- Email: [email protected]
Rapid onset of therapeutic action in major depression: A comparative trial of mirtazapine and paroxetine
S229
PI Affective disorders and antidepressants
present in the MADRS, HAM-A and CC&Severity of Illness and Quality of life scores. Both drugs were well tolerated. Sweating and nausea were significantly more frequent in the citalopram group and increased appetite and weight increase in the mirtazapine group. Conclusions: Mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety, and well tolerated. However, mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on MADRS, HAM-A and CGI-Severity of Illness and Quality of life scales. This finding, consistently present at all major efficacy variables, suggests potentially faster onset of action of mirtazapine.
17-HAMD scores were 27 at baseline, and further decreased to a value of 21 at day 7, 14 at day 21 and 6.5 at day 84. The most frequently reported adverse events were somnolence in 17% and weight gain in 2.3% of patients. Conclusion: The results of this open-label study are in line with the results of randomized, double-blind studies of mirtazpaine. They confirm rapid and sustained antidepressant efficacy of mirtazapine combined with a favorable tolerability profile.
Ip.1.0651
Mirtaxapine
and ECT as combination
therapy
B. Soderstrom. Psychiatric Clinic, Varberg Hospital, Varberg, Sweden (p.1.0631
Tolerability of mirtazapine vs SSRls in short term treatment of major depression
C.M.E. Kremer’, J.T.H. Helsdingen, J.A. Schutte, E. Vester. ‘Organon Inc., Mount Pleasant Ave. 375, West Orange, NJ 07052, USA Aim: To compare overall tolerability of mirtazapine versus SSRIs used
in short-term treatment of major depression. Method: The data from patients who were randomized and took at least one dose of blinded study medication in currently available double-blind, randomized short-term comparisons of mirtazapine (1560 mgday; n = 411) and SSRIs (n = 408) (fluoxetine, 20-40 mgday; paroxetine 20-40 mg/day and citalopram, 20-60 mgday) are pooled and analyzed using descriptive statistics. The following variables are presented: percentages of patients complaining of at least one adverse event, percentages of patients prematurely terminating the studies due adverse events and percentages of patients reporting any adverse event. Results: Sixty-five percent of mirtazapine and 63.5% of SF&I-treated patients have complained of at least one adverse event during the studies, respective percentages of patients prematurely discontinuing the studies due to adverse events were 9% for mirtazapine and 8.6% for SSRIs. In either treatment group adverse events were reported in 5 15% of patients. SSRI-treated patients were complaining more frequently than mirtazapine-treated patients of nausea (15 vs 5.3%, respectively) and sweating (8.3 vs 1.5%, respectively). Mirtazapine treated patients complained more frequently of dry mouth (14 vs 6.6%, respectively) and weight increase (10.0 vs 2.7%, respectively). Conclusions: Similar percentages of patients treated with either mirtazapine or SSRIs were complaining of at least one adverse event or prematurely terminated the studies. The overall incidences of reported adverse events were low, and the most frequent complaints are in line with different pharmacological profiles of compounds. It can be concluded that mirtazapine and SSRIs are equally well tolerated during the short-term treatment of major depression.
Ip.1.0641
An open-label, Argentlna
naturalistic
study of mirtazapine
in
J. Pahissa. Organon Argentina, Buenos Aires, Argentina Objective: To assess antidepressant efficacy and tolerability of mirtazapine in everyday clinical practice. Materials and Methods: Depressed in- and outpatients of both sexes (n = 175), older than 18 years, were treated by psychiatrists (n = 60) in Argentina in an open-label study. Efficacy was assessed by 17-item HAMD at baseline and after 7, 21 and 84 days of treatment. Tolerability was assessed by registering treatment-emergent adverse events. The statistical analysis was performed on Intention-to-Treat basis using the Last Observation Carried Forward method. Qualitative variables were compared by Pearson’s chi-square test and Fisher’s exact test and quantitative variables by univariate analyses of Kruskal-Wallis. P values ~0.05 were considered significant. Results: At baseline, 96% of patients were moderately to severely depressed 82% presented with insomnia, 49% with panic symptoms and 31% with suicidality. Mean dose used was 30 mg/day of mirtazapine. Seven percent of patients dropped out due to adverse events. Mean group
Aim: To review data on 19 patients in whom combination therapy with mirtazapine and electroconvulsive therapy (ECT) was used. Materials and Methods: A retrospective review of patients’ charts was performed. Nineteen hospitalized depressed patients (9 females and 10 males, age range between 26 and 85 years) were treated with combination therapy. ECT has been administered unilaterally in 18 patients in a number ranging between 3-16. One patient received 10 bilateral ECTs, and one patient a single bilateral ECT application in during the ECT series. In patients not previously treated with mirtazapine, the drug was introduced during the ECT series, usually at 15 mg/day and towards the end of the series. The combination therapy lead to a quick resolution of depressive symptoms, without any adverse events observed, and enabled discharge of patients the same day or the day after the last ECT. Conclusions: In contrast to other antidepressants, lithium or benzodiazapines which need to be discontinued during the ECT administration, our experience suggest that introduction of mirtazapine or continuation of treatment with mirtazapine during the ECT series is efficaceous and safe procedure. The possible lowering of a seizure threshold of administered ECT by mirtazapine may be advantageous in combination treatment.
