IS THERE SUCH A THING AS A CURE FOR MENTAL ILLNESS?

TOM SENSKYAssurance Medical and Underwriting Society

March 2011

CURE versus REMISSION

CURE• The complete eradication of

the illnessREMISSION • State of absence of disease

activity (usually in someone with a chronic disease)

WHAT SORTS OF ILLNESSES CAN BE CURED?

Those which have ....• Clear-cut pathology• Simple aetiology (as opposed to

multifactorial)

Illnesses which have multifactorial causes or maintaining factors are likely to be chronic – cure here is unlikely

OVERVIEW – DIFFERENT TYPES OF CONDITIONS

CONDITION TYPE

EXAMPLES MANAGEMENT STRATEGY

Acute Common coldFractured humerus

• Remove pathology• Cure

Potentially Relapsing

Cerebro-vascular accident

• Self-management• Reduce risks where

possible• Contingency plan to

manage relapseChronic Diabetes

Rheumatoid arthritis

• Continue treatment indefinitely

• Shared decision-making• Self-management

OVERVIEW – DIFFERENT TYPES OF MENTAL HEALTH CONDITIONS

CONDITION TYPE

EXAMPLES MANAGEMENT STRATEGY

Acute Specific phobias

• Remove pathology• Cure

Potentially Relapsing

DepressionAnxiety

• Self-management• Reduce risks where

possible• Contingency plan to

manage relapseChronic Some cases

of schizophrenia and bipolar disorder

• Continue treatment indefinitely

• Shared decision-making• Self-management

OVERVIEW

• Focus on depression and anxiety, as common mental disorders

• Review of selective factors contributing to depression being best regarded as a chronic condition

• For anxiety, focus on some primitive psychological factors associated with the persistence of symptoms

DEPRESSION

Depression is often referred to as the common cold of psychiatry. But this analogy is wrong: although common, most depressive disorders are not mild and self limiting. It is time that we treated depression as the chronic disease that it is.

Jan Scott: Br Med J (editorial) (2006)

EPIDEMIOLOGY OF MENTAL DISORDERS (Health of the Nation)

• Of adults aged 16–64 years living in private households ,1 in 6 had suffered from some type of neurotic disorder in the week before the survey interview

• Half of these experienced anxiety and/or depression

Jenkins R et al: Br J Psychiatry (1998)

EPIDEMIOLOGY OF MENTAL DISORDERS (Health of the Nation)

Rates of common mental disorders higher among

• women• those who were separated, divorced and

widowed individuals of both genders, and among cohabiting women

• the unemployed• those with longstanding physical

complaints Jenkins R et al: Br J Psychiatry (1998)

PREVALENCE OF COMMON MENTAL DISORDERS (AGES 18-32 years)

Alcohol dependence

Depression

Anxiety

0 10 20 30 40 50

% Prevalence

1972-3 Dunedin birth cohort, followed up prospectively to age 32 years (95% follow-up)

Moffit TE et al: Psychological Medicine (2010)

Higher prevalence than previously reported attributed to prospective follow-up (likely to be more accurate)

DEPRESSION IN WOMEN : AETIOLOGICAL MODEL

DEPRESSION

PROVOKING AGENTS• Life events• Chronic difficulties VULNERABILITY FACTORS

• Maternal derivation• Parental separation• Social supports• Social circumstances

BACKGROUND• Personality• Genetics

After Brown GW & Harris T (1978)

COMMON MENTAL DISORDERS : AETIOLOGY

RATE OF LIFE EVENTS IMPACT OF

LIFE EVENTSONSET OFDISORDER

• Good parenting• Good marital relationship• Psychological factors

PROTECTIVE FACTORS

VULNERABILITY FACTORS

FAMILY• Parental loss• Lack of care• Child abuse

SOCIAL• Marital discord• Poor social support

SOCIAL ADVERSITY• Poor housing• Unemployment

PHYSIOLOGICAL• Genetic• Emotional reactivity

PERSONALITY• Neuroticism• Low self esteem• Low emotional strength

AETIOLOGICAL FACTORS RELEVANT TO DEPRESSION

Poor social support

Childhood abuse

Unsupportive work environment

Lack of control at work

Lifetime depression history

Discrimination

Anxiety

0 1 2 3 4 5 6

OnsetRecovery

Hazard RatioSample of 10,045 primary care patients, from 7 countries, followed up at 6 and 12 months Bottomley C et al: Br J Psychiatry (2010)

