Review Article
Obsessive-Compulsive Disorder Daniel A. Drubach, MD ABSTRACT Purpose of Review: This article discusses the neurobiology, clinical features, and treatment of obsessive-compulsive disorder (OCD), as well as its association with psychiatric and neurologic disease. Recent Findings: OCD can be associated with various neurologic disorders. Recent studies have better elucidated the neurobiology of OCD, and this new knowledge promises to have a significant impact on future treatments. Summary: OCD is a syndrome characterized by obsessions and compulsions, as well as other neuropsychiatric features, and is often associated with primary psychiatric disorders and various neurologic conditions. If severe, OCD can seriously interfere with the patient’s quality of life. The mainstay of treatment is psychotherapy, especially cognitive-behavioral therapy, and pharmacologic interventions, especially with selective serotonin reuptake inhibitors (SSRIs). Unfortunately, a significant proportion of patients are refractory to these treatment modalities. New understanding about the neurobiology of OCD has led to novel investigational treatments, especially neuromodulation techniques.
Address correspondence to Dr Daniel A. Drubach, Mayo Clinic 200 1st Street SW, Department of Neurology, Rochester, MN 55905, [email protected]. Relationship Disclosure: Dr Drubach has received personal compensation for lectures from Sivananda Ashram Yoga and receives book royalties from Prentice Hall. Unlabeled Use of Products/Investigational Use Disclosure: Dr Drubach discusses the unlabeled/investigational use of pharmacologic agents and neuromodulation techniques to treat obsessive-compulsive disorder. * 2015, American Academy of Neurology.
Continuum (Minneap Minn) 2015;21(3):783–788.
INTRODUCTION Obsessive-compulsive disorder (OCD) is a syndrome characterized by two main features: obsessions and compulsions. Obsessions consist of thoughts, images, or urges to perform a certain task that erupt into consciousness and which are frequently disturbing and anxiety provoking. Compulsions consist of the performance of repetitive motor acts executed with the sole purpose of ameliorating anxiety caused by either the obsession or a belief and conviction that things need to be a certain way. EPIDEMIOLOGY Obsessions and compulsions are part of every person’s daily cognitive repertoire. Thoughts intrude spontaneously into people’s minds. Cultural superstition and religious rituals lead people to perform very meticulous and precise acts, some of which could be conceptualized as Continuum (Minneap Minn) 2015;21(3):783–788
obsessive. Similarly, we all have opinions as to how things should be and can be disturbed if these things are done in a different way. However, what differentiates normal cognition and behavior from pathologic obsessions and compulsions is a matter of degree. Obsessions and compulsions consume a great percentage of the daily energy and time of a person with OCD. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria, pathologic obsessions and compulsions are time consuming (taking up more than 1 hour per day) and cause significant distress or impairment in social, occupational, or other important areas of functioning.1 In fact, patients with OCD experience great variability in the time and energy spent on obsessions and compulsions. Studies addressing the epidemiology of OCD among adults in the United States www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
783
Obsessive-Compulsive Disorder KEY POINTS
h Obsessive-compulsive disorder is a syndrome characterized by two main features: obsessions and compulsions.
h Obsessions consist of thoughts, images, or urges to perform a certain task that erupt into consciousness and which are frequently disturbing and anxiety provoking.
h Compulsions consist of the performance of repetitive motor acts executed with the sole purpose of ameliorating anxiety caused by either the obsession or a belief and conviction that things need to be a certain way.
h What differentiates normal cognition and behavior from pathologic obsessions and compulsions is a matter of degree. Obsessions and compulsions consume a great percentage of the daily energy and time of a person with obsessivecompulsive disorder.
h Obsessive-compulsive disorder can be associated with neurologic conditions, including movement disorders (especially tic disorders), stroke in the left basal ganglia, traumatic brain injury, progressive supranuclear palsy, and various dementias.
h The correlation with basal ganglia atrophy in patients with frontotemporal dementia and obsessive-compulsive disorder may point to involvement of frontal subcortical neuronal networks as well as of the temporal lobes.
