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Obsessive-Compulsive Symptoms in Schizophrenia: Treatment Challenges

Obsessive-compulsive symptoms (OCS) are highly prevalent in schizophrenia, estimated to be present in 14% of schizophrenic patients.1 Optimal treatment options for those patients are yet to be agreed upon, perhaps because mechanisms underlying the interface between both diseases are poorly understood.2 Recent studies have focused on distinguishing the order of development of schizophrenia and obsessivecompulsive disorder in patients with both conditions in an effort to elucidate a response to treatment.3 It has been suggested that OCS leads to severe impairment in functioning that might diminish the quality of life. Here we report two cases: both patients had obsessive-compulsive symptoms, however, they developed at different stages of the illness. Using these cases we present a brief literature review of the treatment challenge of obsessive-compulsive symptoms in schizophrenia. Case 1 “Ms. P,” a 55-year-old female diagnosed with chronic paranoid schizophrenia, had her first psychotic decompensation at age 21. The initial symptoms were disorganized thoughts, paranoia, agitation, and bizarre behavior. She was stable for years on haloperidol 10 mg orally daily. In her mid-40’s she developed contamination obsessions and washing compulsions. The obsessive and compulsive behaviors began more than 20 years after the onset of schizophrenic symptoms. Ms. P. reported intrusive thoughts about

being dirty or coming into contact with viruses or other germs; she washed her hands repeatedly until the soap was gone and her hands were chapped and bleeding. She described these thoughts as being her own and recognized them to be “irrational,” but she could not resist them. Biochemical investigations and brain CT scan were unremarkable. Ms. P. was unsuccessfully treated with a wide range of antipsychotics (haloperidol was titrated to 20 mg orally daily, risperidone titrated up to 8 mg per day, quetiapine titrated up to 800 mg daily), antidepressants (fluvoxamine and clomipramine included), in addition to a variety of adjunctive medications. Ms. P. was started on clozapine treatment due to failure of multiple neuroleptics. During the first week of clozapine treatment Ms. P. experienced a marked exacerbation of her obsessive and compulsive symptoms. The discontinuation of clozapine resulted in reductions of those behaviors. Ms. P. was ultimately treated with a combination of olanzapine 30 mg daily and fluoxetine 80 mg daily, which resulted in a near complete symptomatic remission of OCS and improvement of psychosis. Case 2 Mr. C., a 40-year-old male with history of OCD characterized by doing certain things in order, picking at his face, and taking excessively long showers, was managed since the age of 21 with cognitivebehavioral therapy, clonazepam 2 mg orally twice a day, and fluvoxamine 150 mg orally twice a day. In the following years Mr. C. developed anxiety and paranoia about people following him and videotapping his whereabouts. He became isolated and withdrawn, was unable to care

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for himself, and hence hospitalized. He was diagnosed with schizophrenia and treated with risperidone titrated up to 3 mg orally twice a day. His paranoia continued and so did his OCS, which were incapacitating and preventing him from functioning in the community. Due to limited response to risperidone it was crosstapered with seroquel. The medication change led to improved paranoid symptoms; however, persistent rumination of thoughts with compulsive behaviors limited his functioning even after discharge from the hospital. Throughout his stay he remained resistant to selective serotonin reuptake (SSRI) trial. Discussion As shown in these case vignettes, the treatment of patients with comorbid schizophrenia and obsessivecompulsive disorder can be challenging and difficult to predict as their clinical presentations and treatment responses may vary widely. In 2008, Devulapalli and colleagues4 reported in a meta-analysis of 148 patients with comorbid schizophrenia and obsessive-compulsive disorder. Forty-eight percent developed OCS and were diagnosed with obsessive-compulsive disorder (OCD) first, 30.4% developed schizophrenia first, and 21.6% were diagnosed with both concurrently. In their analysis of the four studies that reported mean age of onset, OCS age (19.8) was lower than that of schizophrenia (22.4), although the small sample size (45) prevented statistical significance from being reached. In a slightly larger study,5 the age of onset of OCS was significantly younger than schizophrenia in subjects with comorbid schizophrenia and obsessivecompulsive disorder (18.5 versus

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LETTERS 22.0). Both of our cases represent different stages of onset of OCS, one prior to onset of schizophrenia and the other after the onset. In 2012, Faragian and colleagues3 reported that in 133 patients with comorbid schizophrenia and obsessivecompulsive disorder, the mean age of onset of psychotic symptoms was 20.4 while the mean age of onset of obsessions or compulsions was 19.1 (p,0.05). When these authors then examined 52 first-episode schizophrenics, they found that clinically significant OCS had been present for approximately 3 years before the schizophrenic symptoms.3 Because so many develop OCS and are diagnosed with OCD before developing schizophrenia, some have suggested that this may indeed be a prodromal-like stage of schizophrenia.4 In one study of 475 OCD probands, 14% had or developed psychosis, and 4% eventually met the full criteria for schizophrenia.5 Problems have arisen in attempting to pharmacologically treat patients with comorbid schizophrenia and obsessive-compulsive disorder, as some studies demonstrate agents as therapeutic while other studies show those same agents exacerbating symptoms.3 For example, the standard of care for OCD typically entails first using an SSRI (fluvoxamine) or a tricyclic antidepressant (clomipramine). However, in some patients with comorbid schizophrenia and obsessive-compulsive disorder (typically those with a history of impulsivity or aggressiveness), there is a worsening of psychosis with the administration of SSRIs or clomipramine.6 In 2000, Reznik and Sirota7 evaluated the efficacy of a combination treatment of an SSRI (fluvoxamine) and standard neuroleptics for the treatment of obsessive-compulsive symptomatology in patients with schizophrenia compared with administration of neuroleptics only.

