- Email: [email protected]
Clozapine: efficacy in treatment-resistant schizophrenic patients
x26
Poster B. Psychopharmaca
avoidance scores dropped from 40.11-23.2 on baseline level to 12.1 k8.8 four weeks later. According to these results, fluoxetine becoming the pharmacological treatment of choice for social phobia.
References Van Amerigen M., Mancini, C., Streimer, D.L. (1993). Fluoxetine efficacy in social phobia. J Clin Psychiatry 54, (1): 27. Versiani, M., Nardi, A.E., Mindim, F.D., Alves, A.B., Liebowitz, M.R., Amrein, R. (1992). Pharmacotherapy in Social Phobia. A controlled Study with Moclobemide and Phenelzine. Br J Psychiatry 161: 353. DeVeaguh-Geiss, J., Bell, J. (1994). Multicentre trial of a 5-HT, antagonist ondantseron, in social phobia. Poster presented at the ACNP, 1994.
I3 61 L-l
Double-blind, placebo-/comparator-controlled study of once daily venlafaxine XR and buspirone in outpatients with generalized anxiety disorder
A.T. De&m, R. Entsuah, T. Haskins and R. Rudolph. For the Venlafaxine XR 214 Study Group Wyeth-Ayers Research, Box 42528, Philadelphia, PA 19101
daily in three intakes. The intensity of the anxious symptoms has been assessed by means of Hamilton Rating Scale for Anxiety and CGI; the evaluations being carried out in weeks 2, 4 and 8 respectively. Findings: We found out a significant decrease of anxious symptoms (Hamilton Rating Scale show a decreasing score from 21-22 to 2-3 in over 79% patients), a reduced influence on psychomotor functioning and a low incidence of side effects. Conclusion: Alprazolam (Xanax) seems to act rapidly and efficiently on anxious symptoms from Generalized Anxiety Disorder, with a good tolerance that recommends it in ambulatory therapy.
B-63 El
Double-blind, placebo-controkled study of once daily venlafaxine XR in outpatients with generalized anxiety disorder
J.T. Haskins, R. Rudolph*, A. Pallay and A.T. Derivan. For the Venlafmine XR 210 Study Group, Wyeth-Ayerst Research, Box 42528, Philudelphia, PA 19101
This randomized, double-blind, placebo- and comparator-controlled, 8week study compared the safety and anxiolytic efficacy of once daily venlafaxine XR (V-XR) 75 mg or 150 mg with placebo (Pbo) and buspirone (Bsp) 30 mg m outpatients with Generalized Anxiety Disorder (GAD). V-XR is a new formulation of the serotonin norepinephrine reuptake inhibitor (SNRI) antidepressant, venlafaxine (Effexor@). Design: Patients (n=405) who met DSM-IV criteria for GAD, but not for major depression, and who did not improve during a 7?3-day pre-study placebo period could be enrolled into the study. Patients who had a current, or within 6 months of study day 1, diagnosis of Major Depressive Disorder (using structured interview as a guide to complete diagnostic criteria), had a Raskin Depression Scale (RDS) score greater than the Covi Anxiety Scale score, had a total RDS score greater than 9 or who had any single RDS item score greater than 3 were excluded from the study. Patients began treatment with V-XR 75 mg, Bsp 15 m, or Pbo. At day 8, one V-XR group increased to 150 mg/da By day 8, the Bsp group had titrated to 30 mg/day. The primary efficacy variables, i.e., HAM-A Total, HAM-A psychic anxiety factor, and CGI-severity, with a secondary variable, the Hospital Anxiety and Depression Scale (HAD) anxiety factor were evaluated at weeks (wks) 1, 2, 3, 4, 6, 8 and final-on-therapy (FOT). Results: Statistically significant (~50.05) results are shown for the observed-cases analysis in the intent-to-treat population (n=369). Overall F-tests are significant unless noted. For the HAM-A Total, V-XR 75 mg was better than Pbo at wks 2, 3, 4 and FOT, overall F-test at FOT p=O.lO. For the HAM-A psychic anxiety factor, V-XR 75 and 150 mg were better than Pbo at wks 2, 3, 4 and FOT. Bsp was not significantly different from Pbo at any time point for either variable, For CGI severity, V-XR 75 and 150 mg were better than Pbo at wks 2, 3, and 4. V-XR 75 mg was also better than Pbo at wk 8 and FOT. For HAD, V-XR 75 mg was better than Pbo and Bsp at wks 1, 2, 3, 4, 6, 8 and FOT; V-XR 150 mg was better than Pbo at wks 3, 4, and FOT and better than Bsp at wks 1, 4, 6, and FOT. For response rates, V-XR 75 mg was better than Pbo for HAM-A Total at wks 6, 8 and FOT and or CGI-Improvement at wks 3,4, 6, 8 and FOT. Safety: The safety profile was consistent with that of EffexorO and V-XR use in depressed patients. Conclusion: This study showed significant advantages for venlafaxine XR (75 or 150 mg/day) vs Pbo to treat outpatients with GAD who do not have comorbid major depression, and suggested that V-XR also has significant advantages vs Bsp.
