Obsessive-compulsive disorder

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Abstract

Obsessive-compulsive disorder Last revised in June 2018 Next planned review by December 2023 Summary Back to topObsessive-compulsive disorder: Summary Obsessive-compulsive disorder (OCD) is characterized by recurrent obsessional thoughts or compulsive acts or, commonly, both.The prevalence rate is 1.0–3.0% in adults and around 0.25% in children and adolescents aged 5 to 15 years.If undertreated, OCD usually persists.OCD is ranked by the World Health Organization in the top ten of the most disabling illnesses by lost income and decreased quality of life.People with OCD often fear stigmatization and fail to disclose their symptoms spontaneously, leading to low rates of recognition and, consequently, undertreatment.Diagnosis of OCD involves:Screening people with symptoms of depression, anxiety, alcohol or substance misuse, body dysmorphic disorder, or an eating disorder. This includes asking questions like: do you wash or clean a lot? Do you check things a lot? Are you concerned about putting things in a special order?Excluding other conditions, which can be misdiagnosed as OCD, including body dysmorphic disorder, illness anxiety disorder, and autism.Assessing the severity of functional impairment as mild, moderate, or severe (to guide management).Assessing the risk of self harm and suicide (especially if there is coexisting depression) as well as the impact of compulsive behaviours on others (in particular children).Management of OCD will depend on the level of functional impairment. Management options include:Cognitive-behavioural therapy (CBT), ideally including exposure and response prevention (ERP). A selective serotonin reuptake inhibitor (SSRI) or clomipramine. SSRIs should only be prescribed to people under 18 years of age following assessment and diagnosis by a child and adolescent psychiatrist.Specialist referral (depending on factors including the person's age, severity of symptoms, and previous treatment failures).Referral for urgent psychiatric assessment should be made for people at suspected high risk of self harm or suicide. Have I got the right topic? Back to topHave I got the right topic? From age 8 years onwards.This CKS topic is based on the National Institute for Health and Care Excellence guideline Obsessive-compulsive disorder and body dysmorphic disorder: treatment [NICE, 2005].This CKS topic covers the diagnosis, assessment, and management in primary care of obsessive-compulsive disorder in adults, young people, and children.This CKS topic does not cover body dysmorphic disorder or obsessive-compulsive personality disorder.There are separate CKS topics on Alcohol - problem drinking, Depression, Depression - antenatal and postnatal, and Generalized anxiety disorder.The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care. How up-to-date is this topic? Back to topHow up-to-date is this topic? Back to top Changes Changes June 2018 — reviewed and updated. A literature search was conducted in June 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made. Back to top Previous changes Previous changes July 2013 — reviewed. A literature search was conducted in July 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. There are no major changes to the recommendations.February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.January 2012 — minor update. Lundbeck Ltd, in collaboration with the Medicines and Healthcare products Regulatory Agency (MHRA), has published new safety data regarding the association of citalopram and escitalopram with dose-dependent QT interval prolongation. This topic has been updated to reflect their advice, including new maximum doses. Issued in January 2012.August to November 2008 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence. Back to top Update Update Back to top New evidence New evidence Evidence-based guidelinesNo new evidence-based guidelines since 1 June 2018.HTAs (Health Technology Assessments)No new HTAs since 1 June 2018.Economic appraisalsNo new economic appraisals relevant to England since 1 June 2018.Systematic reviews and meta-analysesNo new systematic reviews published since 1 June 2018.Primary evidenceNo new randomized controlled trials published in the major journals since 1 June 2018. Back to top New policies New policies No new policies since 1 June 2018. Back to top New safety alerts New safety alerts No new safety alerts since 1 June 2018. Back to top Changes in product availability Changes in product availability No changes in product availability since 1 June 2018. Goals and outcome measures Back to topGoals and outcome measures Back to top Goals Goals To support primary healthcare professionals to:Make a working diagnosis of obsessive-compulsive disorder.Accurately assess its severity and the impact on daily life.Provide appropriate treatment in primary care.Refer to secondary care or other specialist service, when required.Provide appropriate advice to affected people and their families. Back to top Outcome measures Outcome measures No outcome measures were found during the review of this topic. Back to top Audit criteria Audit criteria No audit criteria were found during the review of this topic. Back to top QOF indicators QOF indicators No QOF indicators were found during the review of this topic. Back to top QIPP - Options for local implementation QIPP - Options for local implementation First-choice antidepressant use in adults with depression or generalised anxiety disorder:Review and, where appropriate, revise prescribing of antidepressants in adults to ensure that it is line with NICE guidance.[NICE, 2015] Back to top NICE quality standards NICE quality standards Statement 1. People with a suspected anxiety disorder receive an assessment that identifies whether they have a specific anxiety disorder, the severity of symptoms and associated functional impairment.Statement 2. People with an anxiety disorder are offered evidence-based psychological interventions.Statement 3. People with an anxiety disorder are not prescribed benzodiazepines or antipsychotics unless specifically indicated.Statement 4. People receiving treatment for an anxiety disorder have their response to treatment recorded at each treatment session.[NICE, 2014] Background information Back to topBackground information Back to top Definition What is it? Obsessive-compulsive disorder (OCD) is characterized by recurrent obsessional thoughts or compulsive acts or, commonly, both, which may cause significant functional impairment and/or distress.An obsession is defined as an unwanted intrusive thought, image, or urge that repeatedly enters the person's mind, and that usually causes marked anxiety or distress. Common obsessions in OCD include:Contamination from dirt, germs, viruses (e.g. HIV), bodily fluids or faeces, chemicals, sticky substances, dangerous materials (e.g. asbestos).Fear of harm.Excessive concern with order or symmetry.Superstition, fear of 'bad' numbers 'magical' thinking, religious obsessions.'Forbidden' thoughts or images (such as being a paedophile, blasphemy, violence, sexual or criminal acts, harm to others, harming own baby).Compulsions are repetitive behaviours or mental acts that the person feels driven by their obsession(s) to perform. A compulsion can either be overt and observable by others, or a covert mental act that cannot be observed. Common compulsions in OCD include:Repetitive hand washing  — due to fear of contamination.Checking (e.g. that doors are locked, electrical items unplugged, gas taps are off) — due to fear of harm to self or others.Ordering, arranging, and/or repeating — due to excessive concern with order or symmetry.Mental compulsions (e.g. special words or prayers repeated in a set manner, asking for forgiveness, excessive counting) — due to religious beliefs, 'magical' thinking, superstitions.Memory checking and avoidance of triggers — due to concerns about 'forbidden' thoughts or images.In children and young people:Young children's obsessional thoughts are more likely to include 'magical' or superstitious thinking (e.g. If I don't count up to 20, my parents will die).Members of the family are almost always involved in a young person's compulsive rituals. [NICE, 2005; National Collaborating Centre for Mental Health, 2006; American Psychiatric Association, 2013; Grant, 2014; Veale and Roberts, 2014] Back to top Risk factors What are the risk factors? Risk factors for the development of obsessive-compulsive disorder (OCD) include:Family history:First-degree relatives of people with OCD are at increased risk of developing the disorder.Age:A bimodal onset has been observed, with peak mean ages of onset at approximately 10 years and 21 years.Onset over the age of 30 years is rare.Developmental factorsEmotional, physical, and sexual abuse, neglect, social isolation, bullying.Pregnancy and the postnatal periodIn one study of 59 female OCD patients, 39% of participants described onset of OCD symptoms during pregnancy.Common obsessions in these periods are worries about harming or abusing the baby and/or not being careful enough e.g. with sterilizing feeding equipment. Compulsions include avoidance behaviour, repeatedly seeking approval, checking the baby is still breathing.