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A clinical trial with risperidon on chronic schizophrenics
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S-38 Social Phobia: A Debilitating Disease with a New Treatment Option
I0 -22-81 Controlled Comparison of Terguride and Perphenazine in Acute Schizophrenia 1. Svestka. E. Ceskova, V. Kamenicka, A. Buresova, Psychiatric Department, BI7UJ. Czech Republic The study includes 50 patients of the average age of 35 years with the diagnosis of acute schizophrenic (n = 34) or schizoaffective (n = 16) disorders. The treatment lasted for 21 days. including an initial wash-out interval. The mean minimum and maximum daily doses amounted to 1.6-4.6 mg for terguride and 17-43 mg perphenazine. Perphenazine was proved to be a good antipsychotic for treatment both positive and negative schizophrenic symptoms (82% of responders), being significantly more effective than terguride according to the BPRS. CGI and Sereiski scales. Terguride was successful in therapy of cca 113 of the treated patients; these were especially perphenazine nonresponders. Terguride showed a tendency towards influencing rather the negative than the positive symptoms and it was mostly ineffective in cases of agitation. uncooperativeness, aggressivity, and of manic moods. The zero occurrence of extrapyramidal symptoms and reduced prolactinaemia were among the advantages of terguride. [I] Votavova M. et al., 1988, Archiv VUFB, Prague. [2J Olbrich R. Schanz H. Pharmacopsychiatry 21. 1988.389-3 90. [3J Olbrich R, Schanz H, J. Neural. Trans. 84. 1991. 233- 236.
I0 -22-9 1 ASchizophrenics Clinical Trialwith Risperidon on Chronic T.K. Bastaman, R. Budiman, A. Kumawardhani, Amir N. Irmansyah, R. Salan. Department of Psychiatry, Faculty of Medicine. University of Indonesia, Salemba 6. Jakarta Pusat This is a preliminary report of an open clinical trial with risperidon on chronic schizophrenic patients admitted to the Psychiatric Department of the Medical Faculty of the University of Indonesia. It is an ongoing investigation of a projected sample of 145 patients. The purpose of the study is to assess therapeutic and side effects of risperidon on chronic schizophrenic patients. Measurement was made using the PANSS and the EPRS. All chronic schizophrenic patients admitted since late June 1995 were given risperidon for eight weeks after a washout period of one week. Dosis started with I mg bid for one day followed by 2 mg bid till the end of the first week. During the second week dosages were increased to 3 mg bid and during the following weeks, dosages were further increased according to the patient's condition after a weekly assessment. The maximal dosis was 16 mglday. A weekly assessment was made and rating with the PANSS was done at the beginning of the first, third, fifth and ninth week. Comparison between the rating of the first and the following weeks was made and statistical significancy was measured using the t-test for dependent samples. Preliminary findings of the first 29 patients showed that after 8 weeks patients improved significantly (t value 5.488, df 28 and p < 0.000)
I0 -22-10 I Clinical Trial on Antipsychotic Effects of the Sigma Ligand Panamesine in Schizophrenia A. Steiger, R-M. Frieboes, H. Murck, K. Wiedemann. Max Planck Institute of Psychiatry, Clinical Institute, Department of Psychiatry. Munich, Germany Panamesine (EMD 57 445) is a novel sigma ligand. Preclinical studies suggest that the substance has neuroleptic properties without induction of side effects related to the extrapyramidal motoric system (EPMS). Currently we are examining the clinical efficacy, the appropriate dose range and the safety of the substance in patients with the acute episode of schizophrenia. paranoid subtype. in an open pilot trial during 4 weeks. A first approach in 4 patients revealed insufficient efficacy of a protocol with a stepwise increase of the daily dosage from 7.5 mg during the first week up to 30 mg during the 3rd and 4th week. Thereafter. in 8 patients (5 females. 3 males), who completed the study so far. 15 mg/day were given on day 1. Due to the clinical course the dosage was increased to 60 mglday until day 7 and in some patients up to 90 mg/day on day 14. Maximum daily dosages ranged from 30 to 90 mg. According to the
decrease of the BPRS score by at least 50% 4 patients were judged as responders. 3 showed only a slight improvement, one deteriorated. In all patients prolactin levels increased during treatment. No major side effects occurred, particularly no EPMS symptoms. In one of the responders withdrawal of panamesine and change to clozapine was followed by teappearance of psychotic symptoms. Our preliminary data suggest that panamesine exerts antipsychotic effects in patients with schizophrenia and is a safe compound.