This randomized, double-blind, placebo-controlled, I-week study compared the safety and anxiolytic efficacy of once daily venlafaxine XR (V-XR) 75 mg, 150 mg, and 225 mg with placebo (Pbo) in outpatients with Generalized Anxiety Disorder (GAD). V-XR is a new formulation of the serotonin norepinephrine reuptake inhibitor (SNRI) antidepressant, venlafaxine (Effexor”). Design: Patients (n=377) who met DSM-IV criteria for GAD, but not major depressive disorder, and who did not improve significantly during a 4 to 10 day prestudy washout period could be enrolled into the study. Patients who had a current, or within 6 months of study day 1, diagnosis of Major Depressive Disorder (using structured interview as a guide to complete diagnostic criteria), had a Raskin Depression Scale (RDS) score greater than the Covi Anxiety Scale score, had a total RDS score greater than 9 or who had any single RDS item score greater than 3 were excluded from the study. Patients began treatment with Pbo or V-XR 75 mg/day. At week 2, the V-XR middle-dose and high-dose groups were increased to 150 mglday; at week 3 the V-XR high-dose group was increased to 225 mg/day. Improvement was evaluated at 1, 2, 3, 4, 6, and 8 weeks using the HAM-A total score, the HAM-A psychic anxiety factor, and the Clinical Global Impressions (CGI) scale as the primary outcome measures. Final on-therapy was the primary time point. Efficacy parameters were compared using analysis of covariance for an intent-totreat population (n=349), and the last observation was carried forward for patients who discontinued prematurely. Safety: Discontinuations for adverse events occurred in 7 (7%), 14 ( 15%), 18 (20%), and 17 (19%) of the Pbo and V-XR 75 mg, 150 mg and 225 mg groups respectively. The most common treatment-emergent adverse events reported in the V-XR groups were headache, asthenia, nausea, dizziness, insomnia, nervousness, and somnolence. Results: At week 8 the following changes from baseline were observed on the HAM-A total score (significant differences from placebo indicated by *): Pbo -9.4, V-XR 75 mg -11.1, 150 mg -11.7 and 225 mg -12.3*. The corresponding changes on the HAM-A psychic anxiety factor score were Pbo -5.6, V-XR 75 mg -6.7, 1.50 mg -7.1* and 225 mg -7.3*. Effects were also observed on both CGI Severity (Pbo - 1.3. V-XR 75 mg -1.5, 150 mg -1.6, and 225 mg -1.7*) and CGl Improvement (Pbo 2.6, V-XR 75 mg 2.3, 150 mg 2.3, and 225 mg 2.2*). Conclusion: This study is the first demonstration of the effectiveness of an antidepressant in treating outpatients meeting DSM-IV criteria for GAD who do not have comorbid major depressive disorder or other significant psychiatric illnesses. Significantly, these data suggest that V-XR is an effective, safe, once-daily agent for the treatment of GAD which may provide an important alternative to currently available anxiolvtics.