AFFECTIVE DISORDERS : GENETICS

• Genetic loading : bipolar (BP)>unipolar (UP)• Concordance (MZ twins) : BP=70%,

UP=40%• Risk of mood disorder in 1st degree

relatives : BP=30%, UP=15%• Close relative with BP disorder =

increased lifetime risk of both BP and UP disorder

• Close relative with UP disorder = increased risk of UP disorder only

EFFECT OF 5HT TRANSPORTER POLYMORPHISM ON SUSCEPTIBILITY TO LIFE EVENTS

Individuals homozygous for the short allele of the 5HT Transporter gene [s/s] were significantly more likely to develop a major depressive episode in response to stressful life events than those homozygous for the long allele [l/l]

Caspi A et al: Science (2003)

AUTOBIOGRAPHICAL MEMORY

AUTOBIOGRAPHICAL MEMORY IN DEPRESSION

CONSEQUENCES

• Depressed people recall fewer autobiographical memories (40% cf 70% for non-depressed people)

• Impairment most noticeable for positive events

• Autobiographical memory for negative events less impaired

• Depressed people have difficulty remembering events or activities that give pleasure or satisfaction

• Remember details of unhappy events

• Poor autobiographical memory leads to impaired problem-solving

The ability to recall specific memories in response to cues

ATTRIBUTIONS: AN EXAMPLEBeing criticised for a piece of work

STABLE

She’s right – I don’t think I’m up to this work

UNSTABLE

She must have got out of bed the wrong side today

GLOBAL

Nothing I do is ever good enough SPE

CIFIC

I didn’t put as much effort into this piece of work as I usually do

INTERNA

L

It’s all my faultEXTERNAL

If she hadn’t overloaded me with other assignments, I could have spent more time on this one

REFORMULATION OF THE LEARNED HELPLESSNESS MODEL: ATTRIBUTION TYPES

Abramson LY, Seligman K, Teasdale J: J Abnormal Psychology (1978)

UNSTABLE STABLE

INTERNAL

EXTERNAL

GLOBAL

SPECIFIC

Attributions by depressed people for

NEGATIVE events

Attributions by depressed people for

POSITIVE events

ASSOCIATION OF STRESS AT WORK WITH DEPRESSION: SYSTEMATIC REVIEW

Demand-control model

• High psychological demands

• Low degree of control over one’s tasks

• Combination of factors that prevents the experience of autonomy

• 8 studies• 44,114 respondents• Depression

associated with high demands plus low control

Effort reward imbalance model

• Usually expect reciprocity of contractual exchange at work – efforts compensated by adequate rewards (money, career opportunity, job security and esteem

• Imbalance occurs if rewards are not commensurate with efforts

• 4 studies• 81,582 respondents• Depression

assoiciated with effort-reward imbalance

Sigrist J: Eur Arch Psychiatry Clin Neurosci (2009)

ASSOCIATION OF STRESS AT WORK WITH DEPRESSION: SYSTEMATIC REVIEW

Demand-control model

• High psychological demands

• Low degree of control over one’s tasks

• Combination of factors that prevents the experience of autonomy

• 8 studies• 44,114 respondents

• Depression associated with high demands plus low control

Effort reward imbalance model

• Usually expect reciprocity of contractual exchange at work – efforts compensated by adequate rewards (money, career opportunity, job security and esteem

• Imbalance occurs if rewards are not commensurate with efforts

• 4 studies• 81,582 respondents

• Depression associated with effort-reward imbalance

Sigrist J: Eur Arch Psychiatry Clin Neurosci (2009)

WORK-RELATED FACTORS CONTRIBUTING TO DEPRESSION ONSET

• Longitudinal study examining onset of depression in 7 countries (6 European)

• Examined influence of 39 potential risk factors

• Sample: 7558 people not depressed at baselineFactor Adjusted

HR95% CI of

HR

Discrimination 1.94 1.46-2.58

Distress at work without respect 2.02 1.56-2.63

Difficulties at work without support 2.01 1.49-2.72

Lack of control at work 2.09 1.44-3.02

Bottomley C et al. British Journal of Psychiatry 196 (1):13-17, 2010

OFFSPRING OF SEVERELY DEPRESSED PARENTS

• Prospective 20-year follow-up of offspring of severely depressed patients

• Matched comparison group – offspring of parents without psychiatric morbidity

• Mean age of offspring at follow-up was 35 years

Weissman MMet al: Am J Psychiatry (2006)