784
are complicated by the changes in the diagnostic criteria and in the judgment of what constitutes a normal versus abnormal behavior. One study showed the incidence rate to be 0.55 per 1000 person-years in the United States.2 A cross-national study involving seven countries found a remarkably consistent annual prevalence for OCD in six countries. Other studies found the 12-month prevalence to be 1.2% and the lifetime prevalence to be 2.3% in the United States. While females are affected at a slightly higher rate than males in adulthood, males are more commonly affected in childhood.3Y5 OCD can exist in isolation, in the absence of other neurologic and psychiatric disorders, but other associated neuropsychiatric comorbidities occur in a significant proportion of patients. These include mood disorders (eg, depression and mania), anxiety disorders (eg, phobias, panic disorders), personality disorders, and schizophrenia.6 Of particular relevance to practicing neurologists, OCD can be associated with neurologic conditions, including movement disorders (especially tic disorders), stroke in the left basal ganglia,7 traumatic brain injury, progressive supranuclear palsy,8 and various dementias.9,10 Although the scientific literature on the topic is scant and mostly limited to case reports, more robust data exist on the association of OCD and frontotemporal dementia. One early study found that three of the authors’ patients with dementia secondary to frontal lobe degeneration, as well as their analysis of 78% of 46 proven pathologic cases of frontal lobe degeneration described in the literature, demonstrated repetitive behaviors ranging from motor stereotypes to complex OCD. The authors suggested that combined damage to the frontal lobe, caudate nucleus, and globus pallidus may account for the repetitive behaviors that occur in frontal lobe degenerations, idiopathic OCD, and other neuropsychiatric diseases.11 Another study reported OCD symptoms as the presenting symptom
in 38% of 29 patients with a clinical diagnosis of frontotemporal dementia versus 10% of 48 patients diagnosed with Alzheimer disease.12 In a recent study, 11 patients with behavioral variant frontotemporal dementia underwent MRI and voxel-based morphometry. Nine of these patients displayed OCD symptoms. These individuals were found to have gray matter loss in the bilateral globus pallidus, left putamen, and in the lateral temporal lobe, particularly the left middle and inferior temporal gyri.13 The authors suggest that the correlation with basal ganglia atrophy in patients with frontotemporal dementia and OCD may point to involvement of frontal subcortical neuronal networks as well as of the temporal lobes. The most frequent compulsions in this group of patients were checking, hoarding, ordering/ arranging, repeating rituals, and cleaning. Robust data also exist on the association of OCD with Huntington disease.14 In patients with a primary psychiatric disease, obsessions and compulsions are associated with anxiety and depression, while in frontotemporal dementia, obsessions and compulsions are accompanied by other symptoms commonly seen in the disorder, such as disinhibition, poor judgment, and apathy (Case 12-1). Certain medications utilized in the management of neurologic disease have also been associated with the onset of OCD-like symptoms. For example, recent reports have emerged of patients prescribed dopamine agonists who develop such features as compulsive shopping and gambling.15 It has been suggested that impulse control disorders, including compulsive gambling, shopping, and others brought on by dopaminergic agents in patients with Parkinson disease may be mediated by dopamine D3 receptors.16 Other agents, such as amphetamines and cocaine, have been associated with obsessions. Interestingly, there are anecdotal case studies in the literature that report the resolution of OCD symptoms with focal
www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
June 2015
KEY POINTS
Case 12-1
h Three treatment
A 46-year-old man, previously a healthy and highly successful executive, became obsessed by the intrusive image of his child being struck by a car; in order to ameliorate the anxiety caused by that image he would go to great lengths to be able to ‘‘knock on wood.’’ However, the wooden surface that he would hit could not be covered by varnish or paint since the skin of his knuckles needed to make direct contact with the wood. This compulsion would at times drive him out of business meetings in a frantic search for an appropriate wooden object. Shortly afterward he developed prominent behavioral changes, including impulsivity and poor judgment. MRI showed significant bifrontal (right worse than left) atrophy. Fluorodeoxyglucose positron emission tomography (FDG-PET) scan demonstrated right frontal hypometabolism. The clinical diagnosis of behavioral variant frontotemporal dementia was made. Comment. This patient’s first onset of symptoms at a late age was unlikely to be due to a primary psychiatric disorder. In this clinical setting, the clinician needs to be suspicious that the obsessive-compulsive disorder (OCD) symptomatology is due to a neurodegenerative condition.
damage to the brain, including a case of resolution of severe OCD after a small unilateral nondominant frontoparietal infarct.17
greater connectivity was found between the self subsystem and salience and attention networks.21
NEUROBIOLOGY OF OBSESSIVE-COMPULSIVE DISORDER Diffusion tensor imaging in patients with OCD has found decreased white matter integrity in the cingulate bundle, the corpus callosum, and the anterior limb of the internal capsule.18 Functional imaging, including positron emission tomography (PET), single-photon emission computed tomography (SPECT), and functional MRI (fMRI) studies, have also shown increased cerebral metabolism in cortico-striatothalamo-cortical circuits, particularly in the caudate and putamen, the anterior thalamus, the orbitofrontal cortex, and the anterior cingulate cortex.19 Activation of these circuits occurs with symptom provocation and is reduced with symptomatic improvement after either pharmacotherapy or psychotherapy.20 Some recent studies have shown an alteration in the default mode network in patients with OCD, with significantly reduced connectivity within the dorsal medial prefrontal cortex self subsystem. In addition,
TREATMENT Three treatment modalities are currently available for patients with OCD: psychotherapy, pharmacotherapy, and brain modulation. Each of these modalities has been used in isolation, although they are more often applied concomitantly, especially in the case of psychotherapy and pharmacotherapy.22
Continuum (Minneap Minn) 2015;21(3):783–788
modalities are currently available for patients with obsessive-compulsive disorder: psychotherapy, pharmacotherapy, and brain modulation.
h Although there are many forms of psychotherapy, cognitive-behavioral therapy has had the most success in treating obsessivecompulsive disorder.
