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P.2.132 Analysis of suicidality in adults treated with fluoxetine
P2 Affective disorders and antidepressants with a higher consumption of "second generation" antidepressants (5.18 DHD). Use percentage of the different antidepressant groups in each one of the studied European countries is shown in Table 1. Regarding the SSRI use pattern, this is different in each one of the studied countries. Paroxetine is the most consumed antidepressant in Spain, France and Italy, while the second consumption places correspond to fluoxetine in France, citalopram in Italy and sertraline in Spain. Citalopram is the SSRI most used in Sweden and Germany, followed in both countries by sertraline, while in the United Kingdom fluoxetine is the most used drug, nearly followed by paroxetine. In Germany the most consumed antidepressant is amitriptyline. Table 1: Use of the antidepressant groups in different countries of the Etu'opean Union in 2002 Group a
Use (expressed in percentage) France Germany Italy Spain Sweden UK
SSRIs SNRI TCAs Second-generation antidepressants NaSSA NARI RIMAs MAOIs SARI
65.44 8.53 12.05 11.90
35.3 4.28 46.68 3.21
73.8 5.54 10.04 6.44
75.43 8.97 8.12 3.42
75.39 8.30 6.65 1.45
63.72 9.25 16.4 6.96
1.62 0 0.46 0 0
7.65 0.70 1.34 0.55 0.30
2.88 1.26 0.02 0 0
3.08 0.67 0.14 0.10 0.06
7.10 0.33 0.46 0 0.31
2.56 0.27 0.18 0.33 0.33
aAbbreviations: SSRI, Selective Serotonin Reuptake Inhibitor; SNRI, Serotonin and Noradrenaline Reuptake Inhibitor (Venlafaxine); TCAs, Tricyclic Antidepressants; NaSSA, Noradrenergic and Specific Serotonergic Antidepressants (mirtazapine); NARI, Noradrenaline Reuptake Inhibitors (reboxetine); RIMA, Reversible Inhibitor ofMonoamine-oxidase-A; MAOI, Monoamine Oxidase Inhibitor; SARI, Serotonin 2 Antagonist/Reuptake Inhibitor. C o n c l u s i o n : There are remarkable differences, among the studied European countries in total antidepressants consumption, as well as in antidepressants used standard, in spite of the fact that the SSRI constitute the most used antidepressant group in all the countries, Germany excepted, where the ADTs are the most consumed. Sweden is the country with a higher consumption of antidepressants (60.8 DHD).
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Analysis of suicidality in adults treated with fluoxetine
J. Polzer 1, M. Nilsson 1 , C. Caldwell 1, J. Plewes 1 , N. Acharya 2 *.
]Eli Lilly and Company, Lilly Research Laboratories, USA," 2Eli Lilly and Company Limited, Lilly Research Centre, Erl Wood Manot; VzTndlesham, Surrey, United Kingdom Background/Purpose: The potential risk of suicidality ("suicidal ideation", "suicide attempt" or "self-harm" events) with antidepressant treatment has been the subject of ongoing debate. We undertook an update of previously reported analyses evaluating the incidence of suicide-related events in adult clinical trials across multiple psychiatric and non-psychiatric conditions, comparing fluoxetine with placebo in an expanded database. M e t h o d s : Placebo-controlled fluoxetine studies conducted in adults and contained in the Lilly Corporate database (56 studies; 11,677 patients) were included in the analyses. Analyses were
$449
conducted for all conditions pooled and by condition. The following subgroups were assessed: events within the first 2 weeks, events within the first 4 weeks, 18-<30-year-old patients, females, males, studies that had exclusion criteria for suicidal risk, and studies that did not have exclusion criteria for suicidal risk. The crude incidence (number of patients with an event/number of patients) and the number of patients with an event/number of person years of exposure for completed suicide, non-fatal selfharm, and suicidal ideation were compared between fluoxetine and placebo. Completed suicide and non-fatal self-harm events were assessed using adverse event data. Suicidal ideation was assessed using adverse event data and changes in scores on Item 3 of the Hamilton Depression Rating Scale (HAM-D). The MantelHaenszel incidence difference, the DerSimonian-Laird incidence difference, and the Mantel-Haenszel Time-Adjusted Rate Difference methods stratified by study were used. Results: Among all patients (all conditions pooled), 16 of 7010 (0.2%) fluoxetine- versus 10 of 4667 (0.2%) placebotreated patients reported non-fatal self-harm events (p 0.951). Twenty-five (0.4%) fluoxetine- versus 14 (0.3%) placebo-treated patients reported suicidal ideation (p 0.882) using adverse event data and 470 of 3643 (12.9%) fluoxetine- versus 353 of 2190 (16.1%) placebo-treated patients experienced worsening of suicidal ideation from baseline (p 0.020; placebo higher) using HAMD data. There were two completed suicides (1 fluoxetinetreated patient and 1 placebo-treated patient). Among patients 18-<30 (all conditions pooled), 7 of 1394 (0.5%) fluoxetineversus 3 of 776 (0.4%) placebo-treated patients reported nonfatal self-harm events (p 0.571). Nine (0.6%) fluoxetine- versus 1 (0.1%) placebo-treated patients reported suicidal ideation (p 0.046) using adverse event data and 131 of 876 (15.0%) fluoxetine- versus 70 of 443 (15.8%) placebo-treated patients experienced worsening of suicidal ideation from baseline (p 0.252) using HAM-D data. Among females (all conditions pooled), 12 of 4780 (0.3%) fluoxetine- versus 9 of 3156 (0.3%) placebotreated patients reported non-fatal self-harm events (p 0.657). Twenty one (0.4%) fluoxetine- versus 4 (0.1%) placebo-treated patients reported suicidal ideation (p 0.013; fluoxetine higher) using adverse event data and 310 of 2434 (12.7%) fluoxetineversus 234 of 1432 (16.3%) placebo-treated patients experienced worsening of suicidal ideation from baseline (p 0.035; placebo higher) using HAM-D data. C o n c l u s i o n : These data are consistent with results of previous analyses, and fail to support an increased risk of suicidality in adult patients treated with fluoxetine compared to placebo.
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Antidepressant drug combination from treatment initiation to improve therapeutic response in major depression
R Blier 1., RM. Tremblay 1, H.E. Ward 2, C. Hebert 1, R. Bergeron 1 . j University of Ottawa, Psychiatry, Ottawa,
Canada; 2 University of Florida, Psychiatry, USA The treatment of depression with a single drug is not always time efficient because only about 50% of patients achieve remission with a first agent given at an adequate dose for as sufficient time. In addition, a second medication is often used to manage the most cumbersome symptoms, usually a benzodiazepine. In the present study, two antidepressants were used from treatment initiation: mirtazapine (30mg at bedtime) was given with either fluoxetine (20mg/day), bupropion (150mg/day), or venlafaxine (75 mg/day
Use (expressed in percentage) France Germany Italy Spain Sweden UK
SSRIs SNRI TCAs Second-generation antidepressants NaSSA NARI RIMAs MAOIs SARI
65.44 8.53 12.05 11.90
35.3 4.28 46.68 3.21
73.8 5.54 10.04 6.44
75.43 8.97 8.12 3.42
75.39 8.30 6.65 1.45
63.72 9.25 16.4 6.96
1.62 0 0.46 0 0
7.65 0.70 1.34 0.55 0.30
2.88 1.26 0.02 0 0
3.08 0.67 0.14 0.10 0.06
7.10 0.33 0.46 0 0.31
2.56 0.27 0.18 0.33 0.33
aAbbreviations: SSRI, Selective Serotonin Reuptake Inhibitor; SNRI, Serotonin and Noradrenaline Reuptake Inhibitor (Venlafaxine); TCAs, Tricyclic Antidepressants; NaSSA, Noradrenergic and Specific Serotonergic Antidepressants (mirtazapine); NARI, Noradrenaline Reuptake Inhibitors (reboxetine); RIMA, Reversible Inhibitor ofMonoamine-oxidase-A; MAOI, Monoamine Oxidase Inhibitor; SARI, Serotonin 2 Antagonist/Reuptake Inhibitor. C o n c l u s i o n : There are remarkable differences, among the studied European countries in total antidepressants consumption, as well as in antidepressants used standard, in spite of the fact that the SSRI constitute the most used antidepressant group in all the countries, Germany excepted, where the ADTs are the most consumed. Sweden is the country with a higher consumption of antidepressants (60.8 DHD).
