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Reboxetine augmentation of fluoxetine for patients with major depressive disorder: An 8-week open-label study
R1. Affective disorders and antidepressants Mean HAM-D-17-item total scores decreased markedly from baseline to Week 8 in both treatment groups (reboxetine 28.6 plus or minus 3.1 to 13.4 plus or minus 8.1; venlafaxine 28.8 plus or minus 2.8 to 12.2 plus or minus 7.7). 56% of patients treated with reboxetine had responded (greater than or equal to 50% decrease in the HAM-D-17-item total score) at Week 8 compared with 54% in the venlafaxine group. 24% of patients in each group were classed as in remission (HAM-D-17-item total score less than or equal to 8 points) after 8 weeks. More patients treated with reboxetine achieved symptomatic remission by Week 4 compared with those in the venlafaxine group, although by Week 8 remission rates were comparable. Reboxetine 8-10 mg/day is as effective as venlafaxine 225375 mg/day in the treatment of severe MDD in adults and is well tolerated.
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Reboxetine augmentation of fluoxetine for patients with major depressive disorder: An 8-week open-label study
M. Rapaport 1, C. Wilcox 2, J. Heiser 2, E Londborg 3, G. Schwartz 4. 1University of California, San Diego, Department
of Psychiatry, San Diego, US.A.; 2Pharmacology Research Institute, Los Alamitos, US.A.; 3Summit Research Network, Seattle, U.S.A.; 4pharmacia, Peapaek, U.S.A. A range of antidepressant agents are now available for the management of major depressive disorder (MDD). However, many patients (29-46%) fail to respond adequately to their first-line agent. For partial responders to a selective serotonin reuptake inhibitor (SSRI) augmentation with an agent of a different pharmacological class such as a selective norepinephrine reuptake inhibitor (selective NRI) has been suggested as a potentially useful strategy. The aim of this 8-week, open-label study was to examine the efficacy and safety of augmenting existing SSRI therapy with the selective NRI reboxetine (4-8 mg/day) for patients with MDD who responded partially to 6 weeks therapy with fluoxetine (20 mg/day). Adults (aged 18-65 years) with a confirmed diagnosis of MDD and a partial response to 6 weeks therapy with fluoxetine (20 mg/day) were included. Partial response was defined as a HAM-D 17-item score greater than or equal to 14 points or a less than or equal to 40% decrease in the estimated SSRI pretreatment score. Efficacy was assessed primarily using the HAM-D 17-item rating scale. Tolerability was assessed through direct observation and spontaneous reporting by patients. A total of 33 patients (mean age 43.8 years) took part in the study of whom 26 (79%) completed the planned 8 weeks of treatment. Six patients withdrew prior to study completion due to adverse events and 1 patient who discontinued due to an unintended pregnancy. Adverse events will be discussed in greater detail. By Week 8 the mean HAM-D 17-item total score had decreased from 18.2 to 10.9 points. Of the 33 patients included in the efficacy analysis, 39.4% (n=13) were classed as responders (mean decrease in HAM-D 17-item total score greater than or equal to 50%) by Week 8 and 36.4% (n=12) were classed as in remission (HAM-D 17-item total score less than or equal to 8 points). The combination of reboxetine and ftuoxetine was well tolerated. The most frequently reported adverse events were insomnia, dry mouth, constipation and diaphoresis, most of which were mild to moderate in intensity and transitory. The addition of the selective NRI reboxetine (4-8 mg/day) proved to be an effective and well tolerated strategy for adult
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patients who responded partially to 6 weeks fluoxetine therapy (20 mg/day).