Psychotherapy Psychotherapy is a diagnostic and treatment modality utilizing verbal interaction between a therapist and a patient to address mental discomfort or disorders. Although there are many forms of psychotherapy, cognitive-behavioral therapy has had the most success in treating OCD. Cognitive-behavioral therapy is a problemfocused, goal-directed, and time-limited treatment modality predicated on the theory that obsessions and compulsions are the result of abnormal learned responses and actions. The goals of therapy are to identify and change destructive, disturbing thought patterns that have a www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
785
Obsessive-Compulsive Disorder KEY POINTS
h Numerous studies have highlighted the benefit of selective serotonin reuptake inhibitors and the tricyclic antidepressant clomipramine, supporting the use of these medications as first-line agents.
h The effects of selective serotonin reuptake inhibitors are not solely due to treatment of depression since their benefit in the management of obsessive-compulsive disorder is present even in patients in whom depression has been excluded as a comorbid condition.
h While deep brain stimulation techniques are promising in patients with treatment-resistant obsessive-compulsive disorder, it remains an invasive procedure with unknown long-term treatment effects.
786
negative influence on behaviors, such as obsessions and compulsions. Pharmacotherapy In regard to pharmacotherapy, numerous studies have highlighted the benefit of selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressant clomipramine, supporting the use of these medications. SSRIs are considered firstline agents due to the relative safety and side effect profile for these agents. Clomipramine should be considered if SSRIs are not effective or are not tolerated. Typically, these medications are prescribed at higher dosages (within the higher range of recommended dosages or until side effects preclude further increases) and for longer periods (weeks or months) than they are prescribed for anxiety disorders and depression since response to SSRIs tends to take longer in the treatment of OCD than in the treatment of these disorders. The effects of these medications in treating OCD are not solely due to treatment of depression, since their benefit in the management of OCD is present even in patients in whom depression has been excluded as a comorbid condition. The actions of SSRIs and clomipramine are to block serotonin reuptake by the presynaptic neuron, which increases serotonin availability at postsynaptic receptors. Consequently, the benefits of these medications in the treatment of OCD have highlighted the possible role of deranged serotonergic neurotransmission in the pathophysiology of OCD. Despite the beneficial effect of SSRIs and clomipramine in some patients with OCD, 40% to 60% of patients remain refractory to treatment. Several options have been proposed to help those patients who fail to respond to this treatment. The combination of SSRIs with clomipramine in high doses has been reported to be of some use. Another strategy reported as
beneficial is the augmentation of an SSRI with haloperidol or an atypical antipsychotic medication including risperidone, olanzapine, or quetiapine. Other agents reported to have some benefit, especially in nonresponders to clomipramine or an SSRI or as an adjuvant to them, include buspirone, clonazepam, trazodone, and venlafaxine.22 Memantine has also been reported to be of benefit in patients with refractory OCD.23 While predictors of treatment response have not been well elucidated, some studies suggest that severity and duration of OCD, psychosocial disability, earlier age at onset, older age, comorbidity with depression and personality disorder, absence of a positive family history for OCD, and poor insight, as well as abnormal findings in the neurologic examination, were associated with a poorer response.24 Brain Modulation Brain modulation is an exciting development in the treatment of patients with severe OCD.25 Electroconvulsive therapy26 and transcranial magnetic stimulation27 have been reported to be beneficial in a small number of patients. Deep brain stimulation, specifically stimulation of the subthalamic nucleus or the nucleus accumbens, has been utilized and has shown effectiveness in patients with OCD who are refractory to other forms of treatment.28 One study showed a beneficial effect in patients with OCD and Tourette syndrome with stimulation of the anteromedial globus pallidus internus (GPi).29 While deep brain stimulation techniques are promising in patients with treatmentresistant OCD, it remains an invasive investigational procedure with unknown long-term treatment effects. Guidelines In 2007, the American Psychiatric Association published guidelines for the treatment of patients with obsessivecompulsive disorders. This excellent
www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
June 2015