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Analysis of suicidality in adults treated with fluoxetine
J. Polzer 1, M. Nilsson 1 , C. Caldwell 1, J. Plewes 1 , N. Acharya 2 *.
]Eli Lilly and Company, Lilly Research Laboratories, USA," 2Eli Lilly and Company Limited, Lilly Research Centre, Erl Wood Manot; VzTndlesham, Surrey, United Kingdom Background/Purpose: The potential risk of suicidality ("suicidal ideation", "suicide attempt" or "self-harm" events) with antidepressant treatment has been the subject of ongoing debate. We undertook an update of previously reported analyses evaluating the incidence of suicide-related events in adult clinical trials across multiple psychiatric and non-psychiatric conditions, comparing fluoxetine with placebo in an expanded database. M e t h o d s : Placebo-controlled fluoxetine studies conducted in adults and contained in the Lilly Corporate database (56 studies; 11,677 patients) were included in the analyses. Analyses were
$449
conducted for all conditions pooled and by condition. The following subgroups were assessed: events within the first 2 weeks, events within the first 4 weeks, 18-<30-year-old patients, females, males, studies that had exclusion criteria for suicidal risk, and studies that did not have exclusion criteria for suicidal risk. The crude incidence (number of patients with an event/number of patients) and the number of patients with an event/number of person years of exposure for completed suicide, non-fatal selfharm, and suicidal ideation were compared between fluoxetine and placebo. Completed suicide and non-fatal self-harm events were assessed using adverse event data. Suicidal ideation was assessed using adverse event data and changes in scores on Item 3 of the Hamilton Depression Rating Scale (HAM-D). The MantelHaenszel incidence difference, the DerSimonian-Laird incidence difference, and the Mantel-Haenszel Time-Adjusted Rate Difference methods stratified by study were used. Results: Among all patients (all conditions pooled), 16 of 7010 (0.2%) fluoxetine- versus 10 of 4667 (0.2%) placebotreated patients reported non-fatal self-harm events (p 0.951). Twenty-five (0.4%) fluoxetine- versus 14 (0.3%) placebo-treated patients reported suicidal ideation (p 0.882) using adverse event data and 470 of 3643 (12.9%) fluoxetine- versus 353 of 2190 (16.1%) placebo-treated patients experienced worsening of suicidal ideation from baseline (p 0.020; placebo higher) using HAMD data. There were two completed suicides (1 fluoxetinetreated patient and 1 placebo-treated patient). Among patients 18-<30 (all conditions pooled), 7 of 1394 (0.5%) fluoxetineversus 3 of 776 (0.4%) placebo-treated patients reported nonfatal self-harm events (p 0.571). Nine (0.6%) fluoxetine- versus 1 (0.1%) placebo-treated patients reported suicidal ideation (p 0.046) using adverse event data and 131 of 876 (15.0%) fluoxetine- versus 70 of 443 (15.8%) placebo-treated patients experienced worsening of suicidal ideation from baseline (p 0.252) using HAM-D data. Among females (all conditions pooled), 12 of 4780 (0.3%) fluoxetine- versus 9 of 3156 (0.3%) placebotreated patients reported non-fatal self-harm events (p 0.657). Twenty one (0.4%) fluoxetine- versus 4 (0.1%) placebo-treated patients reported suicidal ideation (p 0.013; fluoxetine higher) using adverse event data and 310 of 2434 (12.7%) fluoxetineversus 234 of 1432 (16.3%) placebo-treated patients experienced worsening of suicidal ideation from baseline (p 0.035; placebo higher) using HAM-D data. C o n c l u s i o n : These data are consistent with results of previous analyses, and fail to support an increased risk of suicidality in adult patients treated with fluoxetine compared to placebo.
•
Antidepressant drug combination from treatment initiation to improve therapeutic response in major depression
R Blier 1., RM. Tremblay 1, H.E. Ward 2, C. Hebert 1, R. Bergeron 1 . j University of Ottawa, Psychiatry, Ottawa,
Canada; 2 University of Florida, Psychiatry, USA The treatment of depression with a single drug is not always time efficient because only about 50% of patients achieve remission with a first agent given at an adequate dose for as sufficient time. In addition, a second medication is often used to manage the most cumbersome symptoms, usually a benzodiazepine. In the present study, two antidepressants were used from treatment initiation: mirtazapine (30mg at bedtime) was given with either fluoxetine (20mg/day), bupropion (150mg/day), or venlafaxine (75 mg/day