Table 2.
Pharmacological Evidence
| Argument | Reference | Number of Patients | Design | Main Findings |
|---|---|---|---|---|
| Association of CLZ with comorbid OCS | Lim et al. 2007 [64] | Total sample: 209, comorbid subsample: 26 | Cross-sectional. Stratification for SZ with or without OCS | CLZ-treatment in 35.9 % of the total sample, but in 76.9 % of the comorbid patients |
| Association of OCS with OLZ or CLZ | Sa et al. 2009 [7] |
CLZ: 40 HAL: 20 |
Cross-sectional. Stratification for treatment with CLZ or HAL | Prevalence of OCS 20 % (CLZ) vs. 10 % (HAL). Higher severity of OCS with CLZ |
| Ertugrul et al. 2005 [65] | CLZ: 50 | Cross-sectional. Stratification of treatment with CLZ | Within 50 patients treated with CLZ, 76% showed OCS. 20 % reported retrospectively de novo onset and 18 % an exacerbation. | |
| Schirmbeck et al. 2011 [62] |
CLZ: 26 OLZ: 13 AMS: 15 APZ:16 |
Cross-sectional. Stratification for treatment with SGAs in monotherapy | Prevalence of OCS 71.8 % in CLZ or OLZ vs. 9.7 % in AMS or APZ. Highest severity of OCS with CLZ | |
| Correlation of OCS with duration of treatment | Lin et al. [63] | CLZ: 102 | Cross-sectional: Stratification for CLZ-treatment with or without OCS | Duration of CLZ-treatment significantly longer in CLZ-OCS-patients (82 vs. 56 months), no difference in duration of illness |
| Schirmbeck et al. [62] | CLZ: 26 | Cross-sectional: Stratification for CLZ-monotherapy | Duration of CLZ-treatment correlates positively with OCS severity (YBOCS, R=0.59). | |
| Correlation of OCS with CLZ-dosage or plasma concentration | Reznik et al. [41] | N=15 | Cross-sectional: Stratification for CLZ-therapy | Dosage-related, pro-obsessive influence of CLZ |
| Mukhopadhaya et al. 2009 [3] | N=59 | Cross-sectional: Stratification for CLZ-therapy | Higher CLZ-dosage in patients with comorbid OCS (432 mg/day) than without (351 mg/day) | |
| Schirmbeck et al. [62] | CLZ: 26 | Cross-sectional: Stratification for CLZ-monotherapy | CLZ-dosage correlates positively with OCS severity (YBOCS, R=0.50). | |
| Lin et al. [63] | CLZ: 102 | Cross-sectional: Stratification for CLZ-treatment with or without OCS | Higher plasma concentrations in CLZ-treated patients with OCS (595 ng/L) than without OCS (434 ng/L). | |
| Improvement after CLZ dose-reduction | Rocha et al. 2006 [77] | 3 | Longitudinal observation of OCS severity | Reduction of OCS severity after CLZ down-tapering in combination with APZ |
| Zink et al. 2006 [59] | 1 | Longitudinal observation of OCS severity | Reduction of OCS severity from YBOCS 24 to 19 after reduction of CLZ from 500 to 250 mg/die and combination with APZ (30 mg) | |
| Englisch et al. 2009 [61] | 7 | Longitudinal observation of OCS severity | Reduction of OCS severity from YBOCS 19 to 12 after reduction of CLZ from 364 to 293 mg/die and combination with APZ (23 mg) |
Pharmacological evidence in favour of an association between clozapine-treatment and OCS. Abbreviations: AMS: amisulpride; APZ: aripiprazole; CLZ: clozapine; FGA: first generation antipsychotics; HAL: haloperidol; OCS: obsessive compulsive symptoms; OLZ: olanzapine; SGA: second generation antipsychotics; SZ: schizophrenia and schizophrenia spectrum disorders; YBOCS: Yale-Brown-Obsessive-Compulsive Scale.