publication delineates factors to consider at each treatment step, treatment algorithms, management of patients with treatment-resistant symptoms, and several other issues pertinent to the management of this population.22 CONCLUSION OCD is a highly disabling neuropsychiatric condition affecting a significant proportion of the population. Certain neurologic disorders, especially frontotemporal dementia and Huntington disease, are frequently associated with obsessions and compulsions. With increased understanding of the neurobiology of OCD, treatment modalities are likely to become more effective. In the meantime, cognitivebehavioral therapy and SSRIs or clomipramine remain the mainstays of treatment. Treatment-refractory cases of OCD may respond to neuromodulation. REFERENCES 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: fifth edition. Washington, DC: American Psychiatric Association, 2013. 2. Nestadt G, Bienvenu OJ, Cai G, et al. Incidence of obsessive-compulsive disorder in adults. J Nerv Ment Dis 1998;186(7):401Y406. 3. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry 2010;15(1):53Y63. doi:10.1038/mp.2008.94. 4. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62(6): 617Y627. doi:10.1001/archpsyc.62.6.617. 5. Weissman MM, Bland RC, Canino GJ, et al. The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry 1994;55(suppl):5Y10. 6. Brady CF. Obsessive-compulsive disorder and common comorbidities. J Clin Psychiatry 2014;75(1):e02. doi:10.4088/JCP.13023tx1c. 7. Lopez-Rodriguez F, Gunay I, Glaser N. Obsessive compulsive disorder in a woman with left basal ganglia infarct: a case report. Continuum (Minneap Minn) 2015;21(3):783–788
Behav Neurol 1997;10(2):101Y103. doi:10.3233/BEN-1997-102-308. 8. Karnik NS, D’Apuzzo M, Greicius M. Non-fluent progressive aphasia, depression, and OCD in a woman with progressive supranuclear palsy: neuroanatomical and neuropathological correlations. Neurocase 2006;12(6):332Y338. doi:10.1080/ 13554790601125957. 9. Potvin O, Hudon C, Dion M, et al. Anxiety disorders, depressive episodes and cognitive impairment no dementia in communitydwelling older men and women. Int J Geriatr Psychiatry 2011;26(10):1080Y1088. doi:10.1002/gps.2647. 10. Pompanin S, Perini G, Toffanin T, et al. Late-onset OCD as presenting manifestation of semantic dementia. Gen Hosp Psychiatry 2012;34(1):102.e1Y102.e4. doi:10.1016/ j.genhosppsych.2011.08.001. 11. Ames D, Cummings JL, Wirshing WC, et al. Repetitive and compulsive behavior in frontal lobe degenerations. J Neuropsychiatry Clin Neurosci 1994;6(2):100Y113. 12. Mendez MF, Perryman KM, Miller BL, et al. Compulsive behaviors as presenting symptoms of frontotemporal dementia. J Geriatr Psychiatry Neurol 1997;10(4):154Y157. doi:10.1177/ 089198879701000405. 13. Perry DC, Whitwell JL, Boeve BF, et al. Voxel-based morphometry in patients with obsessive-compulsive behaviors in behavioral variant frontotemporal dementia. Eur J Neurol 2012;19(6):911Y917. doi:10.1111/j.1468-1331. 2011.03656.x. 14. Anderson KE, Gehl CR, Marder KS, et al. Comorbidities of obsessive and compulsive symptoms in Huntington’s disease. J Nerv Ment Dis 2010;198(5):334Y338. doi:10.1097/ NMD.0b013e3181da852a. 15. McKeon A, Josephs KA, Klos KJ, et al. Unusual compulsive behaviors primarily related to dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 2007; 13(8):516Y519. doi:10.1016/j.parkreldis. 2007.04.004. 16. Seeman P. Parkinson’s disease treatment may cause impulse-control disorder via dopamine D3 receptors (published online ahead of print January 22, 2015). Synapse 2015. doi:10.1002/syn.21805. 17. Diamond A, Ondo WG. Resolution of severe obsessiveYcompulsive disorder after a small unilateral nondominant frontoparietal infarct. Int J Neurosci 2011;121(7):405Y407. doi:10.3109/ 00207454.2011.561941. www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
787
Obsessive-Compulsive Disorder
18. Koch K, Reess TJ, Rus OG, et al. Diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD): a review. J Psychiatr Res 2014;54:26Y35. doi:10.1016/j.jpsychires.2014.03.006. 19. Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci 2012;16(1):43Y51. doi:10.1016/j.tics.2011.11.003. 20. Anticevic A, Hu S, Zhang S, et al. Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol Psychiatry 2014;75(8):595Y605. doi:10.1016/j.biopsych. 2013.10.021. 21. Beucke JC, Sepulcre J, Eldaief MC, et al. Default mode network subsystem alterations in obsessive-compulsive disorder. Br J Psychiatry 2014;205(5):376Y382. doi:10.1192/ bjp.bp.113.137380. 22. Koran LM, Hanna GL, Hollander E, et al. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry 2007;164(7 suppl):5Y53. 23. Haghighi M, Jahangard L, Mohammad-Beigi H, et al. In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD). Psychopharmacology (Berl) 2013;228(4): 633Y640. doi:10.1007/s00213-013-3067-z.
788
24. Shetti CN, Reddy YC, Kandavel T, et al. Clinical predictors of drug nonresponse in obsessive-compulsive disorder. J Clin Psychiatry 2005;66(12):1517Y1523. 25. Aronson JP, Katnani HA, Eskandar EN. Neuromodulation for obsessive-compulsive disorder. Neurosurg Clin N Am 2014;25(1): 85Y101. doi:10.1016/j.nec.2013.08.003. 26. Hanisch F, Friedemann J, Piro J, Gutmann P. Maintenance electroconvulsive therapy for comorbid pharmacotherapy-refractory obsessive-compulsive and schizoaffective disorder. Eur J Med Res 2009;14(8):367Y368. doi:10.1186/2047-783X-14-8-367. 27. Gomes PV, Brasil-Neto JP, Allam N, Rodrigues de Souza E. A randomized, double-blind trial of repetitive transcranial magnetic stimulation in obsessive-compulsive disorder with three-month follow-up. J Neuropsychiatry Clin Neurosci 2012;24(4):437Y443. doi:10.1176/appi.neuropsych.11100242. 28. Lipsman N, Giacobbe P, Lozano AM. Deep brain stimulation in obsessive-compulsive disorder: neurocircuitry and clinical experience. Handb Clin Neurol 2013;116:245Y250. doi:10.1016/B978-0-444-53497-2.00019-X. 29. Nair G, Evans A, Bear RE, et al. The anteromedial GPi as a new target for deep brain stimulation in obsessive compulsive disorder. J Clin Neurosci 2014;21(5):815Y821. doi:10.1016/j.jocn.2013.10.003.
