DLX 1) Acute

treatment phase of 8 wks with Variables at baseline : treatment group significantly lower than that in the escitalopram group (p = 0.036) HAMD17 Mean (SD) : 17.6 (4.8);

Escitalopram 1) Acute treatment phase of 8 wks with Variables at baseline : Female : n=186 ; Age Mean (SD) : 43.3 yrs (13.0) HAMD17 Mean (SD) : 17.8 (5.1);

CGI-S Mean (SD) : 4.2 (0.7) Patients meeting total CSFQ criteria for global sexual dysfunction at baseline : 83.1 %

Discontinuation rates for sexual side effects over the 8- month course study Dysfunction:

For n = 114 who did not meet total CSFQ score criteria for global sexual dysfunction at baseline 1) At 8 wks 2) At 8-month study endpoint

1) 17/51=33.3 % comparison with placebo But no significant differences between active drugs

the judgment of the investigator, would be likely to require intervention, hospitalization, or an excluded medication during the course of the study; lack of response of the current

depressive episode to two or more adequate courses of AD therapy at a clinically

appropriate dose for a minimum of 4 weeks, or treatment-resistant depression; a history of a lack of response, at any time, to an adequate trial of DLX (≥60 mg/ day for ≥4 weeks), escitalopram (≥10 mg/day for ≥4 weeks), or citalopram (≥20 mg/day for ≥ 4 weeks); a current and primary Axis II disorder that could interfere with compliance with the study protocol; DSM-IV-defined history of substance dependence within the past 6 months, excluding nicotine and caffeine; a positive urine drug screen for any substances of abuse;

electroconvulsive therapy or transcranial magnetic stimulation within the past year;

initiating, stopping, or

CGI-S Mean (SD) : 4.2 (0.7) Patients meeting total CSFQ criteria for global sexual dysfunction at baseline : 76.8%

Placebo 1) Acute treatment phase of 8 wks with fixed dose (n=137) 2) + 24 wks extension phase n = 14

Variables at baseline : F : 87;

Age Mean (SD) : 42.5 yrs (12.3);

HAMD17 Mean (SD) : 17.7 (5.2);

CGI-S Mean (SD) : 4.2 (0.7) Patients meeting total CSFQ criteria for global sexual dysfunction at baseline : 78.6 %

Resolution of Sexual Dysfunction at the 8 month study endpoint:

among the 449 patients with global sexual dysfunction at baseline

34/169 = 20.0% Escitalopram, 35/192 = 17.6%

Placebo : 17/88

= 19.3%

No significant differences between treatment groups in the incidence of resolution of sexual dysfunction over the course of the

study.

Time Course of Changes in Sexual Functioning (All Patients with Post baseline CSFQ Data) in MALE group

At 8 wks : overall sexual functioning

1.82 (0.80) Escitalopram 0.08 (0.85);

Placebo : 1.02 (1.07)

Improvement from baseline in overall sexual functioning for both active drugs but significant difference.

At 8 wks : Categorial assessment of changes in global sexual functioning Overall sexual functioning

0.88 (1.21) Escitalopram 1.34 (1.24);

Placebo : 3.20 (2.62)

no significant differences between active drugs after the 8-week time point;

At 8 month (or last obs.) Categorial assessment of changes in global sexual

i) 44.3 %;

no significant differences between active drugs

fluoxetine within 30 days prior to visit 2.

At 8 wks : Overall sexual functioning

1.12 (0.60); Escitalopram 0.36 (0.56);

Placebo : 3.42 (0.85)

Both active drugs groups

experienced significantly less mean improvement from baseline at the 8-week time point compared with placebo At 8 wks :

Categorial assessment of changes in global sexual functioning i)Improvement;

ii) no chang; iii) Worsening

i) 54.9 %;

ii) 9.2 %;

iii) 35.9 %;

Escitalopram i) 52,5 %;

ii) 8.8 %;

iii) 38.8 %

P = 0.88 (DLX vs escitalopram)

At 8 months (or last obs.) Overall sexual functioning

2.95 (0.89) Escitalopram : 1.63 (0.81);

Placebo : 3.53 (1.90)

