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P.6.061 The effect of risperidone on perceptual disturbances in borderline personality disorders
P6
Other topics
The different reasons of admission were: depression 34%, substance abuse 33%, relational conflict 26%, neurotic problems 21% (hyperventilation, anxiety, anorexia, automutilation, somatisation), intoxication 20%, psychosis 14%, agitation 11% generation conflict 6%, social problem 6%, suicide attempt (not intoxication) 3%, delirium 2%, mania 2%. After screening, 26% of the patients were sent home without follow up, 14% were scheduled for a polyclinic, 15% were admitted in a psychiatric department of a general hospital, 34% were admitted in a mental hospital and 7% in a general hospital. 2% ran away and 2% left against advice.
~ T h e
effect of risperidone on perceptual disturbances in borderline personality disorders
S. Tuinier, W.M.A. Verhoeven, Y.W.M.M. van den Berg, G. Marijnissen, EJ.M. van Ooy, L. Pepplinkhuizen. Vincent van Gogh Institute for
Psychiatry Department of Biological Psychiatry, AC Venray, The Netherlands" Biological research in borderline personality disorders (BPD) and treatment studies in BPD with neuroleptics, antidepressants and mood stabilizers have generally yielded inconsistent results. This inconsistency is partly related to the diagnostic heterogeneity of this patient group and partly explained by the difficulties in performing clinical studies in patients with this kind of personality disorders. Based on the extensive preclinical data and the limited findings with hormonal challenge tests in humans, it can be postulated that serotonergic as well as stress hormonal systems and their reciprocal interaction, may be involved in the pathophysiology of BPD (Tuinier et al. 1995, 1996). Since BPD comprises both functional disturbances and subsequent complex behavioral adaptation, the most rational approach is the dissection of the spectrum of psychological and behavioral abnormalities into potentially biologically relevant features. Common in most BPD patients is hypersensitivity for sensory input resulting in LSD-tike symptoms such as derealization, depersonalization, affective instability and visual dysperceptions, that are thought to be mediated via 5-HT2 receptor systems. In line with this dimensional approach, treatment with 5-HT2 receptor antagonistic compounds can be hypothesized to ameliorate this cluster of symptoms. The present study was designed to evaluate treatment effects of the Dz-5-HT2 antagonist risperidone on LSD-like symptoms in a group of carefully diagnosed, both categorically and dimensionally, female inpatients with BPD. Diagnostic procedures included the revised version of the Structured Interview for the Diagnosis of Personality Disorders (SIDP-R), the Three Dimensional Personality Questionnaire (TPQ) and the Experiential World Inventory (EWI). Patients showing sufficient perceptual disturbances according to the scores on the EWI, were subsequently treated with risperidone following an open design for a period of 3 months in dosages varying between 2 and 4 mg daily. Treatment effects were evaluated by means of target scores derived form the EWI, the CGI and the Barret Impulsivity Scale (BIS). In a first pilot experiment, including 8 patients with BPD, 6 improved upon treatment with risperidone (Tuinier et al., 1995). The present study comprised sofar 7 patients of whom 5 entered the treatment period. Two patients prematurely discontinued and 3 completed the study period. Interim analysis of the results of both the pilot experiment and the present study revealed that of the 13 patients who completed the study period of three months, 8 showed a clinically relevant reduction of target symptoms, particularly dysperceptions, derealization and depersonalization. These preliminary results support the hypothesis that abnormalities in 5-HT receptor functionality may underlie a specific cluster of BPD symptoms.
References Tuinier S., Verhoeven W.M.A., Hofma E., Pepplinkhuizen L Borderline personality disorders; new vistas in the pharmacotherapy. Poster presented at the 23rd Congress of the Dutch Society of Psychiatry, 1995. Tuinier S., Verhoeven W.M.A., Van Praag H.M. Serotonin and disruptive behavior; A critical evaluation of the clinical data. Human Psychopharmacology, I I : 469-482; 1996.
