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Treatment for Late-Onset Obsessive-Compulsive Disorder with Parkinsonism
Arunlata Agarwal, M.D.; Devdutta Biswas, M.D.; Raja Sadhu, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2008;20:331-336.
View Author and Article Information

Received March 24, 2007; revised July 10, 2007; accepted July 23, 2007. Drs. Agarwal and Biswas are affiliated with the Department Of Psychiatry at Maulana Azad Medical College and G.B. Pant Hospital in New Delhi; Dr. Sadhu is affiliated with the Department Of Psychiatry, All India Institute of Medical Sciences in New Delhi. Address correspondence to A.L. Agarwal, M.D., D-5, M.A.M.C. Campus, New Delhi- 110002, India; dralagrawal@hotmail.com (e-mail).

Copyright © 2008 American Psychiatric Publishing, Inc.

Abstract

Dysfunction of the basal ganglia and frontal subcortical structures occurs in both obsessive-compulsive disorder and parkinsonism. Treatment of obsessive-compulsive disorder with parkinsonism is a therapeutic challenge, especially in old age as selective serotonin reuptake inhibitors may aggravate motor symptoms and worsen clinical conditions. The authors present a series of patients with late onset obsessive-compulsive disorder demonstrating improvement in obsessive-compulsive disorder as well as parkinsonian signs.

Abstract Teaser
Figures in this Article

An association of obsessive-compulsive disorder (OCD) with movement disorders (e.g., Tourette’s syndrome, Huntington’s disease, and Sydenham’s chorea) has been noted since the recognition of the latter.1 The association of obsessive-compulsive disorder with parkinsonism was recognized during the encephalitis lethargica pandemic in 1917 when its occurrence temporarily provided insight on the importance of the basal ganglia and subcortical structures in movement disorders and OCD.2,3 Although neurology and psychiatry were distancing themselves from each other, it was recognized that disorders affecting the brain were not always clinically expressed in only one of these specialties.1 In the next few decades, neurology focused more on neurobiology and evolved along a parallel yet completely separate line from psychiatry, which took a more biopsychological approach to understanding the human brain.4 The development of structural and functional imaging in the 1980s led to a new era and provided an impetus for the reunification of the neurosciences. A spate of imaging studies in OCD ensued, which demonstrated evidence of the dysfunction of basal ganglia, especially caudate and frontal subcortical structures.59 On the basis of these data, several authors have advanced models of basal ganglia thalamocortical circuits in which behavior is modulated by filtering irrelevant thoughts. Dysfunction of these circuits has been proposed in the pathogenesis of OCD.1012 From 1988 onward, case reports of basal ganglia lesions (diagnosed radiologically) associated with OCD were reported by several authors.1320 These reports spurred studies exploring the prevalence of anxiety disorders,2123 especially OCD, in Parkinson’s disease.2427 The studies were conducted on patients with established Parkinson’s disease, but the results conflicted—some authors reported association22,24,26 and some reported a lack of association.25,27

Despite recognizing for nearly a century the possible association between OCD and parkinsonism, treatment needs of this special group remain relatively unexplored. Common therapeutic strategies for OCD like serotonin reuptake inhibitors (SSRIs) might aggravate motor symptoms by stimulating 5-HT2 receptors and inhibiting dopamine release in the basal ganglia.2833 On the other hand, -dopa for parkinsonism is reported to aggravate compulsive and impulsive symptoms.3436 Patients exhibiting both obsessive and parkinsonian features thus provide a therapeutic challenge for the clinician. A few studies have demonstrated the safety and efficacy of tricyclic antidepressants in depression with parkinsonism but have not clearly commented on the effect on motor features.3740 OCD with parkinsonism, however, has not been satisfactorily addressed.

We present a naturalistic follow-up study of a group of late-onset OCD patients exhibiting parkinsonian signs who demonstrated a response to clomipramine, which might be considered a viable option for such patients.

