Article

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

ABSTRACT

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.
    Full-text · Article · Jun 2014 · Frontiers in Human Neuroscience
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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.
    Full-text · Article · Dec 2013 · Annales Médico-psychologiques revue psychiatrique
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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: Background: Many patients with obsessive-compulsive disorder do not respond adequately to serotonin reuptake inhibitors. Augmentation with antipsychotic drugs can be beneficial in this regard. However, since new relevant randomized controlled trials evaluating new antipsychotics were conducted, a recalculation of the effect sizes appears necessary. Methods: We meta-analyzed all double-blind, randomized, placebo-controlled trials comparing augmentation of serotonin reuptake inhibitors with antipsychotics to placebo supplementation in treatment-resistant obsessive-compulsive disorder. The primary outcome was mean change in the Yale-Brown Obsessive–Compulsive Scale total score. Secondary outcomes were obsessions, compulsions, response rates, and attrition rates. The data collection process was conducted independently by 2 authors. Hedges’s g and risks ratios were calculated as effect sizes. In preplanned meta-regressions, subgroup analyses, and sensitivity analyses, we examined the robustness of the results and explored reasons for potential heterogeneity. Results: Altogether, 14 double-blind, randomized, placebo-controlled trials (n=491) investigating quetiapine (N=4, n=142), risperidone (N=4, n=132), aripiprazole (N=2, n=79), olanzapine (N=2, n=70), paliperidone (N=1, n=34), and haloperidol (N=1, n=34) were incorporated. Augmentation with antipsychotics was significantly more efficacious than placebo in Yale-Brown Obsessive–Compulsive Scale total reduction (N=14, n=478; Hedges’s g=-0.64, 95% CI: -0.87 to -0.41; P=<.01). Aripiprazole (Hedges’s g=-1.35), haloperidol (Hedges’s g=-0.82), and risperidone (Hedges’s g=-0.59) significantly outperformed placebo. Antipsychotics were superior to placebo in treating obsessions, compulsions, and achieving response. There was no between-group difference concerning all-cause discontinuation. The nonsignificant meta-regressions suggest no influence of the antipsychotic dose or baseline symptom severity on the meta-analytic results. Conclusions: According to our findings, antipsychotic augmentation of serotonin reuptake inhibitors can be regarded as an evidence-based measure in treatment-resistant obsessive-compulsive disorder.
    Full-text · Article · Aug 2012 · The International Journal of Neuropsychopharmacology
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