[Grant, 2014; Veale and Roberts, 2014; BMJ Best Practice, 2017a] Back to top Prevalence How common is it? Obsessive compulsive disorder (OCD) is thought to be the fourth most common psychiatric illness after depression, alcohol/substance misuse, and social phobia.The World Health organisation ranks OCD as being among the top 20 causes of illness related disability for people between the ages of 15 and 44.Studies have estimated the population prevalence of OCD to be between 1% and 3%. In children aged 5 to 15 years, the estimated prevalence is 0.25%.Rates are similar throughout the world.The sex ratio overall is approximately 1:1, but in childhood-onset OCD, boys are more commonly affected than girls (male:female ratio, 2:1 to 3:1), whereas the sex ratio shifts among people with onset during or after puberty (male:female ratio, 1:1.4).[NICE, 2005; Grant, 2014; Veale and Roberts, 2014; BMJ Best Practice, 2017a] Back to top Prognosis What is the prognosis? If OCD is untreated, the course is usually chronic, often with waxing and waning symptoms. Without treatment, remission rates among adults are approximately 20%.Psychological therapies can be effective in the treatment of OCD:Analysis of more than 25 randomized, controlled trials has shown that 60% to 85% of people report a considerable reduction in symptoms following exposure and response prevention as a psychological therapy, and improvement is maintained for up to 5 years in a majority of the people who have a response.Cognitive therapy shows similar efficacy, with improvement in 60% to 80% of people, and effect sizes almost as large as those with exposure and response prevention.However, about 30% of people refuse treatment, leave early, or do not respond to cognitive therapy, with similar rates observed for exposure and response prevention.Pharmacotherapy with clomipramine or a selective serotonin-reuptake inhibitor (SSRI) has also been shown to be effective in the treatment of OCD:A meta-analysis of 17 randomized, double-blind, placebo-controlled trials showed that various SSRIs were all superior to placebo and that people were approximately twice as likely to have a response to an SSRI than to placebo.A meta-analysis of 7 controlled trials of clomipramine also showed that this was superior to placebo.[NICE, 2005; Grant, 2014] Back to top Complications What are the complications? Complications of obsessive-compulsive disorder (OCD) include:Reduced quality of life — adverse effects on daily life,  personal relationships, and ability to work and/or study. Fear of contamination can prevent the accessing of appropriate health care. Childhood or adolescent onset may prevent the person from socialising with peers and may eventually cause difficulties with independent living.Dermatitis — due to excessive handwashing.Self-harm and suicide — people with OCD, particularly those who also have depression, may be at increased risk of self-harm and/or suicide.[NICE, 2005; Veale and Roberts, 2014] Diagnosis Back to topDiagnosis of obsessive-compulsive disorder Back to top Diagnosis When should I suspect obsessive-compulsive disorder? Be aware that people with obsessive-compulsive disorder (OCD) are often embarrassed by their condition and may not readily disclose symptoms. Direct questions may be needed. People with OCD may also present in primary care with dermatological symptoms (from excessive washing), genital or anal symptoms (from excessive checking and washing), general stress (for example, from losing a job as a result of repeated lateness or from problems with interpersonal relationships), or doubts about contracting HIV.Screen people with symptoms of depression, anxiety, alcohol or substance misuse, body dysmorphic disorder, or an eating disorder, and those reporting symptoms suggestive of OCD using the following questions:Do you wash or clean a lot?Do you check things a lot?Is there any thought that keeps bothering you that you would like to get rid of, but cannot?Do your daily activities take a long time to finish?Are you concerned about putting things in a special order, or are you upset by mess?Do these problems trouble you?The diagnosis can be supported using criteria from the International Classification of Disease (ICD-10) and/or the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Note: These diagnostic criteria do not offer a minimum number of symptoms or specific time period to support a definitive diagnosis, and should therefore be used in conjunction with clinical judgement.Be aware of other conditions which can be misdiagnosed as OCD. Back to top Differential diagnosis Differential diagnosis The differential diagnoses of obsessive-compulsive disorder (OCD) include:Obsessive-compulsive personality disorder (OCPD) — suggested by a preoccupation with orderliness, details, rules, organisation, or schedules, to the degree that the point of the activity is lost, with absence of obsessions and compulsions, but may involve discomfort if things are sensed not to have been done completely. Body dysmorphic disorder (BDD) — suggested by obsessive preoccupation with a perceived defect in physical appearance.Somatic symptom disorder — suggested by excessive thoughts, feelings, or behaviours related to somatic symptoms or associated health concerns.Illness anxiety disorder (hypochondriasis) — suggested by a preoccupation with having or acquiring serious illness and excessive health-related behaviours, such as repeatedly checking for signs of illness. May demonstrate maladaptive avoidance, such as avoiding medical appointments.Delusional disorder — suggested by a false belief that is firmly sustained and based on incorrect inference about reality. Compulsions may be absent.Autism spectrum disorder (including Asperger's syndrome) — suggested by stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements, impaired social interaction, problems with verbal and non-verbal communication, and unusual, repetitive, compulsive behaviour or severely limited activities and interests. For more information, see the CKS topic on Autism in children.Hoarding disorder — suggested by persistent difficulty in discarding or parting with possessions, regardless of actual value, due to perceived need to save items and distress associated with discarding them.Trichotillomania (hair-pulling disorder) — suggested by recurrent pulling out of hair, resulting in hair loss.Excoriation (skin-picking) disorder — suggested by recurrent picking of skin, resulting in skin lesions.Substance-induced or medication-induced obsessive-compulsive disorder — suggested by OCD-type symptoms that are attributable to effects of medication or drug of abuse, and develop during or soon after substance intoxication or withdrawal or after exposure to substance. Back to top ICD-10 and DSM-5 criteria for OCD ICD-10 and DSM-5 criteria for the diagnosis of obsessive-compulsive disorder International Classification of Disease (ICD-10) criteria for a diagnosis of obsessive-compulsive disorder (OCD) are the presence of recurrent, obsessional thoughts or compulsive acts:Obsessional thoughts are:Ideas, images, or impulses that enter the person's mind again and again in stereotyped form.Almost invariably distressing, and the person often tries, unsuccessfully, to resist them.Recognized as the person's own thoughts, even if they are involuntary or repugnant.Compulsive acts or rituals are:Stereotyped behaviours that are repeated again and again.Not inherently enjoyable, nor do they result in completion of inherently useful tasks.Performed to prevent some objectively unlikely event, often involving harm to, or caused by, the person, which he or she fears might otherwise occur.Usually recognized by the person as pointless or ineffectual and repeated attempts are made to resist them.Anxiety is almost invariably present; if compulsive acts are resisted the anxiety gets worse.Diagnostic and Statistical Manual-5 (DSM-5) criteria for OCD are:Must exhibit obsessions, compulsions, or both.The obsessions and/or compulsions cause marked distress, are time consuming (take more than 1 hour per day), or interfere substantially with the person's normal routine, occupational or academic functioning, or usual social activities or relationships.The obsessions and/or compulsions are not attributable to the physiological effects of a substance or other medical condition.The disorder is not better explained by the symptoms of another mental disorder, such as obsession with food in the context of an eating disorder.Obsessions are:Recurrent and persistent thoughts, urges, or images experienced, at some time during the disturbance, as intrusive and unwanted and in most individuals cause marked anxiety or distress.There is some effort by the affected person to ignore or suppress such thoughts, impulses, or images, or to neutralise them with some other thought or action (i.e., by performing a compulsion).Compulsions are:Repetitive activities (e.g., hand washing, ordering, checking) or mental acts (e.g., praying, counting, repeating words silently) that