A prospective investigation of impacts of comorbid attention deficit hyperactivity disorder (ADHD) on clinical features and long-term treatment response in adult patients with obsessive-compulsive disorder (OCD).

BACKGROUND: A close association between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents has been investigated in previous studies. However, few studies examined the relationship between lifetime comorbidity of ADHD and OCD in adults. Therefore, we sought to investigate the clinical and psychopathological features related to comorbid ADHD in Japanese adult patients with OCD. METHODS: We assessed lifetime comorbidity of ADHD in 93 adult Japanese patients with OCD. Additionally, we used the Japanese version of Conners' Adult ADHD Rating Scales to assess the characteristics and severity of ADHD in each participant. According to the results, we excluded OCD patients that did not have ADHD but who exhibited elevated levels of ADHD traits. We compared OCD patients with ADHD (ADHD+ group) and those without ADHD or its trait (ADHD- group) in terms of background profiles and clinical features, such as OCD symptomatology and psychometric test results. Additionally, the 6-month treatment outcome was compared prospectively between groups. RESULTS: Of the 93 OCD participants, the prevalence of lifetime comorbidity of ADHD was estimated as 16.1%. Compared with the ADHD- group, participants in the ADHD+ group had an earlier age of onset of OCD, higher frequencies of hoarding symptoms, higher levels of depressive and anxiety symptoms and lower quality of life, more elevated levels of impulsivity, and higher rates of substance or behavioral addiction and major depression. Finally, the mean improvement rate on the Yale-Brown Obsessive Compulsive Scale after 6 months of standardized OCD treatment in the ADHD+ group (16.1%) was significantly lower than that in the ADHD- group (44.6%). CONCLUSION: The lifetime comorbidity of ADHD is likely to exert a significant effect on clinical features and treatment outcome in adult patients with OCD. It is important to consider that underlying ADHD pathology may function as a facilitator for increased severity of global clinical features and treatment refractory conditions in OCD patients. Further studies are required to examine treatment strategies for such patients.

Molecular Mechanisms of IL18 in Disease.

Interleukin 18 (IL18) was originally identified as an inflammation-induced cytokine that is secreted by immune cells. An increasing number of studies have focused on its non-immunological functions, with demonstrated functions for IL18 in energy homeostasis and neural stability. IL18 is reportedly required for lipid metabolism in the liver and brown adipose tissue. Furthermore, IL18 (Il18) deficiency in mice leads to mitochondrial dysfunction in hippocampal cells, resulting in depressive-like symptoms and cognitive impairment. Microarray analyses of Il18-/- mice have revealed a set of genes with differential expression in liver, brown adipose tissue, and brain; however, the impact of IL18 deficiency in these tissues remains uncertain. In this review article, we discuss these genes, with a focus on their relationships with the phenotypic disease traits of Il18-/- mice.

Evaluation of hemodynamic changes using near-infrared spectroscopy in patients with tic-related obsessive-compulsive disorder.

AIM: A tic-related specifier is included in the DSM-5 diagnostic criteria to identify a clinically specific obsessive-compulsive disorder (OCD) subtype. The current study sought to evaluate hemodynamic changes during executive function tasks among OCD patients with and without a lifetime history of tic disorder (TD) and healthy controls, and to investigate the relation between brain activation and clinical variables in each group using structured equation modeling. METHODS: Twenty-nine OCD patients diagnosed according to the DSM-IV-TR and 15 healthy controls were recruited. Patients were divided into two groups according to the presence or absence of a lifetime history of TD (TD+, n = 11; TD-, n = 18). Prefrontal hemodynamic changes were measured using multi-channel near-infrared spectroscopy during the Verbal Fluency Task, Trail-Making Task, and Tower of London (ToL) Task. RESULTS: There were significant brain activation differences in the frontopolar cortex between OCD patients with and without TD during Verbal Fluency Task and ToL performance. Brain activation in the dorsolateral prefrontal cortex (DLPFC) during the ToL Task in OCD patients with TD exerted a direct causal effect on the severity of compulsions. In addition, we detected a direct causal effect of the severity of obsessions in OCD patients without TD on brain activation in the DLPFC during the ToL Task. CONCLUSION: Brain activation in the frontopolar cortex exhibits different hemodynamics depending on the task, and DLPFC function may play a different role in the neural basis of developing OCD symptoms between OCD patients with and without TD.