B 62 El
B-64 El
Alprazolam in generalized anxiety disorder
Ana-Maria Grigorescu, Diana Ilies-Alexandru, Carmen Zaharia. ty Hospital of Psychiatry ‘SOCOLA ” Ia,vi, Romania
Universi-
Objective: Assessment of Alprazolam (Xanax) efficiency in Generalized Anxiety Disorder therapy. Method: The investigation is on 45 patients (21 males and 24 females), average age 38.7 with Generalized Anxiety Disorder according to DSM IV criteria. Our therapy comprises doses between 0.75 mgs and 1.5 mgs
Clozapine: efficacy in treatment-resistant schizophrenic patknts
J. Hatzimanolis, L. Lykouras, P. Oulis, G.N. Christodoulou. Department of Psychiatry, Athens University, Eginition Hospital, Athens 11.5 28, Greece Background; The atypical antipsychotic clozapine has been proved to be more effective than conventional antipsychotics in patients considered refractory to treatment. Clozapine has a broad spectrum of pharmacologic
s21
Poster B. Psychopharmaca
effects such as lower affinity for D, receptors and higher affinity for the D,, D, and D, than the classical antipsychotic drugs. It also has antagonistic effects at al-adrenerglc, a2adrenergic, SHT,-serotonergic, H,-histamimc and p-mouscarinic receptors. Which of these or which combination of these may be the mediators of clozapine’s special clinical efficacy is yet unknown. Purpose: The study aimed to investigate the therapeutic effect of clozapine on schizophrenic patients resistant to conventional antipsychotic drugs. Subjects and Method: Patients were included in the study after the agreement of two independent psychiatrists on the diagnosis made using standard clinical interviews and patients records. Forty-five male patients (mean age-+SD: 31.128.4, range 18-50) suffering from DSM-IIIR schizophrenia switched to clozapine from neuroleptics and completed the study. Another three patients discontinued treatment due to side effects. One of the above manifested agranulocytosis. The 45 patients had responded unsatisfactorily to two conventional antipsychotic drugs from different chemical classes. Twenty-six were with undifferentiated, sixteen with paranoid and 3 with disorganized subtype of schizophrenia. Their duration of illness was 10.724.9 years. They all gave written informed consent for participating in the study. Interrater reliability for the BPRS was 0.89. Results: After 6 weeks treatment with clozapine (mean+SD: 300.52 109.2, range 150-500) total BPRS score decreased significantly. Positive, negative and general psychopathology symptom scores from BPRS also decreased significantly (Table). More frequent adverse effects were those of sedation, salivation, hypotension and fatigue. Table Baseline
After
Wreduction F
P
32.0 34.5 21.5 39.5
O.CHXl o.coO 0.002 o.ooo
Table Baseline
After risperdone
84.4217.5 54.3211.2 PANSStotal score PANSSpositivesymptomscore 19.525.5 12.323.4 24.8t6.3 16.8?5.1 PANSSnegativesymptemscore PANSSgeneralpsychopathologyscan 40.628.9 25326.3 mean?SD
F % RedUCtiOtl 37.5 37.0 32.2 37.7
P
41.9 0.8 19.8 39.2
o.ooo O.OC02 O.wO7 0.000
ANOVA
Also, risperidone treatment reduced significantly the total item-score of each one of five factors disclosed after principal component analysis of the PANSS symptoms (256 patients, included risperidone-treated): Negative (Fl): p=O.OOOl, Excited (F2): p=O.OOO, Depressive (F3). Positive (F4): p=O.OOOl and Disorganized (cognitive disturbance, F5): ~~0.01 1. As the patients were exposed to high dose of risperidone, extrapyramidal symptoms were reported. Administration of antiparkinsonian drugs was necessary resulting in reduction of these side effects. Nausia, fat&ability anxiety were also reported. Conclusions: The preliminary results of our ongoing study indicate that risperidone improves both positive and negative symptoms of schizophrenic patients.
References Marder, S.R. (1994) Risperidone in the treatment of schizophrenia. Am. J. Psychiatry 151, 825-835. Ubricht, D. and Kane J. (1995) Risperidone. Schiz. Bull. 21, 593-606.
clozapine Total BPRS score PositiveBPRS score NegativeBPRS score GeneralPsychopathology BPRS score
46.1k9.9 20.626.2 13.5-t4.5 11.9t4.8
31.4~6.7 13.6~3.9 10.6t4.4 7.2+2.6
67.7 41.9 10.8 14.9
mean I SD, ANOVA. Conclusions: These data suggest that clozapine is effective for treatment of patients with schizophrenia who are not responsive to typical antipsychotics.
