Efficacy and safety of varenicline for smoking cessation in people living with HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical trial.

BACKGROUND: Tobacco smoking is common in people living with HIV, but high-quality evidence on interventions for smoking cessation is not available in this population. We aimed to assess the efficacy and safety of varenicline with counselling to aid smoking cessation in people living with HIV. METHODS: The ANRS 144 Inter-ACTIV randomised, parallel, double-blind, multicentre, placebo-controlled phase 3 trial was done at 30 clinical hospital sites in France. People living with HIV who had smoked at least ten cigarettes per day for 1 year or longer, were motivated to stop smoking, were not dependent on another psychoactive substance, and had no history of depression or suicide attempt were eligible. Using a computer-generated randomisation sequence, we allocated (1:1) the patients to receive either varenicline titrated to two 0·5 mg doses twice daily or placebo twice daily for 12 weeks, plus face-to-face counselling. Patients and investigators were masked to treatment group allocation. Patients who were not abstinent at week 24 were offered open-label varenicline for 12 additional weeks. The primary outcome was the proportion of smokers continuously abstinent from week 9 to week 48. Smoking status was confirmed by carbon monoxide in exhaled air. Primary analyses were done in both the intention-to-treat (ITT) population and modified ITT (mITT) population, which comprised all patients who took at least one tablet of their assigned study treatment. The safety analyses were done in the mITT population. The trial is registered at ClinicalTrials.gov, number NCT00918307. The trial status is complete. FINDINGS: From Oct 26, 2009, to Dec 20, 2012, of 303 patients assessed for eligibility, 248 patients were randomly assigned to the varenicline group (n=123) or the placebo group (n=125). After randomisation, one participant initially assigned to the placebo group was excluded from the ITT analysis for a regulatory reason (no French health-care coverage). 102 patients in the varenicline group and 111 patients in the placebo group received at least one dose of their assigned treatment and were included in the mITT analysis. In the ITT analysis, varenicline was associated with a higher proportion of patients achieving continuous abstinence over the study period (week 9-48): 18 (15%, 95% CI 8-21) of 123 in the varenicline group versus eight (6%, 2-11) of 124 in the placebo group, adjusted odds ratio (OR) 2·5 (95% CI 1·0-6·1; p=0·041). In the mITT analysis, varenicline was also associated with higher continuous abstinence: 18 (18%, 95% CI 10-25) of 102 versus eight (7%, 2-12) of 111 in the placebo group (adjusted OR 2·7, 95% CI 1·1-6·5; p=0·029). The incidence of depression was 2·4 per 100 person-years (95% CI 0·6-9·5; two [2%] of 102) in the varenicline group and 12·4 per 100 person-years (95% CI 6·9-22·5; 11 [10%] of 111) in the placebo group. 14 (7%) of 213 participants had 18 cardiovascular events: six (6%) of 102 people in the varenicline group and eight (7%) of 111 people in the placebo group. INTERPRETATION: Varenicline is safe and efficacious for smoking cessation in people living with HIV and should be recommended as the standard of care. FUNDING: The French National Institute for Health and Medical Research (INSERM)-French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Pfizer.

Onset of action of escitalopram compared with other antidepressants: results of a pooled analysis.

In general, antidepressant drugs are regarded as too slow acting. Most patients who benefit from treatment require more than 2 weeks of therapy to respond to treatment. An efficacious and well-tolerated antidepressant drug with an earlier onset of effect would be of greater interest to clinicians and patients. To study the onset of effect of escitalopram, a selective serotonin reuptake inhibitor (SSRI), data were pooled from controlled randomized clinical double-blind trials comparing this drug with other antidepressant drugs (SSRIs and venlafaxine XR) in major depressive disorder (MDD), with assessments of the primary efficacy parameter [mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline, using last observation carried forward]. The mean change in MADRS total scores was significantly higher for escitalopram-treated patients than for patients treated with the comparators on day 7 (-3.9 versus -3.4, respectively, P = 0.029). This difference remained significant and in favour of escitalopram at all subsequent assessments. Using secondary outcomes (Clinical Global Impression of Improvement and Severity scales and early improvement), the results consistently showed a statistically significantly faster onset of effect of escitalopram compared to other antidepressants. In conclusion, by using the MADRS scale and pooling data from the escitalopram clinical trials in MDD comparing escitalopram with other active antidepressant drugs, escitalopram was shown to be a fast-acting antidepressant with a more rapid onset of effect than the comparators, particularly other SSRIs.

[Evolution of depressive disorders]. / Evolution des maladies dépressives.

A MAJOR RISK RECURRENCE: The sparcity of data in the absence of treatment renders assessment of the natural course of depressive disorders difficult. Naturalist studies have identified various elements that characterise the evolution. After an episode of depression, usually lasting 6 to 8 months, the disorder is marked by a high risk of recurrence. Fifty to 85% of the patients having exhibited an episode of major depression will relapse at least once in their life. A CHRONIC DISEASE: The propensity in the repetition of depression and the socio-professional and family impact that results has led to an increasing number of authors to consider the problem as a chronic disease, like asthma or diabetes. IN TERMS OF MANAGEMENT: It is important to replace depression in the progressive perspective of a chronic disease and to avoid, after the first episode, the risk of relapses and recurrences. During treatment of the acute phase, we recommend treatment to be continued up to 12 months after complete remission, so as to reduce the risk of relapse. Regarding prevention of recurrences, treatment should be continued for more than 12 months in patients who have had 3 episodes of depression or, in certain cases, only two. THE CONSEQUENCES OF A LACK OF INFORMATION: Research work has shown that depressive disorders have been insufficiently treated: either the doses are too low or the prescription is withdrawn too quickly, or the patient does not fully comply. In the majority of cases, insufficient management stems from a lack of knowledge on the course of depressive disorders and on treatment modalities, as far as not only the practitioner but also the patient are concerned.

Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study.

BACKGROUND: The prevalence of generalized anxiety disorder (GAD) represents an important public health issue. Hydroxyzine, an antagonist of histamine receptors, showed both efficacy and safety in previous short-term double-blind studies over placebo in this pathology. The aim of the current study was to confirm those positive results over a 3-month period in adult outpatients. METHOD: This multicenter, parallel (hydroxyzine [50 mg/day]; bromazepam [6 mg/day]), randomized, double-blind, placebo-controlled trial included 2 weeks of single-blind run-in placebo, 12 weeks of double-blind randomized treatment, and 4 weeks of single-blind run-out placebo. Three hundred thirty-four of 369 selected outpatients with a diagnosis of GAD according to DSM-IV criteria and a Hamilton Rating Scale for Anxiety (HAM-A) total score >/= 20 were randomized before entering the double-blind period. The primary outcome criterion was the change in the HAM-A score from baseline to 12 weeks of double-blind treatment with hydroxyzine compared with placebo. RESULTS: In the intent-to-treat analysis, the mean +/- SD change in HAM-A scores from baseline to endpoint was -12.16 +/- 7.74 for hydroxyzine and -9.64 +/- 7.74 for placebo (p =.019). Results at endpoint for percentage of responders (p =.003) and remission rates (p =.028), Clinical Global Impressions-Severity scale score (p =.001), maintenance of efficacy (p =.022), and Hospital Anxiety and Depression scale score on day 84 (p =.008) also confirmed the efficacy of hydroxyzine over placebo. The study showed no statistically significant difference between hydroxyzine and bromazepam. Except for drowsiness, which was more frequent with bromazepam, safety results were comparable in the 3 groups. CONCLUSION: Hydroxyzine showed both efficacy and safety in the treatment of GAD and appears to be an effective alternative treatment to benzodiazepine prescription.