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Suicide: The Place of Mental Disorders in its Etiology and Prevention

Suicide: The Place of Mental Disorders in its Etiology and Prevention. Alain Lesage md, MPhilCentre de recherche Fernand-SeguinH

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Suicide: The Place of Mental Disorders in its Etiology and Prevention

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    1. « Ne me parlez pas de la mort, cela me fait mourir » Sacha Guitry (please, don’t talk to me about death, it kills me)

    2. Suicide: The Place of Mental Disorders in its Etiology and Prevention Alain Lesage md, MPhil Centre de recherche Fernand-Seguin Hôpital L-H Lafontaine affiliated to University of Montreal Montréal, Qc, Canada alesage@ssss.gouv.qc.ca

    3. 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

    4. 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

    5. 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

    6. First pieces of evidence

    7. DDD Defined Daily Doses One DDD may be sufficient for one person-day of adequate treatment, and 10 DDDs per 1000 inhabitants per day is therefore considered to represent approximately 1 % point prevalence of treatment. Since antidepressants are also prescribed on other indications than depression, and taking into consideration non-compliance and the frequent use of dosages higher than the DDD, the true treatment prevalence may be considerably lower. The annual differences in suicide rate and in use of antidepressants did not correlate with each other, but the differences between the consecutive 3-year periods did (rho=-0.90, P<0.05, one-tailed) (1979-81, 1982-84, 1985-87, 1988-90, 1991-93, 1994-96). There were in Sweden, during 1990-96, no demographic groups with regard to age, gender or county in which the suicide rate decreased in the absence of an increased use of antidepressants. In women under 30 and over 75 years of age, however, and in four of the 23 Swedish counties suicide rates remained unchanged despite an increased use of antidepressants. Female suicides in these age groups, and suicides in these four counties, constituted 8 % and 14 % of all suicides during the period (data not shown in fig. 1). Data from other Nordic countries similarly show an association between the increase utilisation of antidepressants and a decrease in suicide rates. In Denmark, Norway and Finland the correlation were respectively -0.94, -0.87 and -1.00 during 1990 and 1996, all statistically significant. The annual differences in suicide rate and in use of antidepressants did not correlate with each other, but the differences between the consecutive 3-year periods did (rho=-0.90, P<0.05, one-tailed) (1979-81, 1982-84, 1985-87, 1988-90, 1991-93, 1994-96). There were in Sweden, during 1990-96, no demographic groups with regard to age, gender or county in which the suicide rate decreased in the absence of an increased use of antidepressants. In women under 30 and over 75 years of age, however, and in four of the 23 Swedish counties suicide rates remained unchanged despite an increased use of antidepressants. Female suicides in these age groups, and suicides in these four counties, constituted 8 % and 14 % of all suicides during the period (data not shown in fig. 1). Data from other Nordic countries similarly show an association between the increase utilisation of antidepressants and a decrease in suicide rates. In Denmark, Norway and Finland the correlation were respectively -0.94, -0.87 and -1.00 during 1990 and 1996, all statistically significant. DDD Defined Daily Doses One DDD may be sufficient for one person-day of adequate treatment, and 10 DDDs per 1000 inhabitants per day is therefore considered to represent approximately 1 % point prevalence of treatment. Since antidepressants are also prescribed on other indications than depression, and taking into consideration non-compliance and the frequent use of dosages higher than the DDD, the true treatment prevalence may be considerably lower. The annual differences in suicide rate and in use of antidepressants did not correlate with each other, but the differences between the consecutive 3-year periods did (rho=-0.90, P<0.05, one-tailed) (1979-81, 1982-84, 1985-87, 1988-90, 1991-93, 1994-96). There were in Sweden, during 1990-96, no demographic groups with regard to age, gender or county in which the suicide rate decreased in the absence of an increased use of antidepressants. In women under 30 and over 75 years of age, however, and in four of the 23 Swedish counties suicide rates remained unchanged despite an increased use of antidepressants. Female suicides in these age groups, and suicides in these four counties, constituted 8 % and 14 % of all suicides during the period (data not shown in fig. 1). Data from other Nordic countries similarly show an association between the increase utilisation of antidepressants and a decrease in suicide rates. In Denmark, Norway and Finland the correlation were respectively -0.94, -0.87 and -1.00 during 1990 and 1996, all statistically significant. The annual differences in suicide rate and in use of antidepressants did not correlate with each other, but the differences between the consecutive 3-year periods did (rho=-0.90, P<0.05, one-tailed) (1979-81, 1982-84, 1985-87, 1988-90, 1991-93, 1994-96). There were in Sweden, during 1990-96, no demographic groups with regard to age, gender or county in which the suicide rate decreased in the absence of an increased use of antidepressants. In women under 30 and over 75 years of age, however, and in four of the 23 Swedish counties suicide rates remained unchanged despite an increased use of antidepressants. Female suicides in these age groups, and suicides in these four counties, constituted 8 % and 14 % of all suicides during the period (data not shown in fig. 1). Data from other Nordic countries similarly show an association between the increase utilisation of antidepressants and a decrease in suicide rates. In Denmark, Norway and Finland the correlation were respectively -0.94, -0.87 and -1.00 during 1990 and 1996, all statistically significant.

    8. 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.

    9. 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.

    10. 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).

    11. 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.