References Coward, D.M. (1992) General pharmacology of clozapine. Br. J. Psychiatry. 160 (suppl. 17) S5-Sll. Umbrlcht, D.S.G., Lieberman, J.A. and Kane J.M. (1995) The clinical efficacy of clozapine in the treatment of schizophrenia. Rev. Contemp. Pharmacoth. 6, 165-186.
IB-65
Risperidone in negative symptoms of schizophrenia. Preliminary findings
L. Lykouras, J. Hatzimanolii, I? Oulis, G.N. Christodoulou. Department of Psychiatry, Athens University, Eginition Hospital, Athens 115 28, Greece Purpose: The aim of the study was to assess therapeutic and side effects of risperidone on schizophrenic patients with preponderant negative symptoms. Subjects and Method: The study completed 20 male DSM-IIIR schizophrenic patients (mean age: 32.7 years, SD: 7.8). Another four patients prematurely discontinued treatment with risperidone because of refusal. Assessments were performed at baseline and at the end of a six weeks treatment period with risperidone by means of the Positive and Negative Syndrome Scale for Schizophrenia (PANNS). Extrapyramidal symptoms were assessed by means of Saint Hans Scale. Risperidone was gradually increased according to the patients condition, up to a daily dose of 16 mg in patients. Eight patients received a maximal daily dose of 10 mg and two were treated in a dose of maximally 8 mg daily. Results: After six weeks treatment with risperidone, the 20 patients showed a statistically significant decrease in the total score of the PANSS as well as in the positive, negative and general psychopathology subscales (Table).
I
B-66
Prozac versus anafranil in the therapy of social phobia and agoraphobia
Diana Ilies-Alexandru, Carmen Zaharia, Ana-Maria Grigorescu. ty Hospital of Psychiatry “Socola” Zasi, Romania
Universi-
Social Phobia and Agoraphobia as entities of Anxiety Disorders is to be found in l-2% out of general population with a significant invalidating potential. Various antidepressant drugs have been used in acute and maintenance therapy of these disorders besides cognitive and exposure psychotherapy. Our investigation focuses on a comparative estimation of the efficiency of Prozac (fluxetine) and Anafranil (clomipramine) in two homogeneous groups comprising each 36 patients, average age 33.5 and 32.7 respectively, followed for 1 year. The measurement of the efficiency included CGI and Hamilton Rating Scale for Anxiety. The therapy comprised doses of 20-40 mgslday, single intake of Prozac and 50-100 mgs/day, in two doses of Anafranil respectively. The assessment was performed after CGI and Hamilton Rating Scale for Anxiety after 8 and 10 weeks of therapy with Anafranil and 6 and 8 weeks with Prozac respectively. The rate of negative results (the therapy inefficiency or recurrences) was 25-30% in patients treated with Anafranil and 15-20% in patients with Prozac. Concluding the estimation of the efficiency of both drugs for the treatment of these disorders, we remarked a better improvement of the symptoms’with Prozac and with a satisfactory tolerance in the long term therapy.
1
B-67
Treatment of alcoholism mianserln
with the antidepressant
N.N. Ivanets. Research Institute on Addictions, Ministry of Health of Russian Federation, Moscow Z2192/, Russia Antidepressants, as anticraving drugs, become now a common item of the programs for treatment of alcohol dependence. It was the purpose of this work to study the anticraving efficacy of mianserin. in comparison with that of amitriptyline and relanium, in the treatment of alcohol withdrawal and postwithdrawal syndromes. Besides, the influence of mianserin on metabolism of biogenic amine neurotransmitters was studied and clinicobiological correlations were obtained. 60 patients with alcohol dependence syndrome (DSM-IV) were included in the study. 30 patients were given mianserin (60 mg, during 30 days), 15-amitriptyline (50 mg, during 30 days), and 15-relanium (10 mg, during 7 days). Psychotherapy also was included in the therapeutic
Poster B. Psychopharmaca
avoidance scores dropped from 40.11-23.2 on baseline level to 12.1 k8.8 four weeks later. According to these results, fluoxetine becoming the pharmacological treatment of choice for social phobia.