The patients were seen in the psychiatry clinic of a superspecialty tertiary care hospital in India over a span of 1 year. The hospital serves as the culmination point for many chronic and difficult-to-treat cases. This paper describes 10 patients who were diagnosed with OCD according to ICD-10 criteria and who showed parkinsonian signs (not deemed to be the effect of drugs). Two OCD patients without parkinsonian signs and one who did not undergo investigations were excluded from the study. Patients were rated on the Yale-Brown Obsessive Compulsive Scale, a 10-item scale that rates severity of obsessive-compulsive symptoms,41 and the Webster Scale for severity of parkinsonian features (bradykinesia, rigidity, gait, arm swing, tremor, and facial expression).42 We obtained cardiology, prostate, and glaucoma tests and clearance for starting tricyclic antidepressants. Patients were started on a regimen of clomipramine following the principle of starting low and going slow, and the dose was titrated on the basis of clinical improvement and tolerability. We periodically rated the patients on the Visual Analogue Scale, the Yale-Brown Obsessive-Compulsive Scale, and the Webster Scale through December 2006.

The sociodemographic and clinical profile of patients are summarized in Table 1 . Table 2 demonstrates past treatment history. All patients had late age of onset for OCD, and most had demonstrable basal ganglia/frontal subcortical lesions. Table 3 shows patients’ robust and early responses to low doses of clomipramine.

This case series is notable as it presents a large series of patients presenting with late-onset obsessive-compulsive disorder exhibiting parkinsonian signs, with demonstrable lesions in the basal ganglia and/or frontal subcortical structures on MRI. All patients consulted a psychiatrist due to dysfunction resulting from OCD, and motor signs were elicited on evaluation. Potential confounding factors were avoided as their obsessive symptoms were not -dopa induced, nor were motor signs antipsychotic induced (patient 9, with history of antipsychotic treatment, had a 6 month drug-free interval before baseline assessment). The cases support the view that lesions of the basal ganglia could account for OCD as well as parkinsonism. Recognition of behavioral as well as motor features is essential, as such patients present a diagnostic and therapeutic challenge. A diagnosis of late-onset OCD with parkinsonism is often shrouded in therapeutic nihilism as several authors have observed limited response to psychotropic medication20 and aggravation of motor symptoms with SSRIs.2833 Our case study gives us reason to be hopeful, as all patients (including past nonresponders to SSRIs) showed an early and robust response to low doses of clomipramine without significant adverse effects. A concomitant decline in the Webster score was an added benefit. Sedative and anxiolytic effects of clomipramine obviated the need for benzodiazepines in all except two cases, avoiding drug interactions and the adverse cognitive effects of benzodiazepines noted in parkinsonism. Although our study is limited by the narrow population sample, it indicates a need for evolution of therapeutic strategies that address both behavioral and motor components of obsessive-compulsive disorder with basal ganglia lesions.

TABLE 1. Sociodemographic and Clinical Profiles
TABLE 2. Past Treatment History
TABLE 3. Treatment Response to Clomipramine

This work was presented at the 2nd Annual National Meeting of the Indian Association for Geriatric Mental Health in Chennai, India, on December 1-2, 2006.

.
Maia AF, Barbosa ER, Menezes PR: Relationship between obsessive compulsive disorders and diseases affecting primarily the basal ganglia. Rev Hosp Clin Fac Med S Paulo 1999; 54:213—221
 
.
Cheyette SR, Cummings J: Encephalitis lethargica: lessons for contemporary neuropsychiatry. J Neuropsychiatry Clin Neurosci 1995; 7:125—134
 
.
Schilder P: The organic background of obsessions and compulsions. Am J Psychiatry 1938; 94:1397—1413
 
.
Carsen S, Xia C: Editorial. McGill J Med 2006; 9:80—81
 
.
Baxter LR, Phelps ME, Mazziotta JC, et al: Local cerebral glucose metabolic rates in obsessive-compulsive disorder: a comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry 1987; 44:211—218
 
.
Baxter LR, Schwartz JM, Mazziotta JC, et al: Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder. Am J Psychiatry 1988; 145:1560—1563
 
.
Luxenberg JS, Swedo SE, Flament MF: Neuroanatomical abnormalities in obsessive-compulsive disorder detected with quantitative x-ray computed tomography. Am J Psychiatry 1988; 145:1089—1093
 
.
Robinson D, Wu H, Munne RA, et al: Reduced caudate nucleus volume in obsessive-compulsive disorder. Arch Gen Psychiatry 1995; 52:393—398
 
.
Pujol J, Soriano-Mas C, Alonso P, et al: Mapping structural brain alterations in obsessive-compulsive disorder. Arch Gen Psychiatry 2004; 61:720—730
 
.
Baxter LR, Schwartz JM, Bergman KS: Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 1992; 49:681—689
 
