Pills for the perfectionist – Evidence for pharmacotherapy in obsessive–compulsive personality disorder: A review

The evidence regarding whether co-morbid obsessive compulsive personality disorder (OCPD) is associated with treatment outcomes in obsessive compulsive disorder (OCD) is mixed, with some research indicating that OCPD is associated with poorer response, and some showing that it is associated with improved response. We sought to explore the role of OCPD diagnosis and the personality domain of conscientiousness on treatment outcomes for exposure and response prevention for OCD. The impact of co-morbid OCPD and conscientiousness on treatment outcomes was examined in a clinical sample of 46 participants with OCD. OCPD diagnosis and scores on conscientiousness were not associated with poorer post-treatment OCD severity, as indexed by Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, although the relative sample size of OCPD was small and thus generalizability is limited. This study found no evidence that OCPD or conscientiousness were associated with treatment outcomes for OCD. Further research with larger clinical samples is required.

Alterations of the default mode network connectivity in obsessive–compulsive personality disorder: A pilot study

The relationship between Obsessive Compulsive Disorder (OCD) and Obsessive Compulsive Personality Disorder (OCPD) has been the subject of interest for some time due to the historical assumption that OCPD causes OCD. This study systematically examined the association between OCD and OCPD in terms of prevalence and clinical presentation. The specificity of the association between OCD and OCPD was investigated relative to another axis I anxiety disorder (Panic disorder). Data for this study were drawn from measures taken at initial assessment at a specialist treatment centre for anxiety disorders. Of the 359 participants included in this study, 189 had a principal diagnosis of OCD, while 170 had a principal diagnosis of Panic disorder. Measures included SCID I and II interview modules and self-report measures of anxiety, depression, and OCD syptomatology. Significantly elevated rates of OCPD were found in OCD relative to Panic disorder. Regardless of axis I disorder, individuals with comorbid OCPD reported more severe depression relative to those without. Participants with both OCD and OCPD had greater self-reported OCD symptom severity, doubting, ordering, and hoarding symptoms at assessment relative to those without OCPD. Participants with OCD and comorbid OCPD also reported significantly higher levels of alcohol consumption. There appears to be a significant and specific association between OCD and OCPD. Co-occurring OCD and OCPD is associated with greater severity of impairment in terms of certain OCD symptoms. The significant and specific association between OCD and OCPD suggests that OCPD occurs more frequently with OCD than previously suggested. A comorbid OCPD diagnosis is associated with a greater degree of depression, regardless of axis I disorder, either OCD or Panic disorder. This is an important consideration, as depression can interfere with therapeutic progress (Foa, 1979). Participants with OCD and OCPD had greater self-reported OCD severity, along with doubting, ordering, and hoarding symptoms, relative to those without OCPD. In clinical practice, where OCD symptoms are severe, and the primary OCD symptoms include doubting, ordering, and hoarding, this may indicate a need to assess for comorbid OCPD. This may be useful in terms of including relevant information in formulation with the patient, and in addressing these issues in treatment. There may have been a sampling issue, as the study compared patients from a specialist clinic for the treatment of OCD and Panic disorder. Furthermore, OCD referrals were primary, secondary, or tertiary, whereas Panic disorder referrals were primary or secondary from the immediate catchment area only. This suggests the possibility of greater severity of the OCD sample relative to Panic disorder patients. All participants who met criteria for OCD were assessed for OCPD regardless of whether or not this was indicated by the SCID II screener self-report measure, while participants with Panic disorder were interviewed for OCPD only if indicated by the SCID-II screener. Had participants with Panic disorder been assessed for OCPD regardless of whether or not this was indicated by the SCID-II screener, there is a possibility that a higher rate of OCPD in the Panic disorder sample may have been found.

This review examines the conceptualization of obsessive-compulsive personality disorder (OCPD), its epidemiology and efforts to better understand the relationships between OCPD and other conditions. The alternative Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders conceptualization of OCPD is radically different in that it combines categorical and dimensional diagnostic approaches and introduces a hierarchy of diagnostic criteria. OCPD is one of the most common personality disorders in the general population. The relationship between OCPD and obsessive-compulsive disorder (OCD) is important, but to a large extent obfuscated by the overlap between their diagnostic criteria. Frequent changes in the OCPD diagnostic criteria make it difficult to ascertain the 'true' relationship between OCPD and OCD. It is not uncommon for OCPD to occur with anorexia nervosa, depression, hypochondriasis, certain other personality disorders and Parkinson's disease, but further research is necessary to understand the implications of these links. OCPD is yet to be conceptualized consistently and in the manner that would make a clear and well supported distinction between its core and peripheral features. Future studies need to separate a genuine from overlap-driven co-occurrence of OCPD and other conditions, as that would give a better insight into the way in which OCPD relates to other disorders.