www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
June 2015
Obsessive-Compulsive Disorder Daniel A. Drubach, MD ABSTRACT Purpose of Review: This article discusses the neurobiology, clinical features, and treatment of obsessive-compulsive disorder (OCD), as well as its association with psychiatric and neurologic disease. Recent Findings: OCD can be associated with various neurologic disorders. Recent studies have better elucidated the neurobiology of OCD, and this new knowledge promises to have a significant impact on future treatments. Summary: OCD is a syndrome characterized by obsessions and compulsions, as well as other neuropsychiatric features, and is often associated with primary psychiatric disorders and various neurologic conditions. If severe, OCD can seriously interfere with the patient’s quality of life. The mainstay of treatment is psychotherapy, especially cognitive-behavioral therapy, and pharmacologic interventions, especially with selective serotonin reuptake inhibitors (SSRIs). Unfortunately, a significant proportion of patients are refractory to these treatment modalities. New understanding about the neurobiology of OCD has led to novel investigational treatments, especially neuromodulation techniques.
Address correspondence to Dr Daniel A. Drubach, Mayo Clinic 200 1st Street SW, Department of Neurology, Rochester, MN 55905, [email protected]. Relationship Disclosure: Dr Drubach has received personal compensation for lectures from Sivananda Ashram Yoga and receives book royalties from Prentice Hall. Unlabeled Use of Products/Investigational Use Disclosure: Dr Drubach discusses the unlabeled/investigational use of pharmacologic agents and neuromodulation techniques to treat obsessive-compulsive disorder. * 2015, American Academy of Neurology.
Continuum (Minneap Minn) 2015;21(3):783–788.
INTRODUCTION Obsessive-compulsive disorder (OCD) is a syndrome characterized by two main features: obsessions and compulsions. Obsessions consist of thoughts, images, or urges to perform a certain task that erupt into consciousness and which are frequently disturbing and anxiety provoking. Compulsions consist of the performance of repetitive motor acts executed with the sole purpose of ameliorating anxiety caused by either the obsession or a belief and conviction that things need to be a certain way. EPIDEMIOLOGY Obsessions and compulsions are part of every person’s daily cognitive repertoire. Thoughts intrude spontaneously into people’s minds. Cultural superstition and religious rituals lead people to perform very meticulous and precise acts, some of which could be conceptualized as Continuum (Minneap Minn) 2015;21(3):783–788
obsessive. Similarly, we all have opinions as to how things should be and can be disturbed if these things are done in a different way. However, what differentiates normal cognition and behavior from pathologic obsessions and compulsions is a matter of degree. Obsessions and compulsions consume a great percentage of the daily energy and time of a person with OCD. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria, pathologic obsessions and compulsions are time consuming (taking up more than 1 hour per day) and cause significant distress or impairment in social, occupational, or other important areas of functioning.1 In fact, patients with OCD experience great variability in the time and energy spent on obsessions and compulsions. Studies addressing the epidemiology of OCD among adults in the United States www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
783
Obsessive-Compulsive Disorder KEY POINTS
h Obsessive-compulsive disorder is a syndrome characterized by two main features: obsessions and compulsions.
h Obsessions consist of thoughts, images, or urges to perform a certain task that erupt into consciousness and which are frequently disturbing and anxiety provoking.
h Compulsions consist of the performance of repetitive motor acts executed with the sole purpose of ameliorating anxiety caused by either the obsession or a belief and conviction that things need to be a certain way.
h What differentiates normal cognition and behavior from pathologic obsessions and compulsions is a matter of degree. Obsessions and compulsions consume a great percentage of the daily energy and time of a person with obsessivecompulsive disorder.
h Obsessive-compulsive disorder can be associated with neurologic conditions, including movement disorders (especially tic disorders), stroke in the left basal ganglia, traumatic brain injury, progressive supranuclear palsy, and various dementias.
h The correlation with basal ganglia atrophy in patients with frontotemporal dementia and obsessive-compulsive disorder may point to involvement of frontal subcortical neuronal networks as well as of the temporal lobes.
