The pharmacological evidence-base for the treatment of OCD is becoming increasingly robust. Treatment with SSRIs and clomipramine remains uncontroversial and improvements are sustained over time. Newer compounds targeting serotonin receptor subtypes and other neurotransmitter systems are undergoing evaluation.
Convincing evidence from placebo-referenced randomized controlled trials supports efficacy for clomipramine and selective serotonin reuptake inhibitors for acute treatment of obsessive-compulsive disorder. It remains less conclusively understood whether these agents maintain efficacy over the longer term. This paper systematically reviews long-term medication studies in obsessive-compulsive disorder. Studies of clomipramine, fluoxetine and sertraline investigated 'responders' from acute treatment trials and extended treatment up to 12 months versus placebo. Responses to medication were sustained. A 24-week placebo-controlled trial of escitalopram (10 mg or 20 mg/day) and paroxetine (40 mg/day) demonstrated ongoing efficacy for all three treatments. Studies that randomized treated cases to placebo demonstrated reemergence of symptoms in the placebo-treated cohort. Six relapse prevention trials were found by systematic search. Some, but not all, revealed significant advantages for remaining on medication. Paroxetine (20-60 mg/day) and escitalopram (10 or 20 mg/day) were each found to outperform placebo in preventing relapse during 24 weeks of double-blind, randomized follow-up. Meta-analysis, using Review Manager software (4.2.8), detected overall superiority of selective serotonin reuptake inhibitors to placebo in preventing relapse among adult treatment-responders. Worsening by five Yale-Brown Obsessive Compulsive Scale points emerged from the review as a suggested threshold for relapse. Viewed collectively, these results suggest that selective serotonin reuptake inhibitors are effective long-term treatments and relapse prevention represents the treatment target for obsessive-compulsive disorder.
This article presents a systematic, retrospective case-note survey of a specialist obsessive-compulsive disorder (OCD) outpatient service. We explore the frequency of 'high-dose' selective serotonin reuptake inhibitor (SSRI) prescribing and describe clinical outcomes in a naturalistic clinical setting. Patients receiving high doses were compared with 'control' cases at the following three time-points: referral, initiation of high-dose SSRI and last clinical assessment.Twenty-six (13.5%) out of 192 patients received high-dose treatment for 3-364 weeks (mean 81.5 weeks; SD = ±95.1). At referral, high-dose patients were significantly more likely than controls to be male, and to have received Cognitive Behavioural Therapy (CBT), although illness severity and complexity did not differ. At initiation of dose escalation, however, high-dose patients were significantly more symptomatic than controls (Yale-Brown Obsessive Compulsive Scale score ). At the last assessment, patients on high-dose treatment showed significant within-group improvements (Y-BOCS 25.35 vs. 20.95), although endpoint scores for the high-dose group remained significantly higher than control patients treated for a matched period (Y-BOCS 21.0 vs. 15.5), suggesting enduring treatment-resistance. Frequency of adverse effects did not significantly differ between the two groups. Our results suggest that high-dose SSRI was associated with clinical improvement and well-tolerated in a particularly refractory OCD sample.
Obsessive-compulsive disorder is a prevalent and disabling lifespan disorder. Clomipramine and the SSRIs have been found to be effective across the range of symptoms, both in acute and longer-term studies. Meta-analyses have reported a larger treatment effect for clomipramine relative to the SSRIs, but this is not supported by evidence from head-to-head comparator studies and, based on their superior safety and tolerability, SSRIs are the preferred option for long-term treatment in most cases. The treatment-effect is usually gradual and partial, and many patients fail to respond adequately to first-line treatment. Pharmacological options for refractory cases include switching SRI, increasing the dose, or augmenting with an antipsychotic agent. Novel strategies are under investigation for this highly morbid group. This paper reviews the key questions related to OCD pharmacotherapy, synthesizing evidence derived from randomized controlled trials, meta-analyses and consensus guidelines.
Social anxiety disorder (SAD) is characterised by fear of scrutiny by other people, avoidance of social situations and vegetative/motor symptomatology. The correlation between reduced striatal dopaminergic (DA) function, SAD motor symptoms and the high occurrence of SAD in patients with Parkinson's disease (PD), suggests a link between SAD and movement diseases caused by dopamine dysfunction. However, little is known about the electrophysiological aspects of SAD. We applied single- and paired-pulse transcranial magnetic stimulation (TMS) to investigate excitatory and inhibitory mechanisms of the primary motor cortex (M1) in 15 SAD patients and the relationship between these neurophysiological measures and clinical symptoms or temperamental traits. Data were compared with those obtained in 15 age- and sex-matched healthy volunteers. SAD patients showed significantly higher harm avoidance scores and lower novelty seeking scores when compared to controls. TMS measures did not significantly differ between groups. However, in SAD patients the cortical silent period (CSP) duration and the amount of long-interstimulus interval intracortical inhibition were significantly correlated with the NS score. Accordingly with NS reduction and CSP shortening reported in PD, the relationship between NS levels and the excitability of inhibitory circuits of the M1 may support the hypothesis that DA dysfunction could underlie NS deficits in SAD. Furthermore, these data suggest that "trait variables" (i.e., NS) are more closely related to neurophysiological measures than SAD symptoms, which represent "state variables" linked to social performance.
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