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Reboxetine and sexual side effects
A. Clayton 1, J. Ferguson 2, J. Reisner 3, M. Brown 3, G. Schwartz 4, j. Zajecka 5. 1 University of Virginia, Department of Psychiatric
Medicine, Charlottesville, US.A.; 2University of Utah, Salt Lake City, U.S.A.; 3Pharmacia, Kalamazoo, US.A.; 4pharmacia, Peapack, US.A.; 5Rush University Medical Center, Chicago, US.A. Sexual side effects due to antidepressant treatment are an important consideration when selecting the most appropriate treatment regimen and may often influence patient compliance. Recently, a multicentre, randomized, eight-week double blind study of reboxetine versus fluoxetine versus placebo was completed with 450 outpatients diagnosed with major depressive disorder (MDD). Sexual function was measured by the Rush Sexual Inventory (RSI) that was completed by male and female patients and administered at baseline, Day 28 and Day 56. The results indicate that reboxetine was comparable with placebo and superior to fluoxetine in its effect on overall sexual function. There was a greater overall degree of sexual satisfaction in the reboxetine group in comparison with fluoxetine (p=0.018). Furthermore, the ability to become sexually excited for both males and females was significantly better for reboxetine compared with fluoxetine (p=0.038). These results suggest that reboxetine may be of particular benefit for patients at risk for sexual dysfunction with SSRIs.
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Reboxetine-associated urinary hesitancy is ameliorated by tamsulosin
K. Demyttenaere, R. Huygens, R. Van Buggenhout. University
Hospital Gasthuisberg, Leuven, Belgium Reboxetine, the first selective noradrenaline reuptake inhibitor (selective NRI), is a novel antidepressant with comparable efficacy to imipramine, desipramine and fluoxetine (Ban et al. 1998, Berzewski et al. 1997, Massana 1998) In comparison with the tricyclic antidepressants, reboxetine has a benign tolerability profile which also differs from that of the selective serotonin reuptake inhibitors (SSRIs). Reboxetine has a low affinity for D2, 5HT1, 5HT2, H1, alpha 1, alpha 2, beta and muscarinic receptors. Although reboxetine has no anticholinergic effects, urinary hesitancy/retention has been reported by a small number of male patients and a peripheral noradrenergic mechanism has been suggested. Lower urinary tract symptoms (LUTS) can be caused by both a mechanical obstruction and functional disturbances. Voiding is inhibited by activation of alpha 1-adrenoceptors as a result of noradrenergic stimulation. Activation of musearinic cholinoreceptors, which can be the result of cholinergic activity and antagonism of alpha la-receptors, facilitates voiding. The objective of this study was to investigate the effect of the first selective alpha 1a adrenoceptor antagonist, tamsulosin on the LUTS occasionally associated with reboxetine treatment of patients with depression. Male patients (n=6) receiving reboxetine (4 mg, twice daily) for depressive disorder who reported urinary hesitancy were given tamsulosin (0.4 mg, once daily). The severity of LUTS was assessed using the American Urological Association symptom score
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Reboxetine augmentation of fluoxetine for patients with major depressive disorder: An 8-week open-label study
M. Rapaport 1, C. Wilcox 2, J. Heiser 2, E Londborg 3, G. Schwartz 4. 1University of California, San Diego, Department
of Psychiatry, San Diego, US.A.; 2Pharmacology Research Institute, Los Alamitos, US.A.; 3Summit Research Network, Seattle, U.S.A.; 4pharmacia, Peapaek, U.S.A. A range of antidepressant agents are now available for the management of major depressive disorder (MDD). However, many patients (29-46%) fail to respond adequately to their first-line agent. For partial responders to a selective serotonin reuptake inhibitor (SSRI) augmentation with an agent of a different pharmacological class such as a selective norepinephrine reuptake inhibitor (selective NRI) has been suggested as a potentially useful strategy. The aim of this 8-week, open-label study was to examine the efficacy and safety of augmenting existing SSRI therapy with the selective NRI reboxetine (4-8 mg/day) for patients with MDD who responded partially to 6 weeks therapy with fluoxetine (20 mg/day). Adults (aged 18-65 years) with a confirmed diagnosis of MDD and a partial response to 6 weeks therapy with fluoxetine (20 mg/day) were included. Partial response was defined as a HAM-D 17-item score greater than or equal to 14 points or a less than or equal to 40% decrease in the estimated SSRI pretreatment score. Efficacy was assessed primarily using the HAM-D 17-item rating scale. Tolerability was assessed through direct observation and spontaneous reporting by patients. A total of 33 patients (mean age 43.8 years) took part in the study of whom 26 (79%) completed the planned 8 weeks of treatment. Six patients withdrew prior to study completion due to adverse events and 1 patient who discontinued due to an unintended pregnancy. Adverse events will be discussed in greater detail. By Week 8 the mean HAM-D 17-item total score had decreased from 18.2 to 10.9 points. Of the 33 patients included in the efficacy analysis, 39.4% (n=13) were classed as responders (mean decrease in HAM-D 17-item total score greater than or equal to 50%) by Week 8 and 36.4% (n=12) were classed as in remission (HAM-D 17-item total score less than or equal to 8 points). The combination of reboxetine and ftuoxetine was well tolerated. The most frequently reported adverse events were insomnia, dry mouth, constipation and diaphoresis, most of which were mild to moderate in intensity and transitory. The addition of the selective NRI reboxetine (4-8 mg/day) proved to be an effective and well tolerated strategy for adult
S205
patients who responded partially to 6 weeks fluoxetine therapy (20 mg/day).