Ip.1.0661
Rapid onset of therapeutic action in major depression: a comparative trial of mirtaxapine paroxetine
and
0. Benkert’, A. Szegedi’, R. Kohnen’, A.-J. Schutte3. ‘Johannes Guttenberg-Unioersiriit, Psychitrische Kliniek und Polikliniek, Untere Zuhlbacher Str 8, 55131 Maim; ‘IMEREM, Niiremberg Germany 3NV Organon, Oss, The Netherlands Aim: To compare antidepressant and anxiolytic efficacy as well as tolerability of mirtazapine and paroxetine in a randomized, double-blind, multicentre, 6-weeks’ study. Methods: Outpatients with a Major Depressive Episode-DSM-IV and a baseline score of 2 18 on the 17-HAMD were randomized to 6 weeks’ treatment with either mirtazapine (n = 138, 15-45 mg/day) or paroxetine (n = 136, 20-40 mgday). Efficacy was assessed by the 17-HAMD, HAMA, CGI, and BDI scales, on ITT group using the OC and LOCF methods; and tolerability by the UKU scale and reporting of adverse events. Results: Mean doses were mirtazapine, 32.7 mgday and paroxetine, 22.9 mgday; 24 patients in either treatment group dropped out from the study. Both drugs were equally effective in reducing overall symptoms of depression. At week 1 improvement in 17-HAMD scores was significantly larger under mirtazapine (6 = -6.0 f 5.2) compared to paroxetine (6 = -3.6 f 5.1; p = 0.0004). Significantly more mirtazapine-treated patients were HAMD responders at week 1 (23.8% vs 8.9%, p = 0.002) and week 4 (58.3% vs 44.5%, p = 0.40) Statistically significant differences favoring mirtazapine were also found on other factors/subscales of the HAMD. Tolerability of both treatments was good, with mom complaints of weight increase and influenza-like symptoms in the mirtazapine group, and nausea, vomiting, tremor and sweating in the paroxetine group. Conclusions: Mirtazapine and paroxetine were equally effective and well tolerated. Mirtazapine was significantly more effective than paroxetine especially after the first week of therapy, and consecutively during
P.1 Affective disorders and antidepressants
$230
weeks 2 to 4, as indicated by 17-HAMD scores, several HAMD factors/subscales and the percentage of responders. These results suggest potentially faster onset of action of mirtazapine.
Opioid involvement in antidepressant-type effect of NK3 receptor agonlst, senktide, in the mouse forced swimming test I. Panocka 1, M. Kowalczyk 1 *, B. Sadowski2, I. Lapo 2, M. Masi 3.
