Efficacité et innocuité de la duloxétine provenant des études primaires
- ≥ 1 TEAE Most frequently
Reported TEAEs Nausea
Headache Vomiting Nasopharyngitis Upper respiratory tract infection Upper abdominal pain
Fluoxetine (n=176) 58.0 % groups were not conducted for the extension phase analyses because of selection bias (lack of randomization).
Serious AE (SAE): DLX Placebo
Auteurs, de l’intervention
et de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres cliniques
évalués
Résultats rapportés Résultats Acute and Longer-Term Safety Results from a Pooled Analysis of Duloxetine Studies for the Treatment of Children and Adolescents with Major Depressive Disorder
3.4 %
Serious AE (SAE):
Acute phase Intentional overdose Suicidal ideation Self-injurious behavior Depressive symptom Drug abuse Hallucination Panic attack Social phobia Syncope Aggression Abnormal behavior Gastritis
Lymphadenitis Somnolence Tuberculosis of peripheral lymph nodes
Ulna fracture Homicidal ideation Major depression
DLX
Auteurs, année, pays
Types d’étude
Critères d’inclusion
et d’exclusion
Caractéristiques de l’intervention
et de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres cliniques
évalués
Résultats rapportés Résultats
Intervention
Résultats Comparateur
Effet (IC à 95 %;
valeur p) Acute and Longer-Term Safety Results from a Pooled Analysis of Duloxetine Studies for the Treatment of Children and Adolescents with Major Depressive Disorder
2 (0.9) 0 0 0 0 0 0 0 2 (0.9) 1 (0.4) 1 (0.4) 1 (0.4) 1 (0.4) 1 (0.4) 1 (0.4) 0 0 0
Serious AE (SAE):
Extension phase - Patients with ≥1 SAE
Suicide attempt Depression
DLX (n=237)
2.5 % 3 (1.3) 1 (0.4)
Fluoxetine (n=176) 2.3 %
1 (0.6) 0
Statistical comparisons between treatment groups were not conducted for the extension phase analyses
Auteurs, année, pays
Types d’étude
Critères d’inclusion
et d’exclusion
Caractéristiques de l’intervention
et de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres cliniques
évalués
Résultats rapportés Résultats
Intervention
Résultats Comparateur
Effet (IC à 95 %;
valeur p) Acute and Longer-Term Safety Results from a Pooled Analysis of Duloxetine Studies for the Treatment of Children and Adolescents with Major Depressive Disorder
Stevens-Johnson syndrome Wound Epilepsy
Intentional overdose Adjustment disorder with disturbance of conduct
Convulsion Hypomania Conversion disorder Pilonidal cyst Restlessness Road traffic accident Suicidal ideation
1 (0.4) 0 0 0 0 0 0 0 0 0 0
0 1 (0.6) 1 (0.6) 1 (0.6) 1 (0.6) 1 (0.6)
0 0 0 0 0
Adverse Events Leading to Discontinuation : acute phase
-Patients
discontinuing because of any AE
DLX
8.2 %
Placebo
3.1 %
Fluoxetine 3.0 %
P ≤ 0.05 vs placebo and
fluoxetine
AE leading to
discontinuation : acute DLX Placebo *p ≤ .05 vs.
placebo.
Auteurs, de l’intervention
et de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres cliniques
évalués
Résultats rapportés Résultats Acute and Longer-Term Safety Results from a Pooled Analysis of Duloxetine Studies for the Treatment of Children and Adolescents with Major Depressive Disorder
Self-injurious behavior Confused state Decreased activity Depressive symptom Emotional disorder Fatigue
Hallucinations, mixed Influenza
Muscular weakness Panic attack Somnolence Syncope
Upper respiratory tract infection
Vomiting Frequent bowel movements Initial insomnia Tuberculosis of peripheral lymph nodes Allergic sinusitis Somnambulism
Auteurs, année, pays
Types d’étude
Critères d’inclusion
et d’exclusion
Caractéristiques de l’intervention
et de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres cliniques
évalués
Résultats rapportés Résultats
Intervention
Résultats Comparateur
Effet (IC à 95 %;
valeur p) Acute and Longer-Term Safety Results from a Pooled Analysis of Duloxetine Studies for the Treatment of Children and Adolescents with Major Depressive Disorder
1 (0.4) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 (0.4) 1 (0.4) 1 (0.4)
0 0 Adverse Events
Leading to Discontinuation : extension phase
-Patients
discontinuing because of any AE
DLX (n=237)
5.1 %
Fluoxetine (n=176)
6.3 %
Statistical comparisons between treatment groups were not conducted for the extension phase analyses because of selection bias (lack of randomization).