Personality disorders describe enduring, pervasive, pathologic patterns of behavior and inner experiences that deviate from a patient's culture. Personality disorders are divided into three clusters depending on core features. Diagnosis of a personality disorder is generally made based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, although other diagnostic modalities exist. The most common disorders in primary care settings include obsessive-compulsive personality, narcissistic personality, and borderline personality disorders. Obsessive-compulsive personality disorder is associated with pathologic perfectionism and intense rigidity. Treatment is primarily psychotherapy, although there is some evidence for using selective serotonin reuptake inhibitors. Narcissistic personality disorder is marked by grandiosity, need for admiration, and a lack of empathy. Psychotherapy is the primary treatment. Borderline personality disorder is associated with instability and intense reactivity, and the primary treatment is typically psychotherapy. Dialectical behavior therapy was developed specifically for borderline personality disorder, although evidence suggests other behavior therapies may be as beneficial.

An exploratory analysis of obsessive-compulsive personality traits, pathologic anger and quality of life among trauma-exposed veterans.

To present nationally representative data on the prevalence, sociodemographic correlates, and disability of 7 of the 10 DSM-IV personality disorders. The data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Diagnoses were made using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version, and associations between personality disorders and sociodemographic correlates were determined. The relationship between personality disorders and 3 emotional disability scores (Short-Form 12, version 2) was also examined. Overall, 14.79% of adult Americans (95% CI = 14.08 to 15.50), or 30.8 million, had at least 1 personality disorder. The most prevalent personality disorder in the general population was obsessive-compulsive personality disorder, 7.88% (95% CI = 7.43 to 8.33), followed by paranoid personality disorder 4.41% (95% CI = 4.12 to 4.70), antisocial personality disorder 3.63% (95% CI = 3.34 to 3.92), schizoid personality disorder 3.13% (95% CI = 2.89 to 3.37), avoidant personality disorder 2.36% (95% CI = 2.14 to 2.58), histrionic personality disorder 1.84% (95% CI = 1.66 to 2.02), and dependent personality disorder 0.49% (95% CI = 0.40 to 0.58). The risk of avoidant, dependent, and paranoid personality disorders was significantly greater among women than men (p <.05); the risk of antisocial personality disorder was greater among men compared with women (p <.05); and no sex differences were observed in the risk of obsessive-compulsive, schizoid, or histrionic personality disorders. In general, risk factors for personality disorders included being Native American or black, being a young adult, having low socioeconomic status, and being divorced, separated, widowed, or never married. Avoidant, dependent, schizoid, paranoid, and antisocial personality disorders (p <.02 to p <.0001) were each statistically significant predictors of disability. Obsessive-compulsive personality disorder was inconsistently related to disability. In contrast, disability was not significantly different among individuals with histrionic personality disorder compared with those without the disorder. Personality disorders are prevalent in the general population and are generally highly associated with disability. This study highlights the need to develop more effective and targeted prevention and intervention initiatives for personality disorders.

Few studies have investigated the relationship between stress-related mental health problems and obsessive-compulsive personality disorder (OCPD). Similarly, little research has focused on the moderating effect of OCPD on recovery in clinical patients with stress-related mental health problems. The general aim of this study was to investigate the prevalence of OCPD and the associations between OCPD and level of burnout, anxiety, and depression symptoms, during a 7-years follow-up in a clinical longitudinal sample of female patients with stress-related exhaustion. The included patients (n = 84) were referred to a specialist outpatient clinic for patients with stress-related exhaustion between 2006 and 2011. Data was collected at the initial examination and during a 7-year treatment follow-up. OCPD was the most common personality disorder in the present clinical sample, with 40% of patients fulfilling the criteria. There was a significant association between OCPD and the degree of burnout symptoms as well as the degree of depression, both at baseline and during the 7-year follow-up. No significant association between OCPD and levels of anxiety was observed. The results support the hypothesis that there might be an association between OCPD and stress-related exhaustion, including preservation of symptoms over time. OCPD and its related traits, such as perfectionism, may be important factors to consider when constructing effective treatment and rehabilitation plans for these patients.

