Obsessive-Compulsive Symptoms After Tirzepatide Treatment: A Case Report

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

Practice Parameter for the Assessment and Treatment of Children and Adolescents With Obsessive-Compulsive Disorder

When a patient presents with both psychotic and obsessive-compulsive symptoms, the clinician is faced with a differential diagnosis that includes comorbid schizophrenia and obsessive-compulsive disorder (OCD), OCD with poor insight, and schizophrenia with antipsychotic-induced obsessive-compulsive symptoms. If the psychotic symptoms are subthresh-old or attenuated in form, the individual may have OCD and putative prodromal schizophrenia. The authors present a case to outline a strategy for differentiating among these possible diagnoses and for optimizing treatment.

“Ms. G” is a 22-year-old single woman who pulls hair from the crown of her head on a daily basis. She began pulling at her eyebrows at age 14, but the pulling shifted to her head and became a daily routine during the past 3 years. Ms. G tends to pull her hair during times of stress, but only on approximately 50% of occasions is she aware that she is doing it. The rest of the time, she reports, she pulls “automatically” and then notices a pile of hair on the floor or on her desk after she has “snapped out of it.” Ms. G often pulls her hair for 1–2 hours each day. The urge to pull immediately precedes or is simultaneous with touching the hair, and she reports that she is generally unable to resist this urge. The pulling episode usually ends when she feels the “right” tugging sensation and then sees a “good” root. She then plays with the hair, caressing her lips with the hair shaft and the root and then ingesting the hair. The feeling of accomplishment from the pulling quickly turns into shame and embarrassment. Because of the alopecia from pulling, Ms. G does not date, and she limits her social activities to only a few friends. She had never sought help for her pulling before finding information about it on a web site.<br/><br/>On examination, Ms. G has a 3-inch-diameter area of alopecia on the crown of her head. Although she sometimes swallows hairs, there is no evidence of gastrointestinal problems. Ms. G meets the diagnostic criteria for trichotillomania, and over the course of the next several weeks, she undergoes 12 sessions of habit reversal therapy as well as treatment with N-acetylcysteine. Ms. G is able to reduce her pulling to only 5−10 minutes every several days, which she has generally maintained for over a year.

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

A dysfunction of the fronto-striatal loop has been associated with obsessive-compulsive disorder (OCD). Functional imaging studies suggest that reversal learning is affected by deficits in fronto-striatal brain areas and thus should be impaired in patients with OCD. The authors compared patients with OCD and healthy comparison subjects on a reversal learning task. Correlation analyses and group comparisons showing prolonged reaction times of different response parameters are associated with increasing severity of compulsions. The reversal learning task has been shown to be associated with ventral fronto-striatal brain activation by functional magnetic resonance imaging (fMRI) in healthy comparison subjects. The purpose of this article is to suggest that the reversal learning task can be used as a neuropsychiatric measurement of the ventral fronto-striatal dysfunction in OCD.