the person feels driven to perform in response to an obsession or according to rules that must be applied rigidly.These behaviours or mental acts are performed in order to prevent or reduce distress, or prevent some dreaded event or situation. However, they are either clearly excessive or not connected in a realistic way with what they are designed to neutralise or prevent. Back to top Basis for recommendation Basis for recommendation The information on diagnosis of obsessive-compulsive disorder (OCD) is largely based on expert opinion in the National Institute of Health and Care Excellence (NICE) guideline Obsessive-compulsive disorder and body dysmorphic disorder: treatment [NICE, 2005].Diagnostic criteriaDiagnostic criteria are based on the International Classification of Disease (ICD-10) [WHO, 1992] and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) [American Psychiatric Association, 2013].Direct questionsThe advice that direct questions may be needed is due to the fact that people with OCD are often ashamed of their symptoms and fear stigmatization. This information is derived from the full NICE guideline Obsessive compulsive disorder: core intervations in the treatment of obsessive-compulsive disorder and body dysmorphic disorder [National Collaborating Centre for Mental Health, 2006], and recommendations from two previous expert reviewers of this CKS topic. Differential diagnosisThe information on differential diagnosis of OCD is based on expert opinion in the BMJ Best Practice guideline Obsessive-compulsive disorder [BMJ Best Practice, 2017a]. Management Back to topManagement Scenario: Management: covers the assessment and management of people with OCD. Back to top Scenario: Management Scenario: Management of obsessive-compulsive disorder From age 8 years onwards. Back to top Management How should I manage a person with obsessive-compulsive disorder? For all people with obsessive-compulsive disorder (OCD) assess their degree of distress and functional impairment as mild, moderate, or severe:Ask about the effects on work or school, relationships, social life, and quality of life.Gather more information from the initial responses to the six screening questions used in OCD diagnosis.If time allows, consider using a severity rating scale such as the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS), or questions derived from it.Be aware that OCD may exist with other mental health disorders including depression, anxiety, alcohol or substance misuse, body dysmorphic disorder, and/or an eating disorder. For more information on managing these conditions, please see the CKS topics on Depression, Generalized anxiety disorder, Alcohol - problem drinking, Opioid dependence, and Eating disorders.In children and young people, learning disorders, psychosocial factors such as family discord, or the presence of parental mental health problems, may also be factors, particularly if OCD is not responding to treatment. Note: If the person is exhibiting severe distress and/or functional impairment, co-morbid depression or another mental health disorder, or other concerns have been raised, assess their risk of suicide and self-harm. For more information on assessing risk of suicide, see the section on 'assessing risk of suicide' in the CKS topic on Depression.Also assess for safeguarding concerns for children or vulnerable adults in their care (if applicable). Follow local safeguarding procedures if appropriate.If there is any uncertainty about the risks associated with intrusive sexual, aggressive or death-related thoughts reported by people with OCD, advice should be sought from mental health professionals with specific expertise in the assessment and management of OCD.Refer for specialist treatment people whose OCD and marked functional impairment are assessed as 'severe', and/or those exhibiting, or at risk of:Self-harm. Self-neglect.A significant comorbidity such as substance misuse, severe depression, anorexia nervosa, or schizophrenia.Suicide — refer urgently (same day) to the crisis resolution and home treatment team if the person is at high risk of suicide. For more information see the section on 'managing risk of suicide' in the CKS topic on Depression.Note: For information on what action to take if admission is thought to be necessary but the person refuses, see the 'compulsory admission' section in the CKS topic on Depression. Follow local policy when referring to specialist mental health services.For people being managed in primary care, provide written material about the nature of OCD and its treatment options. Printable leaflets on OCD are available from Mind. The Royal College of Psychiatrists have also produced leaflets on OCD, Perinatal OCD, and OCD in children and young people.For adults with mild functional impairment:Recommend a psychological intervention. This is accessed by referral or self-referral to IAPT (Improving Access to Psychological Therapies). Following assessment, a low intensity cognitive-behavioural therapy (CBT), including exposure and response prevention (ERP) may be offered. The format for low-intensity CBT should be up to 10 therapist-hours per person, of one of the following:Brief individual CBT (including ERP) with structured self-help materials.Brief individual CBT (including ERP) by phone.Group CBT (including ERP) which may be for more than 10 hours.If the person has been unable to engage in low-intensity CBT (including ERP) or the response is inadequate, treat as for moderate functional impairment.For adults with moderate functional impairment, if you are confident of your assessment of moderate functional impairment (expert opinion suggests that it is easy to underestimate this):Offer the choice of intensive CBT including ERP (accessed by referral or self referral to IAPT), or a selective serotonin reuptake inhibitor (SSRI) (see below). Consider prescribing clomipramine (as an alternative first-line drug treatment to an SSRI) if the person prefers clomipramine or has had a previous good response to it, or if an SSRI is contraindicated. For more information on prescribing clomipramine, please see the relevent section in Prescribing information.If you are not confident of your assessment of moderate functional impairment or there is an inadequate response to initial treatment, refer to the secondary care mental health team.For adults with severe functional impairment:Refer to the secondary care mental health team for assessment.Whilst awaiting assessment:Consider offering combined treatment with an SSRI (see below) and CBT (including ERP).Consider prescribing clomipramine (as an alternative first-line drug treatment to an SSRI) if the person prefers clomipramine or has had a previous good response to it, or if an SSRI is contraindicated.When prescribing an SSRI:Escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline are all licensed for the treatment of OCD in adults. Citalopram can also be prescribed as a treatment for OCD, but this is an unlicensed use. Discuss the potential for adverse effects and withdrawal symptoms before drug treatment is initiated. Explain that adverse effects early in treatment with an SSRI may include increased anxiety, agitation, and sleeping problems.Advise the person that in OCD, when compared with depression, treatment with an SSRI usually requires a higher dose and a longer duration of treatment (at least 12 weeks) for an initial response.Be aware that in a minority of people aged under 30 years of age, SSRIs are associated with an increased risk of suicidal thinking and self-harm. Anyone in this age group receiving an SSRI should therefore be seen within 1 week of first prescribing, and the risk of suicidal thinking and self-harm should be monitored weekly for the first month. When adults with comorbid depression are assessed to be at a high risk of suicide, the use of additional support such as more frequent direct contacts with primary care staff or telephone contacts should be considered, particularly during the first weeks of treatment. For people at high risk of suicide, a limited quantity of medication should be prescribed.Adults started on SSRIs who are not considered to be at increased risk of suicide or self-harm should be monitored closely — the effectiveness and adverse effects of the drug should ideally be reviewed every 2 to 4 weeks during the first 3 months of treatment and every 3 months thereafter. Dose adjustment may be required. Bear in mind that an absence of clinical benefit within four weeks suggests that a response to unchanged treatment is unlikely, but that the full efficacy of the drug may take up to 12 weeks to be realised.For more information on prescribing an SSRI, please see the relevant sections in Prescribing information.When prescribing clomipramine, be aware of the need to monitor patients for the emergence of other psychiatric symptoms, as well as the emergence of suicidality. Advise the person to report such symptoms immediately.For more information on prescribing clomipramine, please see the relevant section in Prescribing information.If a pregnant woman requires treatment for OCD:If drug treatment is considered necessary