« Ne me parlez pas de la mort, cela me fait mourir » S acha Guitry (please, don’t talk to me...

« Ne me parlez pas de la mort, cela me fait mourir »

Sacha Guitry

(please, don’t talk to me about death, it kills me)

Suicide: The Place of Mental Disorders in its Etiology and

PreventionAlain Lesage md, MPhilCentre de recherche Fernand-SeguinHôpital L-H Lafontaineaffiliated to University of MontrealMontréal, Qc, [email protected]

•Harvard Injury Control Research Center, Seminar Series, 12 February 2004

Introduction

• Recent controversy over the interpretation of evidence from Scandinavian and other countries of a significant decrease in suicide rates associated with an increase in prescription of antidepressants

• raising the issue of whether treatment of depression would be a key suicide prevention strategy

Introduction

• little evidence, so far, that any suicide prevention strategy available can have a large effect on its own

• many countries adopting a multi-strategies public health suicide prevention approach

Aims

• through a public health demonstration in 6 steps, that the treatment of depression would be a potentially effective suicide prevention strategy, – to discuss the role of mental disorders in the

etiology and prevention of suicide

First pieces of evidence

Suicide and Sales of Antidepressants

2.3 2.1 2 2.53.2 3.5 3.1 2.8 2.5 2.1 1.7 1.5 1.6

3

5.2

8.2 8 7.7 8.17.01 7.10 6.72 6.30 6.45 6.12 6.01 6.07 6.34 6.21 6.40 6.54 6.41 6.28 6.33 6.22 6.31 6.20 6.00

0

5

10

15

20

25

30

35

40

1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996

Year

Su

icid

es

/ 10

0 00

0 In

ha

b.

& D

DD

s /

1000

In

ha

b.

/ D

ay

Suicide , Sweden

Suicide , Finland

Suicide , Denmark

Suicide , NorwayAntidepressants , Sweden

Antidepressants , Norway

Antidepressants , Denmark

Antidepressants , Finland

Alcohol, Sweden (Litres / Person / Year)

Unemployement, Sweden, (percent)

Isaacson, G., 2000, Suicide prevention- a medical breakthrough? Acta Psychiatrica Scandinavica, 102, 113-117.

Iceland’s report on antidepressants and depression– Sales of antidepressants increased from 8.4 daily defined doses per

1000 inhabitants per day in 1975 to 72.7 in 2000, which is a user prevalence of 8.7% for the adult population.

– Suicide rates fluctuated during 1950-2000 but did not show any definite trend. Rates for out-patient visits increased slightly over the period 1989-2000 and admission rates increased even more.

– Helgason T, Tomasson H, Zoega T. Antidepressants and public health in Iceland:

Time series analysis of national data. Br J Psychiatry. 2004 Feb;184:157-62.

Association between antidepressant prescribing and suicide in Australia, 1991-2000: trend analysis (Hall

et al., BMJ 2003; 326: 1008

• overall national rates of suicide did not fall significantly, incidence decreased in older men and women and increased in younger adults.

• In both men (rs=−0.91; P<0.01) and women (rs=−0.76; P<0.05) the higher the exposure to antidepressants the larger the decline in rate of suicide.

Relationship between antidepressant medication treatment and suicide in adolescents. (Olfson et

al., Arch Gen Psychiatry. 2003 Oct;60(10):978-82.)

• MAIN OUTCOME MEASURES: The relationship between regional change in antidepressant medication treatment and suicide rate stratified by sex, age group, regional median income, and regional racial composition.

• RESULTS: There was a significant adjusted negative relationship between regional change in antidepressant medication treatment and suicide during the study period. – A 1% increase in adolescent use of antidepressants was associated

with a decrease of 0.23 suicide per 100 000 adolescents per year (beta = -.023, t = -5.14, P<.001).

Evidence of the effectiveness of suicide prevention strategies

• Gunnel, D., Frankel, S., 1994, Prevention of suicide : aspirations and evidence, British Medical Journal, 308, 1227-1233.