IntroductionThe risk of suicide may be elevated in the presence of personality pathology. Adults with Obsessive Compulsive Personality Disorder (OCPD) may be vulnerable to depression and suicidal thoughts.ObjectivesTo identify factors associated with suicide in cases of OCPD.MethodsPsychological autopsy procedures were used to gather detailed information about adults who died by suicide and natural causes. A total of 75 deceased adults were evaluated using psychological autopsy procedures. Family members were interviewed about a recently deceased adult, using structured diagnostic interviews (SCID and SIDP-IV). Diagnostic summaries, coroner’s reports and police records were reviewed by a psychiatrist, a psychologist, a social worker, and a neuroscientist until agreement was reached about final diagnosis. The final sample included 40 adults who met criteria for OCPD (18 had died by suicide; 20 had died by natural causes). An additional 40 cases were examined in which evidence of PD was absent (19 had died by suicide; 18 had died by natural causes).ResultsThe diagnosis of a Major Depressive Disorder was significantly more common in suicide completers with OCPD compared to suicide completers without OCPD (X2 = 6.74, p &lt; .01) or cases of natural death with OCPD (X2 = 12.70, p &lt; .001). Suicide completers with OCPD displayed many symptoms of depression, more often than suicide completers without OCPD or cases of natural death with OCPD (see Table 1). As compared to the cases of natural death, both groups of suicide completers were more likely to have previously attempted suicide prior to their final act (X2 = 8.52, p &lt; .05). Table 1.Comparison of four groups using psychological autopsy procedures to identify the presence of diagnostic criteria for a Major Depressive Episode at the time of death.OCPD SuicideOCPD Natural DeathNo PD SuicideNo PD Natural DeathX2Sad mood82.4%36.8%78.9%50.0%11.38 **Sleep disturbance82.4%38.9%73.7%46.7%9.53 *Feelings of worthlessness60.0%38.9%84.2%17.6%17.49 ***Reduced concentration58.8%27.8%57.9%14.3%9.89 *Recurrent suicidal ideation88.2%26.3%78.9%0.0%35.57 ***Loss of pleasure82.4%38.9%73.7%40.0%10.80 **Psychomotor changes50.0%33.3%61.1%26.7%5.04Reduced energy64.7%44.4%63.2%33.3%4.12Change of appetite70.6%26.3%42.1%31.3%8.37 *Note:*= p &lt; .05;**= p &lt; .01;***= p &lt; .001ConclusionsAdults with OCPD appear vulnerable to a Major Depressive episode, and the combination of MDD with OCPD creates a significant risk for death by suicide. It is important to appreciate the influence of personality disorder or depression and suicide risk.Disclosure of InterestNone Declared

Obsessive-compulsive personality disorder (OCPD) is an early-onset disorder characterized by perfectionism, need for control, and cognitive rigidity. Its nosological status is currently under review. Historically, OCPD has been conceptualized as bearing a close relationship with obsessive-compulsive disorder (OCD). In this article, we discuss the diagnosis of OCPD in anticipation of its review for the ICD-11, from the perspective of clinical utility, global applicability, and research planning. Considering the recent establishment of an obsessive-compulsive and related disorders (OCRD) category in DSM-5, we focus on the relationship between OCPD and the disorders that are currently thought to bear a close relationship with OCD, including DSM-5 OCRD, and other compulsive disorders such as eating disorder and autistic spectrum disorder (that were not included in the DSM-5 OCRD category), as well as with the personality disorders, focusing on nosological determinants such as phenomenology, course of illness, heritability, environmental risk factors, comorbidity, neurocognitive endophenotypes, and treatment response. Based on this analysis, we attempt to draw conclusions as to its optimal placement in diagnostic systems and draw attention to key research questions that could be explored in field trials.

Forty-seven people with admissions in childhood for obsessive-compulsive disorder (OCD) and 49 child psychiatric controls were followed up in young adulthood and assessed for DSM-III-R personality disorders with the Structured Clinical Interview for DSM-III-R Personality Disorders. The number of personality disorders in OCD patients did not differ significantly from the number in controls. The most common personality disorder was avoidant personality disorder (significantly more frequent than in controls), whereas obsessive-compulsive personality disorder (OCPD) was not found more often in the OCD group. Subjects with OCD in adulthood seemed to have OCPD more often than childhood OCD patients with no OCD at follow-up. In the whole group, histrionic personality disorders were more common in women than in men and OCPD more common in men than in women, whereas borderline personality disorder was most common among women in the OCD group. The presence of a personality disorder in adulthood could not be correlated with such childhood factors as social background, symptoms or age of onset of OCD.

