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P.3.a.018 Two patients with chronic psychotic disorders who completed interferon-alpha plus ribavirin therapy for hepatitis C
S490
P.3.a Psychotic disorders and antipsychotics - Psychotic disorders (clinical)
schizophrenia and for maintenance treatment of schizophrenia. It has - probably as a result of its pharmacokinetic profile - shown robust efficacy, and a favorable tolerability in multiple trials for the treatment of schizophrenia [1]. Our goal was to assess its efficacy and tolerability as acute and maintenance of effect therapy in patients with bipolar I disorder experiencing manic or mixed episodes while on a mood stabilizer. Methods: Six hospitalized patients (two men and four women) with average age 35.6 years and average duration of illness 7.2 years, with acute bipolar I mania (two of them with a mixed episode) were put on paliperidone (three patients on 6mg and three patients on 9 mg). They were all receiving a mood stabilizer (three were on valproate, three on lithium, and one on topirarnate) although compliance was partial in at least four of the cases. The primary outcome measure was the mean change in the Young Mania Rating Scale and secondary measures included the 21-item Hamilton Rating Scale for Depression (HAM-D-21) and Clinical Global Impressions-Bipolar Version (CGI-BP) at Week 4, 8, and 16. Results: Paliperidone ER provided improvement of acute mania within four days, continuing over 4 weeks and sustained over 16 weeks in five of our six patients. It was discontinued in one at day 8 due to worsening of her symptoms. Paliperidone was generally well tolerated and helped patients achieve and maintain remission without occurrence of depressive symptoms. In two of the patients on 9 mg, paliperidone was lowered to 6 mg after 8 weeks without recurrence of symptoms. Conclusion: Well tolerated and effective therapies for bipolar mania are required. It is well known that patients with bipolar disorder appear more sensitive to antipsychotics. Paliperidone provided in our small sample significant improvement of acute mania and maintained its effect for 4 months. Paliperidone ER may be a safe and effective treatment option for acute mania and provide additional benefit over monotherapy for the management of the manic phase but also for control of mood symptoms in the long run, particularly in preventing manic relapses. It should be noticed that our patients suffered moderate to severe manic episodes, four of them with psychotic features, and had to be hospitalized for them. This could partially explain why the addition of an antipsychotic improved rapidly their symptomatology. Studies with exclusively nonpsychotic acute or mixed episodes should be conducted. References [1] Marino, J., Caballero, J, 2008. Paliperidone extended-release for the treatment of schizophrenia. Pharmacotherapy 28 (10), 1283-98.
patients with major psychiatric disorders should not be precluded from IFN+RBV therapy and recommended that antiviral treatment be considered on a case-by-case basis as the best approaches to treating CHC in patients with major psychiatric illness are to be defined. In fact, little is known on safety of antiviral therapy for psychotic patients. Only one case report of a woman with chronic schizophrenia safely treated with IFN+RBV was published [2]. In other study none of the ten patients with a psychotic disorder had exacerbation ofpsychotic symptoms during antiviral treatment due to hepatitis C. However, this report did not focus on psychotic patients [3]. The aim of the paper is the description of two cases of CHC patients who suffered from psychotic disorders prior to antiviral therapy and were observed during 48 week IFN+RBV therapy. Patient A was 66 years old woman with diagnosis of paranoid schizophrenia (F20) who took risperidone 4 mg a day and had been stable for 12 months. Previously, she had florid persecutory delusions. After independent assessments by two psychiatrists, taking into account her strong motivation for antiviral therapy and long-term compliance with antipsychotic treatment, pegylated IFN-alpha-2a+RBV was instituted. The patient came every four weeks for psychiatric consultation and during the course of the antiviral therapy no exacerbation of neither positive nor negative symptoms of schizophrenia was occurred and risperidone dose was constant. The patient had typical side effects of IFN+RBV therapy Le. fatigue, mild insomnia and loss of appetite. Patient B was 53 years old man with diagnosis of organic psychotic disorder (F06.2) who had not relapsed for two