References Van Amerigen M., Mancini, C., Streimer, D.L. (1993). Fluoxetine efficacy in social phobia. J Clin Psychiatry 54, (1): 27. Versiani, M., Nardi, A.E., Mindim, F.D., Alves, A.B., Liebowitz, M.R., Amrein, R. (1992). Pharmacotherapy in Social Phobia. A controlled Study with Moclobemide and Phenelzine. Br J Psychiatry 161: 353. DeVeaguh-Geiss, J., Bell, J. (1994). Multicentre trial of a 5-HT, antagonist ondantseron, in social phobia. Poster presented at the ACNP, 1994.
I3 61 L-l
Double-blind, placebo-/comparator-controlled study of once daily venlafaxine XR and buspirone in outpatients with generalized anxiety disorder
A.T. De&m, R. Entsuah, T. Haskins and R. Rudolph. For the Venlafaxine XR 214 Study Group Wyeth-Ayers Research, Box 42528, Philadelphia, PA 19101
daily in three intakes. The intensity of the anxious symptoms has been assessed by means of Hamilton Rating Scale for Anxiety and CGI; the evaluations being carried out in weeks 2, 4 and 8 respectively. Findings: We found out a significant decrease of anxious symptoms (Hamilton Rating Scale show a decreasing score from 21-22 to 2-3 in over 79% patients), a reduced influence on psychomotor functioning and a low incidence of side effects. Conclusion: Alprazolam (Xanax) seems to act rapidly and efficiently on anxious symptoms from Generalized Anxiety Disorder, with a good tolerance that recommends it in ambulatory therapy.
B-63 El
Double-blind, placebo-controkled study of once daily venlafaxine XR in outpatients with generalized anxiety disorder
J.T. Haskins, R. Rudolph*, A. Pallay and A.T. Derivan. For the Venlafmine XR 210 Study Group, Wyeth-Ayerst Research, Box 42528, Philudelphia, PA 19101
This randomized, double-blind, placebo- and comparator-controlled, 8week study compared the safety and anxiolytic efficacy of once daily venlafaxine XR (V-XR) 75 mg or 150 mg with placebo (Pbo) and buspirone (Bsp) 30 mg m outpatients with Generalized Anxiety Disorder (GAD). V-XR is a new formulation of the serotonin norepinephrine reuptake inhibitor (SNRI) antidepressant, venlafaxine (Effexor@). Design: Patients (n=405) who met DSM-IV criteria for GAD, but not for major depression, and who did not improve during a 7?3-day pre-study placebo period could be enrolled into the study. Patients who had a current, or within 6 months of study day 1, diagnosis of Major Depressive Disorder (using structured interview as a guide to complete diagnostic criteria), had a Raskin Depression Scale (RDS) score greater than the Covi Anxiety Scale score, had a total RDS score greater than 9 or who had any single RDS item score greater than 3 were excluded from the study. Patients began treatment with V-XR 75 mg, Bsp 15 m, or Pbo. At day 8, one V-XR group increased to 150 mg/da By day 8, the Bsp group had titrated to 30 mg/day. The primary efficacy variables, i.e., HAM-A Total, HAM-A psychic anxiety factor, and CGI-severity, with a secondary variable, the Hospital Anxiety and Depression Scale (HAD) anxiety factor were evaluated at weeks (wks) 1, 2, 3, 4, 6, 8 and final-on-therapy (FOT). Results: Statistically significant (~50.05) results are shown for the observed-cases analysis in the intent-to-treat population (n=369). Overall F-tests are significant unless noted. For the HAM-A Total, V-XR 75 mg was better than Pbo at wks 2, 3, 4 and FOT, overall F-test at FOT p=O.lO. For the HAM-A psychic anxiety factor, V-XR 75 and 150 mg were better than Pbo at wks 2, 3, 4 and FOT. Bsp was not significantly different from Pbo at any time point for either variable, For CGI severity, V-XR 75 and 150 mg were better than Pbo at wks 2, 3, and 4. V-XR 75 mg was also better than Pbo at wk 8 and FOT. For HAD, V-XR 75 mg was better than Pbo and Bsp at wks 1, 2, 3, 4, 6, 8 and FOT; V-XR 150 mg was better than Pbo at wks 3, 4, and FOT and better than Bsp at wks 1, 4, 6, and FOT. For response rates, V-XR 75 mg was better than Pbo for HAM-A Total at wks 6, 8 and FOT and or CGI-Improvement at wks 3,4, 6, 8 and FOT. Safety: The safety profile was consistent with that of EffexorO and V-XR use in depressed patients. Conclusion: This study showed significant advantages for venlafaxine XR (75 or 150 mg/day) vs Pbo to treat outpatients with GAD who do not have comorbid major depression, and suggested that V-XR also has significant advantages vs Bsp.