Effects of and exposure to possible suicide prevention strategies (Gunnell et Frankel, 1994, BMJ, 308: 1227-1233)

1 of 3

Setting and intervention Exposureto intervention

EstimatedReduction in totalsuicides

Qualityof evidence

Screening questionnaires Whole population 0 IIHealth promotion (exercice; sensibledrinking; stress management)

Whole population Uncertain III

Reducing unemployment In UK, 1991,unemployment rate6%

1-2% III

* I. At least one RCT; II. Case-control or cohort studies; III. Opinions of respected authorities,descriptive studies; IV. Evidence inadequate owing to methodological problems

Secular trends in unemployment and suicide rates (all methods) 15-44 years old male; England & Wales; Gunnell et

al., 1999; Br J Psychiatry 175:263-270)


2 of 3



Qualityof evidence

Suicide hotspots safety measures 5% suicide byjumping

1-2% III

Safety measures for underground Only in cities Less than 1% IIIMedia_reinforcing reporting guidelines Whole population 1% IIICounselling and Support (Samaritans,prisons support)

High risk, activelysuicidal groups

1% IV

Increased outreach to high risk callers High risk callers toSamaritans

0 III/IV

Improved access (contact phone numbers;regular review)

Suicidal ideation 1-3%

Uncertain III


Cochrane reviews evidence:psychosocial and pharmacological treatments of self-harm

– Reviewers' conclusions: There still remains considerable uncertainty about which forms of psychosocial and physical treatments of self-harm patients are most effective, inclusion of insufficient numbers of patients in trials being the main limiting factor. There is a need for larger trials of treatments associated with trends towards reduced rates of repetition of deliberate self-harm. The results of small single trials which have been associated with statistically significant reductions in repetition must be interpreted with caution and it is desirable that such trials are also replicated.

• Citation: Hawton K, Townsend E, Arensman E, Gunnell D, Hazell P, House A, van Heeringen K.. Psychosocial and pharmacological

treatments for deliberate self harm (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.


3 of 3



Qualityof evidence

Increased care around discharge 10-15% of suicides 2-3% III

GP education and guidelines on thetreatment of depression

25% all suicidesconsult week before;

Uncertain II/III


Contact with services and suicide

• In the UK, 80% of the population saw their GP in the past year

• In a Montreal ’s psychological autopsy study of young male adults aged 18-35– 50% saw their GP in the past year– 25% saw a psychiatrist

Contact with services and suicidal behaviours (Bancroft et al., 1977 reported by Gunnel & Frankel, 1994)

• among self-harmed seen by services– 75% had heard of Samaritans

• 4% contacted Samaritans

– 10% contacted social worker– 13% contacted clergy

Contact with services and suicide (Gunnel & Frankel, 1994)

• average GP will– experience the suicide of a patient every 4-5

years– meet such patient shortly before suicide every

8-10 years

Perspective on suicide behaviours: 1-yr prevalence of suicide, suicide attempts and suicide ideation

(based on Quebec’s vital statistics and population

surveys in the ‘ 90s)

• Suicide: 20 per 100 000 inhabitants

• Attempts : 600 per 100 000 inhabitants

• Ideation: 4000 per 100 000 inhabitants

Estimated sample sizes required for the evaluation of interventions targeted at particular population groups

(Gunnell et Frankel, 1994, BMJ, 308: 1227-1233)

Populationstudied

Proportioncommittingsuicide

% reduction in suicide Total sample size required

Generalpopulation

0.01% peryear

15 12 909 670

Patients afterparasuicide

2.8% insubsequent 8yrs

15 44 914

15 142 258Patients afterdischargefrompsychiatrichospital

0.9% insubsequentyear

50 10 396

Demonstrating the potential effect of a suicide prevention strategy based on the treatment of

depression in the population: 6 necessary steps (1 of 2)

Steps Evidence Quality ofevidence*

Step 1Cases of suicide are associatedwith depression

About 35 % of completed suicide are associatedwith major depression

II

Step 2Cases of depression areassociated with increased risk ofsuicide (suicide as a possible'complication' of the disorder)

About 4 % life time risk of suicide among peoplesuffering from depression in the general population;up to 15% among people treated in specialized care.

II

Step 3There are effective treatment ofdepression

Efficacy has been shown for antidepressantmedication and for specific forms of psychotherapy(for example, cognitive behavioural therapy; interpersonal therapy).

I

•* I. At least one RCT; II. Case-control or cohort studies; III. Opinions of respected authorities, descriptive studies; IV. Evidence inadequate owing to methodological problems






II



II



I


•Partly reported in Lesage AD, et al. Suicide and Mental Disorders: A Case-Control Study of Young Adult Males. The American Journal of Psychiatry, 151(7), 1063-1068, 1994.

Psychological autopsies- systematic review

• 154 reports identified; 76 met the criteria for inclusion; 54 case series and 22 case-control studies.

