What happens with adverse events during 6 months of treatment with selective serotonin reuptake inhibitors?

OBJECTIVE: Although adverse events are a key factor in compliance, their evolution during treatment with antidepressants is poorly documented. Therefore, the time course of adverse events during 6 months of antidepressant treatment was investigated. METHOD: 85 psychiatric outpatients with a DSM-IV diagnosis of major depressive disorder (with the exclusion of other DSM-IV Axis I disorders) were enrolled between September 2002 and March 2003 in a multicenter, randomized, double-blind trial with selective serotonin reup-take inhibitors (fluoxetine [N = 42] and paroxetine [N = 43]). At each visit, the presence and severity of treatment-emergent adverse events were assessed systematically using the UKU Side Effect Rating Scale (UKU). General linear mixed modeling was used to investigate the predictors of the time course of adverse events. RESULTS: Overall, the number of at least moderately severe adverse events decreased with time. More severely depressed patients reported overall more (at least moderately severe) adverse events than less severely depressed patients (p = .0002), but the decrease in reported adverse events was comparable over time. Men (N = 30) and women (N = 55) reported initially the same number of at least moderately severe adverse events, but the habituation was more rapid in men (p < .0001). Completers (N = 58) and dropouts (N = 27) did not differ initially, but completers' habituation was more rapid (p = .014). The habituation of adverse events was also more rapid in recurrent than in first-episode patients but only in men (p = .0025). CONCLUSION: The time course of adverse events varies with the severity of depression, sex, completer or dropout status, and recurrent versus first-episode depression.     

Long-term Results of Polyglactin Mesh for the Prevention of Incisional Hernias in Obese Patients

n = 39) or mail ( n = 6), and 3 (1%) were inaccessible for follow-up since discharge from the hospital. The mean follