Turkish Adaptation, Validity and Reliability Study of the Bush Francis Catatonia Rating and KANNER Scales. / Bush Francis Katatoni Degerlendirme ve KANNER Katatoni Ölçeklerinin Türkçe Uyarlama, Geçerlik ve Güvenirlik Çalismasi.

OBJECTIVE: Catatonia is a common syndrome which can be lifethreatening due to its complications. The aims of the study were to translate the Bush Francis Catatonia Rating Scale (BFCRS) and the KANNER Scale into Turkish, conduct the validity and reliability analyses and to compare the two scales. METHOD: During the study period extending over 20 consecutive months, the Turkish versions of the scales were administered to 84 patients who were hospitalized in the psychiatry ward or who were admitted to the hospitalization list. The clinical and sociodemographic characteristics of all patients were evaluated. The scales were administered to the patients by two raters, one of whom was permanently involved. RESULTS: Convergent and criterion validities revealed a high correlation between the screening instruments of both scales and between the BFCRS total score and 2nd and 3rd part scores of the KANNER Scale. BFCRS total score of ≥6, KANNER Scale 2nd part score of ≥15, or 3rd part score of ≥1 can be used with high accuracy in diagnosing catatonia according to DSM-5. Internal consistency for both scales was found to be high (Cronbach's alpha 0.902 for BFCRS and 0.9, 0.891, 0.806 for KANNER Scale subsections). Inter-rater reliability was also high for most of the scale items (mean Kappa coefficient: 0.885 for BFCRS and 0.904 for KANNER Scale). CONCLUSION: In conclusion, the Turkish adaptations of both scales were found to be valid and reliable, showing strong psychometric properties. This study is the first validity and reliability study for the KANNER Scale.

12 Psychiatrists who Shaped Psychiatry in Turkey in the Republic's First Century. / Cumhuriyetin 100 Yilinda Türkiye'de Psikiyatriyi Sekillendiren 12 Psikiyatr.

Who are the influential figures that molded Turkish Psychiatry into what it is today? This review introduces 12 psychiatrists who shaped psychiatry in Turkey during the first century of the Republic. The article presents Rasit Tahsin, the first neuropsychiatrist who establish an academic psychiatry department in Turkey; Mazhar Osman, who had so much influence that his name became a phrase to describe the mentally ill, and still lives on with the institutions he built; Ihsan Sukru, the founder of neuropathology in Turkey, a historical figure in viral encephalitis research; Fahrettin Kerim Gokay, famous for his political career and his fight against alcohol and tobacco; Rasim Adasal, a Cretian who is a cornerstone in Ankara psychiatry and a well-known figure in Turkish society life; Abdulkadir Ozbek, who introduced psychodrama to Anatolia-his 'earth'; Leyla Zileli, who disseminated psychoanalysis from Ankara to Turkey; Orhan Ozturk, a founding figure for the Journal, the Association, and Hacettepe; Ayhan Songar, a prominent figure in society and also in state bureaucracy; Ozcan Koknel, the amiable face of psychiatry in society and a respected voice; Oguz Arkonaç, a vigorous advocate for the establishment of contemporary psychiatry with DSM III in Bakirköy and then in Turkey; and Gunsel Koptagel-Ilal, who progressed the work in the psychosomatics as one of Turkey's first female psychiatry academics. As with any list, we acknowledge that absolute consensus is not possible; we are preparing a more extensive selection to be published as a book next year. We present our selection to your liking, hoping that one or more of our colleagues reading this article will be included in the selection for the next century, reflecting our collective conscious creation of psychiatry in Turkey. Keywords: Neuropsychiatry, History, Medicine, Turkey, Psychoanalysis, Psychosomatics.

Oral Health Status of Outpatients with Schizophrenia in Ankara, Türkiye: A Descriptive Study. / Ayakta Tedavi Gören Sizofreni Hastalarinin Agiz Sagligi Durumu: Tanimlayici Bir Çalisma (Ankara-Türkiye).

