Bipolärdagen 2014.pptx

PROGRAM •  09.00-­‐09.30 Uppsamlingsfika •  09.30-­‐09.45 Registerhållare för Kvalitetsregistret BipoläR Mikael Landén hälsar alla välkomna •  09.45-­‐10.30 Vad händer på forskningsfronten när det gäller bipolär sjukdom? (Mikael Landén, registerhållare för BipoläR, överläkare vid Sahlgrenska Universitetssjukhuset och professor vid sekOonen för psykiatri och neurokemi, Sahlgrenska Akademin) •  10.30-­‐11.00 Paus •  11.00-­‐12.00 Suicid och suicidprevenOon vid bipolär sjukdom (Bo Runesson, överläkare och professor i psykiatri vid Karolinska InsOtutet i Stockholm) • 
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12.00-­‐13.00 Lunch 13.00-­‐14.00 Work-­‐shops Graviditet vid bipolär sjukdom, Jenny Alfaro och Marie Andersson; Registrera och ta fram rapporter i INCA, Annika Sahlén-­‐Blom; Årsrapporten 2013, Mathias Kardell och Magnus Jansson, Använda anamnesprotokollet i INCA/Forskningsfrågor – Mikael Landén 14.00-­‐14.30 EVermiddagsfika 14.30-­‐15.00 PaOentrapporterande kvalitetsmåX (Magnus Jansson, utvecklingsledare för BipoläR och Annika Sahlén-­‐Blom, koordinator för BipoläR) 15.00-­‐15.50 MiX galna liv -­‐ en beräXelse om aX leva med bipolär sjukdom (Arvid Lagercrantz, förfaXare, vice-­‐ordförande i paOen[öreningen Balans samt styrgruppsmedlem i BipoläR) 15.50-­‐16.00 Registerhållare Mikael Landén sammanfaXar dagen 2014-­‐10-­‐13 Mikael Landén 2 John Cade (1912 -­‐ 1980) 1949 Mogens Schou 1954 •  Mogens Schou: "life-­‐
diagram" från 1954 •  Banbrytande 8 månaders dubbelblind placebokontrollerad studie av 30 paOenter med typisk mani och 8 atypisk mani Schou M, et al. The treatment of manic psychoses by the administraOon of lithium salts. J Neurol Neurosurg Psychiatry 1954;17:250-­‐260 Suicid RCTs
Meta-analysis of RCTs (Cipriani, BMJ 2013)
Ø  Different and relative short follow-up times
Ø  OR not consider effect of time
OR of suicides is 87%
lower in people with
lithium medication
compared to placebo
Ø  Small sample size
Ø  Participants not representative
13 October 2014
Ethical, logistic barriers
8
Table 1. Risk of suicide attempts during medication periods compared to nonmedication periods among Swedish bipolar patients 2006-2009 Between-individual
Within-individual
Medication
Hazard Ratio
95% CI
Hazard Ratio
95% CI
No medication
1
-
1
-
Valproate
0.90
0.76-1.07
0.94
0.75-1.18
Lithium
0.61
0.55-0.67
0.77
0.65-0.92
Lithium and
valproate
0.73
0.58-0.93
0.70
0.47-1.06
Rate of suicide attempts was reduced by 23% during
lithium medication period compared to no lithium
medication period
13 October 2014
Jie Song
9
Table 2. Risk of complete suicide during medication periods compared to nonmedication periods among Swedish bipolar patients 2006-2009 Between-individual
Within-individual
Medication
Hazard Ratio
95% CI
Hazard Ratio
95% CI
No medication
1
-
1
-
Valproate
0.12
0.03-0.48
0.18
0.01-2.69
Lithium
0.12
0.06-0.25
0.17
0.05-0.65
Lithium and
valproate
-
-
-
-
Rate of complete suicides was reduced by 83% during
lithium medication period compared to no lithium
medication period
13 October 2014
Jie Song
10
Litium länsvis 2013.