The rates of co-occurring behavioural addictions in treatment-seeking individuals with obsessive-compulsive disorder: a preliminary report.

Objectives: To assess the rates of co-occurring putative 'behavioural addictions' in patients with obsessive-compulsive disorder (OCD).Methods: Twenty-three international centres specialising in the treatment of OCD were invited to participate in a survey of the rates of behavioural addictions and other relevant comorbidity within their samples.Results: Sixteen of 23 (69.6%) invited centres from 13 countries had sufficient data to participate in the survey. The use of validated diagnostic tools was discrepant, with most centres relying on a 'clinical diagnosis' to diagnose behavioural addictions. The final sample comprised of 6916 patients with a primary diagnosis of OCD. The reported rates of behavioural addictions were as follows: 8.7% for problematic internet use, 6.8% for compulsive sexual behaviour disorder, 6.4% for compulsive buying, 4.1% for gambling disorder and 3.4% for internet gaming disorder.Conclusions: Behavioural addictions should be better assessed for patients with OCD. The absence of diagnostic scales developed specifically for behavioural addictions and overlapping obsessive-compulsive phenomena such as compulsive checking of information on the internet may explain the relatively high rate of problematic internet use in this sample. The study encourages better efforts to assess and to conceptualise the relatedness of behavioural addictions to obsessive-compulsive 'spectrum' disorders.

Treatments used for obsessive-compulsive disorder-An international perspective.

OBJECTIVE: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. RESULTS: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. CONCLUSIONS: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.

Physiological and molecular effects of interleukin-18 administration on the mouse kidney.

BACKGROUND: The cytokine interleukin-18 was originally identified as an interferon-γ-inducing proinflammatory factor; however, there is increasing evidence to suggest that it has non-immunological effects on physiological functions. We previously investigated the potential pathophysiological relationship between interleukin-18 and dyslipidemia, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis, and suggested interleukin-18 as a possible novel treatment for not only these diseases but also for cancer immunotherapy. Before clinical application, the effects of interleukin-18 on the kidney need to be determined. In the current study, we examined the kidney of interleukin-18 knockout (Il18-/-) mice and the effects of interleukin-18 on the kidney following intravenous administration of recombinant interleukin-18. METHODS: Il18-/- male mice were generated on the C57Bl/6 background and littermate C57Bl/6 Il18+/+ male mice were used as controls. To assess kidney damage, serum creatinine and blood urea nitrogen levels were measured and histopathological analysis was performed. For molecular analysis, microarray and quantitative reverse transcription PCR was performed using mice 6 and 12 weeks old. To evaluate the short- and long-term effects of interleukin-18 on the kidney, recombinant interleukin-18 was administered for 2 and 12 weeks, respectively. RESULTS: Compared with Il18+/+ mice, Il18-/- mice developed kidney failure in their youth-6 weeks of age, but the condition was observed to improve as the mice aged, even though dyslipidemia, arteriosclerosis, and higher insulin resistance occurred. Analyses of potential molecular mechanisms involved in the onset of early kidney failure in Il18-/- mice identified a number of associated genes, such as Itgam, Nov, and Ppard. Intravenous administration of recombinant interleukin-18 over both the short and long term showed no effects on the kidney despite significant improvement in metabolic diseases. CONCLUSIONS: Short- and long-term administration of interleukin-18 appeared to have no adverse effects on the kidney in these mice, suggesting that administration may be a safe and novel treatment for metabolic diseases and cancer.

Deficiency in interleukin-18 promotes differentiation of brown adipose tissue resulting in fat accumulation despite dyslipidemia.

