- Email: [email protected]
Fluvoxamine in childhood OCD: Long-term treatment
s307
P3 Anxiety disorders and anxiolytics
treatment due to adverse events (urticaria, eating cessation, headache with gastrointestinal distress, and perceived loss of generalized memory). In those patients continuing treatment, topiramate has remained effective for 30.9 weeks f 23.1 (range 2-70 weeks), without evidence of tolerance. There was no significant association between duration of PTSD symptoms and dosage at full response (r = 0.15, NS). Conclusion: These open-label findings suggest a role for topiramate in the treatment of PTSD. Preliminary observations suggest that bipolar comorbidity may alter therapeutic dosage. Further controlled clinical trials are warranted to investigate the effects of topiramate, particularly in PTSD populations with less comorbidity and with expanded attention to other PTSD symptoms with limited responsiveness to current drug therapies, such as difficulty with concentration.
clinically meaningful laboratory or vital sign abnormalities were seen with long-term fluvoxamine treatment. Conclusions: In this large, long-term pharmacological treatment trial of childhood OCD, fluvoxamine continued to be safe and effective. Subjects treated with fluvoxamine in the long-term trial demonstrated continued improvement with an average of 40-50% reduction in CYBOCS score in the first 4-6 months of treatment. Side effects were mild and resulted in few patients discontinuing treatment.
lP.3.026] Life Events in high-dose and low-dose benzodiazepine
users
N.F! Lekka, C. Paschalis, S. Beratis. Department of Psychiatvy, Uniuersity of Patras Medical School, Patras, Greece
-1
Fluvoxamine in childhood
OCD: long-term
treatment J. Walkup, E. Reeve, J. Yaruyura-Tobias, L. Wong, J. Claghom, G.
GafTney, J. Greist, D. Holland, B. McConville, T. Pibott, M. Pravetz, L. Scahill, M. Riddle. Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Introduction: Obsessive compulsive disorder (OCD) is a common psychiatric disorder that frequently begins in childhood. Fluvoxamine, a selective serotonin reuptake inhibitor, has been demonstrated to be safe and efficacious in the short-term treatment of childhood OCD in a lo-week, multicenter, double-blind, placebo-controlled trial (short-term study, Riddle et al., submitted). Little is known about the long-term safety and efficacy of pharmacological treatment in childhood OCD. The aim of the current study is to evaluate whether fluvoxamine is safe and efficacious in the long-term treatment of childhood OCD. Methods: Subjects, ages 8-17 years, with OCD (DSM-IIIR) who completed the short-term study were eligible to participate in the yearlong safety and efficacy study of fluvoxamine (long-term study). Four subject groups entered the long-term study from the short-term study: Group 1 - subjects on fluvoxarnine who completed the short-term study (N = 34); Group 2 - subjects on placebo who completed the short-term study (N = 36); Group 3 subjects on fluvoxamine (N = 9) who left the short-term study at week six due to lack of efficacy; and Group 4 subjects on placebo (N = 19) who left the short-term study at week six due to lack of efficacy. All subjects (Total N = 99), regardless of treatment status in the short-term study, were titrated up to fluvoxamine 200 mg/day over the first 3 weeks of the long-term study. Subjects were seen monthly for assessments of efficacy and monitoring of adverse events. Laboratory evaluation occurred every three months. Efficacy was measured with the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the NIMH-Global OC Scale and Clinical Global Impression Scales for clinician, parent and child (CGI). The intent-to-treat efficacy sample (ITT, all subjects who received one dose of medication) was analyzed in the last-observation-carry-forward analysis, to endpoint. Results: The overall ITT efficacy sample for the long-term study (N = 98) had a mean short-term study baseline CY-BOCS total score of 24.1. The mean decrease in CY-BOCS score was 10.2 points (42%) at endpoint in the carry forward analysis. Subjects who were treated with placebo in the short-term study (Groups 2 & 4, N = 55) showed marked improvement in symptoms in the long-term trial. From the baseline visit in the short-term study, CY-BOCS scores in subjects from Groups 2 & 4 declined from 24.2 to 12.7 (48%) by the end of the long-term study. Subjects who improved on fluvoxamine in the short-term trial (Group 1, N = 34) continued to improve during the long-term trial. On average subjects in Group 1 experienced a decrease from 24.2 to 16.8 (31%) in CY-BOCS score during the short-term study and a decrease from 16.8 to 14.1 in CY-BOCS score in the long-term study, a total decrease of 10.1 points (42%) in CY-BOCS score. Similar improvements were seen on the secondary outcome measures (NIMH-OC, the CGIs). Of the 9 subjects who did not improve on fiuvoxamine in the short-term study (Group 3), 3 discontinued treatment due to lack of efficacy. Side effects were mild and included insomnia, asthenia, nausea, hyperkinesia and nervousness; 11 subjects discontinued treatment due to side effects. No