.
Model JG, Mountz JM, Cortis GC: Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive compulsive disorder. J Neuropsychiatry Clin Neurosci 1989; 1:27—36
 
.
Graybiel AM, Rauch SL: Toward a neurobiology of obsessive-compulsive disorder. Neuron 2000; 28:343—347
 
.
Laplane D, Levasseur M, Pillon B, et al: Obsessive-compulsive and other behavioral changes with bilateral basal ganglia lesions. Brain 1989; 112:699—725
 
.
Weilburg JB, Mesulam MM, Weintraub S: Focal striatal abnormalities in a patient with obsessive-compulsive disorder. Arch Neurol 1989; 46:233—235
 
.
Croisile B, Tourniaire D, Confavreux C, et al: Bilateral damage to the head of the caudate nuclei. Ann Neurol 1989; 25: 313—314
 
.
Ward C: Transient feelings of compulsion caused by hemispheric lesion: 3 cases. J Neurol Neurosurg Psychiatry 1988; 51:266—268
 
.
Lopez-Rodriguez F, Gunay I, Glaser N: Obsessive compulsive disorder in a woman with left basal ganglia infarct: a case report. Behavioral Neurology 1997; 10:101—103
 
.
Williams AC, Owen C, Heath DA: A compulsive movement disorder with cavitation of the caudate nucleus. J Neurol Neurosurg Psychiatry 1998; 51:447—448
 
.
Chacko RC, Corbin MA, Harper RG: Acquired obsessive-compulsive disorder associated with basal ganglia lesions. J Neuropsychiatry Clin Neurosci 2000; 12:269—272
 
.
Weiss AP, Jenike MA: Late onset obsessive-compulsive disorder: a case series. J Neuropsychiatry Clin Neurosci 2000; 12:265—268
 
.
Stein MB, Heuser IJ, Juncos JL, et al: Anxiety disorders in patients with Parkinson’s disease. Am J Psychiatry 1990; 147:217—220
 
.
Lauterbach EC, Duvoisin RC: Anxiety disorders in familial parkinsonism (letter). Am J Psychiatry 1991; 148:274
 
.
Richard IH, Schiffer RB, Kurian R: Anxiety and Parkinson’s disease. J Neuropsychiatry Clin Neurosci 1996; 8:383—392
 
.
Tomer R, Levin BE, Weiner WJ: Obsessive-compulsive symptoms and motor asymmetries in Parkinson’s disease. Neuropsych Neuropsychol Behav Neurol 1993; 6:26—30
 
.
Muller N, Putz A, Kathmann N, et al: Characteristics of obsessive-compulsive symptoms in Tourette’s syndrome, obsessive-compulsive disorder and Parkinson’s disease. Psychiatry Res 1997; 70:105—114
 
.
Alegret M, Junque C, Vallderiola F: Obsessive-compulsive symptoms in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2001; 70:394—396
 
.
Maia AF, Barbosa ER, Menezes PR: Obsessive-compulsive symptoms, obsessive-compulsive disorder and related disorders in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 2003; 15:371—374
 
.
Chouinard G, Sultan S: A case of Parkinson’s disease exacerbated by fluoxetine. Human Psychopharmacol 1992; 7:63—66
 
.
Steur EN: Increase of Parkinson disability after fluoxetine medication. Neurology 1993; 43: 211—213
 
.
Jimenez-Jimenez FJ, Tejeiro J, Martinez-Junquera G: Parkinsonism exacerbated by paroxetine. Neurology 1994; 44:2406
 
.
Richard IH, Kurian R: A survey of antidepressant drug use in Parkinson’s disease. Parkinson Study Group. Neurology 1997; 49:1168—1170
 
.
van de Vijver DA, Roos RA, Jansen PA: Start of SSRI and increase in antiparkinsonian drug treatment in patients on -dopa. Br J Clin Pharmacol 2002; 54:168—170
 
.
Avila A, Cardona X, Maho P, et al: Does nefazodone improve both depression and Parkinson’s disease? A pilot randomized trial. J Clin Psychopharmacology 2003; 23:509—513
 
.
Cools R, Barker RA: -Dopa increases impulsivity in patients with Parkinson’s disease. Neuropsychologia 2003; 41:1431—1441
 
.
Pontone G, Williams JR, Bassett SS, et al: Clinical features associated with impulse control disorders in Parkinson’s disease. Neurology 2006; 67:1258—1261
 
