Factors explaining suicidal behaviour and mortality in ...

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Factors explaining suicidal behaviour and mortality in alcohol dependence

Philip GORWOOD

ECNP 18 OCT 2014

Joint symposium EPA / ECNP

Disclosures

• Philip Gorwood received during the last 5 years:

– Research grants from

• Eli Lilly and Servier

– Fees for presentations at congresses or participation in scientific boards from

• AstraZeneca, Bristol-Myers-Squibb, Janssen, Lilly, Lundbeck, Naurex, Otsuka, Roche, Sanofi Pasteur MSD, Servier.

Question 1: Frequency

• According to the US Centers for Disease Control and Prevention (CDC), on average, how many suicides were attributable to alcohol annually in 2001-2005

1. 0.023%

2. 0.230%

3. 2.300%

4. 23.00%

Response 1: Frequency

• According to the US Centers for Disease Control and Prevention (CDC), on average, how many suicides were attributable to alcohol annually in 2001-2005

1. 0.023%

2. 0.230%

3. 2.300%

4. 23.00%

http://apps.nccd.cdc.gov/DACH_ARDI/default/default.aspx

Alcohol is largely involved in suicidal risks

• The lifetime prevalence of suicide in individuals with alcohol dependence ranges from 7% to 15% (1)

• Postmortem psychological autopsy studies demonstrated alcohol use disorders in 25% to 35% of suicide victims (2).

• Alcohol was detected in the blood of 20% to 48% suicide completers in different American and European samples (3).

1 Inskip et al.. 1998; 2 Cheng. 1995; Pirkola et al.. 2000; 3 Garlow. 2002; Pirkola et al.. 2003; Varnik et al.. 2007

Psychiatric diagnoses for hospitalized SA in France (2004-2011)

Psychiatric diagnoses Total Males Females

Present 450.726 170.071 280.655

Major depressive disorder 59.8% 51.9% 64.6%

Alcohol use disorder 36.0% 48.8% 28.3%

Anxious disorder 15.1% 12.6% 16.6%

Bipolar disorder 2.5% 2.0% 2.9%

Schizophrenia 1.6% 2.7% 0.9%

Chan Chee & Jezewski-Serra. Hospitalisations et recours aux urgences pour tentative de suicide en France métropolitaine à partir du PMSI-MCO 2004-2011 et d’Oscour® 2007-2011. Saint-Maurice : Institut de veille sanitaire ; 2014. 51 p.

Risk factors for SA in alcohol dependent patients in the literature

• Associated – Depressive disorder (substance induced or not) – Drug use disorder and other addictions

• Family history of suicidal acts • AUD severity • Low social support • Aggression, • Interpersonal stressful life events • Medical illness or complaints • Unemployment or other economic adversity

Am J Prev Med 2014;47(3S2):S204–S208

MDD and alcohol dependence are comparable and (also) independent risk

factors (NCS-R)

Nock et al. Mol Psychiatry. 2010 August ; 15(8): 868–876

MDD, Alcohol Dependence & suicidal risk

• A community-based sample of 1.237 adult Israeli lifetime drinkers assessed for MDD and Suicide-related ideation and behaviors (SRIB)

Shoval et al. Alcohol Clin Exp Res. Vol 38. No 3. 2014: pp 820–825

Facilitating ideas or impulsive acts?

Effect size

Antidepressants, alcohol and suicide

• A nationally representative sample of 950.158 Finnish adults in 1995–2007 for alcohol-related (N=2.859) and non-alcohol-related (N=8.632) suicides.

Moustgaard et al.2014 PLoS ONE 9(6): e98405.

Use or misuse of alcohol before suicide

• 1.83-fold [95%CI: 1.73-1.93] and 2.40-fold [95% CI: 2.24-2.57] increased risk of alcohol ingestion before their death after age, race/ethnicity, and chronic alcohol problems were controlled for.

• Furthermore male and female decedents exhibited a 6-fold (95% CI. 5.57-6.86) and a 10-fold (95% CI. 8.67e11.64) increased risk of being intoxicated before their death after confounders were considered.

