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P.3.11 Cognitive function and psychomotor performance in schizophrenic patients
Clinical Neuropsychopharmacology sition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000; 59: S5-S30. [2] Akiskal HS, Hantouche EG, Allilaire JF, et al. Validating antidepressant-associated hypomania (bipolar III): a systematic comparison with spontaneous hypomania (bipolar II). J Affect Disord 2003; 73: 65–74. [3] Henry C, Van den Bulke D, Bellivier F, et al. Anxiety disorders in 318 bipolar patients: prevalence and impact on illness severity and response to mood stabilizers. J Clin Psychiatry 2003; 64: 331–335.
P.3.10 Combination treatment for panic disorder: a prospective study C. Bergesio, U. Albert, G. Maina, F. Bogetto. Department of Neurosciences, Anxiety and Mood Disorders Unit, University of Turin, Torino, Italy
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of panic attacks: 7.3 weeks vs. 9.9 weeks; p<0.05). The drop-out rate was lower in the combination group (7.5% vs. 15.4%). At the end of the follow-up period, 42.5% of patients in the original combination group were still taking a benzodiazepine, although only two subjects showed benzodiazepine abuse. Two additional patients in the other group fulfilled criteria for benzodiazepine abuse during the follow-up period. Conclusions: Even though combination treatment does not result in greater efficacy, it represents a safe and clinically useful strategy to treat PD resulting in more rapid symptoms relief. The prescription of benzodiazepines could be related with difficulty during the discontinuation phase but it does not increase the risk of abuse and dependence. A longer follow-up should be done to evaluate more appropriately the cost/benefit ratio of a combined treatment strategy. References
Introduction: A combination strategy (SSRIs and benzodiazepines) for Panic Disorder (PD) seems to be a common clinical practice and is even indicated by international practice guidelines. Previous controlled studies have documented that this strategy results in a more rapid response but not in a greater efficacy. In addition, benzodiazepine dosage proved difficult to taper, at least according to some studies, with an increased risk of abuse/dependence. However, it remains controversial whether this strategy should be suggested for all patients or restricted to subjects with a need of a rapid relief of anxiety symptoms. The purpose of this study was to test the efficacy and the response latency of the early coadministration of alprazolam with SSRIs in the treatment of PD. The second aim of the study was to evaluate the proportion of subjects who showed any signs of BDZ abuse/dependence during a follow-up period of six months. Material and methods: 79 DSM-IV PD outpatients were randomly assigned to treatment with either monotherapy (SSRIs) or combined therapy (SSRIs + alprazolam). In the second group, according to Practice Guidelines indications, clinicians tried to taper alprazolam gradually to cessation since the 5th week of treatment. A statistical comparison between the two groups was performed for response latency and efficacy at the endpoint of acute treatment (12 weeks). Moreover, the proportion of patients still taking benzodiazepines or with a diagnosis of abuse/dependence after a period of adjunctive 6 months was recorded. Results: The proportion of responders (no panic attacks at the end of the acute treatment) was similar in both groups (76.9% vs. 75%) but the combination strategy resulted in a more rapid response (time to remission
[1] American Psychiatric Association. Practice Guidelines for the Treatment of Patients with Panic Disorder. American Psychiatric Association, Washington, DC, 1998. [2] Goddard AW, Brouette T, Almai et al. Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry 2001; 58: 681– 686. [3] Simon NM, Safren SA, Otto MW et al. Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder. J Affect Disord 2002; 69: 202–208. P.3.11 Cognitive function and psychomotor performance in schizophrenic patients S. Borgwardt1 , L. Franke2 , R. Uebelhack2 . Psychiatric Outpatient Department, Kantonsspital Basel, Petersgraben 4, CH-4031 Basel, Switzerland; 2 Department of Psychiatry, Humboldt-University Berlin (Charit´e), Germany 1
Background: The cognitive deficits of schizophrenia might represent a separate domain of the illness that is relatively independent of psychotic symptoms (Green et al. 2000). According to the literature, the effects of conventinal neuroleptics on cognitive impairment are generally negligible, whereas the situation with newer antipsychotic medications seems to be more promising (Meltzer and McGurk, 1999). Aim of the study: The aim of the present study was to investigate the effects of typical (haloperidol, flupentixol, fluphenazine) and atypical neuroleptics (clozapine, olanzapine, risperidone) on several cognitive and performance