    12. Effects of and exposure to possible suicide prevention strategies (Gunnell et Frankel, 1994, BMJ, 308: 1227-1233) 1 of 3

    13. 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) A number of different approaches to the analysis of time-series data examining associations between suicide and economic indicators have been used in the literature. One of the main statistical issues raised by such analyses is the autocorrelation of effors, which arises because of the natural tendency of suicide rates in one year to be similar to those in the following year. The preferred method for such analyses is Cochrane-Orcutt regression...the most appropriate models were those based on log-transformed rates and unemployment data. A number of different approaches to the analysis of time-series data examining associations between suicide and economic indicators have been used in the literature. One of the main statistical issues raised by such analyses is the autocorrelation of effors, which arises because of the natural tendency of suicide rates in one year to be similar to those in the following year. The preferred method for such analyses is Cochrane-Orcutt regression...the most appropriate models were those based on log-transformed rates and unemployment data.

    14. Effects of and exposure to possible suicide prevention strategies (Gunnell et Frankel, 1994, BMJ, 308: 1227-1233) 2 of 3

    15. 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.

    16. Effects of and exposure to possible suicide prevention strategies (Gunnell et Frankel, 1994, BMJ, 308: 1227-1233) 3 of 3

    17. 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

    18. 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

    19. 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

    20. 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

    21. Estimated sample sizes required for the evaluation of interventions targeted at particular population groups (Gunnell et Frankel, 1994, BMJ, 308: 1227-1233) 80% power, 2 sided 5% significance level studies are unmatched, with equal numbers in intervention and control groups (EPISTAT package used)80% power, 2 sided 5% significance level studies are unmatched, with equal numbers in intervention and control groups (EPISTAT package used)

    22. Demonstrating the potential effect of a suicide prevention strategy based on the treatment of depression in the population:  6 necessary steps (1 of 2)

    23. Demonstrating the potential effect of a suicide prevention strategy based on the treatment of depression in the population:  6 necessary steps (2 of 2)

    24. Demonstrating the potential effect of a suicide prevention strategy based on the treatment of depression in the population:  6 necessary steps (1 of 2)

    26. 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. The Population Attributable Risk (PAR) represents the proportion of the deaths (in a specified time) in the whole population that may be preventable if a cause of mortality were totally eliminated. You need to calculate a risk estimate for some population, preferably a large population or, better yet, all 250 million Americans. If you can figure the number of cancer cases or premature deaths associated with your risk, you're sure to get instant national attention. But how do you do this? Simple. Tell your statisticians you want to calculate an attributable risk. They know how. Attributable risk is intended to indicate what percentage of deaths in a population are caused by a risk. For example, saying that "16 percent of all deaths are due to being overweight" is an attributable risk. You've attributed 16 percent of all deaths to obesity. All you need to do then is figure out how many deaths there are annually (about 2.2 million in the U.S., according to 1991 statistics), then multiply the number of annual deaths by the attributable risk (16 percent). Voila! A public health crisis is born! The Population Attributable Risk (PAR) represents the proportion of the deaths (in a specified time) in the whole population that may be preventable if a cause of mortality were totally eliminated. You need to calculate a risk estimate for some population, preferably a large population or, better yet, all 250 million Americans. If you can figure the number of cancer cases or premature deaths associated with your risk, you're sure to get instant national attention. But how do you do this? Simple. Tell your statisticians you want to calculate an attributable risk. They know how. Attributable risk is intended to indicate what percentage of deaths in a population are caused by a risk. For example, saying that "16 percent of all deaths are due to being overweight" is an attributable risk. You've attributed 16 percent of all deaths to obesity. All you need to do then is figure out how many deaths there are annually (about 2.2 million in the U.S., according to 1991 statistics), then multiply the number of annual deaths by the attributable risk (16 percent). Voila! A public health crisis is born!

    27. Demonstrating the potential effect of a suicide prevention strategy based on the treatment of depression in the population:  6 necessary steps (1 of 2)

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

    29. 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

    30. Demonstrating the potential effect of a suicide prevention strategy based on the treatment of depression in the population:  6 necessary steps (1 of 2)

    31. 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

    32. 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

    33. 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.

    34. Demonstrating the potential effect of a suicide prevention strategy based on the treatment of depression in the population:  6 necessary steps (2 of 2) In the years before 1995, it was possible to show that only ten to twelve percent of suicides were prescribed antidepressants during the last three months before suicide. Thirdly, this was confirmed by forensic evidence from the Coroners' Office since in Sweden, 90 to 95 percent of all suicide are investigated by forensic toxicology in a single national laboratory. It demonstrated that in 1990 and 1991, based on 3400 cases of suicide, only 16 percent of suicides were having at least traces of antidepressants at the time of death. Similar results were reported to U.S. studies in 1991, 1992 and 1995 in selected sample of suicides. In the years before 1995, it was possible to show that only ten to twelve percent of suicides were prescribed antidepressants during the last three months before suicide. Thirdly, this was confirmed by forensic evidence from the Coroners' Office since in Sweden, 90 to 95 percent of all suicide are investigated by forensic toxicology in a single national laboratory. It demonstrated that in 1990 and 1991, based on 3400 cases of suicide, only 16 percent of suicides were having at least traces of antidepressants at the time of death. Similar results were reported to U.S. studies in 1991, 1992 and 1995 in selected sample of suicides.

    35. Treatment received by individuals with major depression in the last year in early ‘90s Ontario (n=333/8116, 4.1%)

    36. 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.

    37. Demonstrating the potential effect of a suicide prevention strategy based on the treatment of depression in the population:  6 necessary steps (2 of 2)

    38. 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.

    39. 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

    40. 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.

    41. Reasoning about suicide prevention

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

    45. Four strategies to improve the health of populations (UK, Donaldson) change health determinants (‘ causes of causes ’) prevention protection improve quality of services

    46. 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.

    47. 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.

    48. 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.

    49. 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

    50. 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

    51. 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.

    52. 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

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