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A double-blind placebo controlled study with clonazepam in social phobia
FRIDAY, MAY 20
BIOL PSYCHIATRY 677 1994;35:615-747
223. A DOUBLE-BLIND STUDY WITH PAROXETINE VS FLUOXETINE IN DEPRESSIVE PATIENTS
gently used. Our results need to be corroborated in other double-blind placebo controlled studies.
A. Ontiveros I & C. Garcia-Barriga2
225. OPEN CROSS-OVER STUDY WITH FLUOXETINE AND DESIPRAMINE IN MAJOR DEPRESSION
t Department of Psychiatry, University Hospital Jose E. Gonza|ez Monterrey, N.L., 64461 Mexico. 2 Fray Bemardino Alvarez Psychiatric Hospital, Mexico City, Mexico Paroxetine is a potent novel selective serotonin (5-HT) reuptake inhibitor antidepressant (SSRI). As in other SSR! its antidepressant efficacy was tested against placebo and tricyclic antidepressants. This randomized double-blind study was carried out to evaluate the efficacy and safety of peroxetine (PAR) and fiuoxetine (FIX) in a 6.week treatment of depressed outpatients who met DSM-ill-R criteria for major depressive disorder. Inclusion criteria required patients to be of both sexes, 18 to 65 years old and have a HAM-D score > 18 in the first 17 items. Exclusion criteria were: other psychiatric disorders, relevant medical diseases, pregnancy or lactation, other psychopharmacological treatment and/or being in psychotherapy. After a one week washout period, patients were randomized to 20 mg of PAR (N.,60) or FIX (N,,60). Efficacy and safety were assessed with HAM-D, and Clinical Global Impression (CGi) scales. Patients on PAR were older (43 + DS ! !.0 years) than those on FIX (38+ 10.9 years). The analysis of changes in the HAM-D and CG! showed, in both groups of patients, a significant improvement from day 14, with an even greater improvement until day 42 of treatment (p¢0.05). However, at day 14 patients on PAR showed a decrease in 50% of HAM-D scale items against only 13% for patients on FIX (lg0.05). Six patients (20%) on FLX and 3(10%) on PAR finished the treatment prematurely. Even though PAR and FIX were equally effective antidepressant treatments in this study, depressive outpatients seemed to improve faster with PAR. Other studies comparing SSRI need to be done to corroborate our results.
224. A DOUBLE-BLIND PLACEBO CONTROLLED STUDY WITH CLONAZEPAM IN SOCIAL PHOBIA A. Ontiveros & A. Rojas Department of Psychiatry, University Hospital Jose E. Gonzalez, Monterrey N.L. Mexico CP 64461 Case reports and open studies suggest the efficacy of benzodiazepines alprazolam and clonazepam (CLZ) in social phobia (SP). In order to further study this action we carried out a double-blind placebo controlled study with CLZ in patients with SP. We studied 50 consecutive SP patients (DSM-Ili-R) of both sexes, 18 to 65 years of age, with a disorder of at least moderate severity. The exclusion criteria were: relevant medical disorder, other psychopharmacological treatment (except antidepressants currently used) and/or being currently in psychotherapy. After a singleblind week of placebo, patients were randomized to clonazepam (N-25) or placebo (N.,25) in a double-blind treatment for six weeks. CLZ dosage was increased !.0 rag/day each week. Efficacy and safety were assessed weekly [HAM-A and HAM-D scales, CGi 8 points, Fear Questionnaire and Liebowitz Social Phobia Scale]. Both groups of patients on CLZ or placebo were no different in age, sex distribution, age onset and length of disease nor in several measures of severity. An End-point analysis showed that patients on CLZ improved more than those on placebo (p<0.005) with changes since the second week of treatment (p
A. Ontiveros, J. Lugoleos, & A. Rojas Department of Psychiatry, University Hospital Jose E. Gonzalez, Monterrey N.L. Mexico CP 64461 Biological models of"depression could be better understood studying the clinical action of antidepressants. We compared in an open cross-over study two selective reuptake inhibitors: desipramine (DMI) on norepinephrine (NE) vs fluoxetine (FI.,X) on semtonin (5-HT). We studied consecutive patientS with major depression (DSM-lli-R) of both sexes, 18 to 65 years old, with a HAM-D~IS. Exclusion criteria were: other psychiatric disorders and other psychopharmacological treatment. Patients were assigned to two sequences of treatment: I.FLX-DMI (N-8) or li.DMI. FLX (N-8). Patients received a single-blind week of placebo followed by 12 weeks of treatment (6 weeks of DMi and FIX). Both groups of patients were similar in age, sex distribution and final dosage of DM! (!: 194 + DS 32.0 vs !i: 206 :!: DS 43.8 mgr/day). After one week of placebo, patients on sequence ! were more depressed (HAM-D) (26.2 +SD 3.88) than those on sequence !! (21.5 +SD 3.74) (p<0.05). We found no differences in tolerance nor in final HAM-D and CG! scores, after FIX or DMI; and there were no effects due to treatment sequence. Nine (57%) patients improved markedly with FIX and DMI, 3 (! 8%) with FIX, 3 (i 8%) with DM! and only I patient (6%) was resistant to both drugs. A unified 5-HT/ NE model of antidepressant action could be sustained in most of our depressive patients. However, 36% of patients responded preferentially to only one selective reuptake 5-EIT or NE inhibitor, implying a selective response to their action. The findings in this study are relevant to the psychopharmacological treatment of depression.