784
are complicated by the changes in the diagnostic criteria and in the judgment of what constitutes a normal versus abnormal behavior. One study showed the incidence rate to be 0.55 per 1000 person-years in the United States.2 A cross-national study involving seven countries found a remarkably consistent annual prevalence for OCD in six countries. Other studies found the 12-month prevalence to be 1.2% and the lifetime prevalence to be 2.3% in the United States. While females are affected at a slightly higher rate than males in adulthood, males are more commonly affected in childhood.3Y5 OCD can exist in isolation, in the absence of other neurologic and psychiatric disorders, but other associated neuropsychiatric comorbidities occur in a significant proportion of patients. These include mood disorders (eg, depression and mania), anxiety disorders (eg, phobias, panic disorders), personality disorders, and schizophrenia.6 Of particular relevance to practicing neurologists, OCD can be associated with neurologic conditions, including movement disorders (especially tic disorders), stroke in the left basal ganglia,7 traumatic brain injury, progressive supranuclear palsy,8 and various dementias.9,10 Although the scientific literature on the topic is scant and mostly limited to case reports, more robust data exist on the association of OCD and frontotemporal dementia. One early study found that three of the authors’ patients with dementia secondary to frontal lobe degeneration, as well as their analysis of 78% of 46 proven pathologic cases of frontal lobe degeneration described in the literature, demonstrated repetitive behaviors ranging from motor stereotypes to complex OCD. The authors suggested that combined damage to the frontal lobe, caudate nucleus, and globus pallidus may account for the repetitive behaviors that occur in frontal lobe degenerations, idiopathic OCD, and other neuropsychiatric diseases.11 Another study reported OCD symptoms as the presenting symptom
in 38% of 29 patients with a clinical diagnosis of frontotemporal dementia versus 10% of 48 patients diagnosed with Alzheimer disease.12 In a recent study, 11 patients with behavioral variant frontotemporal dementia underwent MRI and voxel-based morphometry. Nine of these patients displayed OCD symptoms. These individuals were found to have gray matter loss in the bilateral globus pallidus, left putamen, and in the lateral temporal lobe, particularly the left middle and inferior temporal gyri.13 The authors suggest that the correlation with basal ganglia atrophy in patients with frontotemporal dementia and OCD may point to involvement of frontal subcortical neuronal networks as well as of the temporal lobes. The most frequent compulsions in this group of patients were checking, hoarding, ordering/ arranging, repeating rituals, and cleaning. Robust data also exist on the association of OCD with Huntington disease.14 In patients with a primary psychiatric disease, obsessions and compulsions are associated with anxiety and depression, while in frontotemporal dementia, obsessions and compulsions are accompanied by other symptoms commonly seen in the disorder, such as disinhibition, poor judgment, and apathy (Case 12-1). Certain medications utilized in the management of neurologic disease have also been associated with the onset of OCD-like symptoms. For example, recent reports have emerged of patients prescribed dopamine agonists who develop such features as compulsive shopping and gambling.15 It has been suggested that impulse control disorders, including compulsive gambling, shopping, and others brought on by dopaminergic agents in patients with Parkinson disease may be mediated by dopamine D3 receptors.16 Other agents, such as amphetamines and cocaine, have been associated with obsessions. Interestingly, there are anecdotal case studies in the literature that report the resolution of OCD symptoms with focal
www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
June 2015
KEY POINTS
Case 12-1
h Three treatment
A 46-year-old man, previously a healthy and highly successful executive, became obsessed by the intrusive image of his child being struck by a car; in order to ameliorate the anxiety caused by that image he would go to great lengths to be able to ‘‘knock on wood.’’ However, the wooden surface that he would hit could not be covered by varnish or paint since the skin of his knuckles needed to make direct contact with the wood. This compulsion would at times drive him out of business meetings in a frantic search for an appropriate wooden object. Shortly afterward he developed prominent behavioral changes, including impulsivity and poor judgment. MRI showed significant bifrontal (right worse than left) atrophy. Fluorodeoxyglucose positron emission tomography (FDG-PET) scan demonstrated right frontal hypometabolism. The clinical diagnosis of behavioral variant frontotemporal dementia was made. Comment. This patient’s first onset of symptoms at a late age was unlikely to be due to a primary psychiatric disorder. In this clinical setting, the clinician needs to be suspicious that the obsessive-compulsive disorder (OCD) symptomatology is due to a neurodegenerative condition.
damage to the brain, including a case of resolution of severe OCD after a small unilateral nondominant frontoparietal infarct.17
greater connectivity was found between the self subsystem and salience and attention networks.21
NEUROBIOLOGY OF OBSESSIVE-COMPULSIVE DISORDER Diffusion tensor imaging in patients with OCD has found decreased white matter integrity in the cingulate bundle, the corpus callosum, and the anterior limb of the internal capsule.18 Functional imaging, including positron emission tomography (PET), single-photon emission computed tomography (SPECT), and functional MRI (fMRI) studies, have also shown increased cerebral metabolism in cortico-striatothalamo-cortical circuits, particularly in the caudate and putamen, the anterior thalamus, the orbitofrontal cortex, and the anterior cingulate cortex.19 Activation of these circuits occurs with symptom provocation and is reduced with symptomatic improvement after either pharmacotherapy or psychotherapy.20 Some recent studies have shown an alteration in the default mode network in patients with OCD, with significantly reduced connectivity within the dorsal medial prefrontal cortex self subsystem. In addition,
TREATMENT Three treatment modalities are currently available for patients with OCD: psychotherapy, pharmacotherapy, and brain modulation. Each of these modalities has been used in isolation, although they are more often applied concomitantly, especially in the case of psychotherapy and pharmacotherapy.22
Continuum (Minneap Minn) 2015;21(3):783–788
modalities are currently available for patients with obsessive-compulsive disorder: psychotherapy, pharmacotherapy, and brain modulation.
h Although there are many forms of psychotherapy, cognitive-behavioral therapy has had the most success in treating obsessivecompulsive disorder.