BACKGROUND: The cytokine, interleukin-18 (IL-18), was originally identified as an interferon-γ-inducing proinflammatory factor; however, there is increasing evidence suggesting that it has non-immunological effects on physiological functions. We have previously investigated the potential pathophysiological relationship between IL-18 and dyslipidemia, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, which were mediated by lipid energy imbalance. Therefore, herein we focused on brown adipocytes (BAs) and brown adipose tissue (BAT) related to energy consumption as non-shivering thermogenesis. METHODS: Il18-/- male mice were generated on the C57Bl/6 background, and littermate C57Bl/6 Il18+/+ male mice were used as controls. To reveal the direct effect of IL-18, primary cell cultures derived from both mice were established. Moreover, for molecular analysis, microarray, quantitative reverse transcription PCR and western blotting were performed using 6 and 12 weeks old mice. To evaluate the short- and long-term effects of IL-18 on BAT, recombinant IL-18 was administered for 2 and 12 weeks, respectively. RESULTS: Compared with Il18+/+ mice, BAT of Il18-/- mice showed earlier differentiation and lipid accumulation. To examine the direct effect of IL-18 on BAT, BA cell cultures were established. Myogenic factor 5-expressing adipose precursor cells were extracted from Il18+/+ and Il18-/- mice. PR domain containing 16 (PRDM16), a differentiation inducer, was strongly expressed in Il18-/- BAs, and uncoupling protein 1, a thermogenic and differentiation marker, was upregulated, resulting in the promotion of BA differentiation. Moreover, PRDM16-dependent and independent molecules related to BAT function, such as fibroblast growth factor 21, were activated. These findings were confirmed by comparing Il18+/+ and Il18-/- mice at 6 and 12 weeks of age. Additional analyses of the molecular mechanisms influencing the 'Quantity of adipocytes' identified three associated genes, apolipoprotein C3 (Apoc3), insulin-induced gene 1 (Insig1) and vitamin D (1,25-dihydroxyvitamin D3) receptor (Vdr). Intravenous administration of IL-18 not only significantly improved the expression of some of these genes, but it also significantly decreased the adipocytes' size. CONCLUSIONS: This study demonstrated the critical function of IL-18 in differentiation and lipid metabolism in BAs. Furthermore, IL-18 may contribute to novel treatments by improving the energy imbalance.

Ten-year follow-up study of Japanese patients with obsessive-compulsive disorder.

AIM: Obsessive-compulsive disorder (OCD) is a well-known chronic illness. This study retrospectively investigated 10-year outcomes and associated clinical factors in Japanese OCD patients. We focused on the impact of several sociocultural factors, including medical expenses and insurance systems specific to each country, on the differences or biases in follow-up procedures of OCD. METHODS: Seventy-nine patients diagnosed with OCD who received a standardized combination of treatments for 10 continuous years were divided into three groups according to their improvement rates on the Yale-Brown Obsessive-Compulsive Scale after 10 years of treatment. RESULTS: A survival analysis revealed that the rate of patients achieving full remission increased every year. Following 10 years of treatment, 56% of OCD patients experienced 'full remission' for at least 1 year. Consequently, 48% exhibited full remission, and 37% exhibited partial remission at the end-point of this study. We identified several factors that were predictive of poorer outcomes, including lower Global Assessment of Functioning Scale scores and the presence of hoarding symptoms or involvement behaviors. In addition, improvement rates after 1 year significantly predicted better 10-year outcomes. CONCLUSION: Our findings highlight the transcultural nature of long-term outcomes of OCD treatment, which appear to be independent of sociocultural differences.

Comparison of sleep disorders in chronic hepatitis C patients treated with interferon-based therapy and direct acting antivirals using actigraphy.

