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  Obsessive compulsive symptoms in patients with Schizophrenia onClozapine and with Obsessive Compulsive disorder: A comparison study Mairead Doyle a, ⁎ , Aoife Ni Chorcorain  b , Eleanor Griffith c , Tim Trimble c ,Eadbard O ’ Callaghan d,e,1 a  Cluain Mhuire Mental Health Service, Blackrock, Co. Dublin, Ireland   b South Lee Mental Health Service, Cork University Hospital, Cork, Ireland  c  Department of Psychology, University of Dublin, Trinity College, Dublin 2, Ireland  d  DETECT, Avila House, Block 5, Blackrock Business Park, Blackrock, Co. Dublin, Ireland  e UCD School of Medicine Abstract Obsessive compulsive symptoms are commonly reported in those with schizophrenia. Clozapine has previously been reported to induce,aggravate and alleviate these symptoms. It is unclear if these are similar to the symptoms experienced by those with obsessive compulsivedisorder. This study describes the obsessive compulsive symptom profile of a population of patients with schizophrenia treated withclozapine (n = 62) and compares this with patients with Obsessive Compulsive Disorder (n = 35). All participants were attending anoutpatient community mental health service. The Obsessive Compulsive Inventory (which measures the frequency and associated distress of a range of   “  behavioural ”  and  “ cognitive ”  symptoms), the Hospital Anxiety and Depression Scale and a demographic questionnaire werecompleted. In addition the schizophrenia group treated with clozapine completed the Brief Psychiatric Rating Scale. The OCD group reportedsignificantly more symptoms for all OCI subscales compared to the clozapine group. Overall fourteen (22%) of the schizophrenia treated withclozapine group had clinically significant total OCI scores. Two (3%) had documented OCS pre clozapine. De novo OCS was reported intwelve (19%) cases. Nine (11%) had documented OC symptoms pre-clozapine while only two (3%) had symptoms after clozapine wasinitiated. In terms of OC symptom profile, the clozapine group scored highest on the Doubting scale, a cognitive symptom whereas the OCDgroup scored highest on Washing, a behavioural symptom. Both groups reported greater distress with cognitive rather than behaviouralsymptoms. Medication including clozapine dose was not correlated with symptom severity. Anxiety correlated highly with obsessivecompulsive symptoms in the Clozapine group but not the OCD group. Within the Clozapine group, Obsessing correlated highly withUnusual Thought Content. Findings suggest that obsessive compulsive symptoms in the Clozapine group may reflect a subtype of 'schizo-obsessive' disorder.© 2014 Elsevier Inc. All rights reserved. 1. Introduction A growing literature suggests obsessive compulsivesymptomatology (OCS) may be present in many of thosewith schizophrenia, and that this is associated with higher rates of both positive and negative psychotic symptoms [1,2].The relationship between OCS and schizophrenia is not clear. Studies have distinguished between OCS and co-morbid Obsessive – compulsive Disorder with the latter beingless prevalent, though much higher than the general population. Clinical and epidemiological studies suggest that more than one-third of individuals with schizophreniadisplay OCS, and prevalence rates for OCD have ranged between 7.8% and 40.5%.[3 – 5].Some have argued that the OCS is medication related,with atypical antipsychotics including clozapine [6 – 9].However the literature regarding the relationship betweenOC symptoms and clozapine therapy is contradictory. Onestudy [10] suggested that dosage of Clozapine is animportant factor in the presence of OC symptoms in psychosis, while another claims no such dose effect exists[11]. A recent review article suggested that atypical anti- psychotics may  ‘ unmask  ’  OCS in those that might begenetically predisposed [12]. Growing evidence suggests the  Available online at ScienceDirect  Comprehensive Psychiatry 55 (2014) 130 – ⁎  Corresponding author.  E-mail address: (M. Doyle). 1 Deceased.0010-440X/$  –  see front matter © 2014 Elsevier Inc. All rights reserved.  