[Author Affiliation]Ahmed Naguy. 1 Child and Adolescent Psychiatry, Kuwait Center for Mental Health, Alamanara Unit, Kuwait City, Kuwait.Bibi Alamiri. 1 Child and Adolescent Psychiatry, Kuwait Center for Mental Health, Alamanara Unit, Kuwait City, Kuwait. 2 Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.Souleiman Al-Khadhari. 1 Child and Adolescent Psychiatry, Kuwait Center for Mental Health, Alamanara Unit, Kuwait City, Kuwait. 3 Department of Psychiatry, Kuwait University, Kuwait City, Kuwait.Konstantinos Francis. 1 Child and Adolescent Psychiatry, Kuwait Center for Mental Health, Alamanara Unit, Kuwait City, Kuwait. 4 Department of Child Psychiatry, Athens University, Chalandri, Greece.Address correspondence to: Konstantinos Francis, MD, PhD, PB 1443, Agios Spyridon Pikermiou, 19009, Rafina, Greece, E-mail: cfrancis@otenet.grTo The Editor:Obsessive compulsive disorder (OCD) is a neuropsychiatric disorder characterized by the presence of persistent, recurrent, and intrusive thoughts, images, or impulses (obsessions) and/or repetitive, purposeful behaviors (compulsions) that are time consuming and cause distress or interference in the patient's life (American Psychiatric Association DSM-5 Task Force 2013). OCD is one of the most prevalent neuropsychiatric disorders, with lifetime prevalence of 1-3%, and with symptom onset before puberty in up to one half of sufferers (Kessler et al. 2005).Selective serotonin reuptake inhibitors (SSRIs) are the first-line medications for OCD in children, adolescents, and adults, either alone or in combination with cognitive behavioral therapy (CBT) (Stein et al. 2012). Albeit their proven effectiveness, both these options often have inadequate results, with almost half of the patients not responding or having residual symptoms (Catapano et al. 2006; Abramowitz et al. 2009). In these cases, clinicians can chose either to switch to an alternative SSRI, bearing in mind that the possibility of response is less likely than expected in naive patients (Ackerman et al. 1998), or follow an augmentation strategy by adding another agent (National Institute for Health and Clinical Excellence 2005; Stein et al. 2012). Agents that are commonly employed are clomipramine (CMI) (Stein et al. 2012) and the atypical antipsychotics (Bloch et al. 2006; Stein et al. 2012), but a multitude of other drugs have also been tried, such as stimulants, gabapentin, sumatriptan, pindolol, inositol, opiates, St. John's wort, N-acetyl cysteine, memantine, and riluzole, without conclusive evidence (Pittenger 2011, 2012).Albeit the predominant role of the monoaminergic systems (mainly that of serotonin and, to a lesser extent, dopamine) in neurobiology, and hence in the treatment of OCD, preclinical and clinical data do implicate other neurotransmitters also. Recent evidence suggests that the excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder (Ting and Feng 2008; Pittenger et al. 2011; Wu et al. 2012). Lamotrigine is an antiepileptic drug and mood stabilizer that was proven to reduce excessive glutamate release (Burstein 1995; Reid et al. 2013). Therefore, it is a good candidate agent for augmentation in refractory cases of OCD. Apart from an initial negative case series study (Kumar and Khanna 2000), research data are quite encouraging for its use, with two positive case reports (Uzun 2010; Arrojo-Romero et al. 2013) of successful use in special populations (Bisol and Lara 2009; Poyurovsky et al. 2010), and one recent double-blind, randomized, placebo-controlled trial, also with positive results (Bruno et al. 2012).Here, we report a case of pediatric OCD who showed a marked response to lamotrigine augmentation. The patient was treatment resistant and received multiple psychotropic trials over a course of >2 years, militating against the possibility of placebo response. …