• median proportion of cases with mental disorder was 91% (95 % CI 81-98%) in the case series. – In the case-control studies 90% (88-95%) in the cases and 27% (14-48%) in the

controls.

• Co-morbid mental disorder and substance abuse in more suicide cases (38%, 19-57%) than controls (6%, 0-13%).

• The population attributable fraction for mental disorder ranged from

47-74% (7 studies) Cavanagh JT, Carson AJ, Sharpe M, Lawrie SM. Psychological autopsy studies of suicide: a systematic review.Psychol Med. 2003 Apr;33(3):395-405.






II



II



I


Suicide as an outcome for mental disorders (Clare & Barraclough, Br J Psychiatry, 1997, 170, 205-228)

SMR 95%CI

Schizophrenia 845 798-895

Majordepression

2035 1827-2259

Bipolardisorders

1535 1235-1844

Dysthymia 1212 1150-1277

Risk of suicide is lower in depression (Blair-West et al., 1997, 1999)

• previously accepted risk of 10-15% lifetime

• based on hospitalised or outpatient cohorts– the majority of people with depression are not

treated

• revised conservative lifetime risk of 3.4%– estimated 7% for males; 1% for females

•Blair-West GW, et al. Down-rating lifetime suicide risk in major depression. Acta Psychiatr Scand. 1997 Mar;95(3):259-63.






II



II



I


RCT antidepressants and cognitive-behavioural psychotherapy in chronic depression

• randomly assigned 681 adults

• 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both.

• all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression

• Remission was defined as a score of 8 or less at weeks 10 and 12.

• a satisfactory response was defined as a reduction in the score by at least 50 percent from base line

• blind assessments

01020304050607080

%

Overall rate of response (both remission and satisfactory response)

nefazodone

CBT

both

•A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. Keller MB et al., N Engl J Med. 2000 May 18;342(20):1462-70.

Cochrane reviews evidence: antidepressants and chronic depression

• Reviewers' conclusions: Drugs are effective in the treatment of dysthymia with no differences between and within class of drugs. Tricyclic antidepressants are more likely to cause adverse events and dropouts. As dysthymia is a chronic condition, there remains little information on quality of life and medium or long-term outcome.

•Citation: Lima MS, Moncrieff J. Drugs versus placebo for dysthymia (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd

Cochrane reviews evidence:active placebos and antidepressants

• Main results: Nine studies involving 751 participants were included. Combining all studies produced a pooled estimate of effect of 0.39 standard deviations (confidence interval, 0.24 to 0.54) in favour of the antidepressant measured by improvement in mood. There was high heterogeneity due to one strongly positive trial. Sensitivity analysis omitting this trial

reduced the pooled effect to 0.17 (0.00 to 0.34).

– Citation: Moncrieff J, Wessely S, Hardy R. Active placebos versus antidepressants for depression (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.

Treatment received by individuals with major depression in the last year in early

‘90s Ontario (n=333/8116, 4.1%)

51

18

9

22

0

10

20

30

40

50

60

no treatment antidepressants otherpsychotropic

other

•Depression in Ontario: undertreatment and factors related to antidepressants use (Parikh, Lesage, Kennedy, Goering, 1999, J Aff Dis, 52, 67-76)

Undertreatment of major depression

• The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). (Kessler et al., JAMA, 2003; 289; 3095-3105)

• 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults).

• 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, – treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of

these cases, resulting

– in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated.

Lower suicide risk with long-term lithium treatment

• Among 5647 patients (33 473 patient-years of risk) in 22 studies,

• suicide was 82% less frequent during lithium-treatment (0.159 vs. 0.875 deaths/100 patient-years).

• the computed risk-ratio in studies with rates on/off lithium was 8.85 (95% CI, 4.12-19.1; P<0.0001).

• Tondo L, Hennen J, Baldessarini RJ Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand. 2001 Sep;104(3):163-72.

Suicide Rates in Clinical Trials of SSRIs, other Antidepressants and Placebo: Analysis of FDA Reports

(Khan et al., Am J Psychiatry 2003; 160: 790-792)

• Suicide rates did not differ among the 3 groups

suicide rates with 95%CI

0,59

0,76

0,450,31

0 0,01

0,871,03

0,89

0

0,2

0,4

0,6

0,8

1

1,2

SSRI (n=26109) other antidepressants(n=17273)

placebos (n=4895)

%

Suicide risk in placebo-controlled studies

of major depression (Storosum JG et al., Am J Psychiatry. 2001;158(8):1271-5)

• In 77 short-term studies with 12,246 patients in dossiers from the Medicines Evaluation Board, the incidence of suicide was 0.1% in both placebo groups and active compound groups.