3,5
3
2,5
2
1,5
PPT
DDD/TIND
1
0,5
0
Gunnar Bergendahl
www.infofarm.se
What causes bipolar disorder? Can be asked at several levels: •  EVOLUTIONARY •  GENETIC •  NEUROCHEMICAL •  PSYCHOLOGICAL •  SOCIAL •  ETC STANLEY-study
based on the Swedish national
QA-register BipoläR
www.ki.se/stanley
STANLEY study
•  Start: May 2009
•  Collection closed in June 2013
•  6483 cases included
•  Upcoming linkage with other national registers
•  Follow-up data will be added as long as the QA-register
is functional
www.ki.se/stanley
Mikael Landén
10/24/12
16
LiOumrespons Jie Song och Sarah Bergen Table 4. Summary of significant Loci comparing lithium responders vs. controls CHR SNP Subjective measurement Allele Sw34 Sw6 Cardiff Meta Genes OR P OR P OR P OR P 4 rs12144699 G/A 0.44 0.02 0.55 0.003 0.62 -­‐4
4.7*10 0.58 -­‐7
4.05*10 7 chr10:35952206:I A/AT 0.81 0.80 2.61 0.005 2.33 2.95*10 -­‐5
1.27 1.01*10 HSD52 -­‐6
No genes
-­‐6
LAMP3 -­‐6
-­‐5
1.34 1.08*10 -­‐6
9 rs12493050 G/A 1.27 0.23 1.25 0.02 1.28 3.72*10 5 chr19:34968272:D CAT/C 1.16 0.52 1.25 0.03 1.40 8.75*10 2.3 1.17*10 No genes 0.25 -­‐8
1.33*10 No genes -­‐6
0.32 2.74*10 -­‐5
0.28 3.93*10 q
0.40 4.33*10 Objective measurement 18 chr11:112118590:D GTA/G -­‐ -­‐ 0.35 0.025 0.22 -­‐7
1.22*10 20 rs116323614 G/A -­‐ -­‐ 0.35 0.004 0.3 1.97*10 7 rs142643109 T/G -­‐ -­‐ 0.25 0.006 0.29 1.85*10 3 rs10049682 C/T -­‐ -­‐ 0.46 0.01 0.36 1.06*10 -­‐8
SESTD1
-­‐7
No genes -­‐7
TLL1 SESTD1 codes for SEC14 domain and spectrin repeat-­‐containing protein 1 •  Binds phospholipids such as phosphaOdylinositol monophosphates, phosphaOdylinositol diphosphates (PIP2s) and phosphaOdic acid •  InosOol monophosphate has historically been believed to be a direct target of lithium •  The inositol depleYon hypothesis: –  Lithium produces its therapueOc effects by inhibiOng IMPase and therefore decreasing levels om myo-­‐inositol Inositol monophosphatase 2 Effectiveness of pyschoeducation in
the Swedish quality assurance registry
Erik Joas
Study design
•  Within-individual
•  Confounding-by-indication
•  Have the patient received PE during the last 12
months?
•  Number of depressive episodes during the last
12 months.
Resultat
Table 2. Effect of psychoeducaYon on different outcomes using condiYonal logisYc regression with separate strata for each individual.
Unadjusted
Fully adjusted1
Outcome
Effect OR (95% CI)
p-­‐value
Effect OR (95% CI)
p-­‐value
HospitalizaYon
0.64 (0.40 , 1.03 )
0.0660 0.65 (0.39 , 1.10 )
0.1078
Compulsory care
1.26 (0.62 , 2.54 )
0.5246 1.18 (0.53 , 2.59 )
0.6889
Suicide a_empts
0.76 (0.35 , 1.66 )
0.4930 1.44 (0.59 , 3.50 )
0.4260
Depressive episodes
0.55 (0.40 , 0.76 )
0.0003 0.66 (0.46 , 0.94 )
0.0205
Manic episode
0.59 (0.32 , 1.10 )
0.0948 0.63 (0.31 , 1.26 )
0.1889
Hypomanic episodes
0.63 (0.45 , 0.88 )
0.0077 0.71 (0.48 , 1.04 )
0.0795
Symptom severity -­‐ CGI
0.75 (0.52 , 1.09 )
0.1287 0.75 (0.50 , 1.13 )
0.1727
All relapses
0.55 (0.39 , 0.77 )
0.0005 0.64 (0.45 , 0.93 )
0.0177
1) Adjusted for age, mood stabilizing treatment, and GAF-­‐symptom. Hälsoekonomi Mamas Ekman Psykiatriska sjukdomar: Vad är det som kostar? • Schizofreni • Bipolär sjukdom • Depression • GAD
Målsättningar med studien:
§  UppskaXa samhällsekonomisk kostnad per paOent för schizofreni, bipolär sjukdom, depression och ångest i Sverige §  Vad är det som kostar? §  Relatera kostnader Oll bl.a. funkOonsnivå, samsjuklighet och episoder/skov 25 Psykiatriska sjukdomar: Vad är det som kostar? • Schizofreni • Bipolär sjukdom • Depression • GAD