This randomized, double-blind, placebo-controlled, I-week study compared the safety and anxiolytic efficacy of once daily venlafaxine XR (V-XR) 75 mg, 150 mg, and 225 mg with placebo (Pbo) in outpatients with Generalized Anxiety Disorder (GAD). V-XR is a new formulation of the serotonin norepinephrine reuptake inhibitor (SNRI) antidepressant, venlafaxine (Effexor”). Design: Patients (n=377) who met DSM-IV criteria for GAD, but not major depressive disorder, and who did not improve significantly during a 4 to 10 day prestudy washout period could be enrolled into the study. Patients who had a current, or within 6 months of study day 1, diagnosis of Major Depressive Disorder (using structured interview as a guide to complete diagnostic criteria), had a Raskin Depression Scale (RDS) score greater than the Covi Anxiety Scale score, had a total RDS score greater than 9 or who had any single RDS item score greater than 3 were excluded from the study. Patients began treatment with Pbo or V-XR 75 mg/day. At week 2, the V-XR middle-dose and high-dose groups were increased to 150 mglday; at week 3 the V-XR high-dose group was increased to 225 mg/day. Improvement was evaluated at 1, 2, 3, 4, 6, and 8 weeks using the HAM-A total score, the HAM-A psychic anxiety factor, and the Clinical Global Impressions (CGI) scale as the primary outcome measures. Final on-therapy was the primary time point. Efficacy parameters were compared using analysis of covariance for an intent-totreat population (n=349), and the last observation was carried forward for patients who discontinued prematurely. Safety: Discontinuations for adverse events occurred in 7 (7%), 14 ( 15%), 18 (20%), and 17 (19%) of the Pbo and V-XR 75 mg, 150 mg and 225 mg groups respectively. The most common treatment-emergent adverse events reported in the V-XR groups were headache, asthenia, nausea, dizziness, insomnia, nervousness, and somnolence. Results: At week 8 the following changes from baseline were observed on the HAM-A total score (significant differences from placebo indicated by *): Pbo -9.4, V-XR 75 mg -11.1, 150 mg -11.7 and 225 mg -12.3*. The corresponding changes on the HAM-A psychic anxiety factor score were Pbo -5.6, V-XR 75 mg -6.7, 1.50 mg -7.1* and 225 mg -7.3*. Effects were also observed on both CGI Severity (Pbo - 1.3. V-XR 75 mg -1.5, 150 mg -1.6, and 225 mg -1.7*) and CGl Improvement (Pbo 2.6, V-XR 75 mg 2.3, 150 mg 2.3, and 225 mg 2.2*). Conclusion: This study is the first demonstration of the effectiveness of an antidepressant in treating outpatients meeting DSM-IV criteria for GAD who do not have comorbid major depressive disorder or other significant psychiatric illnesses. Significantly, these data suggest that V-XR is an effective, safe, once-daily agent for the treatment of GAD which may provide an important alternative to currently available anxiolvtics.