in the first trimester (such as in a women for whom psychological intervention has proved ineffective), the potential risks and benefits should be discussed. For example, it is still unclear whether SSRIs used in the first trimester may slightly increase the risk of infant congenital heart defects above the background rate of approximately 1 in 100. This must be balanced against the risks to both mother and fetus if the maternal condition is not optimally controlled. Consider discussion with a specialist in obstetrics for women who may require SSRI medication in pregnancy. If a woman with OCD who is stabilised on current treatment reports a pregnancy, the risk of relapse must be taken into account when considering discontinuing or switching medication. In cases where drug treatment is continued in pregnancy, the lowest effective dose should be used. Consider discussion with a specialist in obstetrics for women who may require changes to their SSRI medication in pregnancy. Treatment with an SSRI after around 20 weeks of pregnancy may raise the risk of persistent pulmonary hypertension of the newborn (PPHN) and/or can lead to neonatal withdrawal. Women using these medications should therefore be advised to give birth at a unit with the facilities to provide treatment and support for these conditions.Patient information leaflets on use of drugs to treat OCD in pregnancy are available at medicinesinpregnancy.org.For children and young people (under the age of 18 years) with mild functional impairment:If confident of the diagnosis of obsessive-compulsive disorder (OCD) and that functional impairment is mild, refer for guided self-help in conjunction with support and information for the family or carers to your local service provider.If guided self-help is unavailable or ineffective, refer to Child and Adolescent Mental Health Services (CAMHS).For children and young people (under the age of 18 years) with moderate-to-severe functional impairment:Refer to CAMHS.Note: a selective serotonin reuptake inhibitor (SSRI) should only be prescribed to people under 18 years of age following assessment and diagnosis by a child and adolescent psychiatrist.Arrange active monitoring of the person's symptoms, functioning, and response to treatment (if applicable) at intervals determined by clinical judgement. Back to top Yale-Brown Obsessive-Compulsive Scale Yale-Brown Obsessive-Compulsive Scale This list of questions, derived from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), is included as a guide — see Y-BOCS for a full symptom checklist, and http://ocd.stanford.edu for interpretation of the score:How much of your day is occupied by obsessive thoughts or spent performing compulsive acts (mild, less than 1 hour; moderate, 1–3 hours; severe, more than 3 hours)?How much do your obsessive thoughts or compulsive behaviours interfere with your social or work/school functioning (including relationships)?How much distress do your obsessive thoughts cause you? How would you feel if prevented from performing your compulsion(s)? How anxious would you become?How much of an effort do you make to resist the obsessive thoughts or compulsions?How much control do you have over your obsessive thoughts? How strong is the drive to perform the compulsions?The Children's Y-BOCS (CY-BOCS) is similar to the adult version and can be used to assess the nature and severity of symptoms. Back to top Monitoring How should I monitor a person with obsessive-compulsive disorder? During each review:Be alert to suicidal ideation and assess suicide risk, especially if the person has comorbid depression. For more information on depression and assessing the risk of suicide, see the CKS topic on Depression.Monitor progress, taking into account factors including severity, and duration of symptoms, as well as the degree of distress and functional impairment.Consider using the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS), or questions derived from it to compare with previous scores.For a child or young person, if guided self-help is ineffective, refer to Child and Adolescent Mental Health Services (CAMHS).For adults, check adherence to any treatment and inquire about adverse drug effects (if applicable).For people in the initial stages of SSRI treatment, ask about signs of akathisia or restlessness, suicidal ideation, and increased anxiety and agitation. If the person reports prolonged akathisia, restlessness or agitation, consider a switch to a different SSRI. For more information, see the relevant sections on dosage and titration in Prescribing information.If there has not been an adequate response to a standard dose of an SSRI, and there are no significant side effects after 4–6 weeks, a gradual increase in dose should be considered. For more information, see the relevant sections on dosage and titration in Prescribing information. Monitor the person around the time of dose changes for any new symptoms or worsening of their condition. For adults with an inadequate response to initial treatment (a full 12 weeks of treatment with an SSRI, or more than 10 therapist hours of CBT [including ERP]), other treatment options include combined treatment with CBT (including ERP) and an SSRI, and/or switch to a different SSRI, or a switch to clomipramine. If there has been no response to a full trial of at least one SSRI alone, a full trial of combined treatment with CBT (including ERP) and an SSRI, and a full trial of clomipramine alone, the person should be referred to a multidisciplinary team with specific expertise in the treatment of OCD for assessment and further treatment planning.Note: It is advisable to monitor cardiac function with ECG during long-term therapy with clomipramine, at intervals determined by clinical judgement and depending on factors including length of treatment, the persons age, and cardiac risk factors. Advise the person to report cardiac symptoms such as palpitations, vertigo, syncope, or seizures and if these develop during treatment, arrange for the person to have an ECG.If a drug is effective, advise the person to continue taking it for at least a year.Re-evaluate the required frequency of follow-up based on:The person's preference.Severity of symptomsComorbid conditions.Change since last review and response to interventions.Symptoms during treatment changes.When an adult with OCD has taken an SSRI or clomipramine for 12 months after remission (symptoms are not clinically significant and the person is fully functioning for at least 12 weeks), review the need for continued treatment.Consider the severity and duration of the initial illness, the number of previous episodes, the presence of residual symptoms, and concurrent psychosocial difficulties.If treatment is continued for an extended period beyond 12 months after remission, the need for continuation should be reviewed at regular intervals and written in the notes.When reducing or stopping SSRIs or clomipramine, the dose should be tapered gradually over at least several weeks, according to the person's need. The rate of reduction should take into account the starting dose, the drug half-life and particular profiles of adverse effects. Advise the person to seek advice if they experience significant discontinuation/withdrawal symptoms. Back to top Basis for recommendation Basis for recommendation The recommendations on management of people with obsessive compulsive disorder (OCD) are largely based on the National Institute of Health and Care Excellence Guideline Obsessive-compulsive disorder and body dysmorphic disorder: treatment [NICE, 2005] and the full version of this guideline [National Collaborating Centre for Mental Health, 2006].Assessing severity of functional impairmentNICE recommends initial treatments for OCD according to whether the level of functional impairment is mild, moderate, or severe, but does not suggest how the severity of functional impairment should be assessed [NICE, 2005].CKS found no published evidence specifically relating to the most appropriate method of assessing severity of functional impairment in people with OCD in primary care. Recommendations are therefore largely based on expert opinion [Freeston, Personal Communication, 2008; Williams, Personal Communication, 2008] and also from information in the BMJ Best Practice guideline Obsessive-compulsive disorder, which suggests use of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) by 'therapists' [BMJ Best Practice, 2017a].Suicide riskNICE advises that people with severe OCD, particularly with comorbid depression, should be assessed for risk of suicide [NICE, 2005].The advice on how to assess suicide risk is derived from information within the National Institute for Health and Care Excellence (NICE) guideline Depression in adults: recognition and management [NICE, 2016], the British Columbia Medical Association guideline Major depressive disorder in adults - diagnosis and management [British Columbia Medical Association, 2013], and the Singapore Ministry of Health guideline Depression [Singapore Ministry of Health, 2012].The information on comorbidities that should prompt assessment of suicide risk is extrapolated