Psychotherapy Psychotherapy is a diagnostic and treatment modality utilizing verbal interaction between a therapist and a patient to address mental discomfort or disorders. Although there are many forms of psychotherapy, cognitive-behavioral therapy has had the most success in treating OCD. Cognitive-behavioral therapy is a problemfocused, goal-directed, and time-limited treatment modality predicated on the theory that obsessions and compulsions are the result of abnormal learned responses and actions. The goals of therapy are to identify and change destructive, disturbing thought patterns that have a www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
785
Obsessive-Compulsive Disorder KEY POINTS
h Numerous studies have highlighted the benefit of selective serotonin reuptake inhibitors and the tricyclic antidepressant clomipramine, supporting the use of these medications as first-line agents.
h The effects of selective serotonin reuptake inhibitors are not solely due to treatment of depression since their benefit in the management of obsessive-compulsive disorder is present even in patients in whom depression has been excluded as a comorbid condition.
h While deep brain stimulation techniques are promising in patients with treatment-resistant obsessive-compulsive disorder, it remains an invasive procedure with unknown long-term treatment effects.
786
negative influence on behaviors, such as obsessions and compulsions. Pharmacotherapy In regard to pharmacotherapy, numerous studies have highlighted the benefit of selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressant clomipramine, supporting the use of these medications. SSRIs are considered firstline agents due to the relative safety and side effect profile for these agents. Clomipramine should be considered if SSRIs are not effective or are not tolerated. Typically, these medications are prescribed at higher dosages (within the higher range of recommended dosages or until side effects preclude further increases) and for longer periods (weeks or months) than they are prescribed for anxiety disorders and depression since response to SSRIs tends to take longer in the treatment of OCD than in the treatment of these disorders. The effects of these medications in treating OCD are not solely due to treatment of depression, since their benefit in the management of OCD is present even in patients in whom depression has been excluded as a comorbid condition. The actions of SSRIs and clomipramine are to block serotonin reuptake by the presynaptic neuron, which increases serotonin availability at postsynaptic receptors. Consequently, the benefits of these medications in the treatment of OCD have highlighted the possible role of deranged serotonergic neurotransmission in the pathophysiology of OCD. Despite the beneficial effect of SSRIs and clomipramine in some patients with OCD, 40% to 60% of patients remain refractory to treatment. Several options have been proposed to help those patients who fail to respond to this treatment. The combination of SSRIs with clomipramine in high doses has been reported to be of some use. Another strategy reported as
beneficial is the augmentation of an SSRI with haloperidol or an atypical antipsychotic medication including risperidone, olanzapine, or quetiapine. Other agents reported to have some benefit, especially in nonresponders to clomipramine or an SSRI or as an adjuvant to them, include buspirone, clonazepam, trazodone, and venlafaxine.22 Memantine has also been reported to be of benefit in patients with refractory OCD.23 While predictors of treatment response have not been well elucidated, some studies suggest that severity and duration of OCD, psychosocial disability, earlier age at onset, older age, comorbidity with depression and personality disorder, absence of a positive family history for OCD, and poor insight, as well as abnormal findings in the neurologic examination, were associated with a poorer response.24 Brain Modulation Brain modulation is an exciting development in the treatment of patients with severe OCD.25 Electroconvulsive therapy26 and transcranial magnetic stimulation27 have been reported to be beneficial in a small number of patients. Deep brain stimulation, specifically stimulation of the subthalamic nucleus or the nucleus accumbens, has been utilized and has shown effectiveness in patients with OCD who are refractory to other forms of treatment.28 One study showed a beneficial effect in patients with OCD and Tourette syndrome with stimulation of the anteromedial globus pallidus internus (GPi).29 While deep brain stimulation techniques are promising in patients with treatmentresistant OCD, it remains an invasive investigational procedure with unknown long-term treatment effects. Guidelines In 2007, the American Psychiatric Association published guidelines for the treatment of patients with obsessivecompulsive disorders. This excellent
www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
June 2015