OBJECTIVES: To evaluate the oral health status and denture treatment needs of a group of outpatients with schizophrenia. METHODS: One hundred and eighty-eight patients diagnosed with schizophrenia were evaluated. Socio-demographic characteristics, eating habits, alcohol consumption, smoking status, oral hygiene attitudes, medical status, medications and the data related to dental visit were obtained via structured questionnaire of 45 questions. Medication information were confirmed from hospital records. The DMFT score (the Total of decayed, missing and filled teeth), denture status, Community Periodontal Index of Treatment (CPITN) and attachment loss were recorded in accordance with the criteria defined by the WHO. RESULTS: The mean DMFT score was 11.1±8.6. Total number of teeth decreased, while the number of decayed teeth and DMFT scores increased with age (p<0.001). There was no relationship between the anticholinergic effects of antipsychotics and the teeth count, number of decayed, filled and missing teeth, and the DMFT scores. The CPITN assessment revealed that 71.6% of the patients had healthy periodontium, 7.4% exhibited gingival bleeding upon probing, and 21% had dental calculus. Psychotropic medication and tooth brushing habits were associated with CPITN scores. Male sex was associated with higher frequency of denture need (p<0.001), while no association was observed with the education level and antipsychotic use (p>0.001). CONCLUSION: Physicians and dentists have to work in coordination to maintain good oral health of patients with schizophrenia. Patients should be encouraged for regular dental check-ups and dentist should take utmost care of the oral hygiene maintenance.

Valproate, obesity and other causes of clozapine poor metabolism in the context of rapid titration may explain clozapine-induced myocarditis: A re-analysis of a Turkish case series.

INTRODUCTION: Clozapine-induced myocarditis or any clozapine-induced inflammation may be a hypersensitivity reaction due to titration that was too rapid for the patient's clozapine metabolism. Clozapine metabolism is influenced by ancestry, sex, smoking and the presence of confounders including obesity, infections, and inhibitors (e.g., valproate) causing the patient to behave as a clozapine poor metabolizer (PM). A published study in a Turkish hospital identified 1 case of clozapine-induced pancreatitis and hepatitis and 9 cases of clozapine-induced myocarditis. To explore the hypothesis that the 10 patients were clozapine PMs, their serum clozapine concentrations were investigated using concentration-to-dose (C/D) ratios and their titrations carefully reviewed. METHODS: Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed. RESULTS: All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83mg/day). Nine of the 10 patients may have behaved as clozapine PMs due to obesity and/or valproate co-prescription during titration. One also had an undiagnosed infection. Of the 10 patients, 9 had at least 1 of 3 factors: too-rapid titration in the first or second weeks, or a final dosage that was too high. CONCLUSIONS: Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced inflammation could be explained by lack of individualized titration.

A Severe Neuroleptic Malignant Syndrome Treated with Daily Electroconvulsive Therapy: A Case Report. / Günlük Elektrokonvülzif Terapi ile Tedavi Edilen Siddetli Nöroleptik Malign Sendrom: Bir Olgu Sunumu.

Neuroleptic malignant syndrome (NMS) is a rare but life-threatening condition caused by dopamine modulating medications, particularly antipsychotics. First-line treatments of neuroleptic malignant syndrome are supportive care, discontinuation of the offending agent and pharmacotherapy. In drug-resistant and severe situations, electroconvulsive therapy (ECT) is recommended as well. In this paper we present a 23-year old male with bipolar disorder who was treated with multiple injections of zuclopenthixol long acting and depot forms for a recent manic episode and developed NMS. The patient was transferred to an intensive care unit, medical management was initiated including benzodiazepines, bromocriptine and dantrolene. Due to the inadequate response after several days, ECT (bitemporal electrode placement, briefpulse, on a daily basis) was initiated. After 17 sessions, NMS relieved and there was no need for maintenance ECT. The patient is under follow-up care for 3 years with no cognitive and physical sequela. Keywords: Electroconvulsive therapy, neuroleptic malignant syndrome, bipolar disorder.

Renal effects of long-term lithium therapy, revisited.