from the NICE guideline Depression in adults: recognition and management [NICE, 2016].Safeguarding issuesThe advice to assess for safeguarding issues is pragmatic, based on the fact that NICE states that 'Part of the risk assessment [for OCD] should include the impact of their compulsive behaviours on themselves or others'  [NICE, 2005].NICE guidelines on depression also state that marital and family relationships are frequently negatively affected, and parental depression may lead to neglect of children and significant disturbances in children [NICE, 2016]. CKS has extrapolated this advice to also potentially apply to people with OCD, particularly as those severely affected may also have comorbid depression.Frequency of monitoringThe advice on frequency of monitoring for people on SSRIs with or without risk factors for suicide is extrapolated from expert opinion within the NICE guideline Generalised anxiety disorder and panic disorder in adults: management [NICE, 2011].ClomipramineThe advice relating to monitoring people who are prescribed clomipramine for the emergence of other psychiatric symptoms and suicidality, and also regarding the monitoring of cardiac function during long-term therapy,  and gradual drug withdrawal, is contained within the summary of product characteristics for clomipramine [ABPI, 2017a].The advice to monitor cardiac function in people undergoing long-term clomipramine treatment is contained within the summary of product characteristics for clomipramine [ABPI, 2017a]. In the absence of any specific information relating to the frequency of monitoring, the recommendation to apply clinical judgement to routine monitoring, and to arrange immediate monitoring if cardiac symptoms emerge, is pragmatic, based on what CKS considers to be good medical practice.Pregnant womenThe information on use of SSRIs in pregnant women with OCD is extrapolated from expert opinion in the BMJ Best Practice guideline Generalised anxiety disorder [BMJ Best Practice, 2017b], and from a UK Teratology Information Service (UKTIS) monograph on use of SSRIs in pregnancy [UKTIS, 2017].ChildrenThe recommendation to refer children and young people with moderate or severe functional impairment to Child and Adolescent Mental Health Services (CAMHS) is based on a Department of Health recommendation that family and individual therapies for disorders of childhood and adolescence should normally take place within secondary care [RCPsych and RCGP, 2008]. Prescribing information Back to topPrescribing information Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC), or the British National Formulary (BNF). Back to top SSRIs SSRIs Back to top Contraindications and cautions Contraindications and cautions Do not prescribe SSRIs to people:In a manic phase of bipolar disorder.Taking monoamine oxidase inhibitors (MAOIs), or who have recently discontinued a MAOI.Taking pimozide.With uncontrolled epilepsy or new onset seizures.Do not prescribe citalopram to:People with known QT-interval prolongation or congenital long QT syndrome, or those using other medicinal products that are known to prolong the QT-interval.People with severe renal impairment (creatinine clearance less than 20 ml/min).Do not prescribe escitalopram to people with:Known QT interval prolongation, or taking medication known to prolong the QT interval.Congenital long QT syndrome.Do not prescribe fluoxetine or paroxetine in combination with metoprolol.Do not precribe fluvoxamine in combination with tizanidine, terfenadine, astemizole, or cisapride.Do not prescribe paroxetine in combination with thioridazine — this can elevate plasma levels of thioridazine, increasing the risk of QTc interval prolongation with associated serious ventricular arrhythmia such as torsades de pointes, and sudden death.Do not prescribe sertraline to people with severe hepatic impairment.Prescribe SSRIs with caution to people with:Cardiac disease.Risk factors for QTc prolongation such as congenital long QT syndrome, a family history of QT prolongation or other clinical conditions that predispose to arrhythmias (e.g., hypokalemia and hypomagnesemia, bradycardia, acute myocardial infarction or uncompensated heart failure), or concomitant use with medicinal products known to induce hypokalemia and hypomagnesemia, QT prolongation, and/or torsade de pointes — cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post-marketing period. If signs of cardiac arrhythmia occur during treatment with an SSRI, the treatment should be withdrawn and an ECG should be performed. (Note: citalopram is contraindicated in these groups, see above).Epilepsy (discontinue if convulsions develop).A history of bleeding disorders, especially gastrointestinal bleeding.Older people or people taking drugs that can damage the gastrointestinal mucosa or interfere with clotting (for example, NSAIDS or aspirin) may also be at risk. Consider prescribing a gastroprotective drug in these circumstances.Diabetes mellitus.History of mania.Susceptibility to angle-closure glaucoma.Also, prescribe with caution to those undergoing concurrent electroconvulsive therapy.Prescribe fluoxetine and citalopram, and sertraline with caution to people with hepatic impairment — a lower or less frequent dose should be considered and liver function should be closely monitored.Prescribe fluvoxamine and paroxetine with caution to people with hepatic or renal impairment — prescribe a low starting dose and monitor carefully.[ABPI, 2017b; ABPI, 2018; ABPI, 2017c; ABPI, 2017d; ABPI, 2017e; ABPI, 2017f; BNF 75, 2018] Back to top Adverse effects Adverse effects The most common adverse effects associated with use of an SSRI are:Gastrointestinal effects — these are dose-related and include nausea, vomiting, abdominal pain, dyspepsia, constipation, and diarrhoea.Central nervous system effects— including dizziness, agitation, anxiety, insomnia, headache, and tremor.Akathisia — characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In people who develop these symptoms, increasing the dose may be detrimental.Drowsiness — may impair performance of skilled tasks such as driving and operating machinery.Advise the person that it is illegal in England and Wales to drive while taking a prescribed drug if it impairs driving [DVLA, 2015a].Sexual dysfunction.Other adverse effects include:Increased risk of bleeding, especially in older people or people taking other drugs that can damage the gastrointestinal mucosa or interfere with clotting (for example, nonsteroidal anti-inflammatory drugs [NSAIDs]).Increased risk of fractures — the Medicines and Healthcare products Regulatory Agency (MHRA) has advised that SSRIs are associated with a small increased risk of fractures; however, the mechanism leading to this is unclear and may be multifactorial. Hyponatraemia — risk factors for developing hyponatraemia include a history of hyponatraemia, extreme old age (greater than 80 years of age), female sex, low body weight, diuretics, diabetes mellitus, hypertension, reduced renal function, volume depletion, and chronic obstructive pulmonary disease.Monitor the person for signs and symptoms of hyponatraemia (such as dizziness, lethargy, nausea, confusion, cramps, and seizures).Increased suicide risk — this is most likely in younger people (less than 30 years of age) when starting an SSRI.Monitor people carefully during the first few weeks of SSRI treatment; in particular, be alert for signs of suicidal ideation, akathisia, and increased anxiety and agitation. For more information on monitoring suicide risk, see the section on 'assessing suicide risk' in the CKS topic on Depression.Discontinuation symptoms (such as dizziness, sensory disturbances [including paraesthesia], sleep disturbances [including insomnia and intense dreams], agitation or anxiety, nausea and/or vomiting, tremor, and headache).The risk of discontinuation symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Generally these symptoms are mild to moderate; however, in some people, they may be severe.They usually occur within the first few days of discontinuing treatment.Generally, these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2 – 3 months or more).It is therefore advised that an SSRI should be gradually tapered over a period of several weeks or months, according to the person's needs.Paroxetine is associated with a higher incidence of discontinuation symptoms compared with other selective serotonin reuptake inhibitors.For citalopram and escitalopram, QT prolongation and/or ventricular arrhythmias; especially in women, people with hypokalaemia, or people with pre-existing QT prolongation or other cardiac disease.