.
Voon V, Hassan K, Zurowski M, et al: Prevalence of repetitive and reward seeking behaviors in Parkinson’s disease. Neurology 2006; 67:1254—1257
 
.
Laitinen L: Desipramine in treatment of Parkinson’s disease: a placebo controlled study. Acta Neurol Scand 1969; 45:109—113
 
.
Andersen J, Aabro E, Gulmann N: Antidepressant treatment in Parkinson’s disease: a controlled trial of the effect of nortriptyline in patients with Parkinson’s disease treated with -dopa. Acta Neurol Scand 1980; 62:210—219
 
.
Klaassen T, Verhey FR, Sneijders GH: Treatment of depression in Parkinson’s disease: a meta-analysis. J Neuropsychiatry Clin Neurosci 1995; 7:281—286
 
.
Vaida FJ, Solinas C: Current approaches to management of depression in Parkinson’s disease. J Clin Neurosci 2005; 12:739—743
 
.
Goodman WK, Price LH, Rasmussen SA: The Yale-Brown Obsessive Compulsive scale, part 1: development, use, and reliability. Arch Gen Psychiatry 1989; 46:1006—1011
 
.
Webster DD: Critical analysis of the disability in Parkinson’s disease. Mod Treat 1968; 5:257—282
 
TABLE 1. Sociodemographic and Clinical Profiles
TABLE 2. Past Treatment History
TABLE 3. Treatment Response to Clomipramine
+

References

.
Maia AF, Barbosa ER, Menezes PR: Relationship between obsessive compulsive disorders and diseases affecting primarily the basal ganglia. Rev Hosp Clin Fac Med S Paulo 1999; 54:213—221
 
.
Cheyette SR, Cummings J: Encephalitis lethargica: lessons for contemporary neuropsychiatry. J Neuropsychiatry Clin Neurosci 1995; 7:125—134
 
.
Schilder P: The organic background of obsessions and compulsions. Am J Psychiatry 1938; 94:1397—1413
 
.
Carsen S, Xia C: Editorial. McGill J Med 2006; 9:80—81
 
.
Baxter LR, Phelps ME, Mazziotta JC, et al: Local cerebral glucose metabolic rates in obsessive-compulsive disorder: a comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry 1987; 44:211—218
 
.
Baxter LR, Schwartz JM, Mazziotta JC, et al: Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder. Am J Psychiatry 1988; 145:1560—1563
 
.
Luxenberg JS, Swedo SE, Flament MF: Neuroanatomical abnormalities in obsessive-compulsive disorder detected with quantitative x-ray computed tomography. Am J Psychiatry 1988; 145:1089—1093
 
.
Robinson D, Wu H, Munne RA, et al: Reduced caudate nucleus volume in obsessive-compulsive disorder. Arch Gen Psychiatry 1995; 52:393—398
 
.
Pujol J, Soriano-Mas C, Alonso P, et al: Mapping structural brain alterations in obsessive-compulsive disorder. Arch Gen Psychiatry 2004; 61:720—730
 
.
Baxter LR, Schwartz JM, Bergman KS: Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 1992; 49:681—689
 
.
Model JG, Mountz JM, Cortis GC: Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive compulsive disorder. J Neuropsychiatry Clin Neurosci 1989; 1:27—36
 
.
Graybiel AM, Rauch SL: Toward a neurobiology of obsessive-compulsive disorder. Neuron 2000; 28:343—347
 
.
Laplane D, Levasseur M, Pillon B, et al: Obsessive-compulsive and other behavioral changes with bilateral basal ganglia lesions. Brain 1989; 112:699—725
 
.
Weilburg JB, Mesulam MM, Weintraub S: Focal striatal abnormalities in a patient with obsessive-compulsive disorder. Arch Neurol 1989; 46:233—235
 
.
Croisile B, Tourniaire D, Confavreux C, et al: Bilateral damage to the head of the caudate nuclei. Ann Neurol 1989; 25: 313—314
 
.
Ward C: Transient feelings of compulsion caused by hemispheric lesion: 3 cases. J Neurol Neurosurg Psychiatry 1988; 51:266—268
 
.
Lopez-Rodriguez F, Gunay I, Glaser N: Obsessive compulsive disorder in a woman with left basal ganglia infarct: a case report. Behavioral Neurology 1997; 10:101—103
 
.
Williams AC, Owen C, Heath DA: A compulsive movement disorder with cavitation of the caudate nucleus. J Neurol Neurosurg Psychiatry 1998; 51:447—448
 