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The study showed that coadministration of fluvoxamine, an SSRI, and neuroleptics in patients with schizophrenia and obsessivecompulsive symptoms was associated with specific improvements of these symptoms (reduction in Positive and Negative Syndrome Scale 34.3% and Yale-Brown Obsessive Compulsive Scale 29.4% scores). Puyorovsky and colleagues1,8 published an algorithm as a guide for treating patients with comorbid schizophrenia and obsessivecompulsive disorder. The algorithm relies on starting with an atypical antipsychotic (i.e., olanzapine) and then adding an SSRI or clomipramine once psychosis is stabilized. If there is no response, then it is proposed that the following are tried, in order: a typical antipsychotic1SSRI (fluvoxamine) or clomipramine; low dose of clozapine; clozapine1SSRI (sertraline or citalopram); or finally, if all else fails, electroconvulsive therapy (ECT).9,10 Tundo et al. conducted an open naturalistic study to examine the adherence to and the effectiveness of adjunctive cognitive-behavioral therapy (CBT) for patients with schizophrenia and obsessivecompulsive symptoms. Subjects who participated in the study had good adherence to CBT, showed reduction of OCD symptoms, and improvement of insight into their illness.11 Despite published reports, there is no clear consensus as to what treatment is proven effective in patients with both schizophrenia and OCS, respectively. It is unclear whether the onset of symptoms of OCS in relation to the illness would impact the management. In addition, Sevincok and colleagues12 reported that patient with schizophrenia and OCS had a high risk of suicidal attempts and ideations, thus indicating that as OCS increases so does the danger to self.

Whether OCS symptoms arise during the premorbid phase or exist as a comorbid condition they pose a clinical challenge and treatment dilemma. Longitudinal studies are needed to explore whether changes in the level of obsessions and compulsions are similar to remission and exacerbations of psychosis. Future research is needed to focus on developing psychopharmacological and psychological interventions to address the combined symptoms of OCS in schizophrenia. Nabil Kotbi, M.D. Matthew Goodwin, M.D., Ph.D. Dimitry Francois, M.D. Smita Agarkar, M.D. Weill Cornell Medical College, New York. Send correspondence to Smita Agarkar, M.D.; e-mail: [email protected] References 1. Poyurovsky M, Fuchs C, Weizman A: Obsessive-compulsive disorder in patients with first-episode schizophrenia. Am J Psychiatry 1999; 156:1998–2000 2. Poyurovsky M, Koran LM: Obsessivecompulsive disorder (OCD) with schizotypy vs. schizophrenia with OCD: diagnostic dilemmas and therapeutic implications. J Psychiatr Res 2005; 39: 399–408 3. Faragian S, Fuchs C, Pashinian A, et al: Age-of-onset of schizophrenic and obsessive-compulsive symptoms in patients with schizo-obsessive disorder. Psychiatry Res 2012; 197:19–22 4. Devulapalli KK, Welge JA, Nasrallah HA: Temporal sequence of clinical manifestation in schizophrenia with comorbid OCD: review and meta-analysis. Psychiatry Res 2008; 161:105–108 5. Eisen JL, Rasmussen SA: Obsessivecompulsive disorder with psychotic features. J Clin Psychiatry 1993; 54: 373–379 6. Seedat F, Roos JL, Pretorius HW, et al: Prevalence and clinical characteristics of obsessive-compulsive disorder and obsessive-compulsive symptoms in Afrikaner schizophrenia and schizoaffective

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LETTERS disorder patients. Afr J Psychiatry (Johannesbg) 2007; 10:219–224 7. Reznik I, Sirota P: Obsessive and compulsive symptoms in schizophrenia: a randomized controlled trial with fluvoxamine and neuroleptics. J Clin Psychopharmacol 2000; 20: 410–416 8. Poyurovsky M, Weizman A, Weizman R: Obsessive-compulsive disorder in

schizophrenia: clinical characteristics and treatment. CNS Drugs 2004; 18:989–1010 9. Lysaker PH, Whitney KA: Obsessive compulsive symptoms in schizophrenia: prevalence, correlates and treatment. Expert Rev Neurother 2009; 9:99–107 10. Lavin MR, Halligan P: ECT for comorbid obsessive-compulsive disorder and schizophrenia. Am J Psychiatry 1996; 153:1652–1653

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11. Tundo A, Salvati L, Di Spigno D, et al: Cognitive-behavioral therapy for obsessive-compulsive disorder as a comorbidity with schizophrenia or schizoaffective disorder. Psychother Psychosom 2012; 81:58–60 12. Sevincok L, Akoglu A, Kokcu F: Suicidality in schizophrenic patients with and without obsessive-compulsive disorder. Schizophr Res 2007; 90(1–3):198–202

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Obsessive-compulsive symptoms in schizophrenia: treatment challenges.

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