Purpose of the Study: To investigate the role of stressful life circumstances on patients with different patterns of benzodiazepine (BZD) use, which has not been previously studied. Method: 174 patients [37 high-dose regular users (HDRU), 87 lowdose regular users (LDRU), 50 low-dose occasional users (LDOU)] and 37 controls matched with high-dose regular users were examined. The estimation of the BZD dose, the definition of HDRU, and the demographic features of all patients and controls have been previously described’. All subjects were investigated by using the 43-item Holmes and Rahe Social Readjustment Rating Scale (SRRS)*, the DSM-III-R Axis IV Scale (Severity of Psychosocial Stressors Scale), Zung’s selfrating depression scale (SDS) and the 17-item Hamilton rating scale for depression (HAMD). Results: For the SRRS score there was a highly significant difference between HDRU and control subjects (p < 0.0001) and a significant difference between HDRUs and LDRUs (p < 0.017). For the DSM-IIIR axis IV rating there was a highly significant difference between HDRUs and control subjects (p < O.OOOl), whereas the difference between HDRUs and LDRUs just failed to reach statistical significance (p = 0.068). Spearman’s rank correlation showed a highly significant positive correlation between SRRS score and DSM-III-R axis IV ratings @ < 0.0001). All groups of BDZ users and the control subjects differ significantly in the HAMD score and in the SDS score (p < 0.0001 and p < 0.00001 respectively). The Mann-Whitney U test for the HAMD and the SDS scores showed significant differences between all possible combinations of the four groups of subjects studied. Spearman’s rank correlation showed significant positive correlation between BZD dose and both
HAMD and SDS scores (p < 0.0001 and p < 0.0001 respectively), whereas the correlation between BZD dose and SRRS score was not statistically significant (p = 0.44). Conclusions: High-dose and low-dose regular BZD users are taking BZDs not only to protect themselves from the impact of life events, but also to cope with symptoms of depression. Careful consideration of antidepressant treatment and adequate social support may help in many cases to avoid the use, or reduce the dose of BZD taken. References
[ 11 Lekka NP, Paschalis C, Beratis S. Nicotine, caffeine and alcohol use in highand low-dosebenzodiazepineusers. Drug and Alcohol Dependence 1997; 45: 207-212. [2] Holmes TH and Rahe RH. The social readjustment rating scale. Journal of Psychosomatic Research 1967; 11: 213-218.
)p.3.027/
The effect of the benzodiazepine receptor antagonist flumazenil on the anticonflict action of ACPC and CGP 37949 in rats
E. Tatarczyiiska, E. Chojnacka-Wbjcik, E. Przegaliiiski. Znstitute of Pharmacology, Polish Academy of Sciences, Kmkdw, Poland
I-Aminocyclopropanecarboxylic glycinea
receptors
acid (ACPC),
and a functional
antagonist
a partial agonist at at the NMDA receptor
P3 Anxiety disorders and anxiolytics
treatment due to adverse events (urticaria, eating cessation, headache with gastrointestinal distress, and perceived loss of generalized memory). In those patients continuing treatment, topiramate has remained effective for 30.9 weeks f 23.1 (range 2-70 weeks), without evidence of tolerance. There was no significant association between duration of PTSD symptoms and dosage at full response (r = 0.15, NS). Conclusion: These open-label findings suggest a role for topiramate in the treatment of PTSD. Preliminary observations suggest that bipolar comorbidity may alter therapeutic dosage. Further controlled clinical trials are warranted to investigate the effects of topiramate, particularly in PTSD populations with less comorbidity and with expanded attention to other PTSD symptoms with limited responsiveness to current drug therapies, such as difficulty with concentration.
clinically meaningful laboratory or vital sign abnormalities were seen with long-term fluvoxamine treatment. Conclusions: In this large, long-term pharmacological treatment trial of childhood OCD, fluvoxamine continued to be safe and effective. Subjects treated with fluvoxamine in the long-term trial demonstrated continued improvement with an average of 40-50% reduction in CYBOCS score in the first 4-6 months of treatment. Side effects were mild and resulted in few patients discontinuing treatment.
lP.3.026] Life Events in high-dose and low-dose benzodiazepine
users
N.F! Lekka, C. Paschalis, S. Beratis. Department of Psychiatvy, Uniuersity of Patras Medical School, Patras, Greece
-1
Fluvoxamine in childhood
OCD: long-term
treatment J. Walkup, E. Reeve, J. Yaruyura-Tobias, L. Wong, J. Claghom, G.