ABSTRACTObjective: To compare therapeutic response to behavioral therapy for insomnia (BT-I) among hypnotic-dependent insomnia (HDI) patients with and without Cluster C personality disorders. Participants: Twenty-three adults with HDI (17 females), aged between 33 and 68 (M = 53; SD = 9.9) were included in the study. Methods: Participants completed a personality disorder assessment (baseline), as well as sleep diaries, polysomnography (PSG), and an insomnia severity assessment (baseline, posttreatment, and one-year follow-up). Treatment consisted of eight weeks of individual BT-I and gradual hypnotic medication withdrawal. Multilevel mixed-effects linear regression models examined the interaction between study visit and Cluster C personality disorders status on treatment response to BT-I. Results: Obsessive-compulsive personality disorder (OCPD) was the most prevalent of the Cluster C personality disorders with 38% (n = 8) of participants meeting criteria. There were no significant treatment differences by OCPD status across time as measured by sleep diaries and insomnia severity status. However, there were significant treatment differences by OCPD status by one-year follow-up on PSG outcomes, indicating that patients with OCPD status had shorter and more disrupted sleep than patients without OCPD status. Conclusions: Based on self-reported sleep measures, patients with insomnia and features of OCPD responded equivalently to BT-I at one-year follow-up compared to patients without features of OCPD. However, polysomnography outcomes indicated objective sleep deteriorated in these patients, which may suggest greater vulnerability to relapse.

Obsessive compulsive personality disorder as a predictor of exposure and ritual prevention outcome for obsessive compulsive disorder