DIAGNOSISCumulative Rate (%)

Relative RateDepresse

d Control

Any mood disorder 80 50 3.3Major depressive disorder 65 27 3.3Any anxiety disorder 67 34 2.9Any substance abuse 21 18 1.1Any physical illness 78 60 2.5Overweight 51 70 0.4

OFFSPRING OF SEVERELY DEPRESSED PARENTS

• Prospective 20-year follow-up of offspring of severely depressed patients

• Matched comparison group – offspring of parents without psychiatric morbidity

• Mean age of offspring at follow-up was 35 years

Weissman MMet al: Am J Psychiatry (2006)

DIAGNOSISCumulative Rate (%)

Relative RateDepresse

d Control

Any mood disorder 80 50 3.3Major depressive disorder 65 27 3.3Any anxiety disorder 67 34 2.9Any substance abuse 21 18 1.1Any physical illness 78 60 2.5Overweight 51 70 0.4

ADVERSE EVENTS IN CHILDHOOD AND ADULT DEPRESSED MOOD

4+

3

2

1

0

0 1 2 3 4 5

Adjusted Odds Ratio

Num

ber

of a

dver

se

child

hood

eve

nts

•Survey of 9508 adults registered with a health maintenance organisation•Assessed a variety of adverse childhood events, including abuse, violence against mother, parent in prison, etc•Assessed the odds of having at least 2 weeks of depressed mood in the past 12 months

Felitti VJ et al: Am J Prev Med (1998)

ETHNIC DENSITY AND COMMON MENTAL DISORDERS

• Random community sample (N=4281)• After adjusting for confounders, as own-

group ethnic density rose, the prevalence of common mental disorders decreased in (a) the whole ethnic minority sample; (b) the Irish group; (c) the Bangladeshi group

• This was despite areas of high minority ethnic density being socially deprived

• These results were not explained by discrimination, social support or social networks

Das-Munshi J et al : Br Med J (2010)

WILL THE INCIDENCE OF DEPRESSION RISE IN MEN?

• All research to date indicates higher incidence of depression in women

• Women tend to derive their self-esteem from reflected appraisals, while men focus on social comparisons, particularly regarding ‘traditional’ male roles

• Women are increasingly the primary household earners (4% in 1970, 22% in 2007)

• Male jobs are arguable more sensitive to the effects of recession than female jobs

Dunlop BW & Mietzko T: Br J Psychiatry (2011)

DEPRESSION RELAPSE RATES – ANTIDEPRESSANTS vs PLACEBO

6 12 18 24 36 Total0

1020304050607080

Antide-pressant

Months follow-up

S Reid & C Barbui. Long term treatment of depression with selective serotonin reuptake inhibitors and newer antidepressants. BMJ 340 (mar26_1):c1468, 2010.

4.5* 5.0*3.1*

3.1*2.4*

4.2*

* Number Needed to Treat

EFFICACY OF ANTIDEPRESSANT TREATMENT FOR DEPRESSION IN PRIMARY CARE

Arroll B et al. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev (3):CD007954, 2009

UK PRESCRIPTION OF ANTIDEPRESSANT MEDICATIONS

From www.tuesday1st.blogspot.com/ (dated 28 January 2010)

VARIATIONS IN ANTIDEPRESSANT PRESCRIBING IN ENGLAND

http://www.guardian.co.uk/news/datablog/2011/mar/05/data-store-pharmaceuticals-industry?intcmp=239#

Northern doctors prescribe more antidepressants, study revealsPatients in areas such as Blackpool are prescribed up to three times as many antidepressants as those in parts of LondonJames Ball and Sarah Boseley guardian.co.uk, Friday 4 March 2011 21.30 GMT

GP DIAGNOSIS OF DEPRESSION• Meta-analysis of 41 studies involving 50,371

patients• Weighed sensitivity = 50%• Weighed specificity = 81%• GPs tend to rule out non-cases more

effectively than recognising cases, but the modest prevalence of depression means that there are more false positives than missed cases

• For every 100 unselected cases seen, 10 true cases of depression are identified, 10 cases missed, and 15 people diagnosed as false positives Mitchell AJ et al. Lancet 374 (9690):609-619, 2009.