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tasks in schizophrenic patients in comparison to drug-free patients and healthy subjects. Based on the assumption that dosage, namely of conventinal neuroleptics, may influence the results, we additionally analysed the dependence of performance of treated patients on dosage expressed in CPZ equivalents. Methods: The performance of the subjects were evaluated by a comprehensive battery of psychometric tests in healthy subjects (n=51) and hospitalized schizophrenic patients before (n=18) and at week 8–11 (n=26) of treatment. A modified version of a neuropsychological test battery, already validated in patients with epilepsy and depression, was used to cover executive functions, perseveration, memory, attention, concentration, and motor abilities. Due to the small sizes of our samples, only nonparametric tests for data analysis were used: MannWhitney U test and Spearman’s rank-order correlation coefficients. Results: Healthy subjects showed significantly better results than the whole sample of schizophrenic patients in almost all cognitive domains. However, between the three groups of drug-free patients, and patients with conventional or atypical neuroleptics, there were differences in specific cognitive functions. In average, less deficites in executive functions and perseveration was found in patients treated with atypical neuroleptics. The extent of impairments in some cognitive domains was dose depending only in patients treated with typical neuroleptics. High correlation coefficients were found for the tendency to perseveration (n=14, r= −0.89, p<0.001). Conclusion: The results confirm the previous findings of a generalized cognitive deficit in patients with schizophrenia (Bilder et al., 2000). It is concluded that the disruptive effects of typical neuroleptics on some cognitive function and psychomotor performance are dosedepending and that atypical neuroleptics had little or no effect on performance at the used dosage in comparison to drug-free schizophrenic patients. Atypical antipsychotics may be more acceptable in higher dosage treatment of schizophrenia. Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from atypical antipsychotic drugs. References [1] Bilder RM, Goldman RS, Robinson D, Reiter G, Bell L, Bates JA, Pappadopulos E, Wilson DF, Alvir JMJ, Woerner MG, Geisler S, Kane JM, Lieberman JA (2000) Neuropsychology of firstepisode schizophrenia: Initial characterization and clinical correlates. American Journal of Psychiatry 157:549–559. [2] Green MF, Marder SR, Glynn SM, McGurk SR, Wirshing WC, Wirshing DA, Liberman RP, Mintz J
(2002) The Neurocognitive Effects of Low-Dose Haloperidol: A Two-Year Comparison with Risperidone. Biological Psychiatry 51:972–978. [3] Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophrenia Bulletin 25:233–255.
P.3.12 Abnormalities of corpus callosum in schizophrenia: a diffusion-weighted MRI study P. Brambilla1 , R. Cerini2 , A. Gasparini2 , M. Nos`e1 , E. Vittorini2 , C. Barbui1 , A. Versace1 , N. Andreone1 , A. David3 , M.S. Keshavan4 , C. Procacci2 , M. Tansella1 . 1 Department of Medicine and Public Health, Section of Psychiatry, University of Verona, Italy; 2 Department of Morphological and Biomedical Sciences, Section of Radiology, University of Verona, Italy; 3 Section of Cognitive Neuropsychiatry, Institute of Psychiatry and GKT School of Medicine, London, UK; 4 Western Psychiatry Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Introduction: Corpus callosum is the main white matter commissure between the two cerebral hemispheres, connecting homologous areas. Recently, abnormalities in mean diffusivity for splenium of corpus callosum have been reported in schizophrenia by two diffusion tensor imaging (DTI) reports (Agartz et al., 2001; Foong et al., 2000). Consistently, abnormally small splenium size has been shown in childhood-onset schizophrenia in a longitudinal MRI study (Keller et al., 2003). Therefore, corpus callosum may play a key role in the in the structural brain anatomy and pathophysiology of schizophrenia. Diffusion weighted imaging (DWI) is a relatively new MRI technique capable of examining molecular water mobility in brain tissue (e.g. white matter tracts), detecting subtle abnormalities of anatomical structures that cannot be visualized by conventional MR imagings. DTI provides information on both mobility and directionality of water molecules, whereas DWI investigates only tissue water molecular diffusion, which is, anyhow, the crucial measurement for the fine exploration of brain tissue structural integrity. The aim of our study is to further investigate callosal water diffusivity in schizophrenic patients. Methods: Twenty-three right-handed Caucasian patients with schizophrenia diagnosed with the IGC-SCAN interview and 22 right-handed Caucasian normal controls comparable for age and gender were studied (Table). Information on length of illness and lifetime antipsychotic