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$283
Serotonergic parameters and stereotyped behavior in mentally retarded subjects
W.M.A. Verhoeven, S. Tuinier, Y.W.M.M. van den Berg, A.M.W. Coppus, L. Pepplinkhuizen, D. Fekkes. Vincent van Gogh
Institute for Psychiatry, Department of Biological Psychiatry, Venra), 'The Netherlands In mentally retarded subjects, stereotyped behavior (SB) is frequently observed irrespective of the etiology of mental retardation and life-time often precedes self-injurious behavior. In phenomenological terms, SB shows striking similarities with obsessive compulsive disorders. Given the close affinity between compulsivehitualistic behavior and SB, a common neurobiological substrate can be assumed of which 5-hydroxytryptamine (5-HT) systems seem to be of particular importance. Moreover, SB regularly coincides with symptoms of behavioral disinhibition which is in term also closely related to 5-HT-ergic functioning (Tuinier et al., 1996). The enhancement of 5-HT metabolism via treatment with monoamine reuptake inhibitors with a preferential effect on 5-HT neurotransmission such as clomipramine, has been demonstrated to reduce obsessive-compulsive symptoms and stereotyped movement abnormalities (Lewis et al, 1995). The present study was designed to investigate peripheral 5-HT-ergic parameters in a group of mentally retarded subjects with longlasting SB as compared to controls, matched, as close as possible, for age, sex and level of mental retardation. Included were 20 subjects with SB (mean age: 39 yrs; 12 males, 8 females) and 17 controls (mean age 40 yrs; 7 males, 10 females). All were in the range from severe to profound mental retardation. According to ICD-10 criteria, in the SB group atypical autism, unspecified bipolar disorder, unspecified recurrent depressive disorder and OCD could be diagnosed in 4, 2, 2 and 1 subject respectively, whereas the control group comprised only 1 subject with atypical autism. To assess SB, the factors Irritability, Stereotypic Behavior and Hyperactivity of the Aberrant Behavior Checklist (ABC) were rated, yielding mean scores (4- SD) of 7.14 4- 5.5, 10.76 ± 4.1, 7.86 4- 5.0 respectively for the SB group and 1.71 ± 2.3. 0.53 4- 0.8, 1.76 4- 2.3 respectively for the control group. Concerning the biochemical analyses, significant differences between the groups were found, in that phtsma levels of the amino acid tryptophan and of the major 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA) were higher in the SB-group. Ratio's of aminoacids as well as 5-HT in whole blood and platelets did not differ. It is concluded that disturbances in 5-HT metabolism may be implicated in the pathophysiology of SB.
References Lewis, M.H, Bodfish, J.W., Powell, S.B., Golden, R.N. Clomipramine treatment for stereotypy and related repetitive movement disorders associated with mental retardation. American Journal on Mental Retardation, 100: 299-312; 1995. Tuinier S., Verhoeven W.M.A., Van Praag H.M. Serotonin and disnlptive behavior; A critical evaluation of lhe clinical data. Human Psychopharmacology, 11: 469-482" 1996.
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Lorazepam for stupor and mutism: A double-blind placebo-controlled cross-over study
H. Wetzel, C.J. Klawe, M.J. Mfiller, J. Wiesner, O. Benkert. Department
of Psychiatry University of Mainz, German)" In a number of case reports, retrospective studies and open clinical trials, the beneficial effects of benzodiazepines on catatonic symptoms have been described. In order to substantiate these observations and to investigate the efficacy of the benzodiazepine agortist lorazepam in retarded catatonia, a prospective, randomized, double-b]~ind placebo-controlled cross-over study was performed in 10 patients suffering from a catatonic syndrome, irrespective of nosological classification, with stupor and mutism as target symptoms. Patients were randomly assigned to be administered either lorazepam 2 mg or saline i.v. on 2 consecutive days for 2 hours, and a structured interview was recorded on video. For assessment of response, time-blind video ratings were performed using the IMPS subscore "retardation/apathy", a 5-point clinical global improvement scale, and an abridged version of the Bush-Francis Catatonia Rating Scale as outcome parameters.