.
Chacko RC, Corbin MA, Harper RG: Acquired obsessive-compulsive disorder associated with basal ganglia lesions. J Neuropsychiatry Clin Neurosci 2000; 12:269—272
 
.
Weiss AP, Jenike MA: Late onset obsessive-compulsive disorder: a case series. J Neuropsychiatry Clin Neurosci 2000; 12:265—268
 
.
Stein MB, Heuser IJ, Juncos JL, et al: Anxiety disorders in patients with Parkinson’s disease. Am J Psychiatry 1990; 147:217—220
 
.
Lauterbach EC, Duvoisin RC: Anxiety disorders in familial parkinsonism (letter). Am J Psychiatry 1991; 148:274
 
.
Richard IH, Schiffer RB, Kurian R: Anxiety and Parkinson’s disease. J Neuropsychiatry Clin Neurosci 1996; 8:383—392
 
.
Tomer R, Levin BE, Weiner WJ: Obsessive-compulsive symptoms and motor asymmetries in Parkinson’s disease. Neuropsych Neuropsychol Behav Neurol 1993; 6:26—30
 
.
Muller N, Putz A, Kathmann N, et al: Characteristics of obsessive-compulsive symptoms in Tourette’s syndrome, obsessive-compulsive disorder and Parkinson’s disease. Psychiatry Res 1997; 70:105—114
 
.
Alegret M, Junque C, Vallderiola F: Obsessive-compulsive symptoms in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2001; 70:394—396
 
.
Maia AF, Barbosa ER, Menezes PR: Obsessive-compulsive symptoms, obsessive-compulsive disorder and related disorders in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 2003; 15:371—374
 
.
Chouinard G, Sultan S: A case of Parkinson’s disease exacerbated by fluoxetine. Human Psychopharmacol 1992; 7:63—66
 
.
Steur EN: Increase of Parkinson disability after fluoxetine medication. Neurology 1993; 43: 211—213
 
.
Jimenez-Jimenez FJ, Tejeiro J, Martinez-Junquera G: Parkinsonism exacerbated by paroxetine. Neurology 1994; 44:2406
 
.
Richard IH, Kurian R: A survey of antidepressant drug use in Parkinson’s disease. Parkinson Study Group. Neurology 1997; 49:1168—1170
 
.
van de Vijver DA, Roos RA, Jansen PA: Start of SSRI and increase in antiparkinsonian drug treatment in patients on -dopa. Br J Clin Pharmacol 2002; 54:168—170
 
.
Avila A, Cardona X, Maho P, et al: Does nefazodone improve both depression and Parkinson’s disease? A pilot randomized trial. J Clin Psychopharmacology 2003; 23:509—513
 
.
Cools R, Barker RA: -Dopa increases impulsivity in patients with Parkinson’s disease. Neuropsychologia 2003; 41:1431—1441
 
.
Pontone G, Williams JR, Bassett SS, et al: Clinical features associated with impulse control disorders in Parkinson’s disease. Neurology 2006; 67:1258—1261
 
.
Voon V, Hassan K, Zurowski M, et al: Prevalence of repetitive and reward seeking behaviors in Parkinson’s disease. Neurology 2006; 67:1254—1257
 
.
Laitinen L: Desipramine in treatment of Parkinson’s disease: a placebo controlled study. Acta Neurol Scand 1969; 45:109—113
 
.
Andersen J, Aabro E, Gulmann N: Antidepressant treatment in Parkinson’s disease: a controlled trial of the effect of nortriptyline in patients with Parkinson’s disease treated with -dopa. Acta Neurol Scand 1980; 62:210—219
 
.
Klaassen T, Verhey FR, Sneijders GH: Treatment of depression in Parkinson’s disease: a meta-analysis. J Neuropsychiatry Clin Neurosci 1995; 7:281—286
 
.
Vaida FJ, Solinas C: Current approaches to management of depression in Parkinson’s disease. J Clin Neurosci 2005; 12:739—743
 
.
Goodman WK, Price LH, Rasmussen SA: The Yale-Brown Obsessive Compulsive scale, part 1: development, use, and reliability. Arch Gen Psychiatry 1989; 46:1006—1011
 
.
Webster DD: Critical analysis of the disability in Parkinson’s disease. Mod Treat 1968; 5:257—282
 
+
+

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