I0 -22-11 I Dose Response of D-Cycloserine, a Partial
NMDA-Glycine Site Agonist, in Schizophrenia
D.C. D' Souza, D. Abi-Saab, D. Damon, J. White, R. Gil. J.R. Krystal. Department of Psychiatry. Yale University. USA
Background: A leading hypothesis suggest that deficits in NMDA receptor function may contribute to the neurobiology of schizophrenia. The NMDA receptor glycine site offers a safe indirect method of enhancing NMDA receptor function. Based on the NMDA deficit hypothesis, facilitation of NMDA receptor function may have therapeutic potential in schizophrenia. Glycine site partial agonists unlike full agonists, may afford the additional advantage of facilitating function only when a deficit state of the receptor exists. D-Cycloserine (DCS) is the only available glycine-site partial agonist for use in humans. Results of clinical trials with DCS in the treatment of schizophrenia suggest the need to determine the agonist dose-range of DeS, since DeS may have agonist or antagonist effects at different doses. The goal of this study was to establish the agonist dose range of DCS in medicated & unmedicated schizophrenics. Methods: In an ongoing double-blind. placebo-controlled study. 8 unmedicated. 7 medicated schizophrenics and 6 healthy subjects received orally. in random counterbalanced order either: 50 mg DCS, 500 mg DCS. or placebo. over 3 test days. Behavioral. cognitive and neurochemical data were collected. Preliminary Results: Oral DCS dose dependently raised serum DCS levels. DCS may decrease negative symptoms (p < 0.0l) without significant effects on positive symptoms. Low dose DCS significantly (p < 0.02) decreased performance on the STROOP in the unmedicated group. Conclusions: Consistent with clinical trials. our preliminary data suggest that DCS may reduce negative symptoms. Though preliminary data suggest that DCS may effect neuropsychological test performance. no firm conclusions can be reached. These findings warrant further investigation of the role that partial agonists of the glycine site play in the treatment of schizophrenia.
I5-381 Social Phobia: A Debilitating Disease with a New Treatment Option
I8-38 -1 I Treatment of Social Phobia S.A. Montgomerv. D.B. Montgomery, A. Kotak. Department of Psychiatry. Imperial College of Science. Technology and Medicine. London Social phobia responds well to treatment. Early intervention may help prevent severe impairment, the development of harmful coping strategies and the onset of comorbid conditions such as major depression and alcoholism. Treatment should be initiated in cases where symptoms or avoidance behaviour are associated with significant psychosocial impairment. Explaining the rationale for pharmacotherapy and that the treatment is likely to be needed for some time may help patient compliance. The pharmacological agents found to be most effective against social phobia are those that inhibit the monoamine oxidase enzyme in the central nervous system - the RIMAs and MAOIs. Other agents used in the treatment of social phobia include benzodiazepines, beta blockers and SSRls. Psychological therapy used either in isolation or in combination with drug therapy may also be a useful treatment approach.
S-38 Social Phobia: A Debilitating Disease with a New Treatment Option
I0 -22-81 Controlled Comparison of Terguride and Perphenazine in Acute Schizophrenia 1. Svestka. E. Ceskova, V. Kamenicka, A. Buresova, Psychiatric Department, BI7UJ. Czech Republic The study includes 50 patients of the average age of 35 years with the diagnosis of acute schizophrenic (n = 34) or schizoaffective (n = 16) disorders. The treatment lasted for 21 days. including an initial wash-out interval. The mean minimum and maximum daily doses amounted to 1.6-4.6 mg for terguride and 17-43 mg perphenazine. Perphenazine was proved to be a good antipsychotic for treatment both positive and negative schizophrenic symptoms (82% of responders), being significantly more effective than terguride according to the BPRS. CGI and Sereiski scales. Terguride was successful in therapy of cca 113 of the treated patients; these were especially perphenazine nonresponders. Terguride showed a tendency towards influencing rather the negative than the positive symptoms and it was mostly ineffective in cases of agitation. uncooperativeness, aggressivity, and of manic moods. The zero occurrence of extrapyramidal symptoms and reduced prolactinaemia were among the advantages of terguride. [I] Votavova M. et al., 1988, Archiv VUFB, Prague. [2J Olbrich R. Schanz H. Pharmacopsychiatry 21. 1988.389-3 90. [3J Olbrich R, Schanz H, J. Neural. Trans. 84. 1991. 233- 236.
