Fineberg NA, Sivakumaran T, Roberts A, Gale T. Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study. Int Clin Psychopharmacol 20: 223-226

Department of Psychiatry, Mental Health Unit, Queen Elizabeth II Hospital, Howlands, Hertfordshire, Welwyn Garden City, UK.
International Clinical Psychopharmacology (Impact Factor: 2.46). 07/2005; 20(4):223-6. DOI: 10.1097/00004850-200507000-00005
Source: PubMed


This study aimed to determine the efficacy and tolerability of adding quetiapine to a serotonin reuptake inhibitor in treatment-resistant obsessive-compulsive disorder (OCD). Twenty-one adult treatment-resistant OCD patients were randomized to 16 weeks of augmentation with either quetiapine (n = 11) or placebo (n = 10). Patients with significant comorbidities, including tic-spectrum disorders, were not included. The treatment was well tolerated, with only one premature dropout in each treatment-group. The primary analysis showed that individuals in the quetiapine-treated group showed a 14% mean improvement in baseline Yale-Brown Obsessive-Compulsive Scale scores at study endpoint compared with a 6% improvement in those treated with placebo, but this difference did not reach statistical significance (F<1). Three patients treated with quetiapine met criteria for clinical response, compared to one patient who was treated with placebo. Larger studies are needed to explore the efficacy of second generation antipsychotics, such as quetiapine, when used as adjunct treatment in resistant OCD.