years. His mental illness had emerged 14 years earlier follow long lasting cardiosurgical procedure with extracorporeal circulation. He also was compliant with antipsychotic treatment (clozapine 100 mg a day) and highly motivated for anitiviral therapy. Two separate psychiatric assessments were performed and upon consultants' agreement pegylated-IFN-alpha-2b+RBV was started. During 48week course of the therapy patient came every 4-8 weeks for psychiatric assessment and no sings of exacerbation of symptoms of psychosis was noted. Clozapine was continued with stable dose. During IFN+RBV therapy patient suffered from fatigue and occasionally from mild insomnia. Both patients completed antiviral therapy, however did not attain sustained viral response. PANSS scores did not rise significantly (see Table). Conclusions. IFN+RBV therapy may be available option for hepatitis C patients with psychotic disorders who have been stable and compliant with neuroleptic treatment. Close psychiatric monitoring during antiviral therapy of chronic psychotic patients is obligatory. Table. PANSS scores of hepatitis C patients with psychotic disorders prior to and during the course of antiviral therapy
1P.3.a.0181 Two patients with chronic psychotic disorders who completed interferon-alpha plus ribavirin therapy for hepatitis C W. Drozdz 1 ., D. Kozielewicz2, D. Dybowska2 , W. Halota2 , A. Borkowska1 . 1Nicolaus Copernicus University Torun Collegium Medicum, Clinical Neuropsychology Unit, Bydgoszcz, Poland; 2Nicolaus Copernicus University Torun Collegium Medicum, Department of Infectious Diseases and Hepatology, Bydgoszcz, Poland Psychotic disorders may be rare (incidence could be estimated on 1 of 1000 treated patients) but serious complication of interferonalpha plus ribavirin (IFN+RBV) therapy in chronic hepatitis C (CHC) patients [1]. National Institutes of Health Consensus Statement on Management ofCHC, developed in 2002, recognized that
Patient A
Patient B
week 0 week 24 week 48 week 0 week 24 week 48 PANSS PANSS PANSS PANSS
positive negative general total score
24 14 32 70
26 15 33 73
25 15 33 73
16
22 36 74
18 23 37 77
16 22 36 75
References [1] Drozdz, w., Borkowska, A., Rybakowski, J., 2007 Psychotic disorders as a complication of interferon-alpha treatment of hepatitis C. Arch Psych Psychother 9 (1-2), 51-55. [2] Dobmeier, M., Frick, E., Frank, S., Franke, C., Wolfersdorf, M., 2000 Schizophrenic psychosis: a contraindication for treatment of hepatitis C with interferon alpha? Pharmacopsychiatry 33 (2), 72-74.
P.3.a Psychotic disorders and antipsychotics - Psychotic disorders (clinical) [3] Schaefer, M., Hinzpeter, A., Mohmand, A., Janssen, G., et aI., 2007 Hepatitis C treatment in "difficult-to-treat" psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects. Hepatology 46 (4), 991-998.
1P.3.a.0191 Modafinil's efficacy in treating clozapineassociated sedation and sleepiness in patients with schizophrenia N. Kouroumalos 1 ., P. Georgila1, E. Marini 1 , D. Sakkas 1 . 1 General Hospital of Athens "G. Gennimatas", Department of Psychiatry, Athens, Greece Introduction and Objectives: Despite clozapine's (CLZ) efficacy in treating Refractory Schizophrenia, undesired effects may occur with its use. Apart from those which are infrequent but life threatening such as agranulocytosis, sedation and sleepiness seem to be frequent and sometimes debilitating. The latter are probably mediated by CLZ inhibitory actions on histaminic HI and cholinergic M2 receptors. Modafinil (MOD) on the other hand, is a quite novel medication used in narcolepsy to promote wakefulness as well as in other disorders such as multiple sclerosis to combat fatigue, or as augmentation of antidepressant treatments in depression. Its exact mechanism of action is not thoroughly clarified, yet the drug among other actions also shows central dopamine-dependent adrenergic signaling in its wake-promoting mechanism as well as inhibitory action on pallidal and striatal GABA release [1,2]. The aim of this study is to provide evidence for the efficacy of MOD in treating CLZ-associated sedation in patients with Schizophrenia. Method: The study was prospective. Our sample consisted of 10 patients with schizophrenia resistant to various lst line antipsychotic medications, who were hospitalized in our department. CLZ was administered at a mean dose of 370 mgld. Patients were responding well concerning both positive and negative symptoms of the disease. However, after CLZ reaching or exceeding daily dose of 100 mg, patients started complaining of sedation and sleepiness, a fact which was confirmed by the observations of