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Venlafaxine versus paroxetine in the treatment of resistant depression
Poster session IV
@O-43!
Paroxetlne In the treatment of depressed patients with Ischaemlc heart disease
S. Roose '. B. Pollock 2 , J. Kennedy 3 , J. Nelson 4. I. Gergel 5 , J. McCafferty 5 • W. Bushnell 5. R. Kumar'. ' Columbia Presbyterlan
UnlV8rsJty Hospital. New Yorlr. NY, USA, 2 Western Psychiatric Research Institute. Pittsburgh, PA. USA. 3 Vanderbilt University Medical center. Nashville. TN, USA. 4 Yale UnlV8rsity School of Medicine. New Haven. eN. USA. 5 SmithKline Beecham Pharmaceuticals, Collegwille. PA. USA, 'New Frontiers Science Park, Harlow. UK
The cardiovascular safety of the selective serotonin reuptake inhibitor (SSRI) paroxetine (Px) was compared with that of the tricyclic antidepressant (TCA) nortriptyline (Nt) In the treatment of depressed patients (pIS) with concurrent ischaemic heart disease (IHO). Methods: This was a prospective. random/sed, double-blind, multicentre clink:al trial. After a 2-week, single-blind placebo period, 81 pIS with IHO and major depression (OSM-IIIR criteria and Hamilton Depression Scale [HAMO) score:::: 17) were randomised to receive 6 weeks' treatment with Px (20-30 mglday) or Nt (25-125 mglday). Cardiovascular and psychiatric evaluations were carried out at weekly visits. 24 h Holter monitoring was carried out after 2 and 6 weeks of treatment ResultS: 90% (37/41) of Px pIS and 68% (27/40) ot Nt pIS completed the trial. Using the last observation carried torward, response rates (HAMD score ~8) was achieved In 60% of Px and 61% of Nt pts. Among completers, response rates were 68% and 85%. respectively. Significant cardiac events occurred In 1 Px and 7 Nt pts. A significant and sustained Increase In mean heart rate and a significant and sustained decrease in mean heart rate variability was seen In Nt but not Px pts. conclusions: Px and Nt are effective for the treatment of depression In pts with IHD. Treatment with Px Is associated with fewer adverse cardiac events compared with Nt
~-44]
A comparison of paroxetlne and clomipramine In patients with depression and associated anxiety
B. Hunter for the Paroxetine Study Investigators. SmithKl/ne Beecham Pharmacevticals. New Frontiers Science Parle. Harlow, UK In a large proportion of patients the symptoms of anxiety co-exist with a diagnosiS of depression. The objective of the present study was to c0rne the efficacy of paroxetine and clomipramine prospectively In a patient ~latiOn specifically selected for co-existing depression and anxiety. Methods: This was a 12-week, double-blind, parallel group trial comparing paroxetine (20-40 mglday) with cIomlpramin~ (75-1~ rngIday) in 1002 patients with a Montgomery-Asberg Depr8SSlon Rating 5cale (MADRS) soore >20 and a Clinical Anxiety Score (CAS) ~ 11. R"ults: paroxetine and clomipramine reduced the MADRS and CAS ratings at 2. 6 and 12 weeks and at endpoint, with no significant differences betWeen treatment groups at any tlmepolnt. Clinical Global Impression erlty of Illness and global Improvement ratings were similar for both nts throughout the trlal. There were slgniflC8lldy more treatmentent adverse experiences In the group treated with clomipramine than er::~roxetine. and significantly fewer patients withdrew from paroxetine WI nt than from clomipramine (P • 0.025 and p • 0.008, respectively). ~eac;onctuSion. In this 12-week study. paroxetine and clomipramine were of n rable efficacy, but the Improved tolerability with paroxetlne results In :"~nt with a superior overall profile for the treatment of patients with depr~ssion and assoclated anxiety.
::trne trne
~O-4:[J 'ThCJ(rl8s
Biological markers for early prediction of therapeutic outcome In major depression
C. Baghal. Gregor Laakmann, Karin Kuhn, Sigrid Ehrentraut,
eome1iUS SchOle. Hanlhloachlm Kuss. Department of Psychiatry.
