Clozapine-Induced Obsessive-Compulsive Syndromes Improve in Combination With Aripiprazole

Abstract

Patients with schizophrenia often experience comorbid obsessive-compulsive syndromes (OCSs). Within these patients, a significant subgroup developed secondary OCS during treatment with antiserotonergic, atypical antipsychotic agents such as clozapine. Although cognitive behavioral therapy and antiobsessive antidepressants brought up inconsistent results, in some cases, dose reductions of clozapine in combination approaches were able to alleviate OCS. One suggestive agent for antiobsessive add-on treatment is aripiprazole, a partial agonist at dopamine and serotonin receptors.Here, we summarize the courses of 7 patients (6 men; mean age, 37 years; mean duration of psychotic illness, 17 years). They had been treated with clozapine for 9 years. The distressing and treatment-resistant comorbidity with OCS emerged approximately 4 years after the start of clozapine therapy. During combined treatment with mean doses of 22.9 mg of aripiprazole for 9.7 weeks, we assessed a small yet statistically not significant improvement of the psychotic disorder, whereas a marked reduction of obsessions and significant improvements of compulsions could be observed. The mean total Yale Brown Obsessive Compulsive Rating Scale decreased from 18.7 to 12.4 (P = 0.003).These data support the findings of 2 previous case reports and point toward an antiobsessive potency of aripiprazole. The relevant disabling comorbidities of psychosis and OCS need further investigation with multimodal neurobiological approaches. The proposed strategy should be further evaluated in prospective controlled trials with severity of comorbid OCS as a primary end point.

Relationship of obsessive compulsive symptoms/disorder with clozapine: A retrospective study from a multispeciality tertiary care centre

“…However, whenever used, SSRIs were found to be useful in management of de novo OCS/OCD. There are reports of spontaneous resolution (Lykouras et al, 2003) and beneficial effect of dose reduction (Rocha and Hara, 2006;Zink et al, 2006;Englisch et al, 2009) and selective serotonin reuptake inhibitors (SSRIs) (de Haan et al, 1999;Lykouras et al, 2003). These findings suggest that whenever a patient develops de novo OCS/OCD with clozapine, the first strategy could be a wait and watch policy or dose reduction, depending on the severity of primary psychotic illness.…”

“…(Lykouras et al, 2003), while others suggest reduction in symptoms with reduction in doses of clozapine (Rocha and Hara, 2006;Zink et al, 2006;Englisch et al, 2009). Studies have also reported beneficial effect of aripiprazole (Englisch et al, 2009) and selective serotonin reuptake inhibitors (SSRIs) (de Haan et al, 1999;Lykouras et al, 2003). Studies have also reported worsening of OCS/OCD in a small proportion (1.4-20.6%) of patients receiving clozapine (Ghaemi et al, 1995;de Haan et al, 1999;Baker et al, 1992;Lin et al, 2006).…”

Clozapine-Induced Obsessive-Compulsive Symptoms in Schizophrenia: A Critical Review

“…Several case reports [59,60], cases series [61] and systematic evaluations [38,39,42] describe the de-novo emergence of OCS during the treatment with atypical antipsychotics. As described in Table 1 , De Haan et al reported OCS development within several months after treatment initiation with CLZ in 20.6% of recent-onset patients [38].…”

“…Within SGAs, marked differences exist in specific pharmacodynamic properties, in particular regarding inherent serotonergic blockade, monoaminergic reuptake inhibition or even partial serotonergic agonism [66-70]. The partial dopaminergic and serotonergic agonist aripiprazole per se was associated with an inherent anti-obsessive potency [59,61,71-73], quite similar to amisulpride, a substance with nearly exclusive affinity to dopamine D3/D2 receptors [74,75]. Our workgroup conducted a cross-sectional analysis of 70 schizophrenic patients under monotherapy with CLZ or olanzapine (group I) vv amisulpride or aripiprazole (group II).…”

A 44-Year-Old Woman with Intrusive Thoughts

“…10 In addition, there are case reports describing the use of aripiprazole augmentation in the treatment of clozapine-associated OCS. 11,12 In all nine cases, patients developed OCS or experienced a worsening of OCS after initiating clozapine, and in all cases the addition of aripiprazole (average dose 22.9 mg daily in the study by Englisch and colleagues 12 and 30 mg daily in the study by Vallari and colleagues 11 ) was associated with improvement in OCS. Englisch showed a decrease in total Y-BOCS score from 18.7 to 12.43 after initiation of aripiprazol, with a mean observation period of 9.7 weeks.…”