1Department of Pharmacology and Toxicology, Military Institute of Hygiene and Epidemiology, Warsaw,"2Institute of Genetics and Animal Breeding, Polish Academy of Sciences, dastrzebiec, Poland 3Department of Farmacology and Experimental Medicine, University of Camerino, Italy The present study was aimed at evaluationg the influence of the tachykinin NK3 receptor agonist, senktide (SENK) on the immobility observed during forced swimming test (FST) in mice selectively bred for high (HA) and low (LA) stres-induced analgesia and in randomly bred control line (C), from which HA and LA lines have been bred. The effect of SENK was compared to antiimmobility action of wellknown antidepresant, desipramine (DMI). Mice were placed for 6 min in a plexiglass cylinder containing water to a depth of 16 cm at 23°C. The duration of immobility (i.e. time during which mice were making only small movements necesary to keep their head above water) was measured during the last 4 min. Both DMI (10 mg/kg) and SENK (125 or 250 txg/kg) injected intraperitoneally (IP) 30 or 10 min prior to FST, respectively, significantly reduced the immobility time in HA [F (2, 58) = 10.88 and 11.64, respectively; p < 0.001] and C [F (2.58) = 13.084 and 12.65, respectively; p < 0.001] mice, while in LA line these treatments were ineffective. Since: a) in HA and LA mice enhanced (HA) and reduced (LA) activity of opioid system (that is thought to be involved in effects of several antidepresants (1) and in pathogenesis of depression) has been proven and b) tachykinins (that have been recently suggested to be involved in patophysiology of depression) have been shown to stimulate opiOid system activity (2), the influence of naloxone (10 mg/kg injected IP 30 min prior to FST) on antiimmobility effect of SENK has been studied in HA, C and LA mice. Naloxone itself has no effect, but abolished that of SENK both in HA and C mice. None of the drugs used in the present study affected locomotor activity in the open field (except DMI in HA mice that reduced locomotion). Thus, their effects were apparently not a consequence of a general motility changes. These results suggest that antidepressant-like activity of NK3 receptor agonist(s) is mediated to large extent by endogenous opioids.
References [l] De Felipe, M.C., I. Jimenez, A. Castro, J.A. Fuentez. Antidepresant action of imipramine and iprindole in mice is enhanced by inhibitors of enkephalindegrading peptidases. Eur. J. Pharmacol. 159:175; 1989 [2] Hasenohrl, R.U., P. Gerhardt, J.P. Huston. Naloxone blocks conditioned place preference induced by substance P and [pGIu6]-SP (6-11). Reg. Peptides 35: 177-187; 1991.
~ A n
assessment of the potential for SSRI discontinuation syndrome with citalopram
J.S. Markowitz, C.L. DeVane*. Department of Psychiatry and Behav-
ioral Sciences, Medical Universityof South Carolina, Charleston, South Carolina, 29425, USA The development of withdrawal or discontinuation symptoms following cessation of antidepressant medications has been recognized for forth years. However, only recently has this phenomenon been associated with the selective serotonin reuptake inhibitors (SSRI). Among the SSRIs, some drugs appear less problematic than others. We analyzed data from a clinical trial of depressed patients who were openly treated with citalopram (CIT) for 8 weeks. Responders were randomized to doubleblind treatment with placebo (PLO) or CIT. PLO-treated patients (n =
72) were assessed for treatment emergent adverse events associated with abrupt termination of CIT, and data compared to patients continuing double-blind treatment with CIT (n = 150). The proportion of patients that experienced one or more events over a two week period following randomization was similar in the two groups. Events occurring at a higher frequency in the PLO compared to CIT treated patients were: anxiety (5.6% vs. 2.0%); impaired concentration (4.2% vs. 0%); migraine (4.2% vs. 0.7%); tremor 4.2% vs. 0.7%) and paresthesia (4.2% vs. 1.3%). These events could suggest an increase in anxiety accompanying drug withdrawal, but also could reflect re-emergence of depressive symptoms. No exaggerated symptoms were present and most of the events were mild in intensity. No patients randomized to PLO discontinued from the study in the observation period. These data suggest several symptoms may be associated with abrupt termination o f 20-60 mg/day of CIT, but the symptoms were mild and did not result in withdrawal from the study.
References [1] Therrien F, Markowitz JS. Selective serotonin reuptake inhibitors and withdrawal symptoms: A review of the literature. Hum Psychopharmacol 1997; 12: 309-23. [2] Robert Ph, Montgomery SA. Citalopram in doses of 20-60 mg is effective in depression relapse prevention: a placebo-controlled6 month study. Int Clin Psychopharmacol 1995; 10 (Suppl 1): 29-35.
