Table 2.

Arguments supporting SGA-induction of OCS.

Epidemiology	The prevalence rates of OCS in schizophrenia increased after market approval of clozapine (Schirmbeck and Zink, 2012).
	The comorbidity rates in later disease stages are higher than at first manifestation of schizophrenia (see Figure 1).
	Schizophrenia patients with comorbid OCS are most frequently found to be treated with clozapine. Vice versa high OCS prevalence in patients treated with clozapine (Poyurovsky et al., 2004; Lim et al., 2007; Poyurovsky et al., 2007a; Schirmbeck et al., 2011).
Pharmacology	The type of antipsychotic treatment is associated with the risk for OCS: Marked difference between samples treated with first generation antipsychotics or mainly dopaminergic SGAs (such as aripiprazole or amisulpride) compared to clozapine (Ertugrul et al., 2005; Sa et al., 2009; Schirmbeck et al., 2011).
	OCS manifest as a unfavorable drug effect de novo during treatment with potent antiserotonergic SGAs such as clozapine (see Figure 3) (Schirmbeck and Zink, 2012).
	The severity of OCS is positively correlated with duration, dosage and serum levels of clozapine treatment (Lin et al., 2006; Schirmbeck et al., 2011).
	The OCS severity is found stable over time in patients under stable clozapine treatment (Schirmbeck et al., 2013).
	The severity of OCS improves after reduction of clozapine dosage to minimally sufficient levels (due to augmentation or combination) (Rocha and Hara, 2006; Zink et al., 2006; Englisch et al., 2009).

Summary of epidemiological and pharmacological arguments supporting the assumption that OCS can be induced or at least markedly aggravated by SGA-treatment as an unfavorable side effect (Schirmbeck et al., 2012b).