existence of a  ‘ schizo-obsessive ’  subtype within schizophre-nia [12,13]. However little is known about the symptom profile of this group of patients compared to non-schizophrenia OCS patients. Some research [14,15] hassuggested that certain types of obsessions and underlyingmeta-cognitions, specifically cognitive obsessions, may bemore linked to schizophrenia than OCS in non-psychotic patients. This is some limited evidence to suggest that OCSmay be more covert or cognitive than overt or behavioural innature in a psychotic population [16,17].We hypothesised that the prevalence, nature and severityof the obsessive – compulsive symptom complex in a groupof patients with a diagnosis of schizophrenia on clozapinetreatment would differ qualitatively from those with OCD in particular those with schizophrenia would have morecognitive than behavioural obsessive compulsive symptoms. 2. Methods 2.1. Subjects This is a cross sectional observational study and wascarried out in a suburban community based mental healthserviceinageographicallydefinedcatchmentareaof175,000.A list of patients registered with the clozapine monitoringservice was compiled by cross checking registered patientswith the pharmacy service, a nurse led monitoring clinic andconsultant lists of patients. A total of one hundred and twentythree patients were registered with the clozapine monitoringservice at the time of the study in 2007. On the advice of theEthics Committee who approved the study, patients who were participating in another study were excluded. There were noother exclusion criteria. This reduced the sample size to onehundred and one potential candidates. Patients with schizo- phrenia treated with clozapine were recruited at a clozapineclinic situated on two clinical sites.The comparison group was recruited from patientsreferred to a cognitive behaviour therapy group for obsessivecompulsive disorder. Inclusion criterion was a DSM-IVdiagnosis of OCD based on clinical assessment.All participants gave written informed consent to participation in the study. Exclusion criteria were a diagnosisof Dementia, pervasive developmental delay or participationin a concurrent study. Demographic data relating to age,gender, marital status (dichotomized to single or other),employment status (dichotomized to those receiving a state benefit for a disability or other), housing status (dichoto-mized to independent living or not) were compiled.Information regarding hospitalizations, diagnosis and pre-existing obsessive compulsive symptoms, was obtained from patient electronic and paper records. Information was alsogathered on current medication use from the electronic patient record. Patients ’  records were reviewed to determinewhether obsessive compulsive symptoms were recorded before the introduction of clozapine. Accurate dates wereavailable recording the initiation date of clozapine treatment. 2.2. Instruments All participants also completed the Obsessive CompulsiveInventory: a self-report measure of obsessive compulsivesymptoms [18]. This was developed from the MaudsleyObsessive Compulsive Inventory and includes 7 subscales:Washing, Checking, Ordering, and Hoarding (which are moreovert behavioural symptoms) and Obsessing Doubting andMental Neutralizing (which are more covert cognitivesymptoms). The full scale and most subscales havesatisfactory internal consistency. The alpha coefficients of the full scale for the clozapine and OCD groups were bothhigh (range .86 to .95), indicating that the distress andfrequency items within each subscale converge on a commonconstruct. Total scores were used in the analysis as the cut-off has not been determined for a population with schizophrenia.TheHospitalAnxietyandDepressionScale wascompleted by participants [18]. This is a fourteen item questionnaire,seven for anxiety and seven for depression. It has been foundto have good reliability and showed high internal consistencyin this study ( α  = 0.89 for both subscales).The Brief Psychiatric Rating Scale (BPRS) is a clinicianrated questionnaire [19]. The version used in the present study comprised of 24 items rated from 1 to 7 from  ‘  Not Present  ’  to  ‘ Extremely Severe ’ . Previous research has foundhigh inter-rater reliability ( α  = 0.83.) and this study foundgood internal consistency ( α  = 0.767).Data were analyzed using SPSS version 12 and STATAVersion 10. Power calculations were performed usingGPower  [20]. Means and standard deviations were calculat-ed for continuous data. Numbers and percentages wereobtained for categorical variables [21]. Data were normallydistributed, as assessed by p –  p plots. Uni-variate analyseswere performed using t tests and  χ 22 as appropriate.Bonferroni corrections were used and set the statisticalsignificance at p  b  .002. 