ARE ANTIDEPRESSANTS EFFECTIVE IN TREATING DEPRESSION?

•Meta-analysis of all clinical trials submitted to the US (FDA for licensing of the four new-generation antidepressants for which full datasets were available

•35 clinical trials involving 5,133 patients (3,292 randomised to antidepressants, 1,841 to placebo)

Kirsch I et al: Plos Medicine (2008)

COMPARATIVE EFFICACY OF ANTIDEPRESSANT MEDICATIONS

Data from Cipriani et al (2009) – table from Bandolier (http://www.medicine.ox.ac.uk/bandolier)

META-ANALYSIS OF COMPUTER CBT FOR DEPRESSION AND ANXIETY

DIAGNOSIS STUDIES EFFECT SIZE (g) NNT

Major depression 6 0.78 2.39

Social phobia 8 0.92 2.07

Panic disorder 6 0.83 2.26

Generalised anxiety 2 1.12 1.75

All combined 22 0.88 2.15

Andrews Get al : PLoS ONE (2010)

DEPRESSION TREATMENT: SHORT-TERM EFFECTS OF ANTIDEPRESSANT MEDICATION OR COGNITIVE THERAPY

DeRubeis R et al: Nature Reviews Neuroscience (2008)

•Severely depressed patients (n=240) were randomized to ADM (n = 120), CT (n = 60) or a (pill) placebo control (n = 60) treatment. •ADM involved paroxetine, augmented with lithium or desipramine as needed. •Treatment phase lasted 16 weeks.•The clinicians providing either ADM or CT were experienced practitioners who received feedback and supervision throughout the period of the study.

CBT vs ANTIDEPRESSANTS: CHANGE IN COGNITIONS I

40

60

80

100

120

Baseline Week 4 Week 8 EndAuto

mat

ic T

houg

hts Q

uest

ionn

aire

CBTDrugs

Simons AD et al (1984) Arch Gen Psych 41:45-51

CBT vs ANTIDEPRESSANTS: CHANGE IN COGNITIONS II

110

120

130

140

150

160

170

Baseline Week 4 Week 8 End

Dysf

unct

iona

l Att

itude

s Sca

le

CBTDrugs

Simons AD et al (1984) Arch Gen Psych 41:45-51

PROGNOSIS OF PEOPLE DIAGNOSED WITH DEPRESSION

% FOLLOW-UP MONTHS

Episodes of depression 30%

Symptoms of depression 52%

Antidepressant prescription 59%

• Prospective cohort study of people diagnosed with depression

• 8-11 year follow-up (N=61)

Kennedy N et al: Br J Psychiatry (2005)

• 18% of the cohort never achieved asymptomatic status

DEPRESSION TREATMENT: DIFFERENCES WITH/WITHOUT ANXIETY PRESENT

Intolerance

Severe side-effects

Response

Remission

0 10 20 30 40 50 60

Anxiety-Anxiety+

% Patients

Data from STAR*D trial – 2,876 adults with major depressive disorder, started initially on treatment with citalopram

Fava M et al: Am J Psychiatry (2008)

EFFECTS OF PAST HISTORY AND SUBTHRESHOLD DEPRESSIVE SYMPTOMS ON LATER DEPRESSION INCIDENCE

• Prospective cohort study from the Netherlands

• N=1167• Community

sample• 2-year follow-up• Those who had

depression within 6 months of baseline assessment were excluded

Karsten J et al: Br J Psychiatry (2011)

FACTORS PREDICTING LESS FAVOURABLE PROGNOSIS IN PEOPLE DIAGNOSED WITH DEPRESSION

FACTOR Adjusted Odds Ratio

Female gender 5.45

Severe index episode 5.70

Index anxiety 3.64Depression prior to index episode 3.50

Kennedy N et al: Br J Psychiatry (2005)

DEPRESSION: RELAPSE FOLLOWING ANTIDEPRESSANT MEDICATION OR COGNITIVE THERAPY

DeRubeis R et al: Nature Reviews Neuroscience (2008)

•After 16 week treatment phase, patients on ADM were randomised to continuation with ADM or placebo•Patients who had CBT were allowed no more than 3 booster sessions after acute treatment