Participants of expert group on CPG for Obsessive Compulsive Disorder Adarsh Tripathi, Om Prakash Singh, Paramjeet Singh, Tushar Jagawat, M, Aleem Siddiqui, K.K. Verma, D.M. Mathur INTRODUCTION Obsessive-compulsive disorder (OCD) is a common psychiatric illness with lifetime prevalence of 1-3% [1]. It is the fourth-most common psychiatric illness and a leading cause of disability. OCD is associated with significant impairment in functioning, quality of life and disability. If untreated, OCD is a chronic illness with a waxing and waning of symptoms. A recent meta-analysis of long-term naturalistic prospective studies demonstrated that nearly a half of patients experience remission with much higher rates of remission in Indian patients compared to those in the west [2]. Early diagnosis and appropriate treatment may improve outcomes. Despite OCD being a common mental illness, most seek treatment after several years of suffering. Those who suffer from OCD tend to be secretive about their symptoms and suffer from shame and embarrassment. Less than a third of OCD sufferers receive appropriate pharmacotherapy and even less receive evidence-based psychotherapy. Symptoms The hallmarks of OCD are presence of obsessions and compulsions. Obsessions are repetitive, unwanted, intrusive thoughts, images or urges that are mostly ego-dystonic and cause severe distress or anxiety. Compulsions (or rituals) are repetitive behaviours or mental acts that are performed in response to an obsession to reduce anxiety/distress or prevent a dreaded consequence. Obsessions and compulsions are time consuming, distressing and are often resisted unsuccessfully. Clinical manifestations of OCD are remarkably similar across cultures and geographic locations. Common obsessions and compulsions and symptom dimensions identified through factor-analytical studies are shown in Table 1.Table 1: Common symptoms of OCDDiagnosis Many people experience intrusive thoughts and exhibit repetitive behaviours. A diagnosis of OCD is made only if symptoms are time consuming (e.g., more than an hour per day), distressing or cause significant interference in functioning. This is reflected in DSM-5 diagnosis of OCD and in the upcoming ICD-11 [3]. The ICD-11 criteria for OCD are likely to be very similar to the DSM-5 criteria [34]. The ICD-11 may include an insight specifier along the same lines as DSM-5. There are sweeping changes to the description of OCD in the proposed ICD-11. Duration criteria and subtyping of OCD may be removed in the revision for lack of evidence and clinical relevance. In ICD-10, a diagnosis of OCD was discouraged in the presence of schizophrenia, tic disorder or depression. This criterion too may be removed paving the way to make a diagnosis of OCD even in the presence of these comorbid disorders. Another major change to the diagnosis of OCD is creation of OCD and related disorders in DSM-5 (and in the ICD-11) and exit from the group of anxiety disorders. Many disorders are included in this group: body dysmorphic disorder (BDD), trichotillomania (TTM), skin picking disorder, hoarding disorder, substance/medication-Induced obsessive-compulsive and related disorder and obsessive-compulsive and related disorder due to another medical condition. In the upcoming ICD-11, few other conditions find a place in this group that include tic disorders, hypochondriasis and olfactory reference syndrome. All these disorders are grouped together based on shared clinical features (e.g., repetitive behaviours), comorbidity patterns, familiality, neuropsychological deficits, treatment response and importantly shared brain circuitry abnormalities. Hoarding disorder which may not share many features with OCD is grouped along with OCD because of historical association with OCD and obsessive-compulsive personality disorder. Comorbidity OCD is often comorbid with other psychiatric disorders. It is important to assess all patients with OCD for associated psychiatric comorbidity since they may have an effect on treatment outcome if left untreated. Depression and anxiety disorders are present in over a half of patients seeking treatment for OCD. Common comorbid disorders are listed in Table 2. Those with early onset OCD, in particular those with onset in childhood have high rates of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and tic disorders.Table 2: Comorbid disorders in OCDBipolar disorder, in particular type 2, is reported to be not uncommon in OCD [5]. Similarly, OCD is not uncommon in those with primary diagnosis of bipolar disorder [67]. OCD when comorbid with bipolar disorder tends to run an episodic course [8] with worsening of symptoms in depressive phases and improvement in hypomania/ mania phases. It is important to recognise OCD-bipolar comorbidity because of treatment implications. The specific serotonin-reuptake inhibitors (SSRIs) traditionally used to treat OCD may induce switch to mania or rapid cycling course. Obsessive-compulsive symptoms and OCD are not uncommon in schizophrenia. Nearly a third of schizophrenia patients report OC symptoms or OCD. Presence of OCD may have a negative effect on the long-term course of schizophrenia. Therefore treatment of OCD with SSRIs and cognitive-behavior therapy (CBT)/behavior therapy (BT) may have to be considered although there is not much of systematic evidence supporting their efficacy in treatment of OCD in schizophrenia. COMMON INGREDIENTS OF MANAGEMENT PLAN Common ingredients of managing OCD include the following: Detailed assessment of symptoms and comorbid patterns including suicidal behaviours either by unstructured clinical interview alone or supplementation with structured assessments. Decision on setting for treatment (outpatient vs. inpatient care depending upon the severity, treatment resistance etc.) Detailed psychoeducation of the patient and family member (s) about OCD, its course and treatment options including duration of treatment. Choice of treatment: drugs vs. CBT vs. combination In the Indian context, SSRIs are first-line treatments preferred over CBT because of feasibility, affordability and limited number of trained therapists. CBT may be