OBJECTIVE: The aim of this study was to investigate the effect of lithium treatment on renal function and to determine influencing factors. In addition, the utility of spot urine protein/creatinine ratio in detection of lithium induced nephropathy was also investigated. METHODS: Serum concentrations of lithium, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), and urinalysis including protein/creatinine ratio were measured in 375 patients using lithium. RESULTS: Patients taking lithium for ≥8 years had higher BUN, creatinine levels, percentage of proteinuria, percentages of stage 2 and 3 chronic kidney disease (CKD); lower urine density and eGFR compared to patients taking lithium <8 years. Urine density was lower in groups with >0.8 and 0.6-0.8 mmol/L lithium level than <0.6 mmol/L. Predictors of CKD were serum level of lithium, dose of lithium, cumulative duration of lithium use, age at onset of illness, and caffeine consumption. CONCLUSIONS: Detrimental effects of lithium on renal functions were detected after lithium use for ≥8 years. Proteinuria measured by spot urine protein/creatinine ratio can be detected even when eGFR is >90 ml/min/1.73 m2 . Spot urine protein/creatinine ratio, which is a cost-effective and practical laboratory test, can be used to monitor lithium-treated patients.

Spectral Analysis of Lithium Tremor.

INTRODUCTION: Lithium has proven efficacy in bipolar affective disorder (BAD) but induces tremor as a side effect in a quarter of patients. Lithium tremor (LT) shares some clinical characteristics of essential tremor (ET) and Parkinson's disease tremor (PT), which might cause difficulties in differential diagnosis. Furthermore, current knowledge of LT is lacking detailed electrophysiological characterization. Here, we present detailed spectral attributes of accelerometric tremor recordings as a diagnostic tool for LT. METHODS: 10 patients (7 males, 3 females) between ages of 29-68, who were on lithium for BAD for 2-12 years, were evaluated for hand tremor with the spectral analysis of accelerometric recordings with different postures. Tremor severity was rated clinically on WHIGET (Washington Heights-Inwood Genetic Study of Essential Tremor) scale. Results were analyzed in comparison to results of ET (n=19) and PT (n=19) patients from our database. RESULTS: LT was most prominent at extensor postures with an average peak frequency (PF) of 8.0±0.3 Hz and an extremely low amplitude, high harmonic components and high noise level. The average PF of LT was similar to that of ET (7.3±0.4 Hz), but higher than that of PT (5.3±0.2 Hz) (p<0.0001). With weight loading, the PF of LT showed an increase of 1.3 Hz. Average amplitude of PT was higher than that of both LT and ET (p<0.0001); harmonic components of LT was comparable to PT whereas noise levels were similar to that of ET. Mean WHIGET score of LT (6.5±0.5) was significantly lower than that of ET (13.1±1) (p<0.0001). CONCLUSION: Electrophysiological features detected by accelerometry may help in differential diagnosis of LT from ET and PT.

Atypical Neuroleptic Malignant Syndrome Induced by Low Dose Quetiapine in a Patient Treated with Donepezil.

Neuroleptic malignant syndrome is a rare idiosyncratic drug reaction that causes morbidity and mortality. Although muscle rigidity and fever are accepted as major symptoms, there is no consensus on the diagnostic criteria. This flexibility in diagnostic criteria allows for the diagnosis of atypical cases. Keeping in mind that neuroleptic malignant syndrome may also occur with the use of low doses of atypical antipsychotics is important for making the diagnosis quickly and reducing the risk of morbidity and mortality. In this report, we aim to present a case with atypical neuroleptic malignant syndrome associated with the use of very low dose quetiapine and discuss the risk factors that facilitate its emergence.

The cognitive aspect of formal thought disorder and its relationship with global social functioning and the quality of life in schizophrenia.

PURPOSE: It was expected that using a comprehensive scale like the Thought and Language Disorder Scale (TALD) for measurement of FTD would enable assessing its heterogeneity and its associations with cognitive impairment and functionality. This study has aimed to analyze the relationship between formal thought disorder (FTD) and cognitive functions, functionality, and quality of life in schizophrenia. METHODS: This cross-sectional exploratory study included 46 clinical participants meeting the DSM-5 diagnostic criteria for schizophrenia and 35 healthy individuals as the control groups. Data were acquired by means of the Turkish language version of the TALD, the Positive and Negative Syndrome Scale, the Clinical Global Impression Scale, the Functioning Assessment Short Test, the Social Functioning Scale, the World Health Organization Quality of Life Instrument-Short Form, and a neuropsychological test battery on executive functions, working memory, verbal fluency, abstract thinking, and response inhibition. Correlation analyses were conducted to detect significant relationships. RESULTS: The clinical group scored failures in all cognitive tests. The objective positive FTD was associated with deficits in executive functions and social functioning. The objective negative FTD was associated with poor performance in all cognitive domains, physical quality of life, and social and global functioning. The subjective negative FTD was negatively correlated with psychological quality of life. CONCLUSION: This study demonstrated that objective FTD factors reflect different underlying cognitive deficits and correlate with different functioning domains. Significant correlation was determined between subjective negative FTD and psychological quality of life. Given the close relationship of FTD with functioning and quality of life, the FTD-related cognitive deficits should be the key treatment goal in schizophrenia.