226. IMIPRAMINE PLASMA CONCENTRATIONS AND RESPONSE IN PANIC DISORDER M. Mavissakalian ! & J. Perel 2 tThe Ohio State University College of Medicine, Columbus, OH 43210; 2University of Pittsburgh, Clinical Pharmacology Program, Pittsburgh, PA Plasma concentrations of lmipramine (IMI) and N-desmethylimipramine (DMI) were assessed in 48 rm_n_icdi~rder with agoraphobia patients who completed an 8 week randomized double blind dose ranging study with imipramine hydrochloride: low dose (0.5 mg/kg/day, n-17) medium dose (i.5 mg/kg/day, n-17) and high dose (3 mg/kg/day, n-14). Assessments included patient and clinician rated symptom scales of panic and phobias, as well as operationalized criteria of response, which were based on m 50% change from baseline to signify marked improvement or an absolute cutoff score to signify minimal to absent symptoms. Analysis included correlational and dose-response stratifications with total, IM! and DMi concentrations as well as multiple linear regression and logistic regression analysis with total, IMI and DM! levels as predictors of symptom severity and response. Results revealed a sigmoidal/iinear relationship between total plasma levels and response in panic and a onrvilinear relationship between total plasma level and response in phobias (such that maximal response was achieved in the 75-133 ng/ml range, with diminished response below and above this range). The curvilinearity of phobic response
BIOL PSYCHIATRY 677 1994;35:615-747
223. A DOUBLE-BLIND STUDY WITH PAROXETINE VS FLUOXETINE IN DEPRESSIVE PATIENTS
gently used. Our results need to be corroborated in other double-blind placebo controlled studies.
A. Ontiveros I & C. Garcia-Barriga2
225. OPEN CROSS-OVER STUDY WITH FLUOXETINE AND DESIPRAMINE IN MAJOR DEPRESSION
t Department of Psychiatry, University Hospital Jose E. Gonza|ez Monterrey, N.L., 64461 Mexico. 2 Fray Bemardino Alvarez Psychiatric Hospital, Mexico City, Mexico Paroxetine is a potent novel selective serotonin (5-HT) reuptake inhibitor antidepressant (SSRI). As in other SSR! its antidepressant efficacy was tested against placebo and tricyclic antidepressants. This randomized double-blind study was carried out to evaluate the efficacy and safety of peroxetine (PAR) and fiuoxetine (FIX) in a 6.week treatment of depressed outpatients who met DSM-ill-R criteria for major depressive disorder. Inclusion criteria required patients to be of both sexes, 18 to 65 years old and have a HAM-D score > 18 in the first 17 items. Exclusion criteria were: other psychiatric disorders, relevant medical diseases, pregnancy or lactation, other psychopharmacological treatment and/or being in psychotherapy. After a one week washout period, patients were randomized to 20 mg of PAR (N.,60) or FIX (N,,60). Efficacy and safety were assessed with HAM-D, and Clinical Global Impression (CGi) scales. Patients on PAR were older (43 + DS ! !.0 years) than those on FIX (38+ 10.9 years). The analysis of changes in the HAM-D and CG! showed, in both groups of patients, a significant improvement from day 14, with an even greater improvement until day 42 of treatment (p¢0.05). However, at day 14 patients on PAR showed a decrease in 50% of HAM-D scale items against only 13% for patients on FIX (lg0.05). Six patients (20%) on FLX and 3(10%) on PAR finished the treatment prematurely. Even though PAR and FIX were equally effective antidepressant treatments in this study, depressive outpatients seemed to improve faster with PAR. Other studies comparing SSRI need to be done to corroborate our results.