Huvudsakliga datakällor: §  BipoläR §  Norra Stockholms psykiatri (under perioden 2006-­‐2008) §  Data om läkemedel från Läkemedelsregistret §  Data om sjukfrånvaro och förOdspension (sjukbidrag etc.) från Försäkringskassan 26 Resultat: Kostnad per patient 2008
600 000 kr
Indirekta kostnader
500 000 kr
N = 2085† Kommunala vårdkostnader
Läkemedelskostnader
400 000 kr
Slutenvårdskostnader
Öppenvårdskostnader
300 000 kr
N = 1799* 200 000 kr
N = 10 430** N = 337*** Depression
GAD
100 000 kr
0 kr
Bipolär sjukdom
Schizofreni
*Ekman et al. Soc Psychiatry Psychiatr Epidemiol. 2013;48(10):1601-­‐10. **Ekman et al. J Affect Disord. 2013;150(3):790-­‐7. ***Gäller paOenter som enbart lider av generaliserat ångestsyndrom (GAD) och som behandlats inom psykiatrisk vård. †Ekman et al. J Ment Health Policy Econ. 2013;16(1):13-­‐25. 27 DistribuOon of total costs of bipolar disorder by cost item Outpatient cost
7.5%
Inpatient cost
13.0%
Pharmaceuticals
2.4%
Community care
2.3%
Indirect cost
74.9%
Ekman M, Granström O, Jacob J, Omerov S, Landén M. The societal cost of bipolar disorder in Sweden. Social Psychiatry and Psychiatric Epidemiology. 2013. Resultat: Total samhällsekonomisk kostnad 2008
40
Totalt: 75 miljarder kr (75% indirekta kostnader) 35
Miljarder kr
30
25
20
15
10
5
0
Bipolär sjukdom*
Depression**
GAD***
Schizofreni†
*Ekman et al. Soc Psychiatry Psychiatr Epidemiol. 2013;48(10):1601-­‐10. **Sobocki et al. Eur Psychiatry. 2007;22(3):146-­‐52. ***Gäller paOenter som enbart lider av generaliserat ångestsyndrom (GAD) och som behandlats inom psykiatrisk vård. †Ekman et al. J Ment Health Policy Econ. 2013;16(1):13-­‐25. 29 What causes bipolar disorder? Can be asked at several levels: •  EVOLUTIONARY •  GENETIC •  NEUROCHEMICAL •  PSYCHOLOGICAL •  SOCIAL •  ETC EvoluOonary view Sickle-­‐cell example Gene Gene Effect A Connect unrelated ideas B Seek novelty C Take risks Be aware of others' opinions D E High energy level Just a li/le CreaOvity Too much TangenOal, disorganized Jumping from project to Fascinated by change, curious project Courageous Bad judgment about harm Socially polished Anxious, suspicious, paranoid Very producOve Can't stop, slow down Racing thoughts Unable to focus ScaXered acOvity CreaOvity? CreaOvity? BriOsh Journal of Psychiatry, Kyaga et. al , 2011 CreaOvity? •  Persons with bipolar disorder, and their relaOves are overrepresented in creaOve professions. •  This might be coupled to increased fitness Leadership? Evolutionary explanation
Bipolar ”light” (in
relatives) might be
coupled to increased
fitness
Bipolar disorder and anOdepressants = CONTROVERSIES! Bipolar disorder and anOdepressants = CONTROVERSIES! EffecYve? Bipolar disorder and anOdepressants = CONTROVERSIES! EffecYve? Risk of switch? NPR 30,000 MigraYon register Cause of death register SPDR 3,240 3,240 Monotherapy 1,117 X AnOdepressant + mood stabilizer* 1,641 Unambigous mood stabilizer treatment (not included) 482 *Lithium, Valproic acid, or Lamotrigine AnYdepressant monotherapy Hazard raYo (N=1,117) 95% CI P 0-­‐3 months 2.83 (1.12-­‐7.19) 0.028 3-­‐9 months 0.71 (0.23-­‐2.26) 0.567 Concurrent mood stabilizer treatment Hazard raYo (N=1,641) 95% CI P 0-­‐3 months 0.79 (0.54-­‐1.15) 0.214 3-­‐9 months 0.63 (0.42-­‐0.93) 0.020 AnYdepressant monotherapy Hazard raYo (N=1,117) 95% CI P 0-­‐3 months 2.83 (1.12-­‐7.19) 0.028 3-­‐9 months 0.71 (0.23-­‐2.26) 0.567 Concurrent mood stabilizer treatment Hazard raYo (N=1,641) 95% CI P 0-­‐3 months 0.79 (0.54-­‐1.15) 0.214 3-­‐9 months 0.63 (0.42-­‐0.93) 0.020