B 62 El
B-64 El
Alprazolam in generalized anxiety disorder
Ana-Maria Grigorescu, Diana Ilies-Alexandru, Carmen Zaharia. ty Hospital of Psychiatry ‘SOCOLA ” Ia,vi, Romania
Universi-
Objective: Assessment of Alprazolam (Xanax) efficiency in Generalized Anxiety Disorder therapy. Method: The investigation is on 45 patients (21 males and 24 females), average age 38.7 with Generalized Anxiety Disorder according to DSM IV criteria. Our therapy comprises doses between 0.75 mgs and 1.5 mgs
Clozapine: efficacy in treatment-resistant schizophrenic patknts
J. Hatzimanolis, L. Lykouras, P. Oulis, G.N. Christodoulou. Department of Psychiatry, Athens University, Eginition Hospital, Athens 11.5 28, Greece Background; The atypical antipsychotic clozapine has been proved to be more effective than conventional antipsychotics in patients considered refractory to treatment. Clozapine has a broad spectrum of pharmacologic
s21
Poster B. Psychopharmaca
effects such as lower affinity for D, receptors and higher affinity for the D,, D, and D, than the classical antipsychotic drugs. It also has antagonistic effects at al-adrenerglc, a2adrenergic, SHT,-serotonergic, H,-histamimc and p-mouscarinic receptors. Which of these or which combination of these may be the mediators of clozapine’s special clinical efficacy is yet unknown. Purpose: The study aimed to investigate the therapeutic effect of clozapine on schizophrenic patients resistant to conventional antipsychotic drugs. Subjects and Method: Patients were included in the study after the agreement of two independent psychiatrists on the diagnosis made using standard clinical interviews and patients records. Forty-five male patients (mean age-+SD: 31.128.4, range 18-50) suffering from DSM-IIIR schizophrenia switched to clozapine from neuroleptics and completed the study. Another three patients discontinued treatment due to side effects. One of the above manifested agranulocytosis. The 45 patients had responded unsatisfactorily to two conventional antipsychotic drugs from different chemical classes. Twenty-six were with undifferentiated, sixteen with paranoid and 3 with disorganized subtype of schizophrenia. Their duration of illness was 10.724.9 years. They all gave written informed consent for participating in the study. Interrater reliability for the BPRS was 0.89. Results: After 6 weeks treatment with clozapine (mean+SD: 300.52 109.2, range 150-500) total BPRS score decreased significantly. Positive, negative and general psychopathology symptom scores from BPRS also decreased significantly (Table). More frequent adverse effects were those of sedation, salivation, hypotension and fatigue. Table Baseline
After
Wreduction F
P
32.0 34.5 21.5 39.5
O.CHXl o.coO 0.002 o.ooo
Table Baseline
After risperdone
84.4217.5 54.3211.2 PANSStotal score PANSSpositivesymptomscore 19.525.5 12.323.4 24.8t6.3 16.8?5.1 PANSSnegativesymptemscore PANSSgeneralpsychopathologyscan 40.628.9 25326.3 mean?SD
F % RedUCtiOtl 37.5 37.0 32.2 37.7
P
41.9 0.8 19.8 39.2
o.ooo O.OC02 O.wO7 0.000
ANOVA
Also, risperidone treatment reduced significantly the total item-score of each one of five factors disclosed after principal component analysis of the PANSS symptoms (256 patients, included risperidone-treated): Negative (Fl): p=O.OOOl, Excited (F2): p=O.OOO, Depressive (F3). Positive (F4): p=O.OOOl and Disorganized (cognitive disturbance, F5): ~~0.01 1. As the patients were exposed to high dose of risperidone, extrapyramidal symptoms were reported. Administration of antiparkinsonian drugs was necessary resulting in reduction of these side effects. Nausia, fat&ability anxiety were also reported. Conclusions: The preliminary results of our ongoing study indicate that risperidone improves both positive and negative symptoms of schizophrenic patients.
References Marder, S.R. (1994) Risperidone in the treatment of schizophrenia. Am. J. Psychiatry 151, 825-835. Ubricht, D. and Kane J. (1995) Risperidone. Schiz. Bull. 21, 593-606.
clozapine Total BPRS score PositiveBPRS score NegativeBPRS score GeneralPsychopathology BPRS score
46.1k9.9 20.626.2 13.5-t4.5 11.9t4.8
31.4~6.7 13.6~3.9 10.6t4.4 7.2+2.6
67.7 41.9 10.8 14.9
mean I SD, ANOVA. Conclusions: These data suggest that clozapine is effective for treatment of patients with schizophrenia who are not responsive to typical antipsychotics.