224. A DOUBLE-BLIND PLACEBO CONTROLLED STUDY WITH CLONAZEPAM IN SOCIAL PHOBIA A. Ontiveros & A. Rojas Department of Psychiatry, University Hospital Jose E. Gonzalez, Monterrey N.L. Mexico CP 64461 Case reports and open studies suggest the efficacy of benzodiazepines alprazolam and clonazepam (CLZ) in social phobia (SP). In order to further study this action we carried out a double-blind placebo controlled study with CLZ in patients with SP. We studied 50 consecutive SP patients (DSM-Ili-R) of both sexes, 18 to 65 years of age, with a disorder of at least moderate severity. The exclusion criteria were: relevant medical disorder, other psychopharmacological treatment (except antidepressants currently used) and/or being currently in psychotherapy. After a singleblind week of placebo, patients were randomized to clonazepam (N-25) or placebo (N.,25) in a double-blind treatment for six weeks. CLZ dosage was increased !.0 rag/day each week. Efficacy and safety were assessed weekly [HAM-A and HAM-D scales, CGi 8 points, Fear Questionnaire and Liebowitz Social Phobia Scale]. Both groups of patients on CLZ or placebo were no different in age, sex distribution, age onset and length of disease nor in several measures of severity. An End-point analysis showed that patients on CLZ improved more than those on placebo (p<0.005) with changes since the second week of treatment (p
A. Ontiveros, J. Lugoleos, & A. Rojas Department of Psychiatry, University Hospital Jose E. Gonzalez, Monterrey N.L. Mexico CP 64461 Biological models of"depression could be better understood studying the clinical action of antidepressants. We compared in an open cross-over study two selective reuptake inhibitors: desipramine (DMI) on norepinephrine (NE) vs fluoxetine (FI.,X) on semtonin (5-HT). We studied consecutive patientS with major depression (DSM-lli-R) of both sexes, 18 to 65 years old, with a HAM-D~IS. Exclusion criteria were: other psychiatric disorders and other psychopharmacological treatment. Patients were assigned to two sequences of treatment: I.FLX-DMI (N-8) or li.DMI. FLX (N-8). Patients received a single-blind week of placebo followed by 12 weeks of treatment (6 weeks of DMi and FIX). Both groups of patients were similar in age, sex distribution and final dosage of DM! (!: 194 + DS 32.0 vs !i: 206 :!: DS 43.8 mgr/day). After one week of placebo, patients on sequence ! were more depressed (HAM-D) (26.2 +SD 3.88) than those on sequence !! (21.5 +SD 3.74) (p<0.05). We found no differences in tolerance nor in final HAM-D and CG! scores, after FIX or DMI; and there were no effects due to treatment sequence. Nine (57%) patients improved markedly with FIX and DMI, 3 (! 8%) with FIX, 3 (i 8%) with DM! and only I patient (6%) was resistant to both drugs. A unified 5-HT/ NE model of antidepressant action could be sustained in most of our depressive patients. However, 36% of patients responded preferentially to only one selective reuptake 5-EIT or NE inhibitor, implying a selective response to their action. The findings in this study are relevant to the psychopharmacological treatment of depression.
226. IMIPRAMINE PLASMA CONCENTRATIONS AND RESPONSE IN PANIC DISORDER M. Mavissakalian ! & J. Perel 2 tThe Ohio State University College of Medicine, Columbus, OH 43210; 2University of Pittsburgh, Clinical Pharmacology Program, Pittsburgh, PA Plasma concentrations of lmipramine (IMI) and N-desmethylimipramine (DMI) were assessed in 48 rm_n_icdi~rder with agoraphobia patients who completed an 8 week randomized double blind dose ranging study with imipramine hydrochloride: low dose (0.5 mg/kg/day, n-17) medium dose (i.5 mg/kg/day, n-17) and high dose (3 mg/kg/day, n-14). Assessments included patient and clinician rated symptom scales of panic and phobias, as well as operationalized criteria of response, which were based on m 50% change from baseline to signify marked improvement or an absolute cutoff score to signify minimal to absent symptoms. Analysis included correlational and dose-response stratifications with total, IM! and DMi concentrations as well as multiple linear regression and logistic regression analysis with total, IMI and DM! levels as predictors of symptom severity and response. Results revealed a sigmoidal/iinear relationship between total plasma levels and response in panic and a onrvilinear relationship between total plasma level and response in phobias (such that maximal response was achieved in the 75-133 ng/ml range, with diminished response below and above this range). The curvilinearity of phobic response