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.
"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). "
[Show abstract][Hide abstract] 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 · 2.99 Impact Factor
"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). "
[Show abstract][Hide abstract] 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
"Open studies and case reports have evaluated the efficacy of quetiapine as addon therapy in obsessional states.86,87 In OCD patients refractory to at least two SSRI trials, quetiapine 200 mg/day was shown to be significantly more efficacious than SSRI monotherapy in reducing obsessive symptoms, with 40% of patients rated as responders. "
[Show abstract][Hide abstract] ABSTRACT: Obsessional states show an average point prevalence of 1%-3% and a lifetime prevalence of 2%-2.5%. Most treatment-seeking patients with obsessions continue to experience significant symptoms after 2 years of prospective follow-up. A significant burden of impairment, distress, and comorbidity characterize the course of the illness, leading to an increased need for a better understanding of the nature and management of this condition. This review aims to give a representation of the current pharmacological and psychotherapeutic strategies used in the treatment of obsessive-compulsive disorder. Antidepressants (clomipramine and selective serotonin reuptake inhibitors) are generally the first-line choice used to handle obsessional states, showing good response rates and long-term positive outcomes. About 40% of patients fail to respond to selective serotonin reuptake inhibitors. So far, additional pharmacological treatment strategies have been shown to be effective, ie, administration of high doses of selective serotonin reuptake inhibitors, as well as combinations of different drugs, such as dopamine antagonists, are considered efficacious and well tolerated strategies in terms of symptom remission and side effects. Psychotherapy also plays an important role in the management of obsessive-compulsive disorder, being effective for a wide range of symptoms, and many studies have assessed its long-term efficacy, especially when added to appropriate pharmacotherapy. In this paper, we also give a description of the clinical and psychological features likely to characterize patients refractory to treatment for this illness, with the aim of highlighting the need for greater attention to more patient-oriented management of the disease.
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