( More than depression?) Phili lipp ppe e Courtet tet - PowerPoint PPT Presentation

Is sui uici cidal dal depressi epression on a spec pecific ific phe henot notype ype ? (… More than depression?) Phili lipp ppe e Courtet tet

Disclosure closure of conf nflict lict of inter terest • Fonda damental mental Foundation ndation • Exelti ltis • Jans nssen sen • Servier vier • Otsuka uka

Unmet et nee eeds • In depression, the population attributable risk of mood disorders for a first occurrence of SI or SA has been estimated at 51% - 44% • Thus, reducing the duration of depressive episodes might have a major impact on suicidal risk • American Psychiatric Association practice guideline on management of patients with suicidal behaviour: “ Evidence for a lowering of suicide rates with antidepressant treatment is inconclusive ” Total absence of treatments for acutely suicidal patients • Practice guide for the assessment and treatment of patients with suicidal behaviors. Available at https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/suicide.pdf. Accessed August 2018 Nock et al 2010 Sokero et al 2003

SSRI I (n = 5681) placebo bo (n = 2581) HDRS- SI≥3 : < 6%

Su Suic icidal idal depression pression 1. Two cohort hort studies dies : Shor ort t term rm follow low-up up 2. Clinical nical sample ple of depre press ssed ed patients ients : 2 year ars follow llow-up up

Two wo co cohorts orts of unipola ipolar r dep epress essed ed outp tpat atients, ents, 6 w 6 wee eeks follow ow-up up initia iati tion on of a antid idepr pressa essant nt treatm tment nt Week Week Inclusi sion Week 6 1-2 2-4 Coho hort 1 Coho hort 2 Self repor orts ts : Suici icidal dal Ideation tion : MADRS S suicid cide item Depres essi sion on, , anxie iety ty : Hospital spital Anxie iety ty and Depres essio sion n Scale Sleep ( MADRS RS sleep item) Beck Hopel peles essness sness Scale Impu pulsivity sivity ( Plu lutc tchik hik Impu pulsi lsivity vity Scale)

Non n suicida dal Mode derately suic icida dal Severely suic icida dal Total HADS DS- D ≥ 11 depression on depression on depression on popul pulatio ion n (MADRS ≥ 20) (MADRS-SI SI < 2) (MADRS-SI SI [2; 4[) (MADRS- SI ≥ 4) N N % N % N % N % 4845 4845 3969 3969 81,9 671 671 16,9 2292 2292 57,7 1006 1006 25,3 Coho hort 1 3566 3566 2537 2537 71,1 370 370 14,6 1408 1408 55,5 759 759 29,9 Coho hort 2

Bas asel eline ne soci ciodemographi demographic c ch char aract acteris eristics tics Global p-value adjusted on depression severity for COHORT 1 and on depression severity and age for COHORT 2

Bas asel eline ne cl clinical cal ch char aracteri acteristics tics Global p-value adjusted on depression severity for COHORT 1 and on depression severity and age for COHORT 2

Bas asel eline ne psych chopa opatho thology logy Global p-value adjusted on depression severity for COHORT 1 and on depression severity and age for COHORT 2

Suicide de attempt pt during ring 6 we weeks follow low up No SA durin ring g SA durin ring OR [95% CI] p-valu lue OR [95% CI] Adju just sted p- foll llow ow-up up va value foll llow ow-up up (life fetim ime SA) COHORT 1 N= 3567 N= 68 2 (2.9) - <0.001 - <0.001 601 (16.8) No SI 24 (35.3) 3.50 [0.82; 14.83] 2.62 [0.61; 11.20] Moderate SI 2063 (57.8) 42 (61.8) 13.98 [3.37; 57.96] 8.08 [1.90; 34.26] Severe SI 903 (25.3) COHORT 2 N= 2462 N= 15 359 (14.6) 0 No SI 1367 (55.8) 8 (53.3) Moderate SI 726 (29.6) 7 (46.7) Severe SI

Ev Evolution tion of sev ever erity ty of dep epress ession ion • At each h time e point nt: : higher her depressi ression on score res s in Severe ere SI Cohort 1 • Improvement rovement of depres ression sion in each h gr group up • Non differ fference ence in improveme rovement t of depressi ression on between ween groups ps Cohort 2 Unadjusted and Adjusted on age, study level, SA lifetime, MDE duration, treatment associated

Rem emission ion of dep epress ession on (H (HAD- D ≤7) at 6 weeks Remission rates 53.5% 50.1% 39.7% 53.5% 51.0% 42.6%