Other topics
The different reasons of admission were: depression 34%, substance abuse 33%, relational conflict 26%, neurotic problems 21% (hyperventilation, anxiety, anorexia, automutilation, somatisation), intoxication 20%, psychosis 14%, agitation 11% generation conflict 6%, social problem 6%, suicide attempt (not intoxication) 3%, delirium 2%, mania 2%. After screening, 26% of the patients were sent home without follow up, 14% were scheduled for a polyclinic, 15% were admitted in a psychiatric department of a general hospital, 34% were admitted in a mental hospital and 7% in a general hospital. 2% ran away and 2% left against advice.
~ T h e
effect of risperidone on perceptual disturbances in borderline personality disorders
S. Tuinier, W.M.A. Verhoeven, Y.W.M.M. van den Berg, G. Marijnissen, EJ.M. van Ooy, L. Pepplinkhuizen. Vincent van Gogh Institute for
Psychiatry Department of Biological Psychiatry, AC Venray, The Netherlands" Biological research in borderline personality disorders (BPD) and treatment studies in BPD with neuroleptics, antidepressants and mood stabilizers have generally yielded inconsistent results. This inconsistency is partly related to the diagnostic heterogeneity of this patient group and partly explained by the difficulties in performing clinical studies in patients with this kind of personality disorders. Based on the extensive preclinical data and the limited findings with hormonal challenge tests in humans, it can be postulated that serotonergic as well as stress hormonal systems and their reciprocal interaction, may be involved in the pathophysiology of BPD (Tuinier et al. 1995, 1996). Since BPD comprises both functional disturbances and subsequent complex behavioral adaptation, the most rational approach is the dissection of the spectrum of psychological and behavioral abnormalities into potentially biologically relevant features. Common in most BPD patients is hypersensitivity for sensory input resulting in LSD-tike symptoms such as derealization, depersonalization, affective instability and visual dysperceptions, that are thought to be mediated via 5-HT2 receptor systems. In line with this dimensional approach, treatment with 5-HT2 receptor antagonistic compounds can be hypothesized to ameliorate this cluster of symptoms. The present study was designed to evaluate treatment effects of the Dz-5-HT2 antagonist risperidone on LSD-like symptoms in a group of carefully diagnosed, both categorically and dimensionally, female inpatients with BPD. Diagnostic procedures included the revised version of the Structured Interview for the Diagnosis of Personality Disorders (SIDP-R), the Three Dimensional Personality Questionnaire (TPQ) and the Experiential World Inventory (EWI). Patients showing sufficient perceptual disturbances according to the scores on the EWI, were subsequently treated with risperidone following an open design for a period of 3 months in dosages varying between 2 and 4 mg daily. Treatment effects were evaluated by means of target scores derived form the EWI, the CGI and the Barret Impulsivity Scale (BIS). In a first pilot experiment, including 8 patients with BPD, 6 improved upon treatment with risperidone (Tuinier et al., 1995). The present study comprised sofar 7 patients of whom 5 entered the treatment period. Two patients prematurely discontinued and 3 completed the study period. Interim analysis of the results of both the pilot experiment and the present study revealed that of the 13 patients who completed the study period of three months, 8 showed a clinically relevant reduction of target symptoms, particularly dysperceptions, derealization and depersonalization. These preliminary results support the hypothesis that abnormalities in 5-HT receptor functionality may underlie a specific cluster of BPD symptoms.
References Tuinier S., Verhoeven W.M.A., Hofma E., Pepplinkhuizen L Borderline personality disorders; new vistas in the pharmacotherapy. Poster presented at the 23rd Congress of the Dutch Society of Psychiatry, 1995. Tuinier S., Verhoeven W.M.A., Van Praag H.M. Serotonin and disruptive behavior; A critical evaluation of the clinical data. Human Psychopharmacology, I I : 469-482; 1996.