Although standard diagnostic classifications consider obsessive-compulsive disorder (OCD) to be a single diagnostic entity, it has become clear that it is a heterogeneous disorder, with great variability in clinical presentation. This heterogeneity has complicated the interpretation of clinical, neurobiological, and genetic studies in OCD. Therefore, researchers have sought to identify clinically meaningful phenotypes that might be more homogeneous and heritable to facilitate our understanding of the etiology and pathophysiology of OCD and ultimately lead to improved treatments (1). Factor analytic studies have consistently identified four principal OCD symptom dimensions: 1) harm-related, aggressive, sexual, and religious obsessions with checking compulsions; 2) symmetry obsessions with arranging and repeating compulsions; 3) contamination obsessions with cleaning compulsions; and 4) hoarding and saving symptoms (1, 2). These symptom factors are relatively stable over time and show different patterns of genetic inheritance, age at onset, comorbidity, and treatment response (see 1 for review). Cluster analyses, which seek to identify mutually exclusive, categorical subgroups, indicate that some of these symptom factors, such as hoarding, may constitute discrete subtypes of OCD (3, 4). Hoarding is defined as the acquisition of and inability to discard items, even though they appear (to others) to have no value (5). Hoarding behavior has been observed in several neuropsychiatric disorders, including schizophrenia, dementia, eating disorders, autism, and mental retardation, as well as in non-clinical populations, but it is most commonly found in OCD (6). 30% to 40% of OCD patients report hoarding and saving symptoms (6–8), and about 10% to 15% have hoarding as their most prominent symptom factor (3, 6). Compulsive hoarding is most commonly driven by obsessional fears of losing important items that the patient believes will be needed later, distorted beliefs about the importance of possessions, excessive acquisition, and exaggerated emotional attachments to possessions (5). Compulsive hoarding and saving leads to clutter that can cover living and work spaces, rendering them unusable. Hoarding frequently causes significant impairment in social and occupational functioning. In severe cases, it can produce health risks from infestations, falls, fires, and inability to cook or eat in the home (6). In this issue of the Journal, Jack Samuels, Ph.D., et al. report results from the OCD Collaborative Genetics Study, finding “suggestive” linkage of compulsive hoarding to a marker on chromosome 14 in families with OCD. The linkage became stronger when only families with two or more family members with compulsive hoarding were tested. Compulsive hoarding is well known to run in families. Hoarding behaviors are significantly more prevalent in the relatives of hoarding OCD patients than nonhoarding OCD patients (9). In the OCD Collaborative Genetics Study, hoarding was the most strongly familial of the OCD symptom factors, with robust correlations among sibling pairs (10). Only two previous genetic studies have examined the hoarding phenotype. Lochner et al. (8) found that the met/met (L/L) genotype of the catechol O-methyltransferase val158met polymorphism on chromosome 22q11 was significantly more prevalent in Afrikaner OCD patients with

Is Compulsive Hoarding a Genetically and Neurobiologically Discrete Syndrome? Implications for Diagnostic Classification

Long-Term Follow-Up Study of Patients With Refractory Obsessive-Compulsive Disorder

Management of Psychiatric Disorders with HIV and Dermatological Disorders.

Decision letter: Characterizing a psychiatric symptom dimension related to deficits in goal-directed control

Sir: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder. The disorder is characterized by chronic abdominal pain and altered bowel habits in the absence of any organic disorder. Treatment of IBS includes dietary modification, psychotherapies, and medications. Among medications, antidepressants may be beneficial in IBS.1 We report a case in which symptoms of diarrhea-predominant IBS improved with low-dose paroxetine, a widely used antidepressant. Case report. Mr. A, a 43-year-old man, presented to a gastroenterologist in August 2001 complaining of frequent diarrhea and chronic abdominal pain. These symptoms, present for 3 months, had intensified during the previous month with increased stress. There were no abnormal findings on a physical examination or gastrointestinal endoscopy. He was diagnosed as having IBS. Treatment for 5 months with trimebutine maleate, 300 mg/day, and loperamide, 2 mg/day, was not beneficial. Then, he was referred to our department of psychiatry. At a psychiatric evaluation, Mr. A reported feeling stress on the job and had mild obsessional thinking that stress must cause diarrhea and eating must exacerbate diarrhea. He did not meet DSM-IV criteria for major depressive disorder or obsessive-compulsive disorder. Supportive psychotherapy was initiated, and paroxetine, 10 mg/day, was added for 1 week and then increased to 20 mg/day. After 3 weeks of treatment at 20 mg/day, his IBS symptoms disappeared and trimebutine maleate and loperamide were discontinued. For the next year, he experienced no IBS symptoms. Paroxetine treatment was then reduced to 10 mg/day and discontinued after 6 months at this dose. Psychotherapy alone has controlled his IBS symptoms for the past year. This case represents a patient with diarrhea-predominant IBS and mild obsessional thinking. Although treatment with trimebutine maleate and loperamide did not lead to improvement in clinical symptoms, the patient's IBS symptoms disappeared with paroxetine treatment. Paroxetine, a widely used selective serotonin reuptake inhibitor (SSRI), is effective in treating depressive disorders and anxiety disorders, including obsessive-compulsive disorder. A number of randomized controlled trials have demonstrated decreased symptoms in IBS patients taking low-dose tricyclic antidepressants (TCAs). SSRIs may be useful when IBS is accompanied and exacerbated by a mood disorder, but evidence to support their use is lacking.2 The efficacy of SSRIs in patients with IBS has been documented in case reports3 and a pilot open-label study,4 but not in controlled studies.5 The mechanism of action of SSRIs for IBS is not known but may relate to its effects on the central nervous system and the enteric nervous system.5 Low-dose SSRI treatment might be effective for mild obsessional thinking that does not fulfill DSM-IV diagnostic criteria for obsessive-compulsive disorder. Moreover, the anticholinergic effects of paroxetine are milder than those of TCAs, and paroxetine may improve diarrhea and other symptoms of IBS adequately. Patients with IBS often have obsessional thinking about IBS symptoms. Therefore, SSRIs might have efficacy for IBS even without a diagnosable mental disorder. If IBS symptoms are improved with SSRI treatment in diarrhea-predominant IBS, psychotherapy may be helpful in maintaining improvement. As a result, IBS symptoms may be controlled without medication. This suggests that an SSRI, such as paroxetine, administered in a low dose might be a key drug in early treatment for IBS.