References Coward, D.M. (1992) General pharmacology of clozapine. Br. J. Psychiatry. 160 (suppl. 17) S5-Sll. Umbrlcht, D.S.G., Lieberman, J.A. and Kane J.M. (1995) The clinical efficacy of clozapine in the treatment of schizophrenia. Rev. Contemp. Pharmacoth. 6, 165-186.
IB-65
Risperidone in negative symptoms of schizophrenia. Preliminary findings
L. Lykouras, J. Hatzimanolii, I? Oulis, G.N. Christodoulou. Department of Psychiatry, Athens University, Eginition Hospital, Athens 115 28, Greece Purpose: The aim of the study was to assess therapeutic and side effects of risperidone on schizophrenic patients with preponderant negative symptoms. Subjects and Method: The study completed 20 male DSM-IIIR schizophrenic patients (mean age: 32.7 years, SD: 7.8). Another four patients prematurely discontinued treatment with risperidone because of refusal. Assessments were performed at baseline and at the end of a six weeks treatment period with risperidone by means of the Positive and Negative Syndrome Scale for Schizophrenia (PANNS). Extrapyramidal symptoms were assessed by means of Saint Hans Scale. Risperidone was gradually increased according to the patients condition, up to a daily dose of 16 mg in patients. Eight patients received a maximal daily dose of 10 mg and two were treated in a dose of maximally 8 mg daily. Results: After six weeks treatment with risperidone, the 20 patients showed a statistically significant decrease in the total score of the PANSS as well as in the positive, negative and general psychopathology subscales (Table).
I
B-66
Prozac versus anafranil in the therapy of social phobia and agoraphobia
Diana Ilies-Alexandru, Carmen Zaharia, Ana-Maria Grigorescu. ty Hospital of Psychiatry “Socola” Zasi, Romania
Universi-
Social Phobia and Agoraphobia as entities of Anxiety Disorders is to be found in l-2% out of general population with a significant invalidating potential. Various antidepressant drugs have been used in acute and maintenance therapy of these disorders besides cognitive and exposure psychotherapy. Our investigation focuses on a comparative estimation of the efficiency of Prozac (fluxetine) and Anafranil (clomipramine) in two homogeneous groups comprising each 36 patients, average age 33.5 and 32.7 respectively, followed for 1 year. The measurement of the efficiency included CGI and Hamilton Rating Scale for Anxiety. The therapy comprised doses of 20-40 mgslday, single intake of Prozac and 50-100 mgs/day, in two doses of Anafranil respectively. The assessment was performed after CGI and Hamilton Rating Scale for Anxiety after 8 and 10 weeks of therapy with Anafranil and 6 and 8 weeks with Prozac respectively. The rate of negative results (the therapy inefficiency or recurrences) was 25-30% in patients treated with Anafranil and 15-20% in patients with Prozac. Concluding the estimation of the efficiency of both drugs for the treatment of these disorders, we remarked a better improvement of the symptoms’with Prozac and with a satisfactory tolerance in the long term therapy.
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B-67
Treatment of alcoholism mianserln
with the antidepressant
N.N. Ivanets. Research Institute on Addictions, Ministry of Health of Russian Federation, Moscow Z2192/, Russia Antidepressants, as anticraving drugs, become now a common item of the programs for treatment of alcohol dependence. It was the purpose of this work to study the anticraving efficacy of mianserin. in comparison with that of amitriptyline and relanium, in the treatment of alcohol withdrawal and postwithdrawal syndromes. Besides, the influence of mianserin on metabolism of biogenic amine neurotransmitters was studied and clinicobiological correlations were obtained. 60 patients with alcohol dependence syndrome (DSM-IV) were included in the study. 30 patients were given mianserin (60 mg, during 30 days), 15-amitriptyline (50 mg, during 30 days), and 15-relanium (10 mg, during 7 days). Psychotherapy also was included in the therapeutic