Bi-temporal electroconvulsive therapy efficacy in bipolar and unipolar depression: A retrospective comparison.

AIM: Although electroconvulsive therapy (ECT) has been extensively used for depressive episodes in bipolar disorder (BDD), it has received less interest in research compared with major depressive disorder (MDD). Studies comparing the efficacy of ECT in BDD and MDD have been contradictory. This study aimed to compare the effectiveness of ECT in BDD and MDD, analyzing the influence of clinical features on outcome. METHODS: The medical charts and electronic records of 107 patients (MDDn = 75 [70.1 %], BDD n = 32 [29.9 %]) receiving bi-temporal ECT were investigated retrospectively. Features of the index episode, such as the time elapsed until ECT and the effect of diagnosis on efficacy evaluated by the Hamilton Depression Rating Scale (HAM-D), were analyzed. RESULTS: The diagnostic groups were alike concerning clinical features of the index episode, such as the presence of psychotic symptoms and suicidality. Patient age and the number of previous affective episodes were significantly different between the groups. The time elapsed until ECT in the examined episode was significantly longer in the MDD group. Compared with the MDD group, the BDD group had a significantly higher remission rate with ECT. Regression analysis revealed that BDD diagnosis, older age, and shorter time until ECT were significantly associated with remission. CONCLUSION: The significant relationship observed between greater time elapsed until ECT and worse outcome is noteworthy in terms of clinical practice. This finding further challenges the widely accepted place of ECT as the "last resort" for the treatment of depression in bipolar and unipolar affective disorders.

Effect of Clozapine on Proton Magnetic Resonance Spectroscopy Findings in Hippocampus. / Klozapinin Hipokampusta Proton Manyetik Rezonans Spektroskopi Bulgulari Üzerine Etkisi.

OBJECTIVE: The purpose of this study was to investigate the effect of clozapine on proton magnetic resonance spectroscopy (1H-MRS) findings in hippocampus in patients with schizophrenia. In addition, the relationship between the change in 1H-MRS findings and the change in psychopathology and neurocognitive functions was evaluated. METHOD: Patients with schizophrenia (n=16) were assessed with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), a neurocognitive test battery and 1H-MRS at baseline, and twelve weeks after the initiation of clozapine. Healthy controls (n=8) were assessed once with a neurocognitive test battery and 1H-MRS. Bilateral multivoxel and left single voxel NAA/Cr, Cho/Cr, MI/Cr was calculated in the hippocampi. RESULTS: After 12 weeks of clozapine treatment, PANSS and CGI scores decreased; immediate recall, cumulative learning subtests of the Rey Auditory Verbal Learning Test, Category Verbal Fluency Test and Wechsler Memory Scale's visual reproduction delayed subtest scores increased significantly. Compared with healthy controls and patients after clozapine, hippocampi multivoxel and single voxel NAA/Cr, Cho/ Cr, MI/Cr ratios were not different in patients before clozapine. No significant correlations between change in 1H-MRS metabolite ratios and change in psychopathology, neurocognitive functions were detected. CONCLUSION: This study is the first longitudinal study to investigate the effect of clozapine in hippocampus with 1H-MRS. There were no significant changes in 1H-MRS findings in hippocampi after twelve weeks of clozapine treatment. Clozapine's effect in hippocampus should be investigated further in longer follow up studies with larger samples to reach a final conclusion.

Weight Loss Associated with Clozapine: A Case Report. / Klozapin Kullanimina Bagli Kilo Kaybi: Vaka Sunumu.