P.3.10 Combination treatment for panic disorder: a prospective study C. Bergesio, U. Albert, G. Maina, F. Bogetto. Department of Neurosciences, Anxiety and Mood Disorders Unit, University of Turin, Torino, Italy
S53
of panic attacks: 7.3 weeks vs. 9.9 weeks; p<0.05). The drop-out rate was lower in the combination group (7.5% vs. 15.4%). At the end of the follow-up period, 42.5% of patients in the original combination group were still taking a benzodiazepine, although only two subjects showed benzodiazepine abuse. Two additional patients in the other group fulfilled criteria for benzodiazepine abuse during the follow-up period. Conclusions: Even though combination treatment does not result in greater efficacy, it represents a safe and clinically useful strategy to treat PD resulting in more rapid symptoms relief. The prescription of benzodiazepines could be related with difficulty during the discontinuation phase but it does not increase the risk of abuse and dependence. A longer follow-up should be done to evaluate more appropriately the cost/benefit ratio of a combined treatment strategy. References
Introduction: A combination strategy (SSRIs and benzodiazepines) for Panic Disorder (PD) seems to be a common clinical practice and is even indicated by international practice guidelines. Previous controlled studies have documented that this strategy results in a more rapid response but not in a greater efficacy. In addition, benzodiazepine dosage proved difficult to taper, at least according to some studies, with an increased risk of abuse/dependence. However, it remains controversial whether this strategy should be suggested for all patients or restricted to subjects with a need of a rapid relief of anxiety symptoms. The purpose of this study was to test the efficacy and the response latency of the early coadministration of alprazolam with SSRIs in the treatment of PD. The second aim of the study was to evaluate the proportion of subjects who showed any signs of BDZ abuse/dependence during a follow-up period of six months. Material and methods: 79 DSM-IV PD outpatients were randomly assigned to treatment with either monotherapy (SSRIs) or combined therapy (SSRIs + alprazolam). In the second group, according to Practice Guidelines indications, clinicians tried to taper alprazolam gradually to cessation since the 5th week of treatment. A statistical comparison between the two groups was performed for response latency and efficacy at the endpoint of acute treatment (12 weeks). Moreover, the proportion of patients still taking benzodiazepines or with a diagnosis of abuse/dependence after a period of adjunctive 6 months was recorded. Results: The proportion of responders (no panic attacks at the end of the acute treatment) was similar in both groups (76.9% vs. 75%) but the combination strategy resulted in a more rapid response (time to remission
[1] American Psychiatric Association. Practice Guidelines for the Treatment of Patients with Panic Disorder. American Psychiatric Association, Washington, DC, 1998. [2] Goddard AW, Brouette T, Almai et al. Early coadministration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry 2001; 58: 681– 686. [3] Simon NM, Safren SA, Otto MW et al. Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder. J Affect Disord 2002; 69: 202–208. P.3.11 Cognitive function and psychomotor performance in schizophrenic patients S. Borgwardt1 , L. Franke2 , R. Uebelhack2 . Psychiatric Outpatient Department, Kantonsspital Basel, Petersgraben 4, CH-4031 Basel, Switzerland; 2 Department of Psychiatry, Humboldt-University Berlin (Charit´e), Germany 1
Background: The cognitive deficits of schizophrenia might represent a separate domain of the illness that is relatively independent of psychotic symptoms (Green et al. 2000). According to the literature, the effects of conventinal neuroleptics on cognitive impairment are generally negligible, whereas the situation with newer antipsychotic medications seems to be more promising (Meltzer and McGurk, 1999). Aim of the study: The aim of the present study was to investigate the effects of typical (haloperidol, flupentixol, fluphenazine) and atypical neuroleptics (clozapine, olanzapine, risperidone) on several cognitive and performance
S54
Clinical Neuropsychopharmacology