Auteurs, de l’intervention
et de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres cliniques
évalués
Résultats rapportés Résultats Acute and Longer-Term Safety Results from a Pooled Analysis of Duloxetine Studies for the Treatment of Children and Adolescents with Major Depressive Disorder
Suicidal ideation Nausea Suicide attempt Electrocardiogram abnormal (sinus tachycardia) Emotional distress Fatigue
Maculopapular rash Stevens-Johnson syndrome
Activation syndrome Aggression
Diastolic blood pressure decreased
Chest pain Convulsion
Hallucination, auditory Hypomania
Intentional overdose Tremor
Conversion disorder Gastritis
Suicidal ideation and behaviour (CSSRS):
acute phase
Treatment-DLX Placebo *p≤0.05
Auteurs, année, pays
Types d’étude
Critères d’inclusion
et d’exclusion
Caractéristiques de l’intervention
et de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres cliniques
évalués
Résultats rapportés Résultats
Intervention
Résultats Comparateur
Effet (IC à 95 %;
valeur p) Acute and Longer-Term Safety Results from a Pooled Analysis of Duloxetine Studies for the Treatment of Children and Adolescents with Major Depressive Disorder
Improvement in suicidal ideation (end-point) Suicidal behaviors Nonsuicidal self-injurious behavior
22/333 (6.6) 44/52 (84.6) 0/333 (0.0) 10/328 (3.0)
18/220 (8.2) 32/34 (94.1)
1/220 (0.5) 6/216 (2.8) Fluoxetine
18/225 (8.0) 27/35 (77.1)*
2/225 (0.9) 8/224 (3.6)
Suicidal ideation and behaviour (CSSRS):
extension phase
Treatment-emergent compared with lead-in baseline Suicidal ideation
DLX
22/330 (9.6)
Fluoxetine
20/171 (11.7)
Auteurs, année, pays
Types d’étude
Critères d’inclusion
et d’exclusion
Caractéristiques de l’intervention
et de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres cliniques
évalués
Résultats rapportés Résultats
Intervention
Résultats Comparateur
Effet (IC à 95 %;
valeur p) Acute and Longer-Term Safety Results from a Pooled Analysis of Duloxetine Studies for the Treatment of Children and Adolescents with Major Depressive Disorder
Nonsuicidal
self-injurious behavior 9/225 (4.0) 2/169 (1.2)
Conclusion des auteurs :
Results from this pooled analysis of two studies were consistent with the known safety and tolerability profile of duloxetine.
Forces
2 ECRA multicentriques poolés – Recours à des échelles validées - Double aveugle.
Faiblesses
Pooled results from fixed and flexible dose drug treatment arms (no clear assessment of dose effects on safety parameters made). For safety parameters such as growth, a 38 week study is not likely to be sufficient to fully characterize longitudinal safety outcomes. In the two pediatric MDD studies included in this analysis, neither the investigational drug (duloxetine) nor the active control (fluoxetine) demonstrated a statistically significant separation from placebo on the primary efficacy analysis, thus rendering the studies inconclusive (Atkinson et al.) 2014; Emslie et al. 2014); therefore, the safety results presented herein cannot be associated with efficacious treatment of MDD in the pediatric patient population. However, the drug doses used for these studies were in the approved range for pediatric use for fluoxetine and in the approved dose range in adults for duloxetine. Finally, although these studies included double-blind, fluoxetine-controlled ex tension phases, the placebo-controlled phases addressed only acute efficacy (10 weeks of treatment); therefore, longer-term safety outcomes for patients receiving antidepressant treatment could not be evaluated against a no-antidepressant control group in the current analysis.
AE: Adverse effect; CDRS-R: Children’s Depression rating scale-revised; CGI-S; Clinical global impressions- Severity; CSSRS: Columbia-suicide severity rating scale; DLX: Duloxetine;
NA: Non applicable; NR: Non rapporté; NS: Non significatif; SD: Standard deviation; SE: Standard error; TEAE: Treatment-emergent adverse event
ÉTUDES FAITES CHEZ LES ADULTES
Critères d’inclusion (CI) et d’exclusion (CE)
Caractéristiques de l’intervention et
de la population (n; dose; durée)
Caractéristiques du comparateur
et de la population (n; dose; durée)
Description des paramètres
cliniques évalués
Résultats rapportés Résultats Safety and Efficacy of Duloxetine Versus Venlafaxine in Major Depression in Indian Patients
Badyal et
Patients with MDD (DSM-IV criteria);
18-75 years; with (HDRS-17 items score >18; newly diagnosed patients, non-responders or partial responders to the earlier prescribed AD and patients not tolerating earlier prescribed AD.
Exclusion:
suicidal tendencies, schizoaffective disorder, bipolar disorder, seizure disorder, alcohol or substance abuse, concurrent major illness or systemic dysfunction involving hepatic and renal system; current use of cimetidine, warfarin, tryptophan or MAO inhibitors, history of allergy to DLX and venlafaxine;
pregnant women, lactating mothers and patients not using contraceptives or
DLX (n = 13; 20mg BD; 6 wks) NB: increase to 40mg BD after 2 weeks if patient did not achieve response (50 % reduction in HDRS score); increase to 60 mg BD at 4 weeks if patient did not achieve response.
Female: n = 4;
Age (y) (Mean±SD):
41±10.
Duration of illness (median months) = 19.
Newly Diagnosed = 12;
Partial or non Responder for
Venlafaxine (n = 13; 75mg DIE; 6 wks) NB: increase to 150mg DIE after 2 weeks if response not achieved (50 % reduction in HDRS score);
increase to 225mg DIE at 4 weeks if patient did not achieve response.
Female: n = 5;
Age (y) (Mean ± SD): 43±10.
Duration of illness (median months) = 14.
Newly Diagnosed
= 12;
Partial or non Responder for
HDRS (Mean ± SD)
Response to drugs = decrease in HDRS score
>50% from as compared to baseline.
Remission was defined as HDRS score
Baseline = 26.73 ± 2.5
Baseline = 28.7
± 2.25
HDRS scores decreased significantly in both groups at every visit as compared to baseline between the groups at any visit Response rate
after 6 weeks of treatment
96 % 89 % Number of
responders was more in DLX group compared to venlafaxine at 2, 4 and 6 weeks, but this was not statistically significant
Remission rate 69 % 62 %
MADRS MADRS total
scores also significantly