Jacobsen FM. Risperidone in the treatment of affective illness and obsessive-compulsive disorder. J Clin Psychiatry 56: 423-429
Risperidone is a new-generation atypical antipsychotic agent with potent dopaminergic and serotonergic antagonist activity. Compared with traditional dopamine-blocking neuroleptics, risperidone is more effective in treating negative symptoms of schizophrenia and may be less likely to cause extrapyramidal symptoms or tardive dyskinesia. Although risperidone is marketed for the treatment of schizophrenia, its novel psychopharmacologic effects and potentially mild side effect profile suggest the possibility of other therapeutic applications. An open prospective study was undertaken to determine whether risperidone might diminish psychosis, severe agitation, or rapid cycling in patients having acute and chronic primary affective illnesses (bipolar and major depressive disorder) and to document response characteristics and side effects. Additionally, a small number of patients with refractory obsessive-compulsive disorder (OCD) without comorbid tic or delusional disorders were given open trials of risperidone added to their medication.
Outpatients who fulfilled DSM-IV criteria for bipolar I, bipolar II, or major depressive disorder and suffered from psychosis or agitation associated with their illness (N = 20) and those who had treatment-refractory DSM-IV OCD (N = 5) were started on open trials of risperidone at daily doses of 1 to 1.5 mg. Doses were adjusted upwards to a maximum of 6 mg depending on clinical response.
Seventeen (85%) of 20 patients (13 bipolar, 4 major depressive disorder) showed complete or partial improvement after treatment with risperidone doses ranging from 1 to 6 mg/day (mean = 3.5 mg). Beneficial effects included decreases in agitation, psychosis, sleep disturbance, and rapid cycling. Four patients (20%) discontinued risperidone because of intolerable side effects. Five patients with refractory OCD also showed significant symptomatic improvement after the addition of risperidone.
The findings suggest that (1) risperidone may be useful in the acute/p.r.n. and chronic treatment of psychosis, agitation, and cycling accompanying affective illness, and (2) risperidone may be useful in augmenting pharmacologic response in OCD.
Available from: Massimo Pasquini
- "Atypical antipsychotic have also been tested as add-on agents for treatment resistant OCD patients. Trials have been succesfully conducted with risperidone [7-10], olanzapine [11-13], amisulpride  and quietiapine [15, 16]. "
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ABSTRACT: Antipsychotic augmentation is an effective treatment intervention for Obsessive Compulsive Disorder (OCD) patients resistant to Selective Serotonin Reuptake Inhibitors (SSRI) agents. This pilot study was conducted to evaluate the effectiveness and tolerability of Aripiprazole for the augmentation of standard treatments in patients with resistant OCD.
Twenty patients diagnosed with OCD according to DSM-IV TR criteria and having a history of resistance to standard pharmacological treatment were included in the study. Aripiprazole was added to ongoing SSRI or clomipramine treatment with a starting dose of 5 mg/day and titrated up to a maximum of 20 mg/day (mean dose 12.62 mg ± 4.25). Efficacy was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS) and the Clinical Global Improvement-severity scale (CGI-S) at baseline and at week 12 of Aripiprazole augmentation. Side effects were monitored by the Udvalg for Kliniske Undersogelser (UKU) side effect rating scale.
All 20 subjects enrolled in our study completed the full 12-week course of treatment. A significant improvement over the 12-week study period was observed (paired t-test for mean Y-BOCS total score at week 12 as compared with baseline - all patients: t = 13.146, d.f. = 19, p= 0.0001). Aripiprazole was generally well tolerated and no changes were observed in vital signs. The most commonly observed side effects after the introduction of the augmenting agent included: akathysia, nausea/vomiting, hyperkinesia, tension/inner unrest, tremors, asthenia/lassitude/increased fatiguability.
Although results of this pilot study are preliminary and require confirmation in randomized controlled trials, our experience suggested that Aripiprazole is effective and well-tolerated as an augmenting agent in patients with treatment resistant OCD.
Available from: Stefano Erzegovesi
- "Recent studies have tested atypical antipsychotics in OCD. Open-label administration of risperidone in SRIrefractory OCD patients (Giakas, 1995; Jacobsen, 1995; Lombroso et al., 1995; McDougle et al., 1995; Stein et al., 1997) significantly increased the antiobsessional response . In a double-blind placebo controlled study, McDougle et al. (2000) confirmed the open-label results. "
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ABSTRACT: According to previous data, the addition of risperidone in obsessive-compulsive patients refractory to serotonin reuptake inhibitors (SRIs) is shown to be a safe and effective treatment strategy. The aims of our study were to evaluate the efficacy of risperidone addition, in comparison to placebo, in fluvoxamine-refractory obsessive-compulsive patients and to investigate whether risperidone could boost the efficacy of fluvoxamine in fluvoxamine-responder patients. Subjects were 45 obsessive-compulsive inpatients, consecutively recruited at the Department of Neurosciences at the San Raffaele Hospital, Milan. Thirty-nine patients completed the study. All patients received 12 weeks of a standardized open-label fluvoxamine monotherapy and then continued for 6 weeks with placebo or risperidone in a double-blind design. Results showed a significant effect of risperidone addition, at the end of the double-blind phase (18th week), only for fluvoxamine-refractory patients. Five patients on risperidone (50%) and two (20%) on placebo became responders, with a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) decrease > or =35%. Risperidone was generally well tolerated, except for a mild transient sedation and a mild increase in appetite. This preliminary study suggests that even very low (0.5 mg) risperidone doses are effective in OC patients who were nonresponders to a standardized treatment with fluvoxamine.
Available from: Jitender Sareen
- "Risperidone was found in multiple case reports (Stein et al., 1997), four open-label augmentation trials (Saxena et al., 1996; Pfanner et al., 2000; Jacobsen, 1995; Ravizza et al., 1996) and one double-blind study (McDougle et al., 2000) to be effective in alleviating obsessive-compulsive symptoms. "
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ABSTRACT: Paradoxically, some reports in the literature support the use of antipsychotics in the treatment of Obsessive Compulsive Disorder (OCD), while other reports suggest that antipsychotics can exacerbate OCD symptoms. To date, there is no published systematic review of the relationship between OCD symptoms and antipsychotic drugs.
A Medline and PsychInfo search (1980-2003) was conducted to collect published reports of the interactions between antipsychotics and OCD symptoms.
In the treatment of refractory OCD, case series, open label trials and placebo-controlled trials were found suggesting efficacy of antipsychotic augmentation to ongoing antidepressant treatment. In the placebo-controlled trials with haloperidol, risperidone, olanzapine, and quetiapine, a significantly higher response rate (46-71%) was found for the antipsychotic groups, compared to no response for the placebo groups. Reports of exacerbation of OCD symptoms with the use of atypical antipsychotics were limited to individuals with a primary psychotic disorder.
Definition of response in most of these treatment studies was based on a modest reduction of OCD symptoms, and no studies were available on long-term efficacy. There were also no published reports that systematically evaluated the incidence of OCD symptoms associated with atypical antipsychotics.
All antipsychotics mentioned above had short-term controlled evidence to support their use as augmenting agents in the treatment of refractory OCD. The suggested management of OCD induction/exacerbation due to atypical antipsychotics is to increase the dose of the atypical antipsychotic and/or add a selective serotonin reuptake inhibitor.
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