ANXIETY - AETIOLOGY

PSYCHOLOGICAL FACTORS

• Classical conditioning• Operant conditioning• Social learning

GENETIC FACTORS

• Modest genetic contribution overall• Sensitivity of CO2 inhalation ?related to

polymorphism of lactate dehydrogenase gene

• Panic attacks more common in people who have joint hypermotility

NEURO-TRANSMITTERS

• Serotonin and GABA receptors important• Serotonin depletion increases susceptibility

to panic• Treated with benzodiazepines/SSRIs

BRAIN CHANGES

• Anxiety associated with changes in amygdala, cingulate gyrus and prefrontal/anterior temporal cortex

THE EXPERIENCE OF ANXIETY

• Many people who experience anxiety recognise their fears as unwarranted

• Such people know (“intellectually”) that they have no need to be anxious, yet the anxiety persists

• Very simple psychological factors contribute to this persistence• Conditioning (classical and

operant)• Social learning

CLASSICAL CONDITIONING (PAVLOV’S DOG)

Context egplayground

CLASSICAL CONDITIONING

Bullying Anxiety

Context egplayground

Anxiety

Unconditioned stimulus

Unconditioned response

Conditioned stimulus

Conditioned response

Waterway

CLASSICAL CONDITIONING

Accident in boat in water

Anxiety

Waterway Anxiety

Unconditioned stimulus

Unconditioned response

Conditioned stimulus

Conditioned response

PROBLEMS WITH REGARDING SPECIFIC PHOBIAS AS CLASSICALLY CONDITIONED

• There isn’t always a past history of a traumatic event

• If there is a past history of trauma, it does always lead to development of a phobia

Mineka S & Zinbarg R: American Psychologist (2006)

VICARIOUS CONDITIONING

• In ‘normal’ classical conditioning, the individual is exposed directly to the fearful stimulus

• Laboratory-reared rhesus monkeys (not afraid of snakes) became afraid of snake by seeing wild-reared monkeys reacting fearfully to snakes

• Humans can develop fears by watching videotapes of other people reacting fearfully

INDIVIDUAL DIFFERENCES IN VULNERABILITY TO ACQUIRE SPECIFIC PHOBIAS

• Modest genetic vulnerability for phobias (?mediated by genetic contribution to fear conditioning)

• Phobias more likely with certain personality variables• High trait anxiety• Behavioural inhibition (shyness,

timidity)• Differences in life experience (before,

during and after the conditioning event(s))

EXPERIENCES PRIOR TO CONDITIONING EVENT(S)

Exposure to the conditioned stimulus (2) before this is paired with the unconditioned stimulus (3) reduces the extent to subsequent conditioningExample: children visiting the dentistUnlike experimental animals, humans are seldom naïve to any conditioning stimulus

EXPERIENCES DURING CONDITIONING

• Fear is less likely to be conditioned when the aversive event is seen as• escapable• controllable

EXPERIENCES AFTER CONDITIONING

Mild fear (previously conditioned)

Exposure to a more intense but unrelated traumatic experience

Increased fear to the original conditioned

stimulusINFLATION

EFFECT

EXAMPLE• Mild driving phobia after

car accident• Subsequent personal

assault• Driving phobia then

becomes much worse

CONDITIONING OF PHOBIAS – OTHER FACTORS

• In monkeys, easier to condition fears for snakes or crocodiles than for flowers or toy rabbits

• Similar findings in humans – fears are selectively conditioned (people fear spiders more frequently than guns)

• Such prepared fears are probably similar now to the experience of prehistoric man

• Prepared fears more easily acquired, and more difficult to get rid of

EXAMPLES OF SOCIAL LEARNING IN SOCIAL PHOBIA

VICARIOUS LEARNING

Observing someone else being humiliated or ridiculed may be sufficient to generate social phobia

SOCIAL REINFORCEMENT

Parents of anxious children are more likely than other parents to support their childrens’ wishes to avoid social situations

CULTURAL NORMS

In Western cultures, social phobia commonly involves a fear of being scrutinised, while in Japan, it commonly involves a fear of causing offence by staring inappropriately, blushing, etc

OPERANT CONDITIONING

The individual learns by ‘operating’ appropriately on the environmentExampleMouse learns that pressing lever in response to red light results in getting a food pellet, while pressing lever in response to green light leads to electric shock