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Reboxetine and sexual side effects
A. Clayton 1, J. Ferguson 2, J. Reisner 3, M. Brown 3, G. Schwartz 4, j. Zajecka 5. 1 University of Virginia, Department of Psychiatric
Medicine, Charlottesville, US.A.; 2University of Utah, Salt Lake City, U.S.A.; 3Pharmacia, Kalamazoo, US.A.; 4pharmacia, Peapack, US.A.; 5Rush University Medical Center, Chicago, US.A. Sexual side effects due to antidepressant treatment are an important consideration when selecting the most appropriate treatment regimen and may often influence patient compliance. Recently, a multicentre, randomized, eight-week double blind study of reboxetine versus fluoxetine versus placebo was completed with 450 outpatients diagnosed with major depressive disorder (MDD). Sexual function was measured by the Rush Sexual Inventory (RSI) that was completed by male and female patients and administered at baseline, Day 28 and Day 56. The results indicate that reboxetine was comparable with placebo and superior to fluoxetine in its effect on overall sexual function. There was a greater overall degree of sexual satisfaction in the reboxetine group in comparison with fluoxetine (p=0.018). Furthermore, the ability to become sexually excited for both males and females was significantly better for reboxetine compared with fluoxetine (p=0.038). These results suggest that reboxetine may be of particular benefit for patients at risk for sexual dysfunction with SSRIs.
•
Reboxetine-associated urinary hesitancy is ameliorated by tamsulosin
K. Demyttenaere, R. Huygens, R. Van Buggenhout. University
Hospital Gasthuisberg, Leuven, Belgium Reboxetine, the first selective noradrenaline reuptake inhibitor (selective NRI), is a novel antidepressant with comparable efficacy to imipramine, desipramine and fluoxetine (Ban et al. 1998, Berzewski et al. 1997, Massana 1998) In comparison with the tricyclic antidepressants, reboxetine has a benign tolerability profile which also differs from that of the selective serotonin reuptake inhibitors (SSRIs). Reboxetine has a low affinity for D2, 5HT1, 5HT2, H1, alpha 1, alpha 2, beta and muscarinic receptors. Although reboxetine has no anticholinergic effects, urinary hesitancy/retention has been reported by a small number of male patients and a peripheral noradrenergic mechanism has been suggested. Lower urinary tract symptoms (LUTS) can be caused by both a mechanical obstruction and functional disturbances. Voiding is inhibited by activation of alpha 1-adrenoceptors as a result of noradrenergic stimulation. Activation of musearinic cholinoreceptors, which can be the result of cholinergic activity and antagonism of alpha la-receptors, facilitates voiding. The objective of this study was to investigate the effect of the first selective alpha 1a adrenoceptor antagonist, tamsulosin on the LUTS occasionally associated with reboxetine treatment of patients with depression. Male patients (n=6) receiving reboxetine (4 mg, twice daily) for depressive disorder who reported urinary hesitancy were given tamsulosin (0.4 mg, once daily). The severity of LUTS was assessed using the American Urological Association symptom score