Relapse Prevention and the Need for Ongoing Pharmacological Treatment in Body Dysmorphic Disorder.

Although standard diagnostic classifications consider obsessive-compulsive disorder (OCD) to be a single diagnostic entity, it has become clear that it is a heterogeneous disorder, with great variability in clinical presentation. This heterogeneity has complicated the interpretation of clinical, neurobiological, and genetic studies in OCD. Therefore, researchers have sought to identify clinically meaningful phenotypes that might be more homogeneous and heritable to facilitate our understanding of the etiology and pathophysiology of OCD and ultimately lead to improved treatments (1). Factor analytic studies have consistently identified four principal OCD symptom dimensions: 1) harm-related, aggressive, sexual, and religious obsessions with checking compulsions; 2) symmetry obsessions with arranging and repeating compulsions; 3) contamination obsessions with cleaning compulsions; and 4) hoarding and saving symptoms (1, 2). These symptom factors are relatively stable over time and show different patterns of genetic inheritance, age at onset, comorbidity, and treatment response (see 1 for review). Cluster analyses, which seek to identify mutually exclusive, categorical subgroups, indicate that some of these symptom factors, such as hoarding, may constitute discrete subtypes of OCD (3, 4). Hoarding is defined as the acquisition of and inability to discard items, even though they appear (to others) to have no value (5). Hoarding behavior has been observed in several neuropsychiatric disorders, including schizophrenia, dementia, eating disorders, autism, and mental retardation, as well as in non-clinical populations, but it is most commonly found in OCD (6). 30% to 40% of OCD patients report hoarding and saving symptoms (6–8), and about 10% to 15% have hoarding as their most prominent symptom factor (3, 6). Compulsive hoarding is most commonly driven by obsessional fears of losing important items that the patient believes will be needed later, distorted beliefs about the importance of possessions, excessive acquisition, and exaggerated emotional attachments to possessions (5). Compulsive hoarding and saving leads to clutter that can cover living and work spaces, rendering them unusable. Hoarding frequently causes significant impairment in social and occupational functioning. In severe cases, it can produce health risks from infestations, falls, fires, and inability to cook or eat in the home (6). In this issue of the Journal, Jack Samuels, Ph.D., et al. report results from the OCD Collaborative Genetics Study, finding “suggestive” linkage of compulsive hoarding to a marker on chromosome 14 in families with OCD. The linkage became stronger when only families with two or more family members with compulsive hoarding were tested. Compulsive hoarding is well known to run in families. Hoarding behaviors are significantly more prevalent in the relatives of hoarding OCD patients than nonhoarding OCD patients (9). In the OCD Collaborative Genetics Study, hoarding was the most strongly familial of the OCD symptom factors, with robust correlations among sibling pairs (10). Only two previous genetic studies have examined the hoarding phenotype. Lochner et al. (8) found that the met/met (L/L) genotype of the catechol O-methyltransferase val158met polymorphism on chromosome 22q11 was significantly more prevalent in Afrikaner OCD patients with