3. Results 3.1. Demographics The sample size of eligible candidates for the clozapinestudy was 101 representing 82% of patients prescribedclozapine at the time of the study. 62 patients withschizophrenia treated with clozapine agreed to participate;thisrepresentedaresponseratefortheClozapinegroupof62%and a sample rate of 50% of clozapine population in theservice. The 22 (17% of Clozapine registered patients) whowere not eligible to be included on ethical grounds were participatinginafirstepisodestudy.Atotalof35patientswithOCDwhohadparticipatedinastudyonCBTandOCDagreedtoconsent for datatobeusedinthisstudy which represented a95% response rate. The demographic characteristics of thesampleare reportedinTable1.Age profile was similarinbothgroups. There were significant gender differences with moremen in the Clozapine group and more women in the OCD 131  M. Doyle et al. / Comprehensive Psychiatry 55 (2014) 130  –  136   group. Overall the OCD group appeared to be higher functioning as indicated by higher rates of employment,greater homeownership and fewer hospitalisations. 3.2. Clozapine sample: Within group Analysis The mean clozapine dose was 385 (SD = 140). Nine(11%) had documented OC symptoms pre-clozapine.Overall 14 (23%) of the clozapine group had clinicallysignificant total OCI scores, of those 2 (3%) had documentedOCS pre clozapine and 12 (19%) were new casesdocumented. Seven (11%) appeared to have resolvedsymptoms, 12 (19%) developed new symptoms and 2 (3%)remain unchanged. Neither demographics, medication(neither including clozapine dose or use of SSRI, symptomseverity (as measured by BPRS) nor pre-existing OCS was predictive of OCS in Clozapine group. Clozapine group hadlow psychiatric symptom severity on the BPRS, suggesting psychotic symptoms are well controlled on clozapine. 3.3. Differences between Clozapine and OCD group Fifty eight out of 61 patients (94%) with schizophreniatreated with clozapine reported at least one OC symptom onthe OCI. Thirty four out of 35 patients (97%) in the OCDgroup reported at least one OC symptom. Twenty three per cent of the Clozapine group had clinically significant totalscores on the OCI significantly lower than the rate of 60% inthe OCD group ( χ 22 = 13.58, df = 1, p = .000). The meanscores of the Clozapine and OCD groups on the subscaleitems are shown in Table 2. The OCD group had significantlyhigher anxiety scores (t = -3.4, df = 90, p = 0.001). Therewas no significant difference in antidepressant use betweenthe Clozapine group and the OCD group. 3.4. OC Symptom Profile The OCD group reported significantly more OC symp-toms than the Clozapine group (t = -5.540, df = 64 p =0.000). Mean scores on OCI on Washing, Ordering,Obsessing and Hoarding were significantly higher in theOCD group compared to the Clozapine group based onBonferroni correction. Mean scores in the OCD group wereabove the threshold for clinical significance on all subscales bar Ordering and Neutralising. None of the mean scores inthe Clozapine group reached the clinically significant range.The highest mean score for OC symptoms in the OCD groupwas on the Washing subscale. The highest mean score in theClozapine group was on the Doubting symptom scale. Thedistress associated with OC symptoms was greater in theOCD group compared with the Clozapine group (t = -5.38,df = 64, p = .000). Both groups were more distressed bycognitive than behavioural symptoms (Figs. 1 and 2).Overall, the OCD group reported higher rates of  behavioural OCS. Differences in rates of Checking andHoarding were not significantly different, based on Bonfer-roni correction. However, there were significant differences inrates of Ordering and Washing symptoms, with the OCDgroup reporting much greater frequency of these symptoms.Withregard to cognitive symptoms, there werefewer betweengroup differences with similar mean scores for Doubting and Neutralising subscales. There was a significant difference between groups in rates of Obsessing. The OCD reportedsignificantly higher level compared to the Clozapine group. Table 1Demographics of clozapine (CLZ) and OCD group participants.Variables CLZ n = 62 OCD n = 35 t or   χ 2 Power Age M 38.32 38.94  − .256 ES = .051(1  −  β  prob =0.95)SD 9.6 14.1Gender Male N 42 16 4.51 