the medical and paramedical staff of our department. Tolerance to the sedative effects of CLZ did not develop after a month of stabilizing its effective dose. MOD was then added to the treatment scheme at a mean dose of 110 mgld. Epworth Sleepiness Scale (ESS) was used to measure sleepiness before and after MOD addition and t-test was used for comparison. Results: A week after MOD addition to the treatment scheme, patients started improving in the sense that sedation was no longer a subjective complaint. Sleep hours per day had decreased from mean 11 before, to mean 8 after MOD initiation according to staff observations. A significant decrease in ESS score was observed as well. Dose of CLZ did not decrease. The above effect of MOD was maintained at follow-up examinations conducted once a week for 3 months following patients' discharge. Side effects were not noted after MOD addition, both during hospitalization and upon follow-ups after discharge. Conclusions and Discussion: MOD seemed effective in treating CLZ-associated sedation and sleepiness in all 10 cases of our sample, maintaining its effect for at least 3 months. Psychosis was not exacerbated after MOD addition in any of our cases in contrast to one citation traced mentioning one case report
S491
where psychosis worsened after addition of MOD(3). Possibly, further studies with larger patient samples are needed to confirm our findings. Clinical studies with placebo have to be performed as well, in order to establish MOD efficacy in treating sleepiness and sedation associated with CLZ in patients with schizophrenia. References [I] Wisor J.P., Eriksson K.S., "Dopaminergic-adrenergic interactions in the wake promoting mechanism ofmodafinil". Neuroscience, Volume 132, Issue 4, 2005, Pages 1027-1034. [2] Ferraro L., Antonelli T., O'Connor W. T., Tanganelli S., Rambert F. A., Fuxe K., "The effects of modafinil on striatal, pallidal and nigral GABA and glutamate release in the conscious rat: evidence for a preferential inhibition of striata-pallidal GABA transmission". Neuroscience Letters, Volume 253, Issue 2, 4 September 1998, Pages 135-138 [3] Narendran et aI., "Is Psychosis Exacerbated by Modafinil?". Arch Gen Psychiatry.2002; 59: 292-293.
1P.3.a.0201 Gender differences in hospitalised schizophrenic patients M. Serrano Vazquez 1 ., M.M. Serrano Carton1, M.C. Serrano Carton 1 . 1 Complejo Hospitalario Juan Canalejo, psychiatry, Coruna, Spain Background: The results of the current study indicate that men and women have an equal lifetime risk for schizophrenia. However, schizophrenia tends to strike women 3-4 years later than men. Most ofmen develop schizophrenia between 15 and 25 years. For women the period of maximum onset is between 15 and 30 with a smaller peak between 45 and 50 (after menopause). Women also tend to have milder forms of the disease in their younger year than their male counterparts do. But, in the later years, symptoms in men tend to decrease in severity while women often have a renewed onset of psychotic symptoms and a worse course of the disease. Objective: Gender differences in onset of illness, clinical presentation, response to treatment, course, and biologic measures have been consistently reported in patients with chronic schizophrenia. The purpose of this study is to determine possible differences in the average stay, symptoms to admission as well as other gender-related issues. Method: By means of a retrospective analysis of the data gathered in clinical histories of 532 patients admitted to our unit for psychiatric hospitalization during the past five years, several variables were collected and analyzed by statistical methods. The analyzed data make reference to the incidence of the disease, the age, the average stay, the personal and familiar antecedents, the labor and socioeconomic antecedents, the psychopharmacological treatments, the subtype of schizophrenia and the premorbid personality. Diagnosis was made using the Structured Clinical Interview for the DSM-IV-TR. Data analysis was performed using SPSS 10.0 for Windows. Results: The sample constitutes 532 patients (366 men and 166 women), the prevalence ratio of men/women was 2/1. Age differences were significant, with an earlier onset in men. There is no difference, other than age, in the symptom-related course of the disease between men and women. The average stay was similar in both cases. Conclusions: We found concordant results with the obtained in previous studies, with a higher incidence and an earlier onset of schizophrenia in men. The most consistent result found is the 3--4 year age difference between men and women. The protective effects of oestrogen raise the question of new treatments using