•]
$283
Serotonergic parameters and stereotyped behavior in mentally retarded subjects
W.M.A. Verhoeven, S. Tuinier, Y.W.M.M. van den Berg, A.M.W. Coppus, L. Pepplinkhuizen, D. Fekkes. Vincent van Gogh
Institute for Psychiatry, Department of Biological Psychiatry, Venra), 'The Netherlands In mentally retarded subjects, stereotyped behavior (SB) is frequently observed irrespective of the etiology of mental retardation and life-time often precedes self-injurious behavior. In phenomenological terms, SB shows striking similarities with obsessive compulsive disorders. Given the close affinity between compulsivehitualistic behavior and SB, a common neurobiological substrate can be assumed of which 5-hydroxytryptamine (5-HT) systems seem to be of particular importance. Moreover, SB regularly coincides with symptoms of behavioral disinhibition which is in term also closely related to 5-HT-ergic functioning (Tuinier et al., 1996). The enhancement of 5-HT metabolism via treatment with monoamine reuptake inhibitors with a preferential effect on 5-HT neurotransmission such as clomipramine, has been demonstrated to reduce obsessive-compulsive symptoms and stereotyped movement abnormalities (Lewis et al, 1995). The present study was designed to investigate peripheral 5-HT-ergic parameters in a group of mentally retarded subjects with longlasting SB as compared to controls, matched, as close as possible, for age, sex and level of mental retardation. Included were 20 subjects with SB (mean age: 39 yrs; 12 males, 8 females) and 17 controls (mean age 40 yrs; 7 males, 10 females). All were in the range from severe to profound mental retardation. According to ICD-10 criteria, in the SB group atypical autism, unspecified bipolar disorder, unspecified recurrent depressive disorder and OCD could be diagnosed in 4, 2, 2 and 1 subject respectively, whereas the control group comprised only 1 subject with atypical autism. To assess SB, the factors Irritability, Stereotypic Behavior and Hyperactivity of the Aberrant Behavior Checklist (ABC) were rated, yielding mean scores (4- SD) of 7.14 4- 5.5, 10.76 ± 4.1, 7.86 4- 5.0 respectively for the SB group and 1.71 ± 2.3. 0.53 4- 0.8, 1.76 4- 2.3 respectively for the control group. Concerning the biochemical analyses, significant differences between the groups were found, in that phtsma levels of the amino acid tryptophan and of the major 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA) were higher in the SB-group. Ratio's of aminoacids as well as 5-HT in whole blood and platelets did not differ. It is concluded that disturbances in 5-HT metabolism may be implicated in the pathophysiology of SB.
References Lewis, M.H, Bodfish, J.W., Powell, S.B., Golden, R.N. Clomipramine treatment for stereotypy and related repetitive movement disorders associated with mental retardation. American Journal on Mental Retardation, 100: 299-312; 1995. Tuinier S., Verhoeven W.M.A., Van Praag H.M. Serotonin and disnlptive behavior; A critical evaluation of lhe clinical data. Human Psychopharmacology, 11: 469-482" 1996.
•
Lorazepam for stupor and mutism: A double-blind placebo-controlled cross-over study
H. Wetzel, C.J. Klawe, M.J. Mfiller, J. Wiesner, O. Benkert. Department
of Psychiatry University of Mainz, German)" In a number of case reports, retrospective studies and open clinical trials, the beneficial effects of benzodiazepines on catatonic symptoms have been described. In order to substantiate these observations and to investigate the efficacy of the benzodiazepine agortist lorazepam in retarded catatonia, a prospective, randomized, double-b]~ind placebo-controlled cross-over study was performed in 10 patients suffering from a catatonic syndrome, irrespective of nosological classification, with stupor and mutism as target symptoms. Patients were randomly assigned to be administered either lorazepam 2 mg or saline i.v. on 2 consecutive days for 2 hours, and a structured interview was recorded on video. For assessment of response, time-blind video ratings were performed using the IMPS subscore "retardation/apathy", a 5-point clinical global improvement scale, and an abridged version of the Bush-Francis Catatonia Rating Scale as outcome parameters.