[MHRA, 2014; ABPI, 2017b; ABPI, 2018; ABPI, 2017c; ABPI, 2017d; ABPI, 2017e; ABPI, 2017f; BNF 75, 2018] Back to top Drug interactions Drug interactions Key drug interactions with SSRIs as a class include:5HT3 receptor antagonists, dapoxetine, duloxetine, fentanyl, Rasagiline, St John's Wort, tramadol, triptans — increased risk of serotonergic effects.The manufacturer of dapoxetine advises SSRIs should not be started until 1 week after stopping dapoxetine, and to avoid dapoxetine for 2 weeks after stopping SSRIs.Antiepileptics — SSRIs antagonise anticonvulsant effect of antiepileptics (convulsive threshold lowered).Aspirin, dabigatran, and NSAIDs — increased risk of bleeding.Coumarins — SSRIs possibly enhance anticoagulant effect of coumarins.Consider frequent monitoring of the INR. Any change in the person's clinical condition, particularly liver disease, intercurrent illness, or drug administration, necessitates more frequent monitoring of the INR. Cyproheptadine — antidepressant effect of SSRIs possibly antagonised by cyproheptadine.Lithium — increased risk of CNS effects when SSRIs given with lithium (lithium toxicity reported).Advise the person be alert for symptoms such as decreased appetite, diarrhoea, vomiting, ataxia, nystagmus, dysarthria, confusion, and seizures. Consider frequent monitoring of lithium levels.MAOIs — CNS effects of SSRIs increased by MAOIs (risk of serious toxicity).Methylphenidate — metabolism of SSRIs possibly inhibited.Pimozide — SSRIs possibly increase plasma concentration of pimozide (increased risk of ventricular arrhythmias—avoid concomitant use).Ritonavir — plasma concentration of SSRIs possibly increased.Tricyclic antidepressants — SSRIs increase plasma concentration of some tricyclicsVortioxetine — possible increased risk of convulsions.Key drug interactions with specific SSRIs include:Citalopram and escitalopramLinezolid — avoid co-administration unless there are facilities for close observation and monitoring of blood pressure.Drugs that prolong the QT interval (such as Class IA and III antiarrhythmics, antipsychotics [phenothiazine derivatives, pimozide, haloperidol], tricyclic antidepressants, certain antimicrobial agents [sparfloxacin, moxifloxacin, erythromycin IV, pentamidine], anti-malaria treatment particularly halofantrine, certain antihistamines [astemizole, mizolastine], and antiretrovirals [such as ritonavir, saquinavir, and lopinavir].Selegiline — the concomitant use of citalopram and selegiline (in doses above 10mg daily) is contraindicated.Omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine, and cimetidine — co-administration can cause an increase in the average steady-state levels of citalopram. Dose adjustment may be warranted.Propafenone, flecainide, metoprolol, desipramine, clomipramine, nortriptyline, risperidone, thioridazine and haloperidol — co-administration may lead to increased plasma levels of these drugs.Fluoxetine:Mequitazine — increased risk of mequitazine adverse events (such as QT prolongation) because of an inhibition of its metabolism by fluoxetine.Metoprolol used in cardiac failure — increased risk of metoprolol adverse events including excessive bradycardia, because of inhibition of its metabolism by fluoxetine.Drugs that cause QT interval prolongation (such as Class IA and III antiarrhythmics, antipsychotics [phenothiazine derivatives, pimozide, haloperidol], tricyclic antidepressants, certain antimicrobial agents [sparfloxacin, moxifloxacin, erythromycin IV, pentamidine], anti-malaria treatment particularly halofantrine, certain antihistamines [astemizole, mizolastine], and antiretrovirals [such as ritonavir, saquinavir, and lopinavir] — pharmacokinetic and pharmacodynamic studies with fluoxetine have not been performed. An additive effect of fluoxetine and these medicinal products cannot be excluded. Phenytoin — changes in blood levels (and in some cases, toxicity) have been observed in combination with fluoxetine —consider using conservative titration schedules and to monitor clinical status.Drugs that cause hyponatraemia such as diuretics, desmopressin, carbamazepine and oxcarbazepine, as fluoxetine also causes hyponatraemia.Procyclidine — daily administration of paroxetine increases significantly its plasma levels. If anticholinergic effects are seen, the dose of procyclidine should be reduced.Fluvoxamine:Terfenadine, astemizole or cisapride — plasma concentrations may be increased resulting in a higher risk for QT-prolongation/Torsade de Pointes.Tizanidine.Tacrine, theophylline, methadone, mexiletine, phenytoin, carbamazepine and cyclosporine — co-administration with fluvoxamine should be carefully monitored.Triazolam, midazolam, alprazolam, and diazepam — plasma levels are likely to be increased when co-administered with fluvoxamine. The dosage of these benzodiazepines should, therefore, be reduced during co-administration.Ropinirole — plasma concentrations may be increased in combination with fluvoxamine, thus increasing the risk of overdose. Surveillance and reduction in the dosage of ropinirole during fluvoxamine treatment and after its withdrawal may, therefore, be required.Propranolol — as plasma concentrations of are increased in combination with fluvoxamine, the propranolol dose may need to be lowered.Paroxetine:Metoprolol — increased risk of metoprolol adverse events because of inhibition of its metabolism by paroxetine.Tamoxifen — paroxetine is a potent inhibitor of the liver enzyme CYP2D6 and may reduce the plasma concentration of tamoxifen, leading to reduced efficacy.Thioridazine —  this can lead to elevated plasma levels of thioridazine and increased risk of QTc interval prolongation with associated serious ventricular arrhythmia such as torsades de pointes, and sudden death.Aripiprazole, clozapine, darifenacin, galantamine, methadone, metoprolol, pitolisant, procyclidine, ranolazine, risperidone and vortioxetine — paroxetine may increase their plasma concentrations.Atomoxetine, perphenazine, and propafenone — paroxetine may inhibit their metabolism.Asenapine, darunavir, fosphenytoin, phenobarbital, phenytoin, primidone, ritonavir, and terbinafine — may alter plasma concentration of paroxetine.Sumatriptan —there is an increased risk of CNS toxicity when given with paroxetine.Pravastatin — co-administration may lead to an increase in blood glucose levels. People with diabetes mellitus receiving both drugs may require dosage adjustment of oral hypoglycemic agents and/or insulin. SertralinePropafenone and flecainide — co-administration may lead to increased plasma levels of these drugs.Atenolol — co-administration causes a substantial decrease in sertraline clearance.Drugs that prolong the QT interval (such as Class IA and III antiarrhythmics, antipsychotics [phenothiazine derivatives, pimozide, haloperidol], tricyclic antidepressants, certain antimicrobial agents [sparfloxacin, moxifloxacin, erythromycin IV, pentamidine], anti-malaria treatment particularly halofantrine, certain antihistamines [astemizole, mizolastine], and antiretrovirals [such as ritonavir, saquinavir, and lopinavir].[ABPI, 2017b; ABPI, 2018; ABPI, 2017c; ABPI, 2017d; ABPI, 2017e; ABPI, 2017f; BNF 75, 2018] Back to top Dosing Information Dosing information Initial dosage and titration of selective serotonin reuptake inhibitors (SSRIs):Citalopram (unlicensed):Initial dose 20 mg each day.If necessary, increase gradually to a maximum of 40 mg daily (20 mg in the elderly and in those with reduced hepatic function).Escitalopram:Initial dosage is 10 mg once daily (5 mg once daily in the elderly).If necessary, the dose may be increased to a maximum of 20 mg daily (10 mg daily in the elderly).Fluoxetine:Initial dose 20 mg once a day, in the morning.If necessary, increase gradually to a maximum of 60 mg daily.Fluvoxamine:Initial dose 50 mg once a day, at bedtime.Increase to 100 mg, and then gradually in steps of 50 mg to a maximum of 300 mg/day if necessary.Usual maintenance dose is 100–300 mg/day (over 150 mg in divided doses).Paroxetine:Initial dose 20 mg once a day.If necessary, increase gradually in steps of 10 mg to 40 mg daily.If after some weeks on 40 mg/day an insufficient response is seen, a gradual dose increase up to a maximum of 60 mg/day can be considered.Sertraline:Initial dose 50 mg once a day, in the morning or evening.If necessary, increase gradually in steps of 50 mg to a maximum of 200 mg/day.Usual dose range is 50–200 mg daily.[ABPI, 2017b; ABPI, 2018; ABPI, 2017c; ABPI, 2017d; ABPI, 2017e; ABPI, 2017f; BNF 75, 2018] Back to top Clomipramine Clomipramine Back to top Contraindications and cautions Contraindications and cautions Do not prescribe clomipramine to people with:Acute porphyrias.Recent myocardial infarction, any degree of heart block, or other cardiac arrhythmias.Severe liver disease.Concurrent administration with monoamine oxidase inhibitors or within 3 weeks of start or cessation of therapy.Concomitant treatment with selective, reversible MAO-A inhibitors, such as moclobemide.Narrow-angle glaucoma.Retention of urine.Mania.Hypokalaemia — hypokalaemia should be treated before initiating treatment with clomipramine.Prescribe clomipramine with caution to people with:Hepatic or renal impairment — in people with hepatic and renal disease, periodic monitoring of hepatic enzyme levels and renal function is recommended.Cardiovascular disorders, especially cardiovascular insufficiency, conduction disorders, (e.g. atrioventricular block grades I to III), arrhythmias — check blood pressure and conduct an electrocardiogram (ECG) before prescribing clomipramine for adults at significant risk of cardiovascular disease.Epilepsy or other predisposing factors for seizure such as brain damage of varying aetiology, concomitant use of neuroleptics, withdrawal from alcohol or drugs with anticonvulsive properties (e.g. benzodiazepines) — clomipramine reduces the seizure threshold and extreme caution should, therefore, be exercised.A history of increased intraocular pressure, narrow-angle glaucoma, urinary retention or with symptoms of bladder neck obstruction, e.g. diseases of the prostate, such as prostatic hypertrophy— the anticholinergic properties of clomipramine can exacerbate these conditions.Tumours of the adrenal medulla (e.g. phaeochromocytoma, neuroblastoma) — administration of clomipramine may provoke hypertensive crises.Hyperthyroidism or concomitant treatment with thyroid preparations — aggravation of unwanted cardiac effects may occur.Chronic constipation — tricyclic antidepressants may cause paralytic ileus, particularly in people who are older and/or bed-ridden.Note: monitoring of cardiac function and ECG is indicated in elderly people.