P.3.a Psychotic disorders and antipsychotics - Psychotic disorders (clinical)
schizophrenia and for maintenance treatment of schizophrenia. It has - probably as a result of its pharmacokinetic profile - shown robust efficacy, and a favorable tolerability in multiple trials for the treatment of schizophrenia [1]. Our goal was to assess its efficacy and tolerability as acute and maintenance of effect therapy in patients with bipolar I disorder experiencing manic or mixed episodes while on a mood stabilizer. Methods: Six hospitalized patients (two men and four women) with average age 35.6 years and average duration of illness 7.2 years, with acute bipolar I mania (two of them with a mixed episode) were put on paliperidone (three patients on 6mg and three patients on 9 mg). They were all receiving a mood stabilizer (three were on valproate, three on lithium, and one on topirarnate) although compliance was partial in at least four of the cases. The primary outcome measure was the mean change in the Young Mania Rating Scale and secondary measures included the 21-item Hamilton Rating Scale for Depression (HAM-D-21) and Clinical Global Impressions-Bipolar Version (CGI-BP) at Week 4, 8, and 16. Results: Paliperidone ER provided improvement of acute mania within four days, continuing over 4 weeks and sustained over 16 weeks in five of our six patients. It was discontinued in one at day 8 due to worsening of her symptoms. Paliperidone was generally well tolerated and helped patients achieve and maintain remission without occurrence of depressive symptoms. In two of the patients on 9 mg, paliperidone was lowered to 6 mg after 8 weeks without recurrence of symptoms. Conclusion: Well tolerated and effective therapies for bipolar mania are required. It is well known that patients with bipolar disorder appear more sensitive to antipsychotics. Paliperidone provided in our small sample significant improvement of acute mania and maintained its effect for 4 months. Paliperidone ER may be a safe and effective treatment option for acute mania and provide additional benefit over monotherapy for the management of the manic phase but also for control of mood symptoms in the long run, particularly in preventing manic relapses. It should be noticed that our patients suffered moderate to severe manic episodes, four of them with psychotic features, and had to be hospitalized for them. This could partially explain why the addition of an antipsychotic improved rapidly their symptomatology. Studies with exclusively nonpsychotic acute or mixed episodes should be conducted. References [1] Marino, J., Caballero, J, 2008. Paliperidone extended-release for the treatment of schizophrenia. Pharmacotherapy 28 (10), 1283-98.
patients with major psychiatric disorders should not be precluded from IFN+RBV therapy and recommended that antiviral treatment be considered on a case-by-case basis as the best approaches to treating CHC in patients with major psychiatric illness are to be defined. In fact, little is known on safety of antiviral therapy for psychotic patients. Only one case report of a woman with chronic schizophrenia safely treated with IFN+RBV was published [2]. In other study none of the ten patients with a psychotic disorder had exacerbation ofpsychotic symptoms during antiviral treatment due to hepatitis C. However, this report did not focus on psychotic patients [3]. The aim of the paper is the description of two cases of CHC patients who suffered from psychotic disorders prior to antiviral therapy and were observed during 48 week IFN+RBV therapy. Patient A was 66 years old woman with diagnosis of paranoid schizophrenia (F20) who took risperidone 4 mg a day and had been stable for 12 months. Previously, she had florid persecutory delusions. After independent assessments by two psychiatrists, taking into account her strong motivation for antiviral therapy and long-term compliance with antipsychotic treatment, pegylated IFN-alpha-2a+RBV was instituted. The patient came every four weeks for psychiatric consultation and during the course of the antiviral therapy no exacerbation of neither positive nor negative symptoms of schizophrenia was occurred and risperidone dose was constant. The patient had typical side effects of IFN+RBV therapy Le. fatigue, mild insomnia and loss of appetite. Patient B was 53 years old man with diagnosis of organic psychotic disorder (F06.2) who had not relapsed for two years. His mental illness had emerged 14 years earlier follow long lasting cardiosurgical procedure