~ A n
open assessment of the safety and efficacy of venlafexine in mild to moderate and In severe depression in usual care settings in Hungary
J. Demeter, M. Gyenis, K. Steel*, A. Szabo. Wyeth-Lederle Pharma,
Storchengasse 1/3, Henna, Austria Objective: To evaluate the efficacy and safety of venlafaxine in the treatment depressed patients in the usual care settings according to the approved product labeling in Hungary. Design and Methods: Inpatients or outpatients aged 18 to 70 years with a diagnosis of major depression according the DSM-IV were eligible to be included in this open label, noncomparative study. For outpatients, a baseline score between 20 and 25, inclusive, on the 21item Hamilton Depression Rating Scale (HAM-D) was required and the patients had to be considered by the investigator to be mildly to moderately depressed. For inpatients, a minimum baseline score of 25 on the 21-item HAM-D was required; these patients had to be considered severely depressed by the investigator. Outpatients were treated initially with venlafaxine 75 mg/day (37.5 mg BID). Based on clinical response and the clinical judgment of the investigator, the dose could be increased after two weeks of treatment to 150 mg/day (75 mg twice daily). Inpatients initially received 75 rag/day (37.5 mg twice daily). This dose could be increased up to a maximum dose of 375 mg/day. Patients were treated with venlafaxine for a period of 8 weeks. The primary efficacy variables in this study were the change from baseline in the week 8 HAM-D and MADRS total scores. Response was defined as at least 50% decrease from baseline in total HAM-D or MADRS scores and CGI global improvement item 1 or 2. Remission was defined as HAM-D total score < 8. Safety was evaluated by the recording of study events. Results: 50 patients were enrolled in 5 centers. Data are presented for the 31 patients evaluated to date. Mean age at enrollment was 45.3 years. At baseline 24 (77%) patients were classified as severely depressed. Twenty-one (68%) were hospital patients. The mean baseline HAM-D scores among evaluated population was 27.7 (SD + 3.6) and the mean baseline MADRS score was 31.6 (SD + 5.5). The week 8 (LOCF) mean HAM-D score was 8.4 (SD -4- 7.4) and MADRS score was 8.6 (SD + 8.5). Twenty-two (71%) of patients had HAM-D score < 8 in the week 8 and 28 (90%) patients were classified as improved (19%) or very much improved (71%). Based on the HAM-D, 24 (77%) of patients were classified as responders at week 8; 25 (81%) were so classified on the MADRS scale. There were no differences in mean blood pressure, body weight or heart rate throughout the study. These results suggest that venlafaxine used in the usual care setting in Hungary provides a
PI Affective disorders and antidepressants
present in the MADRS, HAM-A and CC&Severity of Illness and Quality of life scores. Both drugs were well tolerated. Sweating and nausea were significantly more frequent in the citalopram group and increased appetite and weight increase in the mirtazapine group. Conclusions: Mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety, and well tolerated. However, mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on MADRS, HAM-A and CGI-Severity of Illness and Quality of life scales. This finding, consistently present at all major efficacy variables, suggests potentially faster onset of action of mirtazapine.
17-HAMD scores were 27 at baseline, and further decreased to a value of 21 at day 7, 14 at day 21 and 6.5 at day 84. The most frequently reported adverse events were somnolence in 17% and weight gain in 2.3% of patients. Conclusion: The results of this open-label study are in line with the results of randomized, double-blind studies of mirtazpaine. They confirm rapid and sustained antidepressant efficacy of mirtazapine combined with a favorable tolerability profile.
Ip.1.0651
Mirtaxapine
and ECT as combination
therapy
B. Soderstrom. Psychiatric Clinic, Varberg Hospital, Varberg, Sweden (p.1.0631
Tolerability of mirtazapine vs SSRls in short term treatment of major depression
C.M.E. Kremer’, J.T.H. Helsdingen, J.A. Schutte, E. Vester. ‘Organon Inc., Mount Pleasant Ave. 375, West Orange, NJ 07052, USA Aim: To compare overall tolerability of mirtazapine versus SSRIs used
in short-term treatment of major depression. Method: The data from patients who were randomized and took at least one dose of blinded study medication in currently available double-blind, randomized short-term comparisons of mirtazapine (1560 mgday; n = 411) and SSRIs (n = 408) (fluoxetine, 20-40 mgday; paroxetine 20-40 mg/day and citalopram, 20-60 mgday) are pooled and analyzed using descriptive statistics. The following variables are presented: percentages of patients complaining of at least one adverse event, percentages of patients prematurely terminating the studies due adverse events and percentages of patients reporting any adverse event. Results: Sixty-five percent of mirtazapine and 63.5% of SF&I-treated patients have complained of at least one adverse event during the studies, respective percentages of patients prematurely discontinuing the studies due to adverse events were 9% for mirtazapine and 8.6% for SSRIs. In either treatment group adverse events were reported in 5 15% of patients. SSRI-treated patients were complaining more frequently than mirtazapine-treated patients of nausea (15 vs 5.3%, respectively) and sweating (8.3 vs 1.5%, respectively). Mirtazapine treated patients complained more frequently of dry mouth (14 vs 6.6%, respectively) and weight increase (10.0 vs 2.7%, respectively). Conclusions: Similar percentages of patients treated with either mirtazapine or SSRIs were complaining of at least one adverse event or prematurely terminated the studies. The overall incidences of reported adverse events were low, and the most frequent complaints are in line with different pharmacological profiles of compounds. It can be concluded that mirtazapine and SSRIs are equally well tolerated during the short-term treatment of major depression.
