1. Treatment with rosuvastatin for severe dyslipidaemia in patients with schizophrenia and schizoaffective disorder
M De Hert1, D Kalnicka1, R van Winkel1,
M Wampers1, L Hanssens2, D Van Eyck1,
A. Scheen3, J. Peuskens1
1University Center St Jozef Kortenberg, Catholic University Louvain, Belgium
2Department of Epidemiology and Public Health, University Liege, Belgium
3 Department of Diabetology, University Liege, Belgium

2. Disclosure
Currents research grants: Astra Zeneca, BMS, Eli Lilly, Janssen Pharmaceutica, Lundbeck, Pfizer, Sanofi-Aventis
Advisory boards: Astra Zeneca, BMS, Eli Lilly, Janssen Pharmaceutica, Lundbeck, Pfizer, Sanofi-Aventis

3. Introduction
Patients with schizophrenia have high rates of cardiovascular morbidity and mortality
Cardiovascular and metabolic risk-factors often remain undetected and untreated
Lipid abnormalities are associated with antipsychotic treatment
No published data on effectiveness of statins in treatment of lipid abnormalities in people with schizophrenia

4. Aims
This study aims at evaluating the effectiveness of statin therapy in schizophrenic patients with documented and severe dyslipidaemia (meeting SCORE-criteria)
Patients were recruited from the UC metabolic study, a prospective dynamic cohort study (N>700)
Severe lipid abnormalities are highly prevalent in patients with schizophrenia treated with antipsychotics: 27% in patients with long-term treatment and up to 17% within 3 months of treatment (poster 171, March 30)

5. Patients and method
100 patients with severe dyslipidaemia meeting SCORE criteria (Framingham adapted for Europe)
52 started on rosuvastatin compared to 48 who did not receive a statin
All remained on the same antipsychotic treatment
All patients got dietary advice
Extensive screening at baseline, 6 weeks and 3 months, including an oral glucose tolerance test

6. Patients
Duration of antipsychotic treatment: longer than 6 months 69%, shorter than 3 months 28%
92% SGA and 18% FGA
Only 1 AP 84% (92.8% SGA and 7.2% FGA)
Additional psychotropic medication: anticholinergic 20%, antidepressant 48%, benzodiazepine 40%, mood stabiliser 19%.
Somatic medication 41%, treatment for diabetes 4%, treatment for hypertension 20%

7. Antipsychotic medication SGA (92% of patients)

8. Patients Statin (52) Control (48) p Mean age 39.4 (±10.1) 37.5 (±10.1)ns
Male % (N)
84.6% (44)
70.8% (34)
Mean BMI
28.2 (±4.7)
27.2 (±4.9)
ATP III MetS
55.8% (29)
41.7% (20)
ATP III A MetS
45.8% (22)
IDF MetS
59.6% (31)
56.2% (27)
FH CVD % (N)
53.8% (28)
54.2% (26)
FH diabetes % (N)
32.7% (17)
33.3% (16)
FH lipid abn % (N)
36.5% (19)

9. Patients, abnormal lipid values

10. Chol : F(1, 98) = 6.46, p = .0126 NonHDL : F(1, 98) = 7.99, p = .0057
TG : ns HDL : ns
LDL : F(1, 98) = 5.22, p = .0245

11. Chol : F(1, 51) = 10. 62, p =. 0020. NonHDL : F(1, 51) = 10. 62, p =
TG : F(1, 51) = 4.29, p HDL : ns LDL : ns

12. Chol : F(1, 98) = 145. 17, p <. 0001. NonHDL : F(1, 98) = 133
Chol : F(1, 98) = , p < NonHDL : F(1, 98) = , p < .0001
TG : F(1, 98) = 23.13, p < HDL : ns
LDL : F(1, 98) = , p < .0001

13. Chol : F(1, 98) = 206. 42, p <. 0001. NonHDL : F(1, 98) = 13
Chol : F(1, 98) = , p < NonHDL : F(1, 98) = 13.77, p < .0003
TG : F(1, 98) = 23.31, p < HDL : F(1, 98) = 5.58, p = .0201
LDL : F(1, 98) = , p < .0001

14. Evolution HDL

15. Chol : F(1, 51) = 221. 54, p <. 0001. NonHDL : F(1, 51) = 204
Chol : F(1, 51) = , p < NonHDL : F(1, 51) = , p < .0001
TG : F(1, 51) = 13.51, p = HDL : ns
LDL : F(1, 51) = , p < .0001

16. Effects on other parameters
No effect on any variable measured in OGTT, no significant between-group effect
No effect on waist, weight or BMI (non significant increase in both groups)
Non significant reduction in rate of MetS in the statin group (ATP III A 55.8% to 42.3%, only component with significant change were TG)
Non significant increase in CK
No overall change in liver enzymes
1 patient treatment stopped because of CK and abnormal liver enzymes after 5 months

17. Conclusions
The high rates of lipid abnormalities observed in patients with antipsychotics warrant close screening and monitoring
If a switch to a metabolic safer antipsychotic agent is not possible or acceptable to the patient statins are an effective and well tolerated treatment for severe dyslipidaemia in patients with schizophrenia
Global effects are similar to treatment in non-psychotic populations
Statin treatment has limited and non significant effects on the prevalence of the metabolic syndrome

19. TG (mg/dl) decreased significantly from baseline to follow-up in both groups (p<.005). There was no group x time interaction (De hert at al., 2006)

20. Phase 2: Tolerability Pathway2†
Alternative strategies Triglycerides* Reported in CATIE
Ziprasidone
Risperidone
Quetiapine
Olanzapine
Perphenazine
N = 212
N = 286
N = 268
N = 262
N = 143
Phase 11
Ziprasidone
Risperidone
Quetiapine
Olanzapine
Phase 2: Tolerability Pathway2†
N = 108
N = 95
N = 104
N = 137
*Fasting results (note: nonfasting results were not excluded).
†Participants who discontinued phase 1 switched treatments and chose either the tolerability or efficacy pathway.
Lieberman JA et al. N Engl J Med. 2005;353: Stroup TS et al. Am J Psychiatry. 2006;163:
3. McEvoy JP et al. Am J Psychiatry. 2006;163:

21. Alternative strategies: CATIE
Cholesterol
Triglycerides
Olanzapine (n=336)
Quetiapine (n=337)
Risperidone (n=341)
Perphenazine (n=261)
Ziprasidone (n=185) 60
Olanzapine (n=336)
Quetiapine (n=337)
Risperidone (n=341)
Perphenazine (n=261)
Ziprasidone (n=185) 15 50 40 10 30
Exposure adjusted mean change in triglycerides (mg/dl) from baseline 20 5 10
Exposure adjusted mean change in cholesterol (mg/dl) from baseline
–10 –5
–20
–30
–10
–40
p<0.001
–15
p<0.001
P values indicate difference between treatment groups. Values based on a ranked analysis of covariance with adjustment for whether the patient had had an exacerbation in the preceding three months and the duration of exposure to the study drug during phase 1
CATIE = Clinical Antipsychotic Trials of Intervention Effectiveness
Lieberman et al. N Eng J Med. 2005;353:1209–1223

22. Improvement in Metabolic Parameters When Switching to Ziprasidone* *
***
****
****
***
Suboptimal control of patients is due to partial response or poor tolerability
A mixed model repeated measures analysis
Statistical significance was evaluated at weeks 6, 32, and 58 (*p < 0.05, ***p < 0.001, ****p < )
Weiden PJ et al, APA 2004