considered if SSRIs alone are not beneficial. Discussion on side-effects of drugs; in women risks vs. benefits of drugs during pregnancy and in the post-partum period Follow-up plan after initiating treatment ASSESSMENT AND EVALUATION In routine clinical practice, use of structured / semistructured interviews and rating scales may not be necessary. They are optional. However, they may be used when the clinician needs supplementary information. A list of useful instruments in the assessment of OCD is provided in Table 3.Table 3: Commonly used instruments to assess OCD (optional)The Yale-Brown Obsessive-Compulsive Scale (YBOCS) is the most widely used severity rating scale for OCD in both adults [9] and children [10] and is considered a gold standard instrument to measure severity of OCD. It is a 10-item observer-rating scale, also available as self-rated instrument. It measures the overall severity of obsessive-compulsive symptoms for the preceding week. The YBOCS is a global measure of symptoms and does not provide severity of individual symptom dimensions. A total score of ≥ 16 is considered to be indicative of clinically significant OCD. The YBOCS severity scale also has an associated symptom check list of 15 categories of obsessions and compulsions including miscellaneous symptoms. The checklist elicits both current (1 month) and past symptoms. On the YBOCS item-11 insight scale, the insight is graded as follows: 0 = excellent (fully rational thinking), 1= good insight (readily acknowledges absurdity or excessiveness but has some lingering doubts), 2 = fair insight (reluctantly admits absurdity, but waivers; has some unrealistic fear but no fixed conviction), 3 = poor insight (overvalued ideas; maintains they are not unreasonable or excessive, but acknowledges validity of contrary evidence), and 4 = lack of insight (delusional). A higher score on the Y–BOCS item-11 indicates poorer insight. FORMULATING A TREATMENT PLAN Formulating a treatment begins with correct diagnosis of OCD as per the DSM or ICD classificatory systems. When feasible a structured clinical interview is recommended to obtain a comprehensive account of patient's problems. Once a diagnosis is established, a detailed assessment of symptom profile is mandatory. Family members often accommodate patient's rituals and contribute to poor outcome. In most severely ill patients, an elaborate family assessment may be needed. Once assessment is complete, short-term and long-term goals of treatment have to be established. Enhancing treatment adherence is a vital aspect of formulating a treatment plan. It is important to educate patients about lag in the onset of action of drugs and that improvement may occur over several months of continuous treatment. Brief education about basic principles of psychotherapy should be explained if psychotherapy is being planned. Essentials of formulating a treatment plan are summarized in Table 4. All patients and their immediate family members should be provided psychoeducation about OCD (Table 5).Table 4: Essentials of formulating a treatment planTable 5: Components of psychoeducationCHOICE OF TREATMENT SETTINGS In the Indian scenario, treatment is either on an outpatient or an inpatient basis. Outpatient treatment is usually sufficient for most OCD patients who are mild to moderately ill and for those who are likely to be adherent to treatment. Patients may be followed-up at periodic intervals, initially once in a month or two and subsequently at longer intervals depending upon the response to treatment and tolerability and side-effects. Hospital treatment may be considered for those who are at high suicide risk, dangerous to self or others, and intolerant to side-effects. Many severely ill and treatment-resistant patients may require prolonged (2-3 months) hospitalization for intensive treatment with CBT and for rationalization of pharmacotherapy. Inpatient care may also be required for severe depression, mania or psychosis that may be comorbid with OCD. Admission in rehabilitation services may be necessary for some patients who may not have benefited from standard treatments including inpatient care. PHARMACOLOGICAL TREATMENT The clinical practice guideline is framed based on a review of relevant scientific literature. As a first step, we framed relevant questions which arise in the minds of the practitioner while treating a patient suffering from OCD. A literature search was conducted in PubMed to answer these questions. We also reviewed the existing guidelines on treatment of OCD [11121314]. After a thorough literature review, the treatment strategies were rated based on the Strength of Recommendation Taxonomy (SORT) [15]. Consistent evidence from multiple randomized controlled trials (RCT) constitutes the highest level of evidence for a recommendation. However, the external validity of RCTs has been questioned due to the rigid protocols in undertaking the studies. A practitioner may make a clinical decision based on the available evidence considering other relevant factors that influence the decision making process. A non-exhaustive list of these factors might include psychiatric and other medical comorbidities, previous treatment trials, affordability, accessibility, hypersensitivity, side-effect profile, patients' values etc. RELEVANT CLINICAL ISSUES First-line pharmacological treatment for OCD Meta-analyses of RCTs show that selective-serotonin reuptake inhibitors (SSRIs) are significantly more effective than placebo in the treatment of OCD [16]. SSRIs are associated with many adverse effects but are usually well tolerated. The only other medication which has shown to be consistently effective in OCD is the serotoninergic tricyclic antidepressant clomipramine. Clomipramine has been found to be significantly more effective than placebo in multiple RCTs and meta-analysis of RCTs [16]. Network meta-analysis comparing the efficacy of clomipramine vs. SSRIs failed to find any efficacy advantage over SSRIs [16]. Most head-to-head comparison trials have not found any significant difference between the efficacy of clomipramine and SSRIs [17]. Further, meta-analyses and individual RCTs