This study aimed to compare the severity of sleep problems between chronic hepatitis C (CHC) patients treated with interferon (IFN)-based triple therapy (pegylated [Peg]-IFN plus ribavirin [RBV] plus simeprevir [SMV]) and those who received IFN-free direct-acting antiviral (DAA) therapy. METHODS: Our study included 31 patients in group A (Peg-IFN/RBV/SMV combination therapy) and 41 patients in the group B (IFN-free DAA therapy). We prospectively compared the effect of each antiviral treatment regimen on sleep conditions between the two groups adding actigraphy data. Five parameters detected by actigraphy (objective assessment) and scores of the Pittsburgh Sleep Quality Index (subjective assessment, n = 30 [group A] and 35 [group B]) were estimated. The causal effect of each therapy on sleep disturbances was evaluated at baseline and at 4 weeks after commencement of therapy. RESULTS: In terms of baseline characteristics, no significant differences between groups were found, except for hepatitis C virus genotype. In group A, sustained virological response 12 rate was 83.9% (26/31), whereas in group B it was 95.1% (39/41). In group A, each score of waking after sleep onset, activity index, wake episodes, and Pittsburgh Sleep Quality Index at 4 weeks significantly increased compared to those evaluated at baseline. In group B, scores of all variables except for sleep episodes at 4 weeks did not significantly change compared to those at baseline. CONCLUSION: Interferon-based triple therapy in patients with CHC may cause significant sleep disturbances. Interferon-free DAA therapy is less likely to deteriorate sleep conditions in patients with CHC.

International prescribing practices in obsessive-compulsive disorder (OCD).

OBJECTIVES: To assess rates of psychotropic medication use in patients with obsessive-compulsive disorder (OCD) in seven different countries on five continents and to compare these with international treatment guidelines. METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their patients with OCD and on their incidence of psychotropic use. Consistency of summary statistics across countries was evaluated. RESULTS: The data came from Brazil (n = 955), Italy (n = 750), South Africa (n = 555), Japan (n = 382), Australia (n = 213), India (n = 202) and Spain (n = 82). The majority (77.9%; n = 2445) of the total sample of 3139 participants received a psychotropic medication. Consistent with international guidelines, selective serotonin reuptake inhibitors (SSRIs) were most commonly used (73.5%, n = 1796), but their use ranged from 59% in Australia to 96% in Japan. Clomipramine use varied from 5% in Japan and South Africa to 26% in India and Italy. Atypical antipsychotic use ranged from 12% in South Africa to 50% in Japan. CONCLUSIONS: Pharmacotherapy for OCD varied significantly across sites. Prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that may play a role in the variation in prescribing practices internationally and whether these variations influence treatment outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

Standards of care for obsessive-compulsive disorder centres.

In recent years, many assessment and care units for obsessive-compulsive disorder (OCD) have been set up in order to detect, diagnose and to properly manage this complex disorder, but there is no consensus regarding the key functions that these units should perform. The International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) together with the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP) and the Anxiety and Obsessive Compulsive Disorders Section of the World Psychiaric Association (WPA) has developed a standards of care programme for OCD centres. The goals of this collaborative initiative are promoting basic standards, improving the quality of clinical care and enhance the validity and reliability of research results provided by different facilities and countries.

[Clinical Significance of Bidirectional Interactions between Obsessive-compulsive Disorder and Depressive Disorders].

Major depressive disorder (MDD) has consistently been regarded as the most frequently diagnosed comorbid disorder in patients with obsessive-compulsive disorder (OCD). More than half of OCD patients have the lifetime comorbidity of MDD, which is more likely to develop after the onset of OCD. MDD may occur in response to the chronic distress and functional impairments associated with OCD, resulting in either a negative impact on the quality of life of these patients or poor responses to treatments and unfavorable prognoses. However, obses- sions, particularly aggressive obsessions, and excessive anxiety have been identified as contrib- uting factors to the occurrence of comorbid MDD, which may support the possible role of an altered relationship between the orbitofrontal cortex and amygdala/parahippocampal region in the development of lifetime MDD in OCD patients. Thus, based on the heterogeneity of OCD, the cognitive (typical) type of OCD, which is characterized by the presence of obsessions or cognitive processes resulting in provoked anxiety and compulsions, is more likely to develop comorbid MDD than the motoric type of OCD that accompanies compulsions to alleviate tension related to sensory phenomena such as feelings of incompleteness and urges to reach a specific sensation of feeling "just right". Even though comorbid MDD does not markedly impact on the phenomenological or psychopathological features of OCD, bidirectional interactions between these disorders need to be considered in order to establish adequate treatment strategies for such OCD patients. Pre- ceding pharmacotherapies such as SSRI are indispensable in these treatments because of the possible refractoriness associated with such a concurrently depressive condition to CBT. Fur- thermore, SSRI augmentations with antidepressants that enhance noradrenergic function may sometimes be effective in the treatment of OCD with comorbid MDD. The influences of environmental factors and/or personality pathology need to be evaluated in order to assess the addition of further treatment options such as environmental manipulations, family-focused interventions, cognitive therapies, or interpersonal psychotherapy, especially for OCD patients with treatment-refractory MDD.