Ip.1.0641
An open-label, Argentlna
naturalistic
study of mirtazapine
in
J. Pahissa. Organon Argentina, Buenos Aires, Argentina Objective: To assess antidepressant efficacy and tolerability of mirtazapine in everyday clinical practice. Materials and Methods: Depressed in- and outpatients of both sexes (n = 175), older than 18 years, were treated by psychiatrists (n = 60) in Argentina in an open-label study. Efficacy was assessed by 17-item HAMD at baseline and after 7, 21 and 84 days of treatment. Tolerability was assessed by registering treatment-emergent adverse events. The statistical analysis was performed on Intention-to-Treat basis using the Last Observation Carried Forward method. Qualitative variables were compared by Pearson’s chi-square test and Fisher’s exact test and quantitative variables by univariate analyses of Kruskal-Wallis. P values ~0.05 were considered significant. Results: At baseline, 96% of patients were moderately to severely depressed 82% presented with insomnia, 49% with panic symptoms and 31% with suicidality. Mean dose used was 30 mg/day of mirtazapine. Seven percent of patients dropped out due to adverse events. Mean group
Aim: To review data on 19 patients in whom combination therapy with mirtazapine and electroconvulsive therapy (ECT) was used. Materials and Methods: A retrospective review of patients’ charts was performed. Nineteen hospitalized depressed patients (9 females and 10 males, age range between 26 and 85 years) were treated with combination therapy. ECT has been administered unilaterally in 18 patients in a number ranging between 3-16. One patient received 10 bilateral ECTs, and one patient a single bilateral ECT application in during the ECT series. In patients not previously treated with mirtazapine, the drug was introduced during the ECT series, usually at 15 mg/day and towards the end of the series. The combination therapy lead to a quick resolution of depressive symptoms, without any adverse events observed, and enabled discharge of patients the same day or the day after the last ECT. Conclusions: In contrast to other antidepressants, lithium or benzodiazapines which need to be discontinued during the ECT administration, our experience suggest that introduction of mirtazapine or continuation of treatment with mirtazapine during the ECT series is efficaceous and safe procedure. The possible lowering of a seizure threshold of administered ECT by mirtazapine may be advantageous in combination treatment.
Ip.1.0661
Rapid onset of therapeutic action in major depression: a comparative trial of mirtaxapine paroxetine
and
0. Benkert’, A. Szegedi’, R. Kohnen’, A.-J. Schutte3. ‘Johannes Guttenberg-Unioersiriit, Psychitrische Kliniek und Polikliniek, Untere Zuhlbacher Str 8, 55131 Maim; ‘IMEREM, Niiremberg Germany 3NV Organon, Oss, The Netherlands Aim: To compare antidepressant and anxiolytic efficacy as well as tolerability of mirtazapine and paroxetine in a randomized, double-blind, multicentre, 6-weeks’ study. Methods: Outpatients with a Major Depressive Episode-DSM-IV and a baseline score of 2 18 on the 17-HAMD were randomized to 6 weeks’ treatment with either mirtazapine (n = 138, 15-45 mg/day) or paroxetine (n = 136, 20-40 mgday). Efficacy was assessed by the 17-HAMD, HAMA, CGI, and BDI scales, on ITT group using the OC and LOCF methods; and tolerability by the UKU scale and reporting of adverse events. Results: Mean doses were mirtazapine, 32.7 mgday and paroxetine, 22.9 mgday; 24 patients in either treatment group dropped out from the study. Both drugs were equally effective in reducing overall symptoms of depression. At week 1 improvement in 17-HAMD scores was significantly larger under mirtazapine (6 = -6.0 f 5.2) compared to paroxetine (6 = -3.6 f 5.1; p = 0.0004). Significantly more mirtazapine-treated patients were HAMD responders at week 1 (23.8% vs 8.9%, p = 0.002) and week 4 (58.3% vs 44.5%, p = 0.40) Statistically significant differences favoring mirtazapine were also found on other factors/subscales of the HAMD. Tolerability of both treatments was good, with mom complaints of weight increase and influenza-like symptoms in the mirtazapine group, and nausea, vomiting, tremor and sweating in the paroxetine group. Conclusions: Mirtazapine and paroxetine were equally effective and well tolerated. Mirtazapine was significantly more effective than paroxetine especially after the first week of therapy, and consecutively during
P.1 Affective disorders and antidepressants
$230
weeks 2 to 4, as indicated by 17-HAMD scores, several HAMD factors/subscales and the percentage of responders. These results suggest potentially faster onset of action of mirtazapine.