University of Munich. 80336 Munich. Gllrmany bemide. a reversible monoamine oxidase Inhibitor, exerts its effect M~J~ibitiOn of the MAO A·form. Endocrinologic investigations Indicated a by In I tion of prolactin (PRL) secretion In healthy volunteers. The aim of our stimu:- lion was the assessment of pituitary hormone plasma levels after lnve;;tI~on of moclobemide In 20 depressive patients. Serum levels of pro• app!i(;a rowth hormone and cortisol were measured every 30 minutes from lactinj 9prior to 150 min after administration of Moclobemlde. Furthermore 60 ~ges of DOPA, DOPAC. HVA, NE- and 5-HIM were calculated to the . te correlations between the degree of MAO Inhibition, endocrtno• Inveatlga
aIOL PSYCHIATRY 1991;42:1S-291S
243S
logiC effects and therapeutic outcome. As expected after Inhibition of the norepinephrine (NE) deamination with MocIobemide the NE plasma levels showed a slight rise which stopped 90' after Moclobemide administration. Due to the inhibition of dopamine metabolisation the average decrease at DOPAC plasma concentration was 50.7% at day 1 and 22.00/0 at day 21. We found a stimulation of prolactin and growth honnone secretion on day 1 and day 21, there were no differences in peak values or AUC's between both days. The Influence on cortisol secretion was only marginal. There were no significant differences between the stimulation tests at both days. A significant coherence between the attJibutes prolactin-stimulation and therapy-response could be found, but most of our endocrinologic and biochemical data were no secure predictors of therapeutic outcome during a 4week Moctobemide therapy. Furthermore it seems to be astonishing. that a desensitisation of the MAO against the Moclobemide Induced Inhibition during the first 3 weeks of treatment could be found. whereas the prolactin stimulation. estimated as a final pathway ot elevated 5-HT concentrations. also due to MAO Inhibition. remained unchanged.
190-461 Sleep quality during fluoxetine therapy In depression M. Dossenbach, F.S. Martenyi. E. De Verga. Eli U1Jy GesmbH. Austria The aim of this study was to evaluate the effects of fluoxetine, an antidepres• sant devoid of sedating action, on sleep quality of depressive outpatients. Methods: 424 depressive patients (131 males, 292 females; mean age: 51.2 years) in Austria were investigated by psychiatrists in a 6 week open label study. Inclusion criteria required a major depressive disorder (OSM-III-R). Efficacy and effects of fluoxetlne on sleep quality were evaluated with the modified HAMO (14-items version by POldinger), the CGI and the Leeds Sleep Evaluation Questionnaire (LSEQ). Response was defined as an improvement on the HAMO scale of ~50%. Results: Mean HAMD score Improved from 20 to 9.2 points A detailed analysis of the four different aspects of sleep [getting to sleep (GTS), per• ceived quality of sleep (OOS), the ease of awaking from sleep (AFS) and the integrity of early moming behaviour following wakefulness (BFW») between responders and non-responders gave the following results. All patients Im• proved significantly In all sleep domains from baseline to endpoint. Patients with a HAMD response of ~5O%. had a significantly better Improvement compared to patients with a HAMO response of <50% (GTS: 6.8 vs. 6.0. COS: 6.8 vs. 5.9. AFS: 6.6 vs. 5.7•• BFW: 7.1 vs. 5.6). In conclusion. the sleep improving effect of fluoxetine In depressive patients without day-time sedation was confirmed with a more significant effect for Responders. Thus. fluoxetine Is also Indicated In depressive disorders with sleep disturbances. especially when undisturbed day time alertness is paramount for the patients.
190-471 VenlafaxIne versus paroxetlne In the treatment of resistant depression M.·F. Poirier. SHU-centre Hospltalier Sainte-Anne. Paris. France ObJective: Compare the efficacy and safety of venlafaxine and paroxetine in the treatment of resistant depression. Methods: This was a double-blind. randomized, multicenter study c0n• ducted in France to compare the efficacy and safety of venlafaxine and paroxetine In 120 patients with treatment-resistant depression. Hospitalized or outpatients satisfying DSM·III-R criteria for major depression in evolution for <8 months. a baseline HAM·D score ~18. and a HAM-D Item 3 score <3 were eligible. In addition, patients were reqUired to have a history of resistance to two previous antidepressant treatments for this episode and a CGJ Improvement score ~3 at the beginning of treatment Venlafaxlne was titrated from 75 to 250 mglday over 10 days. and then adjusted within the range of 200 to 300 mglday. Paroxetine was titrated from 20 to 30 mglday over 7 days, and then adjusted within the range for 30 to 40 mglday. Patients received double-blind therapy for a minimum of 6 weeks but for up to 18 weeks at the investigator's discretion. Primary efficacy variables were the 17·ltem HAM-D and CGllmprovement and severity scores. Results: Baseline demographics and clinical characteristics for both groups will be presented. Comparisons between groups for the primary efficacy variables will be examined. Causes ot treatment discontinuation and the Incldence of common adverse events will be discussed for each treatment group. Conclusion: These results support the efficacy and tolerability of ven• lafaxine lor the treatment of resistant depression among Inpatients and outpatients.