with extracorporeal circulation. He also was compliant with antipsychotic treatment (clozapine 100 mg a day) and highly motivated for anitiviral therapy. Two separate psychiatric assessments were performed and upon consultants' agreement pegylated-IFN-alpha-2b+RBV was started. During 48week course of the therapy patient came every 4-8 weeks for psychiatric assessment and no sings of exacerbation of symptoms of psychosis was noted. Clozapine was continued with stable dose. During IFN+RBV therapy patient suffered from fatigue and occasionally from mild insomnia. Both patients completed antiviral therapy, however did not attain sustained viral response. PANSS scores did not rise significantly (see Table). Conclusions. IFN+RBV therapy may be available option for hepatitis C patients with psychotic disorders who have been stable and compliant with neuroleptic treatment. Close psychiatric monitoring during antiviral therapy of chronic psychotic patients is obligatory. Table. PANSS scores of hepatitis C patients with psychotic disorders prior to and during the course of antiviral therapy
1P.3.a.0181 Two patients with chronic psychotic disorders who completed interferon-alpha plus ribavirin therapy for hepatitis C W. Drozdz 1 ., D. Kozielewicz2, D. Dybowska2 , W. Halota2 , A. Borkowska1 . 1Nicolaus Copernicus University Torun Collegium Medicum, Clinical Neuropsychology Unit, Bydgoszcz, Poland; 2Nicolaus Copernicus University Torun Collegium Medicum, Department of Infectious Diseases and Hepatology, Bydgoszcz, Poland Psychotic disorders may be rare (incidence could be estimated on 1 of 1000 treated patients) but serious complication of interferonalpha plus ribavirin (IFN+RBV) therapy in chronic hepatitis C (CHC) patients [1]. National Institutes of Health Consensus Statement on Management ofCHC, developed in 2002, recognized that
Patient A
Patient B
week 0 week 24 week 48 week 0 week 24 week 48 PANSS PANSS PANSS PANSS
positive negative general total score
24 14 32 70
26 15 33 73
25 15 33 73
16
22 36 74
18 23 37 77
16 22 36 75
References [1] Drozdz, w., Borkowska, A., Rybakowski, J., 2007 Psychotic disorders as a complication of interferon-alpha treatment of hepatitis C. Arch Psych Psychother 9 (1-2), 51-55. [2] Dobmeier, M., Frick, E., Frank, S., Franke, C., Wolfersdorf, M., 2000 Schizophrenic psychosis: a contraindication for treatment of hepatitis C with interferon alpha? Pharmacopsychiatry 33 (2), 72-74.
P.3.a Psychotic disorders and antipsychotics - Psychotic disorders (clinical) [3] Schaefer, M., Hinzpeter, A., Mohmand, A., Janssen, G., et aI., 2007 Hepatitis C treatment in "difficult-to-treat" psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects. Hepatology 46 (4), 991-998.
1P.3.a.0191 Modafinil's efficacy in treating clozapineassociated sedation and sleepiness in patients with schizophrenia N. Kouroumalos 1 ., P. Georgila1, E. Marini 1 , D. Sakkas 1 . 1 General Hospital of Athens "G. Gennimatas", Department of Psychiatry, Athens, Greece Introduction and Objectives: Despite clozapine's (CLZ) efficacy in treating Refractory Schizophrenia, undesired effects may occur with its use. Apart from those which are infrequent but life threatening such as agranulocytosis, sedation and sleepiness seem to be frequent and sometimes debilitating. The latter are probably mediated by CLZ inhibitory actions on histaminic HI and cholinergic M2 receptors. Modafinil (MOD) on the other hand, is a quite novel medication used in narcolepsy to promote wakefulness as well as in other disorders such as multiple sclerosis to combat fatigue, or as augmentation of antidepressant treatments in depression. Its exact mechanism of action is not thoroughly clarified, yet the drug among other actions also shows central dopamine-dependent adrenergic signaling in its wake-promoting mechanism as well as inhibitory action on pallidal and striatal GABA release [1,2]. The aim of this study is to provide evidence for the efficacy of MOD in treating CLZ-associated sedation in patients with Schizophrenia. Method: The study was prospective. Our sample consisted of 10 patients with schizophrenia resistant to various lst line antipsychotic medications, who were hospitalized in our department. CLZ was administered at a mean dose of 370 mgld. Patients were responding well concerning both positive and negative symptoms of the disease. However, after CLZ reaching or exceeding daily dose of 100 mg, patients started complaining of sedation and sleepiness, a fact which was confirmed by the observations of the medical and paramedical staff of our department. Tolerance to the sedative effects of