GafTney, J. Greist, D. Holland, B. McConville, T. Pibott, M. Pravetz, L. Scahill, M. Riddle. Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Introduction: Obsessive compulsive disorder (OCD) is a common psychiatric disorder that frequently begins in childhood. Fluvoxamine, a selective serotonin reuptake inhibitor, has been demonstrated to be safe and efficacious in the short-term treatment of childhood OCD in a lo-week, multicenter, double-blind, placebo-controlled trial (short-term study, Riddle et al., submitted). Little is known about the long-term safety and efficacy of pharmacological treatment in childhood OCD. The aim of the current study is to evaluate whether fluvoxamine is safe and efficacious in the long-term treatment of childhood OCD. Methods: Subjects, ages 8-17 years, with OCD (DSM-IIIR) who completed the short-term study were eligible to participate in the yearlong safety and efficacy study of fluvoxamine (long-term study). Four subject groups entered the long-term study from the short-term study: Group 1 - subjects on fluvoxarnine who completed the short-term study (N = 34); Group 2 - subjects on placebo who completed the short-term study (N = 36); Group 3 subjects on fluvoxamine (N = 9) who left the short-term study at week six due to lack of efficacy; and Group 4 subjects on placebo (N = 19) who left the short-term study at week six due to lack of efficacy. All subjects (Total N = 99), regardless of treatment status in the short-term study, were titrated up to fluvoxamine 200 mg/day over the first 3 weeks of the long-term study. Subjects were seen monthly for assessments of efficacy and monitoring of adverse events. Laboratory evaluation occurred every three months. Efficacy was measured with the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the NIMH-Global OC Scale and Clinical Global Impression Scales for clinician, parent and child (CGI). The intent-to-treat efficacy sample (ITT, all subjects who received one dose of medication) was analyzed in the last-observation-carry-forward analysis, to endpoint. Results: The overall ITT efficacy sample for the long-term study (N = 98) had a mean short-term study baseline CY-BOCS total score of 24.1. The mean decrease in CY-BOCS score was 10.2 points (42%) at endpoint in the carry forward analysis. Subjects who were treated with placebo in the short-term study (Groups 2 & 4, N = 55) showed marked improvement in symptoms in the long-term trial. From the baseline visit in the short-term study, CY-BOCS scores in subjects from Groups 2 & 4 declined from 24.2 to 12.7 (48%) by the end of the long-term study. Subjects who improved on fluvoxamine in the short-term trial (Group 1, N = 34) continued to improve during the long-term trial. On average subjects in Group 1 experienced a decrease from 24.2 to 16.8 (31%) in CY-BOCS score during the short-term study and a decrease from 16.8 to 14.1 in CY-BOCS score in the long-term study, a total decrease of 10.1 points (42%) in CY-BOCS score. Similar improvements were seen on the secondary outcome measures (NIMH-OC, the CGIs). Of the 9 subjects who did not improve on fiuvoxamine in the short-term study (Group 3), 3 discontinued treatment due to lack of efficacy. Side effects were mild and included insomnia, asthenia, nausea, hyperkinesia and nervousness; 11 subjects discontinued treatment due to side effects. No
Purpose of the Study: To investigate the role of stressful life circumstances on patients with different patterns of benzodiazepine (BZD) use, which has not been previously studied. Method: 174 patients [37 high-dose regular users (HDRU), 87 lowdose regular users (LDRU), 50 low-dose occasional users (LDOU)] and 37 controls matched with high-dose regular users were examined. The estimation of the BZD dose, the definition of HDRU, and the demographic features of all patients and controls have been previously described’. All subjects were investigated by using the 43-item Holmes and Rahe Social Readjustment Rating Scale (SRRS)*, the DSM-III-R Axis IV Scale (Severity of Psychosocial Stressors Scale), Zung’s selfrating depression scale (SDS) and the 17-item Hamilton rating scale for depression (HAMD). Results: For the SRRS score there was a highly significant difference between HDRU and control subjects (p < 0.0001) and a significant difference between HDRUs and LDRUs (p < 0.017). For the DSM-IIIR axis IV rating there was a highly significant difference between HDRUs and control subjects (p < O.OOOl), whereas the difference between HDRUs and LDRUs just failed to reach statistical significance (p = 0.068). Spearman’s rank correlation showed a highly significant positive correlation between SRRS score and DSM-III-R axis IV ratings @ < 0.0001). All groups of BDZ users and the control subjects differ significantly in the HAMD score and in the SDS score (p < 0.0001 and p < 0.00001 respectively). The Mann-Whitney U test for the HAMD and the SDS scores showed significant differences between all possible combinations of the four groups of subjects studied. Spearman’s rank correlation showed significant positive correlation between BZD dose and both
HAMD and SDS scores (p < 0.0001 and p < 0.0001 respectively), whereas the correlation between BZD dose and SRRS score was not statistically significant (p = 0.44). Conclusions: High-dose and low-dose regular BZD users are taking BZDs not only to protect themselves from the impact of life events, but also to cope with symptoms of depression. Careful consideration of antidepressant treatment and adequate social support may help in many cases to avoid the use, or reduce the dose of BZD taken. References
[ 11 Lekka NP, Paschalis C, Beratis S. Nicotine, caffeine and alcohol use in highand low-dosebenzodiazepineusers. Drug and Alcohol Dependence 1997; 45: 207-212. [2] Holmes TH and Rahe RH. The social readjustment rating scale. Journal of Psychosomatic Research 1967; 11: 213-218.
)p.3.027/
The effect of the benzodiazepine receptor antagonist flumazenil on the anticonflict action of ACPC and CGP 37949 in rats
E. Tatarczyiiska, E. Chojnacka-Wbjcik, E. Przegaliiiski. Znstitute of Pharmacology, Polish Academy of Sciences, Kmkdw, Poland
I-Aminocyclopropanecarboxylic glycinea
receptors
acid (ACPC),
and a functional
antagonist
a partial agonist at at the NMDA receptor