Ev Evoluti tion on of MADR DRS-SI SI in th the e 3 g 3 groups oups Cohort 1 • At each h time e point nt: : higher her MADRS DRS-SI SI score res in Severe ere SI • Improv proveme ement nt of MADRS DRS-SI SI score res s in each h group up • Better ter Improvement rovement of MADRS DRS- Cohort 2 SI in Severe ere SI Unadj djus usted and Adju justed d on age, study level, SA lif ifetime ime, MDE E duratio ion, n, treatment associated & on Depr pression on at baselin ine or at each h time or to the previou ous evalu luatio ion

Ev Evolution tion of prev evalenc alence of SI SI in th the e 3 g 3 group oups 54.9% 21.9% 7.4% 44.3% 16.7% 12.2% * * * * * * * * Unadj djus usted and Adju justed d on age, study level, SA lif ifetime ime, MDE E duratio ion, n, treatment associated & on Depr pression on at baselin ine or at each h time or to the previou ous evalu luatio ion

Suici icidal dal Remissio issions (MADRS RS-SI= SI=0-1) 1) Our r resul ults : W4 30% Canuso uso: : W4 58% pcb (77% (77% esket) Severe SI (MADRS- SI≥4) Our results : W4 17% Canuso uso: : 10% pcb (7% (7% esket)

A persist rsisting ing severe ere suicidal cidal ideation ation is associat ociated ed with th the risk sk of suicide cide attempt tempt during ring follow low up: : OR OR: 4.38 38 [2.0 .05; 5; 9.35] 35]

Pr Pred edictors ctors of per ersi sist stanc ance e of se seve vere SI SI COHO HORT 1 COHO HORT 2 OR [95%CI] p-value OR [95%CI] p-value Variable Study dy level - - Cur urren ent t MDE duration on ( ≥ 6 month nths) s) 0.58 [0.06; 5.53] - 1.69 [0.79; 3.61] - Numb mber er of MDE lifeti etime me 1.02 [0.94; 1.10] - Age at first st MDE (ye year ars) s) 1.02 [0.98; 1.06] - MADRS-SI SI Bas asel eline ne 6.72 [4.43; 10.18] <0.001 001 2.69 [2.08; 3.49] <0.001 001 Lack of Chan ange in HAD tota tal 1.52 [1.35; 1.70] <0.001 001 1.16 [1.10; 1.21] <0.001 001 Lack of Chan ange in Hopelessn sness 1.10 [0.91; 1.32] - Lack of Chan ange in impulsi sivity vity 1.01 [0.95; 1.08] Lack of Chan ange in MADRS RS-sl slee eep 1.38 [1.12; 1.69] 0.003 003 Lifet etime me SA 1.84 [0.68; 5.01] - 1.28 [0.68; 2.41] - Treatment change 3.00 [1.11; 8.09] 0.03 03 0.92 [0.50; 1.70]

Su Summ mmary ary • In 2 large ge independent ependent cohorts orts of depres ressed sed unipolar polar outpatients atients, , suici icidal dal depressi ression on is : • More re severe ere at basel eline ine (risk k fact ctor ors, , depres ressi sive e illness ness, , anxiety xiety, , depres ressi sion on, , hopelessnes elessness, , impuls ulsivity, ity, sleep, eep, history ory of suici icide de attempts mpts) • During ing the 6 week eks foll llow ow up: – Higher her risk sk of suicid cide e attempts mpts – Suicid cidal al ideati ation on still ll more e severe vere (controll ntrolling ing for r depres ression) sion) – Less ss remiss mission ion of depress ression on

Percenta centage e symptom ptom reduct duction ion from om baseline eline for r depressiv ssive e sy symptoms ptoms and d su suicidal cidal ideation tion

Su Suici cida dal l dep epres ression ion may ay be a su e a subtype type of MDD DD • Dist stinct inct psychiatri ychiatric c comorbi orbidi ditie ties s and clinic inical al and sociodem ciodemogr grap aphic hic feat atures ures – Age ge at onset set of de depress pression on and d child ldhood hood abu buse se – More re freq equent uent history tory of suicid cide e attempt mpt • A propens ensity ity to severe vere suici icida dal l ideati ation • An actual al risk sk of suic icid ide e attempt mpts s in short rt and d long g terms ms • Resp sponse onse to antid idep epress ressant ant ±

Ackn knowl owledgeme edgements nts Dr E Olié ié Dr B Nobi bile le Mr A Alacreu reu