Almost all antipsychotics result in weight gain Metaanalysis

Almost all antipsychotics result in weight gain. Meta-analysis Maarten Bak

Department 2

Severe Mental Illness Health Department 3

People with SMI decease at a younger age Department Munk-Laursen 2014 Ann Rev Clin Psych 4

In SMI life expectancy is shortened Man Female Department Nordentoft 2013 Plos. One 5

Risks of severe physical problems in SMI GAP =General Australian population Department Gladigau 2014 IMJ 6

Physical problems & SMI: review Department De Hert 2011 World Psych 7

DM-II Met. S Department Heald 2010 Eur Psych 8

CVD risico Department Mc. Lean 2014 Schiz Res 9

People with Schizophrenia decease at a younger age Department Munk-Laursen 2014 Ann Rev Clin Psych 10

Treatment of physical problems & SMI OR Meta-analysis of treatment with: Antiviral compounds, ACE-blockers, β-blockers, anticoagulants and Cholesterol decreasing medication Department Mitchell 2012 BJP 11

Severe Mental Illness Health Department Medication 12

Mortality risk & AP Largely explained by reduced risk of suicide Department Tiihonen 2009 Lancet 13

Mortality and medication Department Tenback 2012 J Clin Psy. Pharm 14

Monitor side effects Metabolic Other Body weight changes Movement disorders BMI Cardiovascular disorders Waist circumference Sexual problems Glucose Lipids Department Antipsychotic monitor (APM) 15

Department 16

Department Monitor volksgezondheid 2015 + AP Monitor 2016 17

Department Monitor volksgezondheid 2015 + AP Monitor 2016 18

First review: AP associated with weight gain Department Allison et al, 1999 Am J Psych 19

Weight change: meta-analysis Study duration: 4 -12 wks Compared with haloperidol Department Leucht 2009 Lancet 20

BMI changes in first episode schizophrenia Department Tarricone 2010 Psychol Med 21

Are all AP associated with weight gain? Are AP-naive patients more at risk? Is duration of AP-use related with more weight gain? Department 22

Flow chart Department Bak 2014 Plos. One 23

Figure 2. Weight change (in kg) period per antipsychotic medication. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 24

Figure 3. Weight change (kg) period only including AP-naive samples. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 25

Figure 4. BMI change period. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 26

Figure 5. BMI change in AP naive patients per time period. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 27

Figure 6. Proportion of weight increase per antipsychotic per time period. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 28

Figure 7. Proportion of weight increase in AP naïve. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 29

Figure 8. Proportion of weight reduction. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 30

Table 1. Metaregression of weight changes period. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 31

Table 2. Metaregression of weight changes period in drug-naive patients. Bak M, Fransen A, Janssen J, van Os J, Drukker M (2014) Almost All Antipsychotics Result in Weight Gain: A Meta. Analysis. PLo. S ONE 9(4): e 94112. doi: 10. 1371/journal. pone. 0094112 http: //journals. plos. org/plosone/article? id=info: doi/10. 1371/journal. pone. 0094112 Department 32

Is diagnosis a factor? Data period: 1960 – 2015 437 papers Department 33

No med Light med Moderate med Severe med <6 6 -16 1638 >38 1 1 1 1 Aff 0. 29 1. 64 0. 27 -0. 81 -1. 03 -0. 98 9. 54 -5. 13 -0. 23 -0. 1 -1. 09 -0. 53 -0. 17 -1. 77 1. 14 Cog 0. 37 -1. 92 -4. 75 Sz Psy NAO 0. 46 -0. 1 Add -1. 27 -2. 0 2. 97 No 0. 34 Rest -0. 98 Department -0. 8 0. 52 -0. 9 -1. 51 34

Remt “reward” systeem D 2 blokkade negatieve feedback Leptine stijgt Appetite stijgt Department Vergroot honger gevoel en eetlust Meer voedsel intake 35

Intake changes in rats after AP use Department Kaur & Kulkarni 2002 PNBP 36

Conclusion • All antipsychotics result in weight gain • Three risk groups – Limited: aripiprazol, amisulpride, ziprasidone – Moderate: haloperidol, risperidon, paliperidon, quetiapine – Severe: olanzapine & clozapine • Weight gain is not associated with diagnosis Department 37