OPERANT CONDITIONING – EXAMPLE OF A CHILD HAVING A TANTRUM

Mother gives child immediate

attentionPOSITIVE

REINFORCEMENTTantrums repeated

Mother withdraws

NEGATIVE REINFORCEMENT

Tantrum ends

Mother gives attention when tantrum ended

POSITIVE REINFORCEMENTTantrums reduce

OPERANT CONDITIONING IN ANXIETY: EXAMPLES

• Avoidance of phobic stimuli or of vicarious conditioning• Child avoids dogs because mother

is afraid of them• Persistent ‘safety’ behaviours

• Always going out accompanied• Taking alcohol before going out

SAFETY BEHAVIOURS INHIBIT IMPROVEMENT IN PATIENTS WITH SOCIAL PHOBIA

0

10

20

30

40

50

% Im

prov

emen

t

Keep SB Drop SB

BeliefsAnxiety

Wells A et al: Behavior Therapy (1995)

• Case series (N=8)• Within-subjects

crossover design• One therapy

session with safety behaviours, one session without

• Monitored in-session anxiety and thoughts

CONCLUSIONS

• Chronic conditions can seldom be cured

• Disorders like schizophrenia and bipolar disorder are often considered chronic

• However, even common mental disorders (depression and anxiety) are best understood and managed as chronic conditions

CONTACT DETAILS

t.sensky@imperial.ac.uk

PTSD and subsyndromal PTSD, and change of diagnoses over three years (N=90)

5

19

66 624

134

223

2 weeks post accident1

4

9

7773

4

44

21

78

10

2

1

1

3 yearfollow-up

1 yearfollow-up

SubsyndromalPTSD

PTSD

no PTSD

1 Time criterion for PTSD not fulfilled

Psychiatric comorbidity at one-year follow-up (N=106)

Schnyder et al. (2001) Am J Resp Crit Care Med 164: 653-656

PTSDfull or subsyndromal

Anxiety(HADS)

Depression(HADS)

3 + 3*

8

4

421

2

PERSONALITY DISORDER versus NEUROSIS

PERSONALITY DISORDER NEUROSIS

ONSET Childhood/ adolescence

May be in adulthood

ENVIRONMENTAL PRECIPITANTS ?? Present

DISCRETE SYMPTOMS

No (except transiently) Yes

SYMPTOMS CHANGE OVER

TIMENo Usually

DURATION Always chronic May be brief

Affective disorders : prognosis• UNIPOLAR DEPRESSIVE DISORDER

• First episode lasts 4-6 months• 25% recurrence after 1 year• 75% recurrence within 10 years, 93% within 20 years• Average gap is 65 months• Typically 4-6 episodes over 20 years• 10% will eventually have hypomanic / manic episode (diagnosis then =

Bipolar Disorder)

• BIPOLAR DISORDER• Recurrence common (depression or mania)• Average gap is 48 months• Remission periods become shorter• Average 6.5 episodes in lifetime

Suicide rate in severe affective disorder = 10 - 15%

DEPRESSION : AETIOLOGY

GENETIC Family history

Emotional deprivation Early maternal separation Parental discord

EARLY DEVELOPMENT

Childhood abuse

PERSONALITY Neuroticism

Loss events Chronic difficulties

SITUATIONAL FACTORS

Lack of social supports

PROGNOSIS OF PEOPLE DIAGNOSED WITH DEPRESSION

• Prospective cohort study of people diagnosed with bipolar affective disorder, symptomatic at baseline (N=1469)

• 24-month follow-up

Perlis RH et al: Arch Gen Psychiatry (2006)

• 58% achieved recovery• 48% had a recurrence (depression 34%, other 13%)

FACTORS INDEPENDENTLY ASSOCIATED WITH TIME TO RECURRENCERELAPSE TYPE FACTOR HAZARD

RATIO

Depression Residual manic symptoms 1.22% days depression (past yr) 1.02% days anxiety (past yr) 1.01

Mania/Mixed Episodes depression (past yr) 1.07% days depression (past yr) 0.99% days elevated mood (past yr) 1.02

SELECTIVE PUBLICATION OF ANTIDEPRESSANT TRIALS

Turner EH et al. N Engl J Med 358 (3):252-260, 2008

• Obtained reviews from FDA for studies of 12 antidepressants (12,564 patients)