Clinically related or predictive factors and impacts on long-term treatment outcomes of involvement behaviors in patients with obsessive-compulsive disorder.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) frequently exhibit involvement behaviors (IBs) in which they accommodate their caregivers to their OCD symptoms by 1) asking them for reassurance, 2) forcing them to participate in their rituals, or 3) forcing them to assist in avoidance according to the patients' rules or demands. Such behaviors correspond to those of their caregivers, and are referred to as family accommodation (FA). METHODS: We performed multifactorial comparisons between 256 OCD patients with and without IBs in order to examine the clinical characteristics and long-term treatment outcomes of OCD patients with IBs. A multiple logistic regression analysis was also performed to identify the related and predictive factors of IBs. RESULTS: A total of 108 out of the 256 OCD patients examined (42%) were determined to exhibit IBs. OCD patients with IBs were differentially characterized by demographic and phenomenological characteristics (e.g. female predominance and poorer insight), more severe psychopathological features (e.g. lower GAFS, higher anxiety, or a depressive status), and poorer treatment outcomes. Furthermore, the predictive factors of IBs such as being female, having a higher compulsive score, and lower GAFS were identified by logistic analyses and structural equation modeling. CONCLUSION: The presence of IBs correlated with the severe clinical features, treatment refractoriness, and poorer long-term outcome of OCD. The severity of compulsions, being female, and lower GAFS were identified as predictive factors for the presence of IBs. Similar to FA, these findings appear to support the effectiveness of early identification and family-focused intervention in the treatment of OCD patients with IBs.

[A Case with Multiple Comorbidities of Obsessive-Compulsive and Related Disorders].

Obsessive-compulsive and related disorders (OCRDs) have been introduced in a revision to DSM-5 as a novel category that is distinct from other anxiety disorders in DSM-IV. OCRDs consist of 5 primary disorders: obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder (HD), skin picking disorder (SPD), and hair pulling disorder (HPD), which share core clinical features such as preoccupation or recurrent thoughts and/or repetitive behaviors. Repetitive behaviors in BDD and HD can be differentially characterized by the presence of cognitive components associated with preceding anxiety from those in SPD or HPD, which are only observed as motoric components that regulate emotions or alleviate tension. Thus, the validity of the OCRD category and specific interrelationships between each OCRD remain uncertain. In the present study, therefore, we presented a case of multiple comorbidities of OCRDs in order to discuss the nature of the OCRD category. Our patient was a 20-year-old female university student. At the age of 11 years old, she started picking at acne on her face. The psychopathological, and treatment features observed in this case indicated possible interrelationships among OCRDs, especially between cognitive and motoric OCRDs, which supported the clinical utility and continuous nature of this category.

The impacts of elevated autism spectrum disorder traits on clinical and psychosocial features and long-term treatment outcome in adult patients with obsessive-compulsive disorder.

BACKGROUND: While a close relation between obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) has been pointed out, there are few studies that have investigated whether highly elevated ASD traits may have significant impacts on clinical and psychosocial features as well as long-term treatment outcome in adult OCD patients. METHODS: We assessed ASD traits using the Autism Spectrum Quotient (AQ) in 81 Japanese patients with OCD. The relation between degree of ASD traits and clinical and psychosocial variables and the 48-week treatment outcomes was analyzed in the subjects. RESULTS: A substantial proportion of the subjects showed higher ASD traits (35%) with more severe depressive or pervasive anxiety status, and social impairments and lower QOL compared to other OCD individuals. However, elevated ASD traits may exert rather smaller impact on the OCD phenomenology along with on the long-term treatment outcome than expected. CONCLUSIONS: Elevated ASD traits may further emphasize the general psychopathological and socio-dysfunctional features rather than clinical aspects associated with OCD. Co-existing depressive or anxious symptom severity may further exacerbate the core-deficits related to ASD pathology. Thus the assessment of ASD traits should be important for understanding the clinical and psychosocial features and treatment responses in OCD patients.