I0 -22-9 1 ASchizophrenics Clinical Trialwith Risperidon on Chronic T.K. Bastaman, R. Budiman, A. Kumawardhani, Amir N. Irmansyah, R. Salan. Department of Psychiatry, Faculty of Medicine. University of Indonesia, Salemba 6. Jakarta Pusat This is a preliminary report of an open clinical trial with risperidon on chronic schizophrenic patients admitted to the Psychiatric Department of the Medical Faculty of the University of Indonesia. It is an ongoing investigation of a projected sample of 145 patients. The purpose of the study is to assess therapeutic and side effects of risperidon on chronic schizophrenic patients. Measurement was made using the PANSS and the EPRS. All chronic schizophrenic patients admitted since late June 1995 were given risperidon for eight weeks after a washout period of one week. Dosis started with I mg bid for one day followed by 2 mg bid till the end of the first week. During the second week dosages were increased to 3 mg bid and during the following weeks, dosages were further increased according to the patient's condition after a weekly assessment. The maximal dosis was 16 mglday. A weekly assessment was made and rating with the PANSS was done at the beginning of the first, third, fifth and ninth week. Comparison between the rating of the first and the following weeks was made and statistical significancy was measured using the t-test for dependent samples. Preliminary findings of the first 29 patients showed that after 8 weeks patients improved significantly (t value 5.488, df 28 and p < 0.000)
I0 -22-10 I Clinical Trial on Antipsychotic Effects of the Sigma Ligand Panamesine in Schizophrenia A. Steiger, R-M. Frieboes, H. Murck, K. Wiedemann. Max Planck Institute of Psychiatry, Clinical Institute, Department of Psychiatry. Munich, Germany Panamesine (EMD 57 445) is a novel sigma ligand. Preclinical studies suggest that the substance has neuroleptic properties without induction of side effects related to the extrapyramidal motoric system (EPMS). Currently we are examining the clinical efficacy, the appropriate dose range and the safety of the substance in patients with the acute episode of schizophrenia. paranoid subtype. in an open pilot trial during 4 weeks. A first approach in 4 patients revealed insufficient efficacy of a protocol with a stepwise increase of the daily dosage from 7.5 mg during the first week up to 30 mg during the 3rd and 4th week. Thereafter. in 8 patients (5 females. 3 males), who completed the study so far. 15 mg/day were given on day 1. Due to the clinical course the dosage was increased to 60 mglday until day 7 and in some patients up to 90 mg/day on day 14. Maximum daily dosages ranged from 30 to 90 mg. According to the
decrease of the BPRS score by at least 50% 4 patients were judged as responders. 3 showed only a slight improvement, one deteriorated. In all patients prolactin levels increased during treatment. No major side effects occurred, particularly no EPMS symptoms. In one of the responders withdrawal of panamesine and change to clozapine was followed by teappearance of psychotic symptoms. Our preliminary data suggest that panamesine exerts antipsychotic effects in patients with schizophrenia and is a safe compound.
I0 -22-11 I Dose Response of D-Cycloserine, a Partial
NMDA-Glycine Site Agonist, in Schizophrenia
D.C. D' Souza, D. Abi-Saab, D. Damon, J. White, R. Gil. J.R. Krystal. Department of Psychiatry. Yale University. USA
Background: A leading hypothesis suggest that deficits in NMDA receptor function may contribute to the neurobiology of schizophrenia. The NMDA receptor glycine site offers a safe indirect method of enhancing NMDA receptor function. Based on the NMDA deficit hypothesis, facilitation of NMDA receptor function may have therapeutic potential in schizophrenia. Glycine site partial agonists unlike full agonists, may afford the additional advantage of facilitating function only when a deficit state of the receptor exists. D-Cycloserine (DCS) is the only available glycine-site partial agonist for use in humans. Results of clinical trials with DCS in the treatment of schizophrenia suggest the need to determine the agonist dose-range of DeS, since DeS may have agonist or antagonist effects at different doses. The goal of this study was to establish the agonist dose range of DCS in medicated & unmedicated schizophrenics. Methods: In an ongoing double-blind. placebo-controlled study. 8 unmedicated. 7 medicated schizophrenics and 6 healthy subjects received orally. in random counterbalanced order either: 50 mg DCS, 500 mg DCS. or placebo. over 3 test days. Behavioral. cognitive and neurochemical data were collected. Preliminary Results: Oral DCS dose dependently raised serum DCS levels. DCS may decrease negative symptoms (p < 0.0l) without significant effects on positive symptoms. Low dose DCS significantly (p < 0.02) decreased performance on the STROOP in the unmedicated group. Conclusions: Consistent with clinical trials. our preliminary data suggest that DCS may reduce negative symptoms. Though preliminary data suggest that DCS may effect neuropsychological test performance. no firm conclusions can be reached. These findings warrant further investigation of the role that partial agonists of the glycine site play in the treatment of schizophrenia.
I5-381 Social Phobia: A Debilitating Disease with a New Treatment Option
I8-38 -1 I Treatment of Social Phobia S.A. Montgomerv. D.B. Montgomery, A. Kotak. Department of Psychiatry. Imperial College of Science. Technology and Medicine. London Social phobia responds well to treatment. Early intervention may help prevent severe impairment, the development of harmful coping strategies and the onset of comorbid conditions such as major depression and alcoholism. Treatment should be initiated in cases where symptoms or avoidance behaviour are associated with significant psychosocial impairment. Explaining the rationale for pharmacotherapy and that the treatment is likely to be needed for some time may help patient compliance. The pharmacological agents found to be most effective against social phobia are those that inhibit the monoamine oxidase enzyme in the central nervous system - the RIMAs and MAOIs. Other agents used in the treatment of social phobia include benzodiazepines, beta blockers and SSRls. Psychological therapy used either in isolation or in combination with drug therapy may also be a useful treatment approach.