publication delineates factors to consider at each treatment step, treatment algorithms, management of patients with treatment-resistant symptoms, and several other issues pertinent to the management of this population.22 CONCLUSION OCD is a highly disabling neuropsychiatric condition affecting a significant proportion of the population. Certain neurologic disorders, especially frontotemporal dementia and Huntington disease, are frequently associated with obsessions and compulsions. With increased understanding of the neurobiology of OCD, treatment modalities are likely to become more effective. In the meantime, cognitivebehavioral therapy and SSRIs or clomipramine remain the mainstays of treatment. Treatment-refractory cases of OCD may respond to neuromodulation. REFERENCES 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: fifth edition. Washington, DC: American Psychiatric Association, 2013. 2. Nestadt G, Bienvenu OJ, Cai G, et al. Incidence of obsessive-compulsive disorder in adults. J Nerv Ment Dis 1998;186(7):401Y406. 3. Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry 2010;15(1):53Y63. doi:10.1038/mp.2008.94. 4. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62(6): 617Y627. doi:10.1001/archpsyc.62.6.617. 5. Weissman MM, Bland RC, Canino GJ, et al. The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry 1994;55(suppl):5Y10. 6. Brady CF. Obsessive-compulsive disorder and common comorbidities. J Clin Psychiatry 2014;75(1):e02. doi:10.4088/JCP.13023tx1c. 7. Lopez-Rodriguez F, Gunay I, Glaser N. Obsessive compulsive disorder in a woman with left basal ganglia infarct: a case report. Continuum (Minneap Minn) 2015;21(3):783–788
Behav Neurol 1997;10(2):101Y103. doi:10.3233/BEN-1997-102-308. 8. Karnik NS, D’Apuzzo M, Greicius M. Non-fluent progressive aphasia, depression, and OCD in a woman with progressive supranuclear palsy: neuroanatomical and neuropathological correlations. Neurocase 2006;12(6):332Y338. doi:10.1080/ 13554790601125957. 9. Potvin O, Hudon C, Dion M, et al. Anxiety disorders, depressive episodes and cognitive impairment no dementia in communitydwelling older men and women. Int J Geriatr Psychiatry 2011;26(10):1080Y1088. doi:10.1002/gps.2647. 10. Pompanin S, Perini G, Toffanin T, et al. Late-onset OCD as presenting manifestation of semantic dementia. Gen Hosp Psychiatry 2012;34(1):102.e1Y102.e4. doi:10.1016/ j.genhosppsych.2011.08.001. 11. Ames D, Cummings JL, Wirshing WC, et al. Repetitive and compulsive behavior in frontal lobe degenerations. J Neuropsychiatry Clin Neurosci 1994;6(2):100Y113. 12. Mendez MF, Perryman KM, Miller BL, et al. Compulsive behaviors as presenting symptoms of frontotemporal dementia. J Geriatr Psychiatry Neurol 1997;10(4):154Y157. doi:10.1177/ 089198879701000405. 13. Perry DC, Whitwell JL, Boeve BF, et al. Voxel-based morphometry in patients with obsessive-compulsive behaviors in behavioral variant frontotemporal dementia. Eur J Neurol 2012;19(6):911Y917. doi:10.1111/j.1468-1331. 2011.03656.x. 14. Anderson KE, Gehl CR, Marder KS, et al. Comorbidities of obsessive and compulsive symptoms in Huntington’s disease. J Nerv Ment Dis 2010;198(5):334Y338. doi:10.1097/ NMD.0b013e3181da852a. 15. McKeon A, Josephs KA, Klos KJ, et al. Unusual compulsive behaviors primarily related to dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 2007; 13(8):516Y519. doi:10.1016/j.parkreldis. 2007.04.004. 16. Seeman P. Parkinson’s disease treatment may cause impulse-control disorder via dopamine D3 receptors (published online ahead of print January 22, 2015). Synapse 2015. doi:10.1002/syn.21805. 17. Diamond A, Ondo WG. Resolution of severe obsessiveYcompulsive disorder after a small unilateral nondominant frontoparietal infarct. Int J Neurosci 2011;121(7):405Y407. doi:10.3109/ 00207454.2011.561941. www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
787
Obsessive-Compulsive Disorder
18. Koch K, Reess TJ, Rus OG, et al. Diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD): a review. J Psychiatr Res 2014;54:26Y35. doi:10.1016/j.jpsychires.2014.03.006. 19. Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci 2012;16(1):43Y51. doi:10.1016/j.tics.2011.11.003. 20. Anticevic A, Hu S, Zhang S, et al. Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol Psychiatry 2014;75(8):595Y605. doi:10.1016/j.biopsych. 2013.10.021. 21. Beucke JC, Sepulcre J, Eldaief MC, et al. Default mode network subsystem alterations in obsessive-compulsive disorder. Br J Psychiatry 2014;205(5):376Y382. doi:10.1192/ bjp.bp.113.137380. 22. Koran LM, Hanna GL, Hollander E, et al. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry 2007;164(7 suppl):5Y53. 23. Haghighi M, Jahangard L, Mohammad-Beigi H, et al. In a double-blind, randomized and placebo-controlled trial, adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders (OCD). Psychopharmacology (Berl) 2013;228(4): 633Y640. doi:10.1007/s00213-013-3067-z.
788
24. Shetti CN, Reddy YC, Kandavel T, et al. Clinical predictors of drug nonresponse in obsessive-compulsive disorder. J Clin Psychiatry 2005;66(12):1517Y1523. 25. Aronson JP, Katnani HA, Eskandar EN. Neuromodulation for obsessive-compulsive disorder. Neurosurg Clin N Am 2014;25(1): 85Y101. doi:10.1016/j.nec.2013.08.003. 26. Hanisch F, Friedemann J, Piro J, Gutmann P. Maintenance electroconvulsive therapy for comorbid pharmacotherapy-refractory obsessive-compulsive and schizoaffective disorder. Eur J Med Res 2009;14(8):367Y368. doi:10.1186/2047-783X-14-8-367. 27. Gomes PV, Brasil-Neto JP, Allam N, Rodrigues de Souza E. A randomized, double-blind trial of repetitive transcranial magnetic stimulation in obsessive-compulsive disorder with three-month follow-up. J Neuropsychiatry Clin Neurosci 2012;24(4):437Y443. doi:10.1176/appi.neuropsych.11100242. 28. Lipsman N, Giacobbe P, Lozano AM. Deep brain stimulation in obsessive-compulsive disorder: neurocircuitry and clinical experience. Handb Clin Neurol 2013;116:245Y250. doi:10.1016/B978-0-444-53497-2.00019-X. 29. Nair G, Evans A, Bear RE, et al. The anteromedial GPi as a new target for deep brain stimulation in obsessive compulsive disorder. J Clin Neurosci 2014;21(5):815Y821. doi:10.1016/j.jocn.2013.10.003.
www.ContinuumJournal.com
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
June 2015