[ABPI, 2017a; BNF 75, 2018] Back to top Adverse effects Adverse effects The most common adverse effects of clomipramine include:Increased or decreased appetite.Psychiatric effects — restlessness, confusion, disorientation, hallucinations (particularly in older patients and those with Parkinson's disease), anxiety, agitation, sleep disorder, mania, hypomania, aggression, depersonalisation, aggravation of depression, insomnia, nightmares, delirium.CNS effects — dizziness, tremor, headache, myoclonus, fatigue, somnolence, speech disorder, paraesthesia, hypertonia, dysgeusia, memory impairment, disturbance in attention, tinnitus.Advise the person that it is illegal in England and Wales to drive while taking a prescribed drug if it impairs driving [DVLA, 2015b].Eye disorders — accommodation disorder, blurred vision, mydriasis.Cardiac disorders — sinus tachycardia, palpitation, orthostatic hypotension, clinically irrelevant ECG changes (e.g. ST and T changes) in people of normal cardiac status.Gastrointestinal disorders — nausea, dry mouth, constipation, vomiting, diarrhoea.Other — hot flush, yawning, hyperhidrosis, allergic dermatitis (skin rash, urticaria), photosensitivity reaction, pruritus, muscular weakness, micturition disorder, urinary retention, libido disorder, erectile dysfunction, galactorrhoea, breast enlargement.[ABPI, 2017a; BNF 75, 2018] Back to top Drug interactions Drug interactions Key drug interactions with clomipramine include:MAOIs — do not give clomipramine for at least 3 weeks after discontinuation of treatment with MAO inhibitors as there is a risk of severe symptoms consistent with Serotonin Syndrome such as hypertensive crisis, hyperpyrexia, myoclonus, agitation, seizures, delirium and coma). The same applies when giving a MAO inhibitor after previous treatment with clomipramine. In both instances, the treatment should initially be given in small gradually increasing doses and its effects monitored. 5HT3- receptor antagonists, dapoxetine, duloxetine, fentanyl, Rasagiline, St John's wort, tramadol, triptans, SSRIs, SNRIs, tricyclic antidepressants and lithium — increased risk of serotonergic effects. Concurrent use not recommended.Fluoxetine, paroxetine, sertraline, and fluvoxamine — may increase plasma concentrations of clomipramine with corresponding adverse effects.For fluoxetine, a wash-out period of two to three weeks is advised before commencing clomipramine treatment, with clomipramine wash-out also required if fluoxetine is subsequently to be administered.Diuretics — concurrent use may lead to hypokalaemia, which increases the risk of QTc prolongation and torsades de pointes. Concurrent use not recommended.Quinidine — should not be given concurrently with clomipramine.Pimozide — increased risk of ventricular arrhythmias. Avoid concomitant use.Terbinafine, cimetidine, methylphenidate, sodium valproate  — co-administration may lead to increased plasma levels of clomipramine.Phenothiazines — may result in increased plasma levels of clomipramine, a lowered convulsion threshold, and seizures. Concurrent use with thioridazine may produce severe cardiac arrhythmias.Rifampicin, anticonvulsants (such as barbiturates, carbamazepine, phenobarbital and phenytoin), cholestyramine or colestipol, St. John's wort — concurrent use may decrease plasma levels of clomipramine.Anticholinergic agents (such as phenothiazines, antiparkinsonian agents, antihistamines, atropine, biperiden),  CNS depressants (such as barbiturates, benzodiazepines, or general anaesthetics), sympathomimetic drugs, (such as adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine, and phenylpropanolamine contained in local and general anaesthetic preparations and nasal decongestants) — co-administration may potentiate the effects of these drugs. Caution is therefore advised.Coumarins — clomipramine possibly enhances the anticoagulant effect of coumarins.Consider frequent monitoring of the INR. Any change in the person's clinical condition, particularly liver disease, intercurrent illness, or drug administration, necessitates more frequent monitoring of the INR. Guanethidine, betanidine, reserpine, clonidine and alpha-methyldopa— clomipramine may diminish or abolish the antihypertensive effects of these drugs. People requiring co-medication for hypertension should, therefore, be given antihypertensives of a different type (e.g. vasodilators, or beta-blockers).Drugs that prolong the QT interval (such as such as certain antiarrhythmics [including quinidine, disopyramide, procainamide, amiodarone and sotalol], tricyclic antidepressants [such as amitriptyline], certain tetracyclic antidepressants [such as maprotiline], certain antipsychotic medications [such as phenothiazines and pimozide], certain antihistamines [such as terfenadine]; lithium, quinine,  and pentamidine) — co-administration increases the risk of QTc prolongation and torsades de pointes.Drugs that increase the plasma levels of clomipramine (including antiarrhythmics, certain antidepressants including SSRIs, tricyclic antidepressants and moclobemide; certain antipsychotics; β-blockers; protease inhibitors, opiates, cimetidine, and terbinafine) may also increase the risk of QTc prolongation and torsades de pointes if co-administered.Non-steroidal anti-inflammatory drugs — co-administration may lead to increased risk of bleeding.Analgesics — possible increased side effects with nefopam; possible increased risk of convulsions with tramadol; possible increased sedation with opioid analgesics; increased risk of ventricular arrhythmias with levacetylmethadol.Dopaminergics — concomitant use with entacapone should be avoided; central nervous system toxicity has been reported with selegiline.Muscle relaxants — concomitant use may enhance the muscle relaxant effect of baclofen.[ABPI, 2017a; BNF 75, 2018] Back to top Dosing information Dosing information Initially, prescribe 25 mg each day (or 10 mg daily in the elderly).If there are no significant adverse effects:Increase gradually over 2 weeks to 100–150 mg daily (increase more slowly in the elderly).At 4–6 weeks, if there is an inadequate treatment response, increase gradually up to a maximum dose of 250 mg daily.[ABPI, 2017a; BNF 75, 2018] Supporting evidence Back to topSupporting evidence This CKS topic is largely based on the National Institute of Health and Care Excellence guideline Obsessive-compulsive disorder and body dysmorphic disorder: treatment [NICE, 2005]. The recommendations relevant to primary care were developed from the expert opinion of the guideline development group following narrative reviews of the evidence, where available. The evidence for specialist management strategies is not discussed as they are beyond the scope of this CKS topic. Back to top Psychological treatments in adults Evidence on psychological treatments in adults There is evidence from four systematic reviews that cognitive-behavioural therapy (CBT) is superior in efficacy to treatment as usual or control treatments for the treatment of obsessive-compulsive disorder (OCD).CKS found four systematic reviews of psychological interventions versus control interventions for the treatment of OCD. One review was published by the Cochrane Collaboration [Gava et al, 2007] and a second was commissioned by the National Institute for Health and Care Excellence (NICE) [National Collaborating Centre for Mental Health, 2006]. Both of these reviews were limited by issues of external validity: it is difficult, in practice, to differentiate between ERP, other types of CBT, cognitive therapy, and behavioural therapy, and there is considerable overlap [Gava et al, 2007]. Indeed, in contrast to NICE, the Cochrane review makes no distinction between ERP and other forms of CBT in its meta-analysis. Subsequent to the publication of the NICE and Cochrane systematic reviews CKS identified two smaller systematic reviews, the results of which are consistent with those of the Cochrane and NICE reviews [Jonsson and Hougaard, 2009; Olatunji et al, 2013].Psychological treatments versus treatment as usual [Gava et al, 2007]:Included 11 studies, seven (ten comparisons) of which had usable data for meta-analysis (241 participants).All