Opioid involvement in antidepressant-type effect of NK3 receptor agonlst, senktide, in the mouse forced swimming test I. Panocka 1, M. Kowalczyk 1 *, B. Sadowski2, I. Lapo 2, M. Masi 3.
1Department of Pharmacology and Toxicology, Military Institute of Hygiene and Epidemiology, Warsaw,"2Institute of Genetics and Animal Breeding, Polish Academy of Sciences, dastrzebiec, Poland 3Department of Farmacology and Experimental Medicine, University of Camerino, Italy The present study was aimed at evaluationg the influence of the tachykinin NK3 receptor agonist, senktide (SENK) on the immobility observed during forced swimming test (FST) in mice selectively bred for high (HA) and low (LA) stres-induced analgesia and in randomly bred control line (C), from which HA and LA lines have been bred. The effect of SENK was compared to antiimmobility action of wellknown antidepresant, desipramine (DMI). Mice were placed for 6 min in a plexiglass cylinder containing water to a depth of 16 cm at 23°C. The duration of immobility (i.e. time during which mice were making only small movements necesary to keep their head above water) was measured during the last 4 min. Both DMI (10 mg/kg) and SENK (125 or 250 txg/kg) injected intraperitoneally (IP) 30 or 10 min prior to FST, respectively, significantly reduced the immobility time in HA [F (2, 58) = 10.88 and 11.64, respectively; p < 0.001] and C [F (2.58) = 13.084 and 12.65, respectively; p < 0.001] mice, while in LA line these treatments were ineffective. Since: a) in HA and LA mice enhanced (HA) and reduced (LA) activity of opioid system (that is thought to be involved in effects of several antidepresants (1) and in pathogenesis of depression) has been proven and b) tachykinins (that have been recently suggested to be involved in patophysiology of depression) have been shown to stimulate opiOid system activity (2), the influence of naloxone (10 mg/kg injected IP 30 min prior to FST) on antiimmobility effect of SENK has been studied in HA, C and LA mice. Naloxone itself has no effect, but abolished that of SENK both in HA and C mice. None of the drugs used in the present study affected locomotor activity in the open field (except DMI in HA mice that reduced locomotion). Thus, their effects were apparently not a consequence of a general motility changes. These results suggest that antidepressant-like activity of NK3 receptor agonist(s) is mediated to large extent by endogenous opioids.
References [l] De Felipe, M.C., I. Jimenez, A. Castro, J.A. Fuentez. Antidepresant action of imipramine and iprindole in mice is enhanced by inhibitors of enkephalindegrading peptidases. Eur. J. Pharmacol. 159:175; 1989 [2] Hasenohrl, R.U., P. Gerhardt, J.P. Huston. Naloxone blocks conditioned place preference induced by substance P and [pGIu6]-SP (6-11). Reg. Peptides 35: 177-187; 1991.