@O-43!
Paroxetlne In the treatment of depressed patients with Ischaemlc heart disease
S. Roose '. B. Pollock 2 , J. Kennedy 3 , J. Nelson 4. I. Gergel 5 , J. McCafferty 5 • W. Bushnell 5. R. Kumar'. ' Columbia Presbyterlan
UnlV8rsJty Hospital. New Yorlr. NY, USA, 2 Western Psychiatric Research Institute. Pittsburgh, PA. USA. 3 Vanderbilt University Medical center. Nashville. TN, USA. 4 Yale UnlV8rsity School of Medicine. New Haven. eN. USA. 5 SmithKline Beecham Pharmaceuticals, Collegwille. PA. USA, 'New Frontiers Science Park, Harlow. UK
The cardiovascular safety of the selective serotonin reuptake inhibitor (SSRI) paroxetine (Px) was compared with that of the tricyclic antidepressant (TCA) nortriptyline (Nt) In the treatment of depressed patients (pIS) with concurrent ischaemic heart disease (IHO). Methods: This was a prospective. random/sed, double-blind, multicentre clink:al trial. After a 2-week, single-blind placebo period, 81 pIS with IHO and major depression (OSM-IIIR criteria and Hamilton Depression Scale [HAMO) score:::: 17) were randomised to receive 6 weeks' treatment with Px (20-30 mglday) or Nt (25-125 mglday). Cardiovascular and psychiatric evaluations were carried out at weekly visits. 24 h Holter monitoring was carried out after 2 and 6 weeks of treatment ResultS: 90% (37/41) of Px pIS and 68% (27/40) ot Nt pIS completed the trial. Using the last observation carried torward, response rates (HAMD score ~8) was achieved In 60% of Px and 61% of Nt pts. Among completers, response rates were 68% and 85%. respectively. Significant cardiac events occurred In 1 Px and 7 Nt pts. A significant and sustained Increase In mean heart rate and a significant and sustained decrease in mean heart rate variability was seen In Nt but not Px pts. conclusions: Px and Nt are effective for the treatment of depression In pts with IHD. Treatment with Px Is associated with fewer adverse cardiac events compared with Nt
~-44]
A comparison of paroxetlne and clomipramine In patients with depression and associated anxiety
B. Hunter for the Paroxetine Study Investigators. SmithKl/ne Beecham Pharmacevticals. New Frontiers Science Parle. Harlow, UK In a large proportion of patients the symptoms of anxiety co-exist with a diagnosiS of depression. The objective of the present study was to c0rne the efficacy of paroxetine and clomipramine prospectively In a patient ~latiOn specifically selected for co-existing depression and anxiety. Methods: This was a 12-week, double-blind, parallel group trial comparing paroxetine (20-40 mglday) with cIomlpramin~ (75-1~ rngIday) in 1002 patients with a Montgomery-Asberg Depr8SSlon Rating 5cale (MADRS) soore >20 and a Clinical Anxiety Score (CAS) ~ 11. R"ults: paroxetine and clomipramine reduced the MADRS and CAS ratings at 2. 6 and 12 weeks and at endpoint, with no significant differences betWeen treatment groups at any tlmepolnt. Clinical Global Impression erlty of Illness and global Improvement ratings were similar for both nts throughout the trlal. There were slgniflC8lldy more treatmentent adverse experiences In the group treated with clomipramine than er::~roxetine. and significantly fewer patients withdrew from paroxetine WI nt than from clomipramine (P • 0.025 and p • 0.008, respectively). ~eac;onctuSion. In this 12-week study. paroxetine and clomipramine were of n rable efficacy, but the Improved tolerability with paroxetlne results In :"~nt with a superior overall profile for the treatment of patients with depr~ssion and assoclated anxiety.
::trne trne
~O-4:[J 'ThCJ(rl8s
Biological markers for early prediction of therapeutic outcome In major depression
C. Baghal. Gregor Laakmann, Karin Kuhn, Sigrid Ehrentraut,
eome1iUS SchOle. Hanlhloachlm Kuss. Department of Psychiatry.