• In eight long-term studies with 1,949 patients, the incidence of suicide in the placebo groups was 0.0% and 0.2% in the active compound groups.

Reasoning about suicide prevention

Suicide rates in Canada 1950-1998/9, per 100 000 inhabitants

0

5

10

15

20

25

QuébecOntarioCanada

Suicide rates by sex, Québec, 1976-1978 to 1997-1999

21,824,1

26,8 27,125,1

28,0

31,0 31,5

8,0 8,0 8,7 7,86,4 7,0

8,2 8,4

14,715,8

17,5 17,115,5

17,319,4 19,8

0

5

10

15

20

25

30

35

76-78 79-81 82-84 85-87 88-90 91-93 94-96 97-99

Ag

e a

dju

ste

d r

ate

s p

er

10

0 0

00

males

females

total

Adjusted life years lost for various causes of death, Men, Québec, 1976-1978 to 1997-1999

0

5

10

15

20

25

30

35

76-78 79-81 82-84 85-87 88-90 91-93 94-96 97-99

Ra

tes

pe

r 1

00

00

0

suicide

road accidents

lung cancer

heart attack

vascular diseases

Four strategies to improve the health of populations (UK, Donaldson)

• change health determinants (‘ causes of causes ’)

• prevention

• protection

• improve quality of services

UK National policy of reducing depression and suicide

• The Government set targets for reducing psychiatric morbidity and suicide.

• A public information strategy was launched to increase understanding and reduce stigma, including a five year 'Defeat Depression' Campaign.

• updating General Practitioners in the recognition, detection and management of depression.

• Government departments worked with employers and trade union organisations to attempt to reduce work-induced stress.

Paton J, Jenkins R, Scott J. Collective approaches for the control of depression

in England Soc Psychiatry Psychiatr Epidemiol. 2001 Sep;36(9):423-8.

UK National policy of reducing depression and suicide (continued)

• Universal and selective prevention measures aimed to reduce factors associated with depression, such as unemployment.

• Measures to reduce suicide include education of health and social care professionals, supporting high-risk groups and restricting access to means of suicide.

• The overall suicide rate fell by 11.7% in five years.

Paton J, Jenkins R, Scott J. Collective approaches for the control of depression

in England Soc Psychiatry Psychiatr Epidemiol. 2001 Sep;36(9):423-8.

Interpretation of association of increased antidepressants utilisation and decreasing

suicide rates (Hall et al., 2003)• We think that antidepressant prescribing is a proxy

measure for exposure to psychosocial and pharmacological interventions delivered by a general practitioner for depression, anxiety, and other comorbid psychological disorders.

• Data from Australian general practice surveys indicate that general practitioners identify a wide range of psychological disorders, provide more non-pharmacological than pharmacological interventions, and, when they use pharmacological treatments, rarely provide them without psychosocial assessment and support.

Interpretation of association of increased antidepressants utilisation and decreasing

suicide rates (Hall et al., 2003) (continued)• Recognition of psychological disorders in general practice and

general practitioners' use of psychosocial and pharmacological treatments for depression may have improved.

• Given these trends in general practice, the association we observed between antidepressant prescribing and suicide may reflect increased recognition, diagnosis, and treatment of depression by general practitioners as much as any pharmacological effects of antidepressant medication.

• If this proves to be the most plausible explanation of our data, it supports the public policy of encouraging general practitioners to improve community mental health

Your opinion counts !

• Strength of the evidence that treatment of depression is an effective suicide prevention strategy?– Missing links (step VI)– Secular trends (step V)– confounders (treatment of depression)

• Risks with a total population approach– G Rose ’s prevention paradox

Rose’s prevention paradox

• arises because many interventions that aim to improve health have relatively

small influences on the health of most people. – Thus, for one person to benefit, many

people will have to change their behaviour and receive no benefit from these changes.

Argument to Rose’s prevention paradox for treatment of depression

• Burden of diseases’ studies showed that depression is the 2nd and will become first cause of incapacity in industrialised countries

• depression is largely undertreated and if treated, often not adequately

• increasing treatment of depression may yield important population health gains by reduction of incapacity

« Ne me parlez pas de la mort, cela me fait mourir » S acha Guitry (please, don’t talk to me...

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