tasks in schizophrenic patients in comparison to drug-free patients and healthy subjects. Based on the assumption that dosage, namely of conventinal neuroleptics, may influence the results, we additionally analysed the dependence of performance of treated patients on dosage expressed in CPZ equivalents. Methods: The performance of the subjects were evaluated by a comprehensive battery of psychometric tests in healthy subjects (n=51) and hospitalized schizophrenic patients before (n=18) and at week 8–11 (n=26) of treatment. A modified version of a neuropsychological test battery, already validated in patients with epilepsy and depression, was used to cover executive functions, perseveration, memory, attention, concentration, and motor abilities. Due to the small sizes of our samples, only nonparametric tests for data analysis were used: MannWhitney U test and Spearman’s rank-order correlation coefficients. Results: Healthy subjects showed significantly better results than the whole sample of schizophrenic patients in almost all cognitive domains. However, between the three groups of drug-free patients, and patients with conventional or atypical neuroleptics, there were differences in specific cognitive functions. In average, less deficites in executive functions and perseveration was found in patients treated with atypical neuroleptics. The extent of impairments in some cognitive domains was dose depending only in patients treated with typical neuroleptics. High correlation coefficients were found for the tendency to perseveration (n=14, r= −0.89, p<0.001). Conclusion: The results confirm the previous findings of a generalized cognitive deficit in patients with schizophrenia (Bilder et al., 2000). It is concluded that the disruptive effects of typical neuroleptics on some cognitive function and psychomotor performance are dosedepending and that atypical neuroleptics had little or no effect on performance at the used dosage in comparison to drug-free schizophrenic patients. Atypical antipsychotics may be more acceptable in higher dosage treatment of schizophrenia. Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from atypical antipsychotic drugs. References [1] Bilder RM, Goldman RS, Robinson D, Reiter G, Bell L, Bates JA, Pappadopulos E, Wilson DF, Alvir JMJ, Woerner MG, Geisler S, Kane JM, Lieberman JA (2000) Neuropsychology of firstepisode schizophrenia: Initial characterization and clinical correlates. American Journal of Psychiatry 157:549–559. [2] Green MF, Marder SR, Glynn SM, McGurk SR, Wirshing WC, Wirshing DA, Liberman RP, Mintz J
(2002) The Neurocognitive Effects of Low-Dose Haloperidol: A Two-Year Comparison with Risperidone. Biological Psychiatry 51:972–978. [3] Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophrenia Bulletin 25:233–255.
P.3.12 Abnormalities of corpus callosum in schizophrenia: a diffusion-weighted MRI study P. Brambilla1 , R. Cerini2 , A. Gasparini2 , M. Nos`e1 , E. Vittorini2 , C. Barbui1 , A. Versace1 , N. Andreone1 , A. David3 , M.S. Keshavan4 , C. Procacci2 , M. Tansella1 . 1 Department of Medicine and Public Health, Section of Psychiatry, University of Verona, Italy; 2 Department of Morphological and Biomedical Sciences, Section of Radiology, University of Verona, Italy; 3 Section of Cognitive Neuropsychiatry, Institute of Psychiatry and GKT School of Medicine, London, UK; 4 Western Psychiatry Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Introduction: Corpus callosum is the main white matter commissure between the two cerebral hemispheres, connecting homologous areas. Recently, abnormalities in mean diffusivity for splenium of corpus callosum have been reported in schizophrenia by two diffusion tensor imaging (DTI) reports (Agartz et al., 2001; Foong et al., 2000). Consistently, abnormally small splenium size has been shown in childhood-onset schizophrenia in a longitudinal MRI study (Keller et al., 2003). Therefore, corpus callosum may play a key role in the in the structural brain anatomy and pathophysiology of schizophrenia. Diffusion weighted imaging (DWI) is a relatively new MRI technique capable of examining molecular water mobility in brain tissue (e.g. white matter tracts), detecting subtle abnormalities of anatomical structures that cannot be visualized by conventional MR imagings. DTI provides information on both mobility and directionality of water molecules, whereas DWI investigates only tissue water molecular diffusion, which is, anyhow, the crucial measurement for the fine exploration of brain tissue structural integrity. The aim of our study is to further investigate callosal water diffusivity in schizophrenic patients. Methods: Twenty-three right-handed Caucasian patients with schizophrenia diagnosed with the IGC-SCAN interview and 22 right-handed Caucasian normal controls comparable for age and gender were studied (Table). Information on length of illness and lifetime antipsychotic