Intoxication is more associated with suicide than simple consumption

Male Female

Consomption (BAC>0.00 g/dL)* 1.83 [1.73-1.93] 2.40 [2.24- 2.57]

Intoxication (BAC>0.08 g/dL)* 6.18 [5.57-6.86] 10.04 [8.67-11.64]

*Age. race/ethnicity. and chronic alcohol problems were controlled for. BAC: blood alcohol content From Pooled 2003-2011 National Violent Death Reporting System data

Kaplan et al. Annals of Epidemiology 24 (2014) 588e592

Question 2: Risk factors (SA)

• What are the 5 main risk factors that distinguish patients with alcohol dependence with (vs w/o) suicidal attempt 1. Males

2. Early onset of alcohol dependence

3. Tobacco dependence

4. Severity of alcohol dependence

5. Associated mood disorder

6. Childhood trauma

7. Family history of suicidal behavior

Answer 2: Risk factors (SA)

• What are the 5 main risk factors that distinguish patients with alcohol dependence with (vs w/o) suicidal attempt 1. Males

2. Early onset of alcohol dependence

3. Tobacco dependence

4. Severity of alcohol dependence

5. Associated mood disorder

6. Childhood trauma

7. Family history of suicidal behavior

Roy A et al. Arch Suicide Res. 2007;11(2):211-7. Deisenhammer et al. ACER. 2006;30(3):460-5.

Question 3: Psychological mechanisms

• How could alcohol facilitate suicidal behaviours? 1. Increasing impulsivity (facilitating aggressive and

immediate responses)

2. Lowering mood

3. Increasing suicidal ideation

4. Generating stressful life events

5. Being deleterious on social suports

6. Decreasing the quality of cognitive/coping strategies

7. Modifying the accurate assessment of harm and pain

Answer 3: Psychological mechanisms

• How could alcohol facilitate suicidal behaviours?

1. Increasing impulsivity (facilitating aggressive and immediate responses)

2. Lowering mood

3. Increasing suicidal ideation

4. Generating stressful life events

5. Being deleterious on social suports

6. Decreasing the quality of cognitive/coping strategies

7. Altering the accurate assessment of harm and pain

Question 4: Biological markers

• Which biological markers are associated with a higher risk of SB in alcohol-dependence? 1. High cytokine(s) (S-IL-2R)

2. Low plasma cholesterol

3. Low cortisol level

4. Low monoamine oxydase B (MOA-B)

5. Low 5-hydroxyindoleacetic acid (5HIAA)

6. Increased tryptophan pyrrolase enzyme

7. Carrying the short allele of the 5HTT gene

Answer 4: Biological markers

• Which biological markers are associated with a higher risk of SB in alcohol-dependence? 1. High cytokine(s) (S-IL-2R)

2. Low plasma cholesterol

3. Low cortisol level

4. Low monoamine oxydase B (MOA-B)

5. Low 5-hydroxyindoleacetic acid (5HIAA)

6. Increased tryptophan pyrrolase enzyme

7. Carrying the short allele of the 5HTT gene

Lindqvist et al. Acta Psychiatr Scand. 2011 Jul;124(1):52-61.

Question 5: Treatment

• What are the most validated technics to reduce suicidal risks in patients with alcohol dependence

1. Risk assessment

2. Increasing interventions (crisis-line calls)

3. Antidepressants

4. Brief intervention (motivational interview)

5. Benzodiazepine

6. Treating the abuse of alcohol

7. Antipsychotics

Answer 5: Treatment

• What are the most validated technics to reduce suicidal risks in patients with alcohol dependence

1. Risk assessment

2. Increasing interventions (crisis-line calls)

3. Antidepressants

4. Brief intervention (motivational interview)

5. Benzodiazepine

6. Treat the abuse of alcohol

7. Antipsychotics

Preliminary results of the SABAD study: Suicide And suicidal Behavior in Alcohol-Dependence

• 758 patients with alcohol dependence. recruited and assessed after (>Day8) detoxication as inpatients in five psychiatric departements in Paris area.

• Clinical, biological, genetic and neuro-psychological analyses.

• Two-years follow-up (cumulative incentives, and at least 3 other contactsto decrease attrition rate).

The recruited sample

• 67.26% males, average age: 45 years old (+/-9.43), 1.34 children in average

• Maximum educational training stopped at 18 on average

• First problem with alcohol 26 years (+/-14.08) • CAGE 3.4 (1.64) • Comorbide cannabis (N=186), Opiates (N=75), Cocaïne

(N=71), Sedatives (N=59), Stimulants (N=39), Pathological gambling (N=40).