have found that the tolerability of clomipramine is worse than that of SSRIs [1317]. The anticholinergic, cardiac and neurological side effects of clomipramine may be problematic in this regard. CONSIDERING THE CONSISTENT EFFICACY AND BETTER TOLERABILITY, GUIDELINES RECOMMEND SSRIs AS FIRST LINE TREATMENT FOR OCD (TABLE 6). Choice of SSRITable 6: Medications recommended as monotherapy in OCDMeta-analyses comparing the different SSRIs [16] and direct head-to-head comparisons [1718] have not shown superiority of any one SSRI over the other. SSRIs differ to some extent in their propensity to cause certain adverse effects and drug interactions. However, there is no unequivocal evidence to suggest that these differences may be clinically meaningful. Recently, concerns have been raised regarding cardiac adverse effects with high dose of citalopram, which is commonly used in OCD. Hence, high-dose citalopram may be used with caution in those with risk for arrhythmias. THE PRACTITIONER IS RECOMMENDED TO CHOOSE AN SSRI FOR AN INDIVIDUAL PATIENT BASED ON FACTORS SUCH AS PREVIOUS RESPONSE, COMORBIDITY, TOLERABILITY, ACCEPTABILITY, ADVERSE EFFECTS, COST AND DRUG INTERACTIONS. Dose of SSRI It is generally recommended that OCD be treated with a higher dose of SSRI than that used in depression (Table 5). A meta-analysis of fixed-dose comparison studies have found a greater efficacy with higher doses of SSRI (60-80 mg fluoxetine equivalent) compared to medium (40-50 mg fluoxetine equivalent) and low doses (20-30 mg fluoxetine equivalent) [19]. However, all three dose ranges were significantly more effective than placebo. The increased efficacy comes at the cost of poor tolerability as evidenced by increased dropouts due to adverse effects [19]. A review of individual fixed-dose comparison studies found that the dose-response relationship is more evident for escitalopram, fluoxetine and paroxetine, while it is less clear-cut for citalopram and sertraline [17]. Clomipramine has not been tested in such fixed dose comparison studies. However, most studies have employed a flexible dosing at 150-250 mg [17]. It should be remembered that there is likely to be inter-individual differences in pharmacokinetic profile of drugs due to intrinsic variations in drug metabolism and drug interactions. GUIDELINES RECOMMEND TREATMENT OF OCD WITH HIGHER DOSE OF SSRIs. HOWEVER, IF AN INDIVIDUAL PATIENT IS NOT ABLE TO TOLERATE HIGHER DOSE, LOW TO MEDIUM DOSE TREATMENT CAN BE CONSIDERED. Duration of trial and dose titration A recent meta-analysis of 17 RCTs found that SSRIs separate from placebo as early as 2 weeks and that majority of improvement occurs early on in the course of treatment [20]. However, improvements seen early in the course of treatment may not be always clinically meaningful. In many patients, clinically meaningful improvements may be seen only after weeks or months of treatment. It is recommended that an adequate trial of a SSRI (or clomipramine) should be at least for 12 weeks to account for the lag in the onset of action. The APA guidelines recommend upward titration to the maximum FDA-approved doses by 4-6 weeks and continuation in that dose for another 6-8 weeks or so to determine efficacy [11]. Certain clinical and biological predictors of treatment response to SSRIs have been identified but they are not robust predictors (Table 7).Table 7: Predictors of response to SSRIsGUIDELINES RECOMMEND CONTINUING MAXIMALLY TOLERATED EFFECTIVE DOSE OF A SSRI FOR AT LEAST 12 WEEKS FOR JUDGING ITS EFFICACY. GUIDELINES ALSO RECOMMEND DOSE ESCALATION TO EFFECTIVE DOSE RANGES WITHIN 4-6 WEEKS AND CONTINUATION IN THE SAME DOSE FOR ANOTHER 6-8 WEEKS. 2. Other medications that can be tried as monotherapy in OCD Venlafaxine, a serotonin-norepinephrine reuptake inhibitor with preferential serotonergic action, has been studied in comparison to paroxetine in a double blinded study and clomipramine in a single blinded study. The studies found no difference in the efficacy between venlafaxine and the comparator agents in acute control of OCD. Given the absence of evidence from placebo-controlled trials, venlafaxine is not the first-line treatment for OCD. Hence, the guidelines consider venlafaxine as a second-line monotherapy agent in the treatment of OCD. Mirtazapine has been studied as a monotherapy in two small open-label trials with inconsistent findings. Therefore, mirtazapine cannot be recommended as monotherapy in treatment of OCD. 3. Treatment strategy for non-responders to first-line treatment Definitions of treatment outcome [21] are given in Table 8. Estimates suggest that around 40-70% patients show an adequate response to a trial of SSRI with a remission rate of 10-40% [16]. Clinicians often face the subsequent challenge of partial and non-response to SSRIs. Continuing improvement has been noticed with prolonged trial of SSRIs as discussed above. Hence, the initial trial may be continued further if there is evidence of ongoing improvement. A general treatment algorithm for OCD and for non-responders to SSRIs is shown in Figures 1 and 2 respectively.Table 8: Definitions of treatment outcome in OCDFigure 1: Treatment algorithm for treating a patient with OCD. *First line treatment chosen based on feasibility and severity of illness, #CBT/BT- Cognitive behavior therapy/Behavior therapy, @SSRI – Selective serotonin reuptake inhibitor, %rTMSrepetitive transcranial magnetic stimulation, $ - tDCS- transcranial direct current stimulation. ** Preferred for severe OCDFigure 2: Strategies for non-responders to SSRIs. SSRI-Selective serotonin reuptake inhibitors, CBT/BT-Cognitive behavior therapy/behavior therapy, rTMS- repetitive transcranial magnetic stimulationa. Switching to another medication Switching to another first-line medication has been found to be effective; experts provide a rough estimate of 40-50% response rate for the second SSRI and decreasing response rates with further trials. Switching to a second SSRI is suggested for non-responders to a first SSRI. In partial responders, changing medication may entail loss of the response to the earlier medication. Hence, switching is recommended in partial