Antipsychotic drug exposure and risk of venous thromboembolism: a systematic review and meta-analysis of observational studies

Corrado Barbui,1 MD; Valentino Conti, 2 StatD; Andrea Cipriani,1 PhD

1 Department of Public Health and Community Medicine, Section of Psychiatry,

University of Verona, Verona, Italy

2 Regional Centre for Pharmacovigilance, Lombardy Region, Milano, Italy

DRUG SAFETY

ELECTRONIC SUPPLEMENTARY MATERIAL 5

GRADE summary table

Quality assessment / No of patients / Effect / Quality / Importance
No of comparisons / Design / Risk of bias / Inconsistency / Indirectness / Imprecision / Other considerations / Antipsychotic drugs / Control / Relative
(95% CI) / Absolute
pulmonary embolism - all antipsychotics
3 / observational studies / serious1 / very serious2 / no serious indirectness / serious3 / none / - / 0% / OR 4.90 (0.77 to 30.98) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism - all antipsychotics
12 / observational studies / serious4 / serious2 / no serious indirectness / no serious imprecision / reporting bias5 / - / 0% / OR 1.54 (1.28 to 1.86) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism - second generation antipsychotics
5 / observational studies / no serious risk of bias / no serious inconsistency / no serious indirectness / no serious imprecision / none / - / 0% / OR 2.07 (1.74 to 2.52) / - / ÅÅOO
LOW / CRITICAL
venous thromboembolism - first generation antipsychotics
6 / observational studies / no serious risk of bias / serious2 / no serious indirectness / no serious imprecision / none / - / 0% / OR 1.74 (1.28 to 2.37) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – aripiprazole
1 / observational studies / serious6 / no serious inconsistency / no serious indirectness / serious7 / none / - / 0% / OR 0.98 (0.83 to 1.15) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – chlorpromazine
2 / observational studies / serious8 / serious2 / no serious indirectness / serious3 / none / - / 0% / OR 1.52 (0.87 to 2.66) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – clozapine
3 / observational studies / serious9 / no serious inconsistency / no serious indirectness / serious3 / none / - / 0% / OR 1.53 (0.94 to 2.52) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism - clozapine + quetiapine
1 / observational studies / no serious risk of bias / no serious inconsistency / no serious indirectness / serious7 / none / - / 0% / OR 4.88 (2.03 to 11.72) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – haloperidol
2 / observational studies / serious8 / serious2 / no serious indirectness / serious3 / none / - / 0% / OR 1.35 (0.90 to 2.02) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – olanzapine
3 / observational studies / serious8 / serious2 / no serious indirectness / serious3 / none / - / 0% / OR 1.35 (0.97 to 1.89) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – quetiapine
2 / observational studies / serious8 / serious2 / no serious indirectness / serious3 / none / - / 0% / OR 1.79 (0.49 to 6.52) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – risperidone
3 / observational studies / serious8 / serious2 / no serious indirectness / no serious imprecision / none / - / 0% / OR 1.51 (0.96 to 2.36) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – ziprasidone
1 / observational studies / very serious8 / no serious inconsistency / no serious indirectness / serious7 / none / - / 0% / OR 1.21 (1.06 to 1.34) / - / ÅOOO
VERY LOW / CRITICAL
venous thromboembolism – polypharmacy
2 / observational studies / no serious risk of bias / serious2 / no serious indirectness / no serious imprecision / none / - / 0% / OR 2.50 (0.68 to 9.10) / - / ÅOOO
VERY LOW / CRITICAL

1 In one study (Allenet 2011) it is unclear if the exposure variable preceded the outcome of interest. In the other two studies (Hamanaka 2004 and Parkin 2003) it is unclear if groups were comparable.
2 Visual inspection of forest plot suggested heterogeneity.
3 The confidence interval ranges from no risk to clinically appreciable harm associayed with antipsychotic drug exposure.
4 In three studies (Ishiguro 2011, Masopust 2007 and Thomassen 2001) it is unclear if groups were comparable.
5 The funnel plot was not symmetrical.
6 It is unclear if the exposure variable preceded the outcome of interest.
7 Only one study contributed to this analysis.
8 In one study (Allenet 2011) it is unclear if the exposure variable preceded the outcome of interest.
9 In one study (Allenet 2011) it is unclear if the exposure variable preceded the outcome of interest. In another study (Wolstein 2000) it is unclear if groups were comparable.