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.
Obsessive‐compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence ...links these conditions with underlying dysregulation of fronto‐striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of ‘false alarms’ for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.
LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐4
Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two ...computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.
In response to the emerging crisis and growing calls from patients and clinicians for guidance 5, a working group of clinical experts from the International College of Obsessive Compulsive Spectrum ...Disorders (ICOCS) and the Obsessive-Compulsive and Related Disorders Research Network of the European College of Neuropsychopharmacology (OCRN) have produced this consensus statement with the aim of delivering pragmatic guidance at the earliest opportunity to clinicians for managing this complex challenge. Based on the risks associated with exposure and response prevention (ERP) in the pandemic (see below), and uncertainty as to which of the two evidence-based treatments, pharmacotherapy or cognitive behaviour therapy (CBT), represents the most efficacious first line treatment modality 11, pharmacotherapy should be the first option for adults and children with OCD with contamination, washing or cleaning symptoms during the COVID-19 pandemic. Consider A) type of medication; most patients should receive an SSRI, or if not responsive, another SSRI and as a third choice clomipramine (for which an ECG may be required in certain patient groups); Note US Food and Drug Administration "black box" warnings or advice from equivalent national regulatory authorities regarding increased risk in young people and other vulnerable patient groups. Check for adverse effects and be available for any concerns related to "activation" or newly emergent or increased suicidal ideation, which in the young can be mitigated by starting treatment at a low dose and titrating more gradually; B) dosage; if the patient is on a suboptimal dose, consider increasing it, paying attention to any contraindications; C) SSRI-resistance; consider a low dose of adjunctive antipsychotic (aripiprazole, risperidone, quetiapine, olanzapine), especially if a tic is present; D) adherence; ensure the patient is able to obtain an adequate supply and is taking the treatment regularly.
OCD is characterized by obsessions (recurrent, intrusive, unwanted thoughts, images or impulses and compulsions (repetitive behaviors or mental acts that the individual feels compelled to perform), ...which can manifest together or separately (Fineberg et al., 2020). NICE guidelines suggest that low intensity psychological treatments (including ERP) is the first line treatment for OCD, and that a “stepped care” treatment approach for OCD reserves combination treatment for adults with OCD with severe functional impairment, and for adults without an adequate response to: 1) treatment with an SSRI alone (12 weeks duration) or 2) CBT (including ERP) alone (NICE, 2005). Existing US treatment guidelines (APA guidelines) suggest that there are three first-line treatments for OCD (SSRI, CBT, SSRI+CBT) and recommends combined treatment for patients with an unsatisfactory response to monotherapy or for patients with severe OCD. Although, systematic review and meta-analysis of studies published in 1993–2014 suggest that combination treatment was not significantly better than CBT plus placebo (Ost et al., 2015), based on data from a recent systematic and meta-analysis which searched the two controlled trials registers maintained by the Cochrane Collaboration Common Mental Disorders group, the combination treatment approach is likely to be more effective than psychotherapeutic interventions alone, at least in severe obsessive-compulsive disorder (Skapinakis et al., 2016a). Based on data from Optimal treatment for OCD study conducted by Fineberg et al., (2018) combined treatment appeared to be the most effective especially when compared to CBT monotherapy, but SSRI monotherapy was found as the most cost effective. In this review we summarize available treatment recommendations.
•This manuscript examines whether or not combination treatment with an SSRI and low intensity psychological treatment (ERP or CBT with or without ERP) is the optimal initial treatment for OCD in comparison to monotherapy treatments (CBT or SSRI).•NICE guidelines suggest that low intensity psychological treatments (including ERP) is the first line treatment for OCD, and that a “stepped care” treatment approach for OCD reserves combination treatment for adults with OCD with severe functional impairment, and for adults without an adequate response to: 1) treatment with an SSRI alone (12 weeks duration) or 2) CBT (including ERP) alone (Fineberg et al., 2020).•NICE guidelines further suggest that more research is needed as to the effect of combination treatment versus single-strand treatments and involve a follow-up of 1, 2 and 5 years (Fineberg et al., 2020).•Questions remain as to whether combination treatment is better for improving treatment response or for disease remission.
The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the ...Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.
Obsessive compulsive disorder (OCD) is a highly debilitating neuropsychiatric condition with estimated lifetime prevalence of 2–3%, more than twice that of schizophrenia. However, in contrast to ...other neuropsychiatric conditions of a comparable or lesser prevalence, relatively little is understood about the aetiology, neural substrates and cognitive profile of OCD. Despite strong evidence for OCD being familial, with risk to first-degree relatives much greater than for the background population, its genetic underpinnings have not yet been adequately delineated. Although cognitive dysfunction is evident in the everyday behaviour of OCD sufferers and is central to contemporary psychological models, theory-based studies of neurocognitive function have yet to reveal a reliable cognitive signature, and interpretation has often been confounded by failures to control for co-morbidities. The neuroimaging findings in OCD are amongst the most robust reported in the psychiatric literature, with structural and functional abnormalities frequently reported in orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus. In spite of this, our relative lack of understanding of OCD neurochemical processes continues to impede progress in the development of novel pharmacological treatment approaches. Integrating the neurobiological, cognitive, and clinical findings, we propose that OCD might usefully be conceptualised in terms of lateral orbitofrontal loop dysfunction, and that failures in cognitive and behavioural inhibitory processes appear to underlie many of the symptoms and neurocognitive findings. We highlight existing limitations in the literature, and the potential utility of endophenotypes in overcoming these limitations. We propose that neurocognitive indices of inhibitory functions may represent a useful heuristic in the search for endophenotypes in OCD. This has direct implications not only for OCD but also for putative obsessive-compulsive spectrum conditions including attention deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania (compulsive hair pulling).
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 Y-BOCS 25.4 vs. 17.7). 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.
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