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    • "Pharmacotherapy for OCD consists mainly of SSRIs, which suggests involvement of the serotonin system in the pathophysiology of the disorder. Nevertheless, an estimated 40–60% of patients does not respond to this treatment and require additional treatment with atypical antipsychotics, which affects both the serotonergic and dopaminergic system (Denys et al., 2004a; Fineberg et al., 2005). Neuroimaging studies have strengthened the notion of serotonergic dysfunction in OCD by providing evidence for reduced availability of SERTs in the midbrain, thalamus, and brainstem and reduced availability of serotonin 2A receptors in prefrontal, parietal, and temporal brain regions (Hesse et al., 2005; Perani et al., 2008). "
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    ABSTRACT: Over the past 20 years, motor response inhibition and interference control have received considerable scientific effort and attention, due to their important role in behavior and the development of neuropsychiatric disorders. Results of neuroimaging studies indicate that motor response inhibition and interference control are dependent on cortical-striatal-thalamic-cortical (CSTC) circuits. Structural and functional abnormalities within the CSTC circuits have been reported for many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD) and related disorders, such as attention-deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania. These disorders also share impairments in motor response inhibition and interference control, which may underlie some of their behavioral and cognitive symptoms. Results of task-related neuroimaging studies on inhibitory functions in these disorders show that impaired task performance is related to altered recruitment of the CSTC circuits. Previous research has shown that inhibitory performance is dependent upon dopamine, noradrenaline, and serotonin signaling, neurotransmitters that have been implicated in the pathophysiology of these disorders. In this narrative review, we discuss the common and disorder-specific pathophysiological mechanisms of inhibition-related dysfunction in OCD and related disorders.
    Frontiers in Human Neuroscience 06/2014; 8:419. DOI:10.3389/fnhum.2014.00419 · 3.63 Impact Factor
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    • "a inclus les études contrôlées randomisées évaluant l'efficacité des antipsychotiques versus placebo dans le traitement du TOC résistant : dix études étaient incluses, évaluant l'halopéridol [33], la risperidone [18] [20] [31], l'olanzapine [8] [47] et la quetiapine [3] [9] [13] [19]. Les risques relatifs des dix études étaient hétérogènes (chi 2 = 26,45 ; p = 0,002 ; IC = 66 %). "
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    ABSTRACT: Introduction Forty to sixty percent of patients with obsessive compulsive disorder (OCD) are resistant to well conducted treatment with selective serotonin reuptake inhibitors (SSRIs) over 8 weeks. The data concerning effectiveness of the addition of antipsychotics in this indication is controversial. Aims of the study To synthesize the neurobiological mechanisms at work in order to understand the action of pharmacological treatments in this disease and to propose a systematic review of the literature on effectiveness of different antipsychotic drugs according to their pharmacological profiles, in monotherapy or in combination with SSRIs in OCD. Method We conducted a systematic review of the literature using the criteria according to the PRISMA research paradigm “obsessive compulsive disorder AND antipsychotic agents”. Research bases MEDLINE, Cochrane and Web of science have been explored. Results Unlike the classical serotonergic hypothesis, OCD may result from striatal dopaminergic hyperactivity, modulated in some patients by an underlying serotonergic hypoactivity. Most studies report effectiveness of first-generation antipsychotics (amisulpride and haloperidol) and some second-generation antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine) in combination with an SSRI in the treatment of resistant OCD. Recrudescence or onset of OCD in patients with schizophrenia have been described in a relay from first generation antipsychotic to olanzapine, risperidone, aripiprazole or clozapine in case reports, but not amisulpride and quetiapine.
    Annales Médico-psychologiques revue psychiatrique 12/2013; 171(10):725–732. DOI:10.1016/j.amp.2013.09.001 · 0.22 Impact Factor
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    • "The blinding was insufficiently indicated in 4 trials (Bystritsky et al., 2004; Shapira et al., 2004; Fineberg et al., 2005; Kordon et al., 2008) for both participants/personnel (performance bias) and outcome assessment (detection bias). Overall attrition (outcome data reporting) was low (<10%) in 6 studies (McDougle et al., 1994, 2000; Denys et al., 2004; Carey et al., 2005; Erzegovesi et al., 2005; Fineberg et al., 2005), moderate (10%-25%) in 4 (Hollander et al., 2003; Shapira et al., 2004; Sayyah et al., 2012; Simpson et al., 2013), and high (>25%) in 4 trials (Bystritsky et al., 2004; Kordon et al., 2008; Muscatello et al., 2011; Storch et al., 2013). Outcome data necessary to accomplish this meta-analysis have not been sufficiently reported (missing standard deviations) in 2 studies (McDougle et al., 1994; Erzegovesi et al., 2005). "
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    ABSTRACT: Because of the high number of patients with obsessive-compulsive disorder (OCD) not responding satisfactorily to initial monotherapy with serotonin reuptake inhibitors (SRIs), the evaluation of additional treatment options is highly relevant. To examine efficacy of add-on pharmacotherapy with antipsychotics, a systematic literature search was applied to identify all double-blind, randomized, placebo-controlled trials (DB-PC-RCTs) determining the efficacy of antipsychotic augmentation of SRIs in treatment-resistant OCD. The primary outcome of the pooled meta-analytic data analysis was response to the adjunctive antipsychotic treatment measured by both the rates of participants achieving response [defined as ⩾35% reduction in Yale-Brown Obsessive-Compulsive Scale (YBOCS)] and mean changes in YBOCS total score. Twelve DB-PC-RCTs investigating quetiapine (N = 5), risperidone (N = 3), olanzapine (N = 2), aripiprazole (N = 1) and haloperidol (N = 1) with a total of 394 subjects were included. Significantly more patients responded to augmentation with antipsychotics than with placebo [relative risk = 2.10, 95% confidence intervals (CI) 1.16-3.80]. Additionally, the mean reduction of the YBOCS total score revealed an efficacy in favour of the antipsychotic medication [standardized mean difference (SMD) = 0.54, 95% CI 0.15-0.93]. Significant efficacy was identifiable only for risperidone, but not for quetiapine and olanzapine. The results regarding aripiprazole and haloperidol were inconsistent. Overall, about one-third of SRI-resistant OCD patients benefited from an augmentation strategy with antipsychotics. Based on the favourable risk:benefit ratio, risperidone can be considered as the agent of first choice and should be preferred to quetiapine and olanzapine. Further trials, mainly with higher antipsychotic doses, are required to optimize pharmacological treatment recommendations for SRI-refractory OCD.
    The International Journal of Neuropsychopharmacology 08/2012; 16(3):1-18. DOI:10.1017/S1461145712000740 · 4.01 Impact Factor
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