CLZ did not develop after a month of stabilizing its effective dose. MOD was then added to the treatment scheme at a mean dose of 110 mgld. Epworth Sleepiness Scale (ESS) was used to measure sleepiness before and after MOD addition and t-test was used for comparison. Results: A week after MOD addition to the treatment scheme, patients started improving in the sense that sedation was no longer a subjective complaint. Sleep hours per day had decreased from mean 11 before, to mean 8 after MOD initiation according to staff observations. A significant decrease in ESS score was observed as well. Dose of CLZ did not decrease. The above effect of MOD was maintained at follow-up examinations conducted once a week for 3 months following patients' discharge. Side effects were not noted after MOD addition, both during hospitalization and upon follow-ups after discharge. Conclusions and Discussion: MOD seemed effective in treating CLZ-associated sedation and sleepiness in all 10 cases of our sample, maintaining its effect for at least 3 months. Psychosis was not exacerbated after MOD addition in any of our cases in contrast to one citation traced mentioning one case report
S491
where psychosis worsened after addition of MOD(3). Possibly, further studies with larger patient samples are needed to confirm our findings. Clinical studies with placebo have to be performed as well, in order to establish MOD efficacy in treating sleepiness and sedation associated with CLZ in patients with schizophrenia. References [I] Wisor J.P., Eriksson K.S., "Dopaminergic-adrenergic interactions in the wake promoting mechanism ofmodafinil". Neuroscience, Volume 132, Issue 4, 2005, Pages 1027-1034. [2] Ferraro L., Antonelli T., O'Connor W. T., Tanganelli S., Rambert F. A., Fuxe K., "The effects of modafinil on striatal, pallidal and nigral GABA and glutamate release in the conscious rat: evidence for a preferential inhibition of striata-pallidal GABA transmission". Neuroscience Letters, Volume 253, Issue 2, 4 September 1998, Pages 135-138 [3] Narendran et aI., "Is Psychosis Exacerbated by Modafinil?". Arch Gen Psychiatry.2002; 59: 292-293.
1P.3.a.0201 Gender differences in hospitalised schizophrenic patients M. Serrano Vazquez 1 ., M.M. Serrano Carton1, M.C. Serrano Carton 1 . 1 Complejo Hospitalario Juan Canalejo, psychiatry, Coruna, Spain Background: The results of the current study indicate that men and women have an equal lifetime risk for schizophrenia. However, schizophrenia tends to strike women 3-4 years later than men. Most ofmen develop schizophrenia between 15 and 25 years. For women the period of maximum onset is between 15 and 30 with a smaller peak between 45 and 50 (after menopause). Women also tend to have milder forms of the disease in their younger year than their male counterparts do. But, in the later years, symptoms in men tend to decrease in severity while women often have a renewed onset of psychotic symptoms and a worse course of the disease. Objective: Gender differences in onset of illness, clinical presentation, response to treatment, course, and biologic measures have been consistently reported in patients with chronic schizophrenia. The purpose of this study is to determine possible differences in the average stay, symptoms to admission as well as other gender-related issues. Method: By means of a retrospective analysis of the data gathered in clinical histories of 532 patients admitted to our unit for psychiatric hospitalization during the past five years, several variables were collected and analyzed by statistical methods. The analyzed data make reference to the incidence of the disease, the age, the average stay, the personal and familiar antecedents, the labor and socioeconomic antecedents, the psychopharmacological treatments, the subtype of schizophrenia and the premorbid personality. Diagnosis was made using the Structured Clinical Interview for the DSM-IV-TR. Data analysis was performed using SPSS 10.0 for Windows. Results: The sample constitutes 532 patients (366 men and 166 women), the prevalence ratio of men/women was 2/1. Age differences were significant, with an earlier onset in men. There is no difference, other than age, in the symptom-related course of the disease between men and women. The average stay was similar in both cases. Conclusions: We found concordant results with the obtained in previous studies, with a higher incidence and an earlier onset of schizophrenia in men. The most consistent result found is the 3--4 year age difference between men and women. The protective effects of oestrogen raise the question of new treatments using