Clozapine is one of the second generation antipsychotics most commonly associated with serious metabolic side effects including weight gain. Unexpectedly, weight loss can also be seen as a rare side effect of clozapine. The mechanism underlying clozapine induced weight loss is not clearly understood. Several factors including certain brain areas, neurotransmitters, neuropeptides and genetic variants were identified to play a role in weight loss associated with clozapine. In some patients who were reported to have a significant weight loss (13.5-50% of body weight) with clozapine, weight loss might not be associated with any underlying physical disorder. Weight loss may be due to the patients' engagement in diet and exercise after clinical improvement, pharmacodynamic effects of clozapine, or other medical problems such as gastrointestinal tract hypomotility caused by clozapine. Some case reports suggested that clozapine-associated weight loss might be a sign of poor response to clozapine. Clinicians should keep in mind the fact that a specific group of patients may lose weight during clozapine treatment. In this case report, possible causes of weight loss due to clozapine use is discussed. We also discussed the possible relationship between clozapine dose and weight loss which has not drawn attention in previous case reports.

A follow-up study of metabolic syndrome in schizophrenia.

The prevalence of metabolic syndrome (MetS) in schizophrenia patients is increasing worldwide. The aim of the current study was to examine the progress of MetS in a schizophrenia cohort we had previously investigated and determine the role of various related factors, including sociodemographic and clinical variables, nutritional status and physical activity. Of the 319 patients investigated in the first study, 149 patients agreed to be included in the follow-up. Physical measurements and laboratory tests were performed in addition to evaluations with the Positive and Negative Syndrome Scale, Udvalg for Kliniske Undersogelser Side Effects Scale, International Physical Activity Questionnaire, 24 h dietary recall method and Nutrition Information Systems Package Program. According to the ATPIII, ATPIIIA and IDF criteria, the MetS prevalences had increased from 35.6 to 44.3%, 38.9 to 53% and 43.6 to 55.7%, respectively. Patients with MetS had a shorter period of hospitalization and a higher UKU total side effects score, and most of them were married or divorced/widowed. Patients with MetS also had a higher daily consumption of added sugar, cholesterol, polyunsaturated fatty acids and omega 3 fatty acid, and the daily added sugar intake was found to be related to the increase in MetS. Unexpectedly, the physical activity level was not found to significantly differ in the patients with and without MetS. In conclusion, the MetS prevalence was found to be increased among schizophrenia patients over time, and the increase in the young age group was particularly striking. Among all of the factors investigated, nutritional status was found to play a major role in this increased prevalence.

A comparative study of detection of myocarditis induced by clozapine: With and without cardiac monitoring.

The aim of this study was to investigate and compare the incidence of suspected or definite cases of clozapine induced myocarditis (SDM) and clinical factors which could influence its onset in two different time periods, defined by pre- and post-cardiac monitoring at an inpatient setting, during the initiation phase of clozapine treatment. Hospital records of patients started on clozapine in the inpatient unit between 2011 and 2018 were investigated. Eight in 38 patients (11.3%) were classified as SDM after the initiation of the monitoring protocol, whereas only 1 in 33 patients (1.4%) was classified as SDM, before. Monitored and non-monitored patient groups were similar with regard to demographic and clinical variables. Diagnosis of schizoaffective disorder and use of concominant lithium, valproic acid and atypical antipsychotics were higher in patients with SDM, while clozapine dose titration was similar compared to the rest of the patients. Cardiac monitoring seems to be the main factor leading to the increase in the detection of clozapine induced myocarditis (CIM). If not monitored, the outcome of CIM can be fatal without any warning signs and symptoms. Concominant use of mood stabilizers including valproic acid and lithium, are important risk factors for the development of CIM.

Examination of formal thought disorder and its clinical correlates with the Turkish Version of the Thought and Language Disorder Scale (TALD-TR) in schizophrenia.