responders only if there are severe persisting symptoms or upon failure of other augmenting strategies such as CBT and atypical antipsychotics. b. Switching / Augmenting with CBT/BT It is uncertain whether initiating a combination of BT/CBT simultaneously with SSRI is advantageous compared to either treatment alone. However, CBT/BT has been proven to be effective as an augmenter in partial/non-responders to SSRIs [182223]. Where feasible, CBT/BT is a potential first-line augmenting option for partial/non-responders to SSRI treatment. c. Augmenting with another medication (Table 9)Table 9: Pharmacological augmenting agents in medications have been commonly tried as to SSRIs. and have the are the most widely studied augmenting agents of SSRIs The literature on is with including small doses and duration of treatment with both and of treatment resistance etc. recent meta-analyses of RCTs on found that as a group was significantly more effective than placebo in decreasing YBOCS a third of patients to and are consistently found to be effective as augmenting The evidence for should be with caution as it was based on a single study. A comparing and placebo of SSRI found that not separate from placebo in augmenting efficacy This study has raised questions on the efficacy of as an and have not been consistently found to be while other have not been studied Meta-analyses not any on adequate dose and duration of treatment should be used in low doses (e.g., mg of mg for a period of at least weeks for an adequate of in the should be considered after the benefits and risks of long-term BASED ON THE AND BE THE FIRST FOR PHARMACOLOGICAL agents There is a supporting the use of drugs in OCD. The agents have been studied in OCD found effective in 2 double blinded and one single blinded found effective in 2 double blinded RCTs effective in 2 small but inconsistent in two RCTs from three has to be studied BASED ON THE AND ITS BETTER TOLERABILITY, IS AS THE FIRST agents including and are reported to be effective and well in small RCTs However, due to the of the individual are recommended as second line augmenting agents along with evidence that clomipramine can be an effective augmenting Clomipramine and SSRI combination should be used with fluoxetine and as they may clomipramine related adverse effects cardiac serotonin due to pharmacokinetic interactions. Clomipramine of SSRI may be tried but adequate to be in the potential adverse effects of the Mirtazapine has been found to the response with no significant benefits and may be considered as an augmenting agent in partial responders and Other augmenting agents and have not been found effective and are not recommended as augmenting The and efficacy of and drugs have to be studied they are recommended for routine clinical has been found to have acute effects in a which needs and the strategy can be recommended for routine clinical Other strategies there to be some short-term benefits for clomipramine in treatment patients, the benefits are This is not available in and is not recommended at present for clinical There are a few trials the of higher than recommended doses of SSRIs to mg of mg of in This strategy should be considered and may be used only in patients after other OF of patients not to available pharmacological and and treatments the have been tried in has not been for the treatment of OCD. in the of and not provide evidence for the efficacy of Hence, is not recommended as a treatment for OCD and may be considered for the treatment of comorbid conditions severe and disorders, if 2. transcranial magnetic the of and of or decreasing their based on the of stimulation. The in OCD are usually not with available of has been tried in which have with other in OCD. trials of low or high over either have but low over supplementary and However, the evidence has not been very the have to be in with There is no evidence that effects for longer than the trial The guideline as an for further and not for routine clinical 3. direct current is another and which either or the of the depending on the of the There are only a few and an open-label trial on in OCD. It has to be more it can be recommended for clinical use in OCD. in specific of the which is to be in OCD. can be with the of or with the of and a of as are in treatment OCD in a few to the these are generally employed in treatment patients (Table in the of studies that around of patients improve over months There is some that may be more effective in OCD and that its efficacy may be similar to that of brain may be associated with short-term and adverse effects including personality and adverse effects although rates are not criteria for brain brain is a high of in the the of action is it is to for OCD has been in controlled studies of and A recent meta-analysis found a rate of with a YBOCS of around is an and is associated with and adverse Further, the needs to be which may be can be recommended in OCD patients (Table after regarding the and of the The are not in and the are only one aspect of a comprehensive treatment which should may be considered only in patients after of patients for treatment severity of illness and Patients should be explained about the of benefits and They should be by an of a a and a for for The treatment should be conducted of a of and with of adverse criteria for to are shown in Table FOR OCD (TABLE Cognitive / and in has been shown to be in the treatment of OCD All treatment guidelines have suggested the use of CBT as a first-line treatment CBT for OCD is a first-line treatment option for OCD. is the most important of CBT along with When are monotherapy may be recommended in mild to moderately ill In severely ill patients a combination of CBT and SSRI is CBT as an strategy It is uncertain whether initiating a combination of and SSRI is advantageous compared to either treatment alone. However, CBT/BT is found to be effective in augmenting SSRIs in partial/non-responders to SSRIs [34]. A recent study found CBT to be to and placebo in augmenting SSRIs in OCD Patients in the CBT group

OBSESSIVE COMPULSIVE PERSONALITY AND FATIGUE IN PATIENTS WITH ANXIETY AND MOOD DISORDERS