 10%.
[Equal chance of mood incongruent and congruent]

Pathological guilt – ruminating over past indiscretions or failures [Ask

about sense of deserving to be punished];

Profound psychomotor disturbance (may be mute and psychotic

features not able to be elicited).

‘Pseudo-dementia’ picture
Treatment Efficacy – Psychotic
Depression
Antidepressant + Antipsychotic* = 80%
ECT = 80%
Antipsychotic alone = 33%
Antidepressant alone = 25%
Placebo = 5%
*Efficacy of atypical vs typical Antipsychotic drugs is not
known
Treatment Efficacy – Melancholic
Depression
• ECT – highly efficacious
• Broader the spectrum of the AD drug, the higher the
overall efficacy (ie TCA, MAOI > dual action drugs >
SSRI and single-action drugs)
• Age effect: if <40 yrs: SSRI = if TCA; 40 – 60 yrs, TCA
twice as effective; if > 60 yrs, TCA is 4 times as
effective.
– [Reflects phenotypic picture of increased
psychomotor disturbance with age]
NOTE: Placebo response rate of 10%
 Modelling

Non-Melancholic Depression
Non-Melancholic Depression

Social impairment

More than 2 weeks

Modelling Non-Melancholic
Depression
Current models simply weight
severity and duration.

We argue for modelling (a) acute

and chronic stress, and (b)
personality and temperament.
Acute Precipitant-driven (‘Reactive
Depression’, ‘Adjustment Disorder’)
• Common in the general community. Rare in clinical
practice, where there is high spontaneous remission
and placebo response rate.
• Should respond well to empathic and common sense
counselling, or problem solving.
• Additional contribution from antidepressant medication
conceptually doubtful in ‘pure’ states. Additional
contribution from manualised psychotherapies not
known.
Chronic Situational Depression
• Can be viewed according to a ‘learned helplessness’
model (eg dysfunctional marriage).
• May respond to appropriate ‘lever’ of determinant being
reversed (eg divorce) or addressed (eg couples therapy) -
psychosocial strategies.
• Antidepressant drugs? Clinical experience suggests that
the SSRIs may assist by reducing worrying, with patients
reporting that while problems are still present, they are
“swimming” with them rather than “sinking” - SSRIs ARE
ANTIDEPRESSANTS AND ANTI-WORRY AGENTS.
How does temperament and
personality relate to non-
melancholic depression?
Can influence
(a) the chance of becoming depressed,
(b) the clinical features shown when
depressed (assisting diagnosis)
and
(c) (c) indicate the most useful
treatments.
‘Anxious Depression’

HIGH TRAIT ANXIOUS PERSONALITY STYLE separates into:

– I: ‘Internalizing’ anxious worrying style

(i.e. worriers, who stress easily, are
highly strung, tense, nervy, stew over
things and catastrophise)
– II: ‘Externalizing’ irritability (when
stressed), who get rattled, snappy,
and are hot and quick tempered
‘Hostile/Volatile/Self-Centred’
Temperament Style
• High spontaneous remission rate as they
externalise their distress (‘pus’) on those
around them. They feel better, others feel
worse with the collateral damage.
• Anger management strategies may assist.
• Role (and efficacy) of antidepressant
medication unclear, particularly when
compliance frequently low.
Intraversion/Avoidant
Temperament Style
• Early behavioural intervention to the forerunning
style of ‘behavioural inhibition’ (‘shyness’) has been
shown by Kagan to reduce their later development
of anxiety and depression.
• Literature problematic in terms of demonstrating and
distinctly effective treatment in adults.
• Theoretically, CBT or BT (especially) suggested.
‘Perfectionistic’
• Control their world so exposed to fewer life
event stressors.
• If depressed, denial level high.
• If not denying, still resist referral to practitioner.
If get to a practitioner, resist most medications
as dislike surrendering ‘control’.
• Do poorly with most interventions over time.
Need to work with them to bring their life back
into ‘control’.
Characterological ‘Self-Blamers’
• Depressed from “the moment I left the uterus, doctor”.
• Commonly recipients of developmental deprivation or
abuse, and often a lack of socio-economic resources.
• Usually do poorly with most interventions due to
intrinsic limitations to resilience, their general negative
expectations, personality styles tending to be
ineffective and self-defeating, so reducing
opportunities for them.
• SSRIs may assist a number of them - not resolve but
assist.
‘Atypical Depression’
• In DSM-IV, a non-melancholic disorder with:
(i) Reactive mood;
(ii) Personality style of interpersonal sensitivity
rejection; and who develop ‘atypical features’
when depressed (eg hypersomnia,
hyperphagia, ‘leaden paralysis’).
• MAOIs held to showed superior efficacy to
TCAs. Now know that SSRIs as useful as
MAOIs.
Atypical Depression - Our Model
[Parker et al, Amer J Psychiat; vol 159, 1470-1479.]

• A dimensional syndrome, whereby individuals with

social phobic/rejection sensitivity and panic capacity
respond to stress with certain homeostatic
mechanisms.
• Hypersomnia restores slow wave sleep during
stress.
• Hyperphagia to comfort foods (carbohydrates,
chocolate, cause:
– increased endorphins (“feel good”);
– release of multiple brain and gut peptides; and
– foods with L-Tryptophan increase brain 5-HT levels.
Summary
• Arguing for a matrix whereby certain
disorders are differentially responsive to
different treatments (i.e. a ‘hores for
courses’ model).
• SSRIs are now the standard antidepressant drug
strategy and are usually the best initial drug to
trial - but, if the patient has a
melancholic/psychotic depression, other
strategies may well be required.