Differential effects of antipsychotic agents on obsessive–compulsive symptoms in schizophrenia: a longitudinal study

Abstract

Indirect evidence supports the assumption that antiserotonergic second-generation antipsychotics (SGA) induce and aggravate obsessive-compulsive symptoms (OCS) in schizophrenia. However, multimodal studies assessing the long-term interaction of pharmacotherapy and psychopathology are missing. Over 12 months, we followed-up 75 schizophrenia patients who were classified into two groups according to antipsychotic treatment: clozapine or olanzapine (group I) versus aripiprazole or amisulpride (group II). We applied the Yale Brown Obsessive Compulsive Scale (YBOCS) and investigated between-group changes over time as the primary endpoint. Group I showed markedly higher YBOCS scores at both time points. Repeated measure analyses of variance (ANOVAs) revealed significant interaction effects of group and time (per protocol sample (PP): p=0.006). This was due to persistently high OCS severity within group I, and decreasing YBOCS scores within group II. OCS severity correlated significantly with the negative and general psychopathology subscales of the Positive and Negative Syndrome Scale (PANSS), as well as with depressive symptoms. The progressive differences in OCS severity between our groups support the assumption of differential pharmacodynamic effects on comorbid OCS in schizophrenia. Further studies should address the pathogenetic mechanism, define patients at risk and facilitate early detection as well as therapeutic interventions.

Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia

“…This neuroimaging approach was conducted as part of a large multimodal assessment comparing patients with schizophrenia who were treated with different SGAs based on comorbid OCS, neurocognitive performance 12,13 and genetic risk factors. 27 Thus, study participants represent a partially overlapping subgroup of the predescribed samples.…”

Suicidality in clozapine-treated patients with schizophrenia: Role of obsessive-compulsive symptoms

“…This scale is considered suitable for assessing OCS in schizophrenia (de Haan et al, 2006;Boyette et al, 2011). A cut-off score of 8 was established to determine the presence of OCS as previously used by Schirmbeck et al (2011;2013a). In addition, the corresponding section of the MINI was used to assess the presence of OCD.…”

“…This profile of antiserotoninergic properties is thought to be the cause of the OC symptomatology. Three lines of evidence supports this: first, SSRI drugs alleviate SGA induced OCS (Dodt et al, 1997;Rahman et al, 1998), second, first generation antipsychotics do not cause and even improve OCS (Keuneman et al, 2005) and finally, the disinhibition of the dopaminergic neurotransmission caused by the blockade of 5HT2a receptors is thought to activate the circuits involved in the OC symptomatology as explained by the antiobsessive effects of others SGA characterized by a more antidopaminergic effect (Schirmbeck et al, 2011;2013a;Zink, 2012, 2013).…”

“…Additionally, there is evidence of a causal relationship between OC symptomatology and treatment with SGA, particularly clozapine. This comes from retrospective cohort studies (Mahendran et al, 2007) and prospective ones (Schirmbeck et al, 2013a). Furthermore, a dose-response pattern (Lin et al, 2006;Schirmbeck et al, 2011) and an association between duration of clozapine treatment and OCS severity (Schirmbeck et al, 2011) have been described.…”

Eine Domäne der Psychotherapie

“…Es bietet zudem den Vorteil der fehlenden Gewichtszunahme, kann allerdings Unruhe und Schlafstörungen verursachen. Aripiprazol induziert bei Patienten mit Schizophrenie außerdem deutlich weniger Zwangssymptome als die dort bisher verwendeten Substanzen Clozapin und Olanzapin [6]. Auch achtsamkeitsbasierte Psychotherapie zusätzlich zur Exposition ist nach einer ersten kontrollierten Studie signi kant wirksam [7].…”