NS

At 8 months (or last obs.) Categorial assessment of changes in global sexual functioning i)Improvement;

ii) no chang; iii) Worsening

i) 59.2 %; ii) 5.6%; iii) 35.2 %

Escitalopram : i) 56.8 %; ii)9.3

%; iii) 34.0 %

P=0.49 (DLX vs escitalopram)

Depression remission at 8 wks

40 % Escitalopram :

33 %

P=0.25

Depression remission at 8 months

70 % Escitalopram :

75 %

P=0.44

Conclusion des auteurs :

Short-term treatment demonstrated a higher incidence of treatment-emergent sexual dysfunction with escitalopram compared with duloxetine and placebo. After 12 weeks, there were no statistically significant differences between drugs; however, MDD outcome (regardless of treatment) had a significant impact on improvement in global sexual functioning.

Forces

ECRA multicentrique (n de sites = 36) – Recours à des échelles validées – analyse en ITT - Double aveugle – long suivi (total de 8 mois). This study providedblinded comparison of duloxetine and escitalopram using a validated assessment to elicit patient data related to changes in sexual functioning over the long-term course of treatment.

Faiblesses

This study was not explicitly powered to address comparisons of sexual functioning between active drug; this study employed a blinded placebo rescue option after the 8-week, acute-treatment phase, and due to normal attrition and placebo rescue, few patients contributed data on placebo (N = 14) compared with duloxetine (N = 99) or escitalopram (N = 121) by the end of the study (thus power to detect a difference between the active treatments and placebo significantly decrease). It allowed for blinded flexible dosing to optimize treatment after the acute-treatment phase, and given the distribution of doses used during longer-term treatment, a clear assessment of dose-related changes in

sexual functioning over time was not possible.

CSFQ: Changes in sexual functioning questionnaire; CGI-S: Clinical global impressions- Severity ; DLX: Duloxetine; HDRS (HAMD): Hamilton depression rating scale; MADRS:

Montgomery and Asberg depression rating scale; MDD: Major depressive disorder; NA: Non applicable; NR: Non rapporté; NS: Non significatif;; SD: Standard deviation; SE: Standard error; TEAE: Treatment-emergent adverse event

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 Extended release quetiapine fumarate monotherapy in major depressive disorder: a placebo- and duloxetine-controlled study

Cutler et al.

2009

NB : 8 weeks (6 wks active treatment + 2 wks DLX = active comparator

ERRATUM IN:

J Clin

Psychiatry. 2009 Dec;70(12):1729.

ECRA (n = 38)

Inclusion :

18-65 yrs; MDD (single or recurrent) (DSM-IV);

diagnosis confirmed by MINI; HAM-D≥22 and HAM-D item 1 (depressed mood) score ≥ 2 at enrollment and randomization.

Exclusion :

DSM-IV axis I disorder other than MDD within 6 months prior enrollment;

any DSM-IV axis II disorder; if the duration of the current MDD episode

>12 months or < 4 wks;

inadequate response to at least 6 wks of treatment with 2 or more classes of AD during the current episode. Psychotehrapy allowed only if it has been going for at least 3 months prior to randomization; clinically significant medical illness (including diabetes) or any clinically significant finding on physical examination, lab tests, ECG; current serious suicidal or homicidal risk;

antipsychotic, mood stabilizer, AD use within 7

Quetiapine XR (150mg) n=152; 6 wks;

Female : 63.3 % Diagnosis of MDD :

-Single episode : 11.6 %;

-recurrent : 88.4 % Nbr of

depressive episode in past year (mean SD) : 1.0 (1.6);

Nbr of depressive episode over lifetime (mean SD) : 8.6 (13.1) -HAM-D total score ≥ 28 : 33 (22.4)

DLX 60mg/d;

n=151; 6 wks;

Female : 62.4 % Diagnosis of MDD :

-Single episode : 11.3 %;

-recurrent : 88.7 % Nbr of

depressive episode in past year (mean SD) : 0.9 (1.4);

Nbr of depressive episode over lifetime (mean SD) : 7.1 (8.8); -HAM-D total score ≥ 28 : 29 (20.6)

MADRS total score (change between baseline and at week 6)

HAM-D scale item 1 Sleep Quality Index)

NA DLX vs Placebo : -3.24 vs

-2.95;

P =0.481