• 218 adult ADHD, with 186 during childhhod, 34 ASPD. • 509 lifetime MDE, 30 BPD, 64 agoraphobia, 33 social

phobia, 14 OCD. • 314 already made a Suicidal Attempt

Outcome at 24-month

• 42 suicidal attempts (5.54%, 2.8% per year)

• Including 12 suicides (1.58%, 0.8% per year)

• And 30 deaths (3.96%, 2.0% per year) altogether

Clinical specificities of patients with future suicidal attempt

With SA (N=42) Witout SA (N=714)

Gender (males) 78.6% 64.5%

Age 45.2 +/- 9.0 45.3 +/- 8.8

Age at onset of alcohol dependence

35.8 +/-11.4 35.5 +/- 9.2

Maximum LT consumption*

440 +/- 40 330 +/-20

Number of LT withdrawal symptoms**

4.70 +/- 1.8 4.10 +/- 2.1

Number of past SA 5.00 +/- 12.5 2.96 +/- 3.6

ADHD score 33.5 +/-21.1 34.8 +/19.0

Fageström score*** 8.54 +/- 1.63 7.65 +/- 2.30

Past or present MDE 69.05%

68.48% LT=lifetime, * p<0.10, ** p<0.05, *** p=.0039

TCI in prospective suicidal attempts

Novelty Harm Reward Persistence Self- Cooperativeness Self- Seeking* Avoidance Dependence directedness transcendence

*p<10-3

*21.3 19.3 *17.3

14.3 14.1

3.7 3.5

*24.5 22.8

*24.6 23.8

15.9 15.2

Suicidal attempts. N=27

Controls. N=662

Decision making: IGT & rGT

de Visser et al. Frontiers in Neurosciences. doi: 10.3389/fnins.2011.00109

IGT and prospective suicidal attempts

2.7 2.6

Suicidal attempts. N=25

Controls. N=662

Total=-0.1

Total= 8.9*

-1.2 1.7

*p=.044 **=p=.014

0 to 20 21 to 40 41 to 60 61 to 80 81 to 100

GABA genes and suicidal risk

• GABA system is involved in the acute and chronic behavioral effects of ethanol including anxiolysis, sedation, withdrawal signs, and ethanol preference.

• GABA-A receptor is a transmembrane ligand-gated ion channel which is directly modulated by ethanol

• Conflicting results for the genes coding for these receptors.

rs11742028 rs11135176

GABRG2

Suicidal Attempt no Suicidal Attempt OR p Allele 1 Allele 2 Allele 1 Allele 2 GABRA1 rs35166395 14 36 405 1047 1.01 0.99 GABRA6 rs3219151 27 23 651 801 1.44 0.20 GABRB2 rs2229944 3 47 159 1291 0.52 0.27 GABRG2 rs11742028 16 34 267 1179 2.08 0.02* rs11135176 1 49 87 1355 3.15 0.23

Clinical characteristics of patients

with allele 2 (rs1174202)

Trait With allele 1 Without allele 1 Statistics

N Av SD N Av SD F p-value

Igt1 1 to 20 25 -0.160 6.504 630 -1.768 5.983 0.387 0.534

Igt 21 to 40 25 -0.480 6.640 631 0.678 7.339 0.065 0.799

Igt 41 to 60 25 1.040 10.410 631 1.170 8.549 0.928 0.336

Igt 61 to 80 25 2.240 10.775 631 0.602 9.504 0.103 0.749

Igt 81 to 100 25 3.920 8.953 631 -0.640 9.326 0.315 0.575

Novelty Seeking 25 21.280 4.587 645 21.211 4.368 2.164 0.142

Harm avoidance 25 17.600 4.573 645 17.264 4.190 7.620 0.006

Reward Dependence 25 14.880 2.774 645 14.284 2.741 1.395 0.238

Persistence 25 3.480 1.475 645 3.670 1.511 1.319 0.251

Self-Directedness 25 25.480 5.531 645 24.436 5.312 0.574 0.449

Cooperativeness 25 25.720 3.974 645 24.605 3.590 2.515 0.113

Self-transcendence 25 15.680 5.154 645 15.873 5.684 2.481 0.116

SRE: first 5 24 3.878 2.957 643 3.348 2.480 7.938 0.005

AOO_AD 27 37.394 9.200 656 35.430 9.211 1.880 0.171

MaxConsAlc 27 29.222 13.849 715 33.185 21.584 0.133 0.715

NBWithDrSp 27 3.704 2.072 715 4.124 2.139 0.003 0.960

NbSA 14 3.929 4.999 318 2.965 4.117 0.094 0.760

ADHD 26 36.654 18.836 681 34.659 19.140 0.022 0.883

Fagerstrom 26 7.808 1.833 657 7.702 2.311 0.014 0.906

Conclusions

• Alcohol consumption (mainly abuse) increases per se the risk of suicidal acts (mainly impulsive ones) and mortality (rather than ideas)

• In this specific –at risk- population, assess severity, comorbidity and environment to better predict suicidal risk… and propose the related treatments.

Factors explaining suicidal behaviour and mortality in ...

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