psychological treatments were superior to treatment as usual in reducing obsessive-compulsive symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (standardized mean difference, SMD –1.24, 95% CI –1.61 to –0.87).CBT (with or without ERP) was superior to treatment as usual in reducing the Y-BOCS (WMD –7.73, 95% CI –9.92 to –5.55).Behavioural therapy was superior to treatment as usual (weighted mean difference, WMD –11.73, 95% CI –14.52 to –8.95).There was no statistically significant difference between cognitive therapy and treatment as usual (SMD –1.21, 95% CI –2.66 to +0.25) but, with just 39 subjects, the numbers were perhaps too small to detect a difference.Psychological interventions versus control (systematic relaxation, anxiety management or waiting list):The NICE review included 17 studies with efficacy data on 820 participants and tolerability data on 734 participants [National Collaborating Centre for Mental Health, 2006]:NICE found one small study which showed that ERP is superior to anxiety management control in reducing clinician-rated Y-BOCS (n = 18; SMD –2.89, 95% CI –4.30 to –1.48); one further study found statistically significant differences compared with systematic relaxation control in favour of both clinician-guided ERP (n = 121; SMD –1.10, 95% CI –1.49 to –0.72) and computer-guided ERP (n = 121; SMD –0.68, 95% CI –1.05 to –0.31). When both studies were combined, no significant difference between groups was detected in the number of withdrawals (relative risk, RR 4.47, 95% CI 0.51 to 38.92).One study found group-CBT to be superior to waiting list control in terms of both treatment response (35% or greater reduction in clinician-led Y-BOCS) (n = 47; RR 0.32, 95% CI 0.17 to 0.59) and reduction in clinician-rated Y-BOCS (n = 47; SMD –1.18, 95% CI –1.98 to –0.38). Another study also found a small but statistically significant reduction in OCD symptoms (as measured by clinician-rated Y-BOCS) for CBT compared with waiting list (n = 29; SMD –1.18, 95% CI –1.81 to –0.56). No significant difference in rates of withdrawal was found between each group in both studies.A recently published systematic review included 16 randomised controlled trials that compared the efficacy of CBT with control conditions [Olatunji et al, 2013]. The primary outcome measured was the difference between Y-BOCS and the children's Y-BOCS scores pre and post treatment. This review found evidence that CBT was superior to control conditions at post treatment. The effect size (measured using a Hedges g score) was 1.39 (95% CI 1.04–1.74, p = 0.0000).Therapist time in psychological interventionsNICE commissioned a systematic review to determine whether the number of hours spent by a therapist per client predicted the efficacy of psychological interventions in adults with OCD [National Collaborating Centre for Mental Health, 2006].Across all 29 studies, there was statistically significant heterogeneity.Effect sizes demonstrated a gradient favouring higher intensity over lower intensity:Low intensity group: n = 261; SMD –0.93, 95% CI –1.11 to –0.75.Medium intensity group: n = 461; SMD –1.44, 95% CI –1.59 to –1.29.High intensity group: n = 157; SMD –1.65, 95% CI –1.91 to –1.38.Using meta-regression analysis to control for publication date, study design, and treatment modality, the number of therapist-hours per client significantly predicted change in efficacy scores following treatment (z = –2.09; p = 0.04), and this result was unaffected by removing outliers.Individual CBT versus group CBTA systematic review assessed the efficacy of group ERP or group CBT with placebo, waiting list or other active treatments [Jonsson and Hougaard, 2009]. This review identified 13 trials, however, only four of these were randomised controlled trials. The primary outcome measure was the difference in effect size pre and post treatment using the YBOCS. Pooled data for three randomised controlled trials found that group CBT or group ERP was superior to waiting list control. The effect size was 1.12 (95% CI 0.78–1.46). Back to top SSRIs in adults Evidence on SSRIs in adults There is evidence from two systematic reviews (10 and 17 randomized controlled trials [RCTs]; 1629 and 3097 participants; not including escitalopram) that selective serotonin reuptake inhibitors (SSRIs) as a group are superior in efficacy to placebo, but are associated with more (relatively tolerable) adverse effects [National Collaborating Centre for Mental Health, 2006; Soomro et al, 2008]. There is evidence from one RCT (n = 228) that a newer SSRI, escitalopram (at a dose of 20 mg daily), is also superior in efficacy to placebo. There is evidence from a systematic review (eight RCTs; n = 1019) that SSRIs are equal in efficacy to clomipramine, but are better tolerated. The evidence is inconclusive with regard to any one SSRI being superior in efficacy or tolerability to another.SSRIs versus placebo:Evidence is based on a Cochrane review [Soomro et al, 2008] and another systematic review commissioned by the National Institute for Health and Clinical Excellence (NICE) [National Collaborating Centre for Mental Health, 2006]. There were differences between the reviews in terms of the studies included, despite no new studies being published in the interim: NICE included six studies not found or included in the Cochrane review, and, conversely, the Cochrane review included five studies not included by NICE. However, the results were broadly similar.Both systematic reviews found a statistically significant difference favouring SSRIs over placebo in achieving clinical (treatment) response (as defined by 25% or 35% reduction in Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score):Relative risk (RR) 1.84, 95% CI 1.56 to 2.17 (13 studies; n = 2697) [Soomro et al, 2008].RR 0.77, 95% CI 0.73 to 0.82 (10 studies; n = 2588) [National Collaborating Centre for Mental Health, 2006].Both systematic reviews found SSRIs to be superior to placebo in reducing obsessive-compulsive disorder (OCD) symptoms as measured by clinician-rated Y-BOCS:Weighted mean difference (WMD) –3.21, 95% CI –3.84 to –2.57 (17 studies; n = 3097) [Soomro et al, 2008].Standardized mean difference (SMD) –0.42, 95% CI –0.53 to –0.31 (12 studies; n = 1629) [National Collaborating Centre for Mental Health, 2006].SSRIs were associated with an increased risk of adverse effects (most commonly nausea, headache, and insomnia) (RR 1.16, 95% CI 1.1 to 1.23) but no statistically significant difference in withdrawals, leading to the conclusion that SSRIs are relatively well tolerated [National Collaborating Centre for Mental Health, 2006].Continuation of SSRIs appears to be significantly more effective than placebo for up to 48 weeks, and long-term treatment up to 12 months appears to prevent relapse [National Collaborating Centre for Mental Health, 2006].Different doses of SSRIs:There is limited evidence from a systematic review commissioned by NICE that higher doses are superior to lower doses for citalopram, fluoxetine, and paroxetine and that higher doses may be associated with a lower risk of withdrawals [National Collaborating Centre for Mental Health, 2006].SSRIs versus other SSRIs:Evidence is based on a systematic review commissioned by NICE and appraisal of one of the original studies from that review [Mundo et al, 1997; National Collaborating Centre for Mental Health, 2006].There is limited evidence suggesting a difference favouring sertraline over fluoxetine for reducing obsessive-compulsive symptoms as measured by the clinician-rated Y-BOCS (n = 148; SMD 0.39, 95% CI 0.07 to 0.72).NICE states that 'there is limited evidence suggesting a difference favouring fluvoxamine over citalopram on reducing obsessive-compulsive symptoms as measured by the National Institute of Mental Health Obsessive-Compulsive Global Scale (NIMH-OC) (n = 21)'. However, the reported results appear to be incorrect: SMD 21.22, 95% CI –2.17 to –0.27. In the original single-blind study, which randomized just 30 inpatients to fluvoxamine, citalopram, or paroxetine, the authors report no significant differences between the groups in terms of NIMH-OC and Y-BOCS total scores, although the statistical data were not presented [Mundo et al, 1997].The evidence was inconclusive for any differences in tolerability.SSRIs versus clomipramine:Evidence is based on a systematic review commissioned by NICE [National Collaborating Centre for Mental Health, 2006].There is no statistically significant difference between SSRIs and clomipramine in either treatment response (n = 1019; RR 1.02, 95% CI 0.89 to 1.17) or OCD symptoms (Y-BOCS) (n = 739; SMD 0.14, 95% CI –0.01 to +0.29).SSRIs may be better tolerated: when compared with SSRIs, clomipramine increased the risk of leaving the study early for any reason (n = 1139; RR 0.72, 95% CI 0.59 to 0.88) or due to adverse effects (n = 1095; RR 0.62, 95% CI 0.46 to 0.84).Escitalopram versus placebo and paroxetine:One double-blind, RCT (sponsored by the manufacturer of escitalopram) found that escitalopram 20 mg daily is superior to placebo in reducing OCD symptoms as measured by clinician-rated Y-BOCS (mean difference –3.21, 95% CI –5.19 to –1.23; p