Impact of trait anxiety on psychological well-being in men with prostate cancer.

OBJECTIVE: The aim of the present study was to determine state anxiety following radical treatment for localized prostate cancer (PCa), and the impact of trait anxiety on psychological well-being in affected patients. MATERIAL AND METHODS: The present study was a cross-sectional survey of 70 men with localized PCa performed between February 2012 and July 2012. Of those, 21, 24, and 25 patients were treated by radical retropubic prostatectomy (RRP), permanent prostate brachytherapy (PPB), and external beam radiotherapy (EBRT), respectively. State anxiety, trait anxiety, and general health were assessed using the State-Trait Anxiety Inventory and 8 Items Short Form Health Survey (SF-8). RESULTS: The rate of very high and high state anxiety in patients who received RRP was 47.6%, while that in patients who received PPB and EBRT was 40.0% and 37.5%, respectively. In contrast, the rate of very high and high trait anxiety in the RRP group was much lower (23.7%). Trait anxiety showed a high correlation with state anxiety and the mental health component summary of SF-8 (correlation coefficient=0.715, -0.504). CONCLUSIONS: Trait anxiety was associated with the degree of state anxiety regarding treatments for PCa, followed by change in state anxiety, which might have effects on psychological well-being. Information regarding state anxiety as a consequence of treatments and trait anxiety measurement tool are important considerations for treatment decision-making in newly diagnosed PCa patients.

[Clinical features, treatments and outcome of obsessive-compulsive disorder (OCD) focusing on the assessment and characteristics of patients with treatment-refractory OCD].

Obsessive-compulsive disorder (OCD) is fairly common, with prevalence estimates ranging from 1 to 2%. OCD is generally described as having a chronic course with periods of waxing and waning of symptoms, and most individuals with OCD are at risk for other comorbid psychiatric disorders such as major depression. It is associated with considerable impairment and disability, in that individuals with OCD often experience severe social and interpersonal difficulties, familial dysfunction, occupational problems and impaired quality of life. Indeed, WHO classifies OCD as one of the top 10 most debilitating illnesses. Despite the proven effectiveness of cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) in the treatment of OCD, these 2 treatment strategies have demonstrated inadequate responses in at least 40% of OCD patients. Moreover, even when the best available treatments are applied, a number of patients remain severely affected and experience treatment-refractory OCD. Long-term follow-up (up to 40 years) studies also suggest that OCD often results in a chronic and lifelong condition with low rates of remission and with a relatively high probability of relapse. Thus, a "treatment-refractory" status should be assessed in each OCD individual according to responses to all available therapeutic alternatives, along with the long-term course and outcome. For further exploration of the treatment strategies for OCD patients assessed as "treatment-refractory", definition of the condition as well as the optimization and standardization of the currently best available treatments is needed. In particular, taking into account the psychopathologically and biologically heterogeneous nature of OCD, optimal and rational treatment strategies should be independently examined for each distinct OCD subtype. Further advance of social support and educational systems may also be helpful to promote earlier intervention for the treatment of individuals at high risk of developing chronic or treatment-refractory OCD.

A 2012 evidence-based algorithm for the pharmacotherapy for obsessive-compulsive disorder.

There is a need to synthesize the growing body of literature on the pharmacotherapeutic management of patients with obsessive-compulsive disorder for clinicians working at a primary care level. We have aimed to generate a simple, easy-to-follow algorithm for the primary care practitioner. This seven-step algorithm addresses diagnosis of obsessive-compulsive disorder, initiation of pharmacotherapy, monitoring and maintenance treatment, and guidelines for the management of patients who are resistant to initial therapy. In creating this algorithm, we have drawn on the body of published evidence, as well as on expert opinion.