~ A n
assessment of the potential for SSRI discontinuation syndrome with citalopram
J.S. Markowitz, C.L. DeVane*. Department of Psychiatry and Behav-
ioral Sciences, Medical Universityof South Carolina, Charleston, South Carolina, 29425, USA The development of withdrawal or discontinuation symptoms following cessation of antidepressant medications has been recognized for forth years. However, only recently has this phenomenon been associated with the selective serotonin reuptake inhibitors (SSRI). Among the SSRIs, some drugs appear less problematic than others. We analyzed data from a clinical trial of depressed patients who were openly treated with citalopram (CIT) for 8 weeks. Responders were randomized to doubleblind treatment with placebo (PLO) or CIT. PLO-treated patients (n =
72) were assessed for treatment emergent adverse events associated with abrupt termination of CIT, and data compared to patients continuing double-blind treatment with CIT (n = 150). The proportion of patients that experienced one or more events over a two week period following randomization was similar in the two groups. Events occurring at a higher frequency in the PLO compared to CIT treated patients were: anxiety (5.6% vs. 2.0%); impaired concentration (4.2% vs. 0%); migraine (4.2% vs. 0.7%); tremor 4.2% vs. 0.7%) and paresthesia (4.2% vs. 1.3%). These events could suggest an increase in anxiety accompanying drug withdrawal, but also could reflect re-emergence of depressive symptoms. No exaggerated symptoms were present and most of the events were mild in intensity. No patients randomized to PLO discontinued from the study in the observation period. These data suggest several symptoms may be associated with abrupt termination o f 20-60 mg/day of CIT, but the symptoms were mild and did not result in withdrawal from the study.
References [1] Therrien F, Markowitz JS. Selective serotonin reuptake inhibitors and withdrawal symptoms: A review of the literature. Hum Psychopharmacol 1997; 12: 309-23. [2] Robert Ph, Montgomery SA. Citalopram in doses of 20-60 mg is effective in depression relapse prevention: a placebo-controlled6 month study. Int Clin Psychopharmacol 1995; 10 (Suppl 1): 29-35.
~ A n
open assessment of the safety and efficacy of venlafexine in mild to moderate and In severe depression in usual care settings in Hungary
J. Demeter, M. Gyenis, K. Steel*, A. Szabo. Wyeth-Lederle Pharma,
Storchengasse 1/3, Henna, Austria Objective: To evaluate the efficacy and safety of venlafaxine in the treatment depressed patients in the usual care settings according to the approved product labeling in Hungary. Design and Methods: Inpatients or outpatients aged 18 to 70 years with a diagnosis of major depression according the DSM-IV were eligible to be included in this open label, noncomparative study. For outpatients, a baseline score between 20 and 25, inclusive, on the 21item Hamilton Depression Rating Scale (HAM-D) was required and the patients had to be considered by the investigator to be mildly to moderately depressed. For inpatients, a minimum baseline score of 25 on the 21-item HAM-D was required; these patients had to be considered severely depressed by the investigator. Outpatients were treated initially with venlafaxine 75 mg/day (37.5 mg BID). Based on clinical response and the clinical judgment of the investigator, the dose could be increased after two weeks of treatment to 150 mg/day (75 mg twice daily). Inpatients initially received 75 rag/day (37.5 mg twice daily). This dose could be increased up to a maximum dose of 375 mg/day. Patients were treated with venlafaxine for a period of 8 weeks. The primary efficacy variables in this study were the change from baseline in the week 8 HAM-D and MADRS total scores. Response was defined as at least 50% decrease from baseline in total HAM-D or MADRS scores and CGI global improvement item 1 or 2. Remission was defined as HAM-D total score < 8. Safety was evaluated by the recording of study events. Results: 50 patients were enrolled in 5 centers. Data are presented for the 31 patients evaluated to date. Mean age at enrollment was 45.3 years. At baseline 24 (77%) patients were classified as severely depressed. Twenty-one (68%) were hospital patients. The mean baseline HAM-D scores among evaluated population was 27.7 (SD + 3.6) and the mean baseline MADRS score was 31.6 (SD + 5.5). The week 8 (LOCF) mean HAM-D score was 8.4 (SD -4- 7.4) and MADRS score was 8.6 (SD + 8.5). Twenty-two (71%) of patients had HAM-D score < 8 in the week 8 and 28 (90%) patients were classified as improved (19%) or very much improved (71%). Based on the HAM-D, 24 (77%) of patients were classified as responders at week 8; 25 (81%) were so classified on the MADRS scale. There were no differences in mean blood pressure, body weight or heart rate throughout the study. These results suggest that venlafaxine used in the usual care setting in Hungary provides a