• Identified relevant published papers

• Examined papers to determine whether their conclusions agreed with FDA decision, or conflicted with it

ETHNIC DENSITY, PHYSICAL ILLNESS AND ANTIDEPRESSANT PRESCRIBING

• Data from 8515 GP practices in England

• Performance data from Quality and Outcomes Framework (QOF) (2004-5)

• Sociodemographic data from 2001 census

• Prescribing from Prescribing Analysis and CosT (PACT) data

• Multiple regression analysis

Walters P et al: Br J Psychiatry (2008)

ANTIDEPRESSANT PRESCRIBING – UNIVARIATE ASSOCIATIONSVARIABLE VARIANCE

EXPLAINEDUNADJUSTED

BETA

Chronic respiratory disease 25% 574

Coronary heart disease 22% 329% Black ethnic patients 12% -52% Chinese ethnic patients 9% -179% S Asian ethic patients 7% -19% White ethnic patients 15% 20Index of multiple deprivation 4% 12

Group practice 4% 465List size 3% -0.2

ETHNIC DENSITY, PHYSICAL ILLNESS AND ANTIDEPRESSANT PRESCRIBING

• Data from 8515 GP practices in England

• Performance data from Quality and Outcomes Framework (QOF) (2004-5)

• Sociodemographic data from 2001 census

• Prescribing from Prescribing Analysis and CosT (PACT) data

• Multiple regression analysis

Walters P et al: Br J Psychiatry (2008)

ANTIDEPRESSANT PRESCRIBING – UNIVARIATE ASSOCIATIONSVARIABLE VARIANCE

EXPLAINEDUNADJUSTED

BETA

Chronic respiratory disease 25% 574

Coronary heart disease 22% 329% Black ethnic patients 12% -52% Chinese ethnic patients 9% -179% S Asian ethic patients 7% -19% White ethnic patients 15% 20Index of multiple deprivation 4% 12

Group practice 4% 465List size 3% -0.2

EPIDEMIOLOGY OF MENTAL DISORDERS (Health of the Nation)

DisorderPoint

Prevalence

Lifetime Risk

Schizophrenia 0.2-0.5% 0.7-0.9%

Bipolar affective disorder 0.1-0.5% 1%

Depressive disorder 3-6% 20%

Dementia at age >65 years 5%

Dementia at age >80 years 20%

Jenkins R et al: Br J Psychiatry (1998)

PANIC DISORDER: REDUCTION IN GABA RECEPTOR BINDING

GABAA receptor binding measured by positron emission tomography (PET) imaging with 11C-flumazenil (benzodiazepine antagonist)

Malizia AL et al: Arch Gen Psychiatry (1998)

Marked reduction noted in GABAA receptor binding throughout the brain, with greatest decrease in orbitofrontal and temporal cortex (?involved in the experience of anxiety)

THE BURDEN OF DEPRESSION

• Depression is the third most common presentation among GP referrals

• 20% of those with depression will not recover fully from the index episode

• 70-80% of those achieving remission will have at least 1 recurrence

• 15% will eventually commit suicide Scott J: Br Med J (2006)

WORLDWIDE DISABILITY BY DISEASE

Source: WHO Collaborative Project on Psychological Problems in General Health Care

DEPRESSION : AETIOLOGY

GENETIC Family history

Emotional deprivation Early maternal separation Parental discord

EARLY DEVELOPMENT

Childhood abuse

PERSONALITY Neuroticism

Loss events Chronic difficulties

SITUATIONAL FACTORS

Lack of social supports

DEPRESSION AND THE RESPONSE OF OTHERS

• Female undergraduates (N=45) randomised to 3 groups to have phone conversations with:• Depressed people (N=15)• People with a history of

depression (N=15)• Controls with no history of

depression (N=15)

Coyne JC: J Abnormal Psychology (1976)

DEPRESSION AND THE RESPONSE OF OTHERS

• Those subjects talking to depressed patients reported:• more depression, anxiety and hostility• increased reluctance to re-engage

• The speech of the depressed patients contained more self-references, particularly of negative personal and private events

Coyne JC: J Abnormal Psychology (1976)

Depression is not a social skills deficit but depressed patients tend to alienate others, leading to less positive reinforcement