University of Munich. 80336 Munich. Gllrmany bemide. a reversible monoamine oxidase Inhibitor, exerts its effect M~J~ibitiOn of the MAO A·form. Endocrinologic investigations Indicated a by In I tion of prolactin (PRL) secretion In healthy volunteers. The aim of our stimu:- lion was the assessment of pituitary hormone plasma levels after lnve;;tI~on of moclobemide In 20 depressive patients. Serum levels of pro• app!i(;a rowth hormone and cortisol were measured every 30 minutes from lactinj 9prior to 150 min after administration of Moclobemlde. Furthermore 60 ~ges of DOPA, DOPAC. HVA, NE- and 5-HIM were calculated to the . te correlations between the degree of MAO Inhibition, endocrtno• Inveatlga
aIOL PSYCHIATRY 1991;42:1S-291S
243S
logiC effects and therapeutic outcome. As expected after Inhibition of the norepinephrine (NE) deamination with MocIobemide the NE plasma levels showed a slight rise which stopped 90' after Moclobemide administration. Due to the inhibition of dopamine metabolisation the average decrease at DOPAC plasma concentration was 50.7% at day 1 and 22.00/0 at day 21. We found a stimulation of prolactin and growth honnone secretion on day 1 and day 21, there were no differences in peak values or AUC's between both days. The Influence on cortisol secretion was only marginal. There were no significant differences between the stimulation tests at both days. A significant coherence between the attJibutes prolactin-stimulation and therapy-response could be found, but most of our endocrinologic and biochemical data were no secure predictors of therapeutic outcome during a 4week Moctobemide therapy. Furthermore it seems to be astonishing. that a desensitisation of the MAO against the Moclobemide Induced Inhibition during the first 3 weeks of treatment could be found. whereas the prolactin stimulation. estimated as a final pathway ot elevated 5-HT concentrations. also due to MAO Inhibition. remained unchanged.
190-461 Sleep quality during fluoxetine therapy In depression M. Dossenbach, F.S. Martenyi. E. De Verga. Eli U1Jy GesmbH. Austria The aim of this study was to evaluate the effects of fluoxetine, an antidepres• sant devoid of sedating action, on sleep quality of depressive outpatients. Methods: 424 depressive patients (131 males, 292 females; mean age: 51.2 years) in Austria were investigated by psychiatrists in a 6 week open label study. Inclusion criteria required a major depressive disorder (OSM-III-R). Efficacy and effects of fluoxetlne on sleep quality were evaluated with the modified HAMO (14-items version by POldinger), the CGI and the Leeds Sleep Evaluation Questionnaire (LSEQ). Response was defined as an improvement on the HAMO scale of ~50%. Results: Mean HAMD score Improved from 20 to 9.2 points A detailed analysis of the four different aspects of sleep [getting to sleep (GTS), per• ceived quality of sleep (OOS), the ease of awaking from sleep (AFS) and the integrity of early moming behaviour following wakefulness (BFW») between responders and non-responders gave the following results. All patients Im• proved significantly In all sleep domains from baseline to endpoint. Patients with a HAMD response of ~5O%. had a significantly better Improvement compared to patients with a HAMO response of <50% (GTS: 6.8 vs. 6.0. COS: 6.8 vs. 5.9. AFS: 6.6 vs. 5.7•• BFW: 7.1 vs. 5.6). In conclusion. the sleep improving effect of fluoxetine In depressive patients without day-time sedation was confirmed with a more significant effect for Responders. Thus. fluoxetine Is also Indicated In depressive disorders with sleep disturbances. especially when undisturbed day time alertness is paramount for the patients.
190-471 VenlafaxIne versus paroxetlne In the treatment of resistant depression M.·F. Poirier. SHU-centre Hospltalier Sainte-Anne. Paris. France ObJective: Compare the efficacy and safety of venlafaxine and paroxetine in the treatment of resistant depression. Methods: This was a double-blind. randomized, multicenter study c0n• ducted in France to compare the efficacy and safety of venlafaxine and paroxetine In 120 patients with treatment-resistant depression. Hospitalized or outpatients satisfying DSM·III-R criteria for major depression in evolution for <8 months. a baseline HAM·D score ~18. and a HAM-D Item 3 score <3 were eligible. In addition, patients were reqUired to have a history of resistance to two previous antidepressant treatments for this episode and a CGJ Improvement score ~3 at the beginning of treatment Venlafaxlne was titrated from 75 to 250 mglday over 10 days. and then adjusted within the range of 200 to 300 mglday. Paroxetine was titrated from 20 to 30 mglday over 7 days, and then adjusted within the range for 30 to 40 mglday. Patients received double-blind therapy for a minimum of 6 weeks but for up to 18 weeks at the investigator's discretion. Primary efficacy variables were the 17·ltem HAM-D and CGllmprovement and severity scores. Results: Baseline demographics and clinical characteristics for both groups will be presented. Comparisons between groups for the primary efficacy variables will be examined. Causes ot treatment discontinuation and the Incldence of common adverse events will be discussed for each treatment group. Conclusion: These results support the efficacy and tolerability of ven• lafaxine lor the treatment of resistant depression among Inpatients and outpatients.