P  b  .05% 68 46Female N 20 46% 32 54Married N 4 8 7.605% 6.5 22.9 27.43 P  b  .000Employment Status Employed N 10 18% 17 51Disability N 26 0% 45 0 13.24 P  b  .00Housing Status Homeowner N 7 13% 12 37Transitional N 12 1% 20.3 2.9 4.87 P  b  .000Hospitalisations M 7.03 1.06SD 6.6 2.9Clozapine Dose M 385.6SD 140.2 ES = 1.17(1  −  β  prob =0.95)132  M. Doyle et al. / Comprehensive Psychiatry 55 (2014) 130  –  136   3.5. Relationship between OC symptoms and other  psychiatric symptoms In the OCD group, anxiety did not correlate significantlywith any OCI subscales whereas in the Clozapine group,anxiety correlated with Obsessing (r = .640, p = .000) andTotal Frequency r = .500, p = .000). This suggests that anxiety has a possible impact on the presence of OCsymptoms, specifically Obsessing in the Clozapine group.There was no significant relationship between OCI totalfrequency and BPRS total score (r = .356, p = .005). None of the individual BPRS items correlated significantly with TotalOCIscore.TheOCIObsessingsubscalewastheonlysubscalethat correlated strongly with the BPRS total score (r = .535, p = .000).WhentheindividualBPRSitemsandtheObsessingsubscalewereassessedforcorrelationsonlyoneitem,UnusualThought Content was significant (r = .553, p = .000). Thissuggests that the association is specific; there is a highcorrelation between different subscales Unusual Thought Content and Obsessing. When the effect of anxiety wascontrolled for using a partial correlation, the following itemscorrelated significantly with Obsessing subscale: Unusualthoughts remains highly correlated (r = .595, p = .000) andtwo new items: Grandiosity (r = .571, p = .000) and Hallu-cinations(r = .595,p = .000)emergedascorrelatingstrongly.When the potential effect of Clozapine was controlled for using a partial correlation, Unusual Thought Content was theonly variable to correlate significantly with the Obsessingsubscale (r = .635, p = .000). 4. Discussion Overall, the Clozapine group reported significantly lower mean scores on of all OC symptoms compared to the OCDgroup and none of the OC symptoms in the Clozapine Table 2Symptom profile of clozapine and OCD group.CLZ OCD t-test Power HADS Anxiety a  XSD8.75  b 4.6212.18  N 4.55df = 90t =  − 3.435 p = 0.001ES = .74 (1  −  β  prob = 0.95)Depression XSD5.34 b 4.557.61  b 3.91df = 90t =  − 2.403 p = 0.018ES = .53 (1  −  β  prob = 0.95)OCI OCI Wash F a  XSD0.74  b 0.891.97  N 1.67df = 95t =  − 4.724 p = 0.000ES = .92 (1  −  β  prob = 0.95)OCI Wash D a  XSD0.54 b 0.771.65 N 1.30df = 95t =  − 5.314 p = 0.000ES = 1.04 (1  −  β  prob = 0.95)OCI Check F XSD1.12 b 0.871.75 N 1.02df = 61.723  b , t =  − 3.078 p = 0.003 ES = .66 (1  −  β  prob = 0.95)OCI Check D a  XSD0.80 b 0.791.64 N 1.03df = 95 t =  − 3.822 p = 0.000 ES = .92 (1  −  β  prob = 0.95)OCI Doubt F XSD1.30 b 1.141.92 N 1.42df = 95, t =  − 2.362, p = 0.02 ES = .48 (1  −  β  prob = 0.95)OCI Doubt D a  XSD1.01 b 1.021.91 b 1.42df = 95, t =  − 3.628, p = 0.000 ES = .73(1  −  β  prob = 0.95)OCI Order F a  XSD0.86 b 0.861.66 b 1.12df = 57.040  b , t =  − 3.651, p = 0.001 ES = .80 (1  −  β  prob = 0.95)OCI Order D a  XSD0.59 b 0.711.44 b 1.11df = 95, t =  − 4.603, p = 0.000 ES = .91 (1  −  β  prob = 0.95)OCI Obsess F a  XSD1.17 b 0.921.92 N 1.03df = 64.396  b , t =  − 3.582, p = 0.001 ES = .77 (1  −  β  prob = 0.95)OCI Obsess D a  XSD1.11 b 0.931.92 N 0.99df = 67.049, t =  − 3.957, p = 0.000 ES = .84 (1  −  β  prob = 0.95)OCI Hoard F XSD0.93 b 0.921.63 N 1.35df = 95, t =  − 3.031, p = 0.003 ES = .61 (1  −  β  prob = 0.95)OCI Hoard D XSD0.56 b 0.871.25 N 1.30df = 95, t =  − 3.098, p = 0.003 ES = .62 (1  −  β  prob = 0.95)OCI Neut F XSD0.95 b 0.891.32 b 0.94df =  − 1.903  b , t =  − 1.903, p = .061 ES = .40 (1  −  β  prob = 0.95)OCI Neut D a  XSD0.64 b 0.721.20 b 0.95df = 95, t =  − 3.204, p = 0.002 ES = .66 (1  −  β  prob = 0.95)OCI Total F a  XSD41.04 b 30.5971.77 N 29.56df = 64.012  b , t =  − 5.540, p = 0.000 ES = 1.02 (1  −  β  prob = 0.95)OCI Total D a  XSD31.94 b 27.9067.28 N 31.38df = 64, t =  − 5.383, p = 0.000 ES = 1.19 (1  −  β  prob = 0.95) b  below clinical cut off,  N  above clinical cut off. a  Bonfenorri correction sets alpha at .002.  b  Note these subtests had unequal variance based on Levine test for equality of variance.133  M. Doyle et al. / Comprehensive Psychiatry 55 (2014) 130  –  136 
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