BACKGROUND: Formal thought disorder (FTD) is considered to be a fundamental feature of schizophrenia. This study aims to analyze psychometric properties of the Turkish version of "Thought and Language Disorder Scale (TALD)" and investigate the relationship between FTD and various clinical characteristics in patients with schizophrenia. METHODS: TALD was adapted into Turkish and applied to a total of 149 participants of which 114 had DSM-5 psychiatric diagnoses (schizophrenia N = 70, mania N = 20, depression N = 24) and 35 were healthy controls. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impression were administered to detect illness severity. RESULTS: The principal component analyses revealed that the Turkish version of TALD (TALD-TR) consisted of four factors including the Objective Positive (OP), Subjective Negative (SN), Objective Negative (ON) and Subjective Positive (SP) symptom dimensions which were in line with the original TALD factorial structure. It was concluded that TALD-TR shows strong construct validity and high interrater reliability. The correlation analyses with TALD-TR and PANSS showed that there are positive correlations between the TALD-TR total score and the PANSS total and subscale scores. Each diagnostic group showed the distinct pattern of FTD. The mania group exhibited the highest mean total score in the OP, whereas the schizophrenia group exhibited the highest mean total score in the ON factor. In the schizophrenia group, the severity of FTD correlated positively with duration of illness and negatively with age at onset of illness. CONCLUSION: Adaptation of TALD into different languages seems to be possible, bringing in an international tool for research on FTD.

Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine.

Clozapine use is associated with leukopenia and more rarely agranulocytosis, which may be lethal. The drug and its metabolites are proposed to interact with the multidrug resistance transporter (ABCB1/MDR1) gene product, P-glycoprotein (P-gp). Among various P-glycoprotein genetic polymorphisms, nucleotide changes in exons 26 (C3435T), 21 (G2677T), and 12 (C1236T) have been implicated for changes in pharmacokinetics and pharmacodynamics of many substrate drugs. In this study, we aimed to investigate the association between these specific ABCB1 polymorphisms and clozapine-associated agranulocytosis (CAA). Ten patients with a history of CAA and 91 control patients without a history of CAA, despite 10 years of continuous clozapine use, were included. Patient recruitment and blood sample collection were conducted at the Hacettepe University Faculty of Medicine, Department of Psychiatry, in collaboration with the members of the Schizophrenia and Other Psychotic Disorders Section of the Psychiatric Association of Turkey, working in various psychiatry clinics. After DNA extraction from peripheral blood lymphocytes, genotyping was performed using polymerase chain reaction and endonuclease digestion. Patients with CAA had shorter duration of clozapine use but did not show any significant difference in other clinical, sociodemographic characteristics and in genotypic or allelic distributions of ABCB1 variants and haplotypes compared with control patients. Among the 10 patients with CAA, none carried the ABCB1 all-variant haplotype (TT-TT-TT), whereas the frequency of this haplotype was approximately 12% among the controls. Larger sample size studies and thorough genetic analyses may reveal both genetic risk and protective factors for this serious adverse event.

Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment.

BACKGROUND: Several placebo controlled studies investigating lamotrigine augmentation of clozapine in schizophrenia patients with partial response have shown varying results. The aim of this study was to further investigate the efficacy and safety of this augmentation strategy, and its effect on the glutamatergic system through utilizing mismatch negativity (MMN) component of auditory event related potentials. METHODS: The study was designed to evaluate the efficacy and safety of lamotrigine augmentation of clozapine in a 12-week, double-blind, placebo-controlled, prospective, randomized design. Thirty-four patients diagnosed according to DSM-IV schizophrenia criteria and with partial response to clozapine were included. Patients were randomized to 25mg/day of lamotrigine or placebo, gradually increasing up to 200mg/day on the 6th week. The change in psychopathology was assessed with Positive and Negative Syndrome (PANSS), Calgary Depression (CDS) and Clinical Global Impression-Severity (CGI-S) scales. A neuropsychological test battery was administered and MMN measurements were also obtained at baseline and endpoint. Safety evaluation included physical examination, UKU Side Effect Rating Scale (UKU) assessment and serum drug level measurements. RESULTS: No significant differences were found between the two treatment groups in PANSS Positive and General Psychopathology, CDS, neurocognitive test and UKU scores, as well as MMN measurements. PANSS Total, Negative and CGI-S scores showed significant improvement compared to lamotrigine in the placebo group. CONCLUSION: This study did not show any benefit of augmentation of clozapine with lamotrigine in schizophrenia patients with partial response. The need for further investigation of other augmentation strategies of clozapine in partially responsive schizophrenia patients is evident.

A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.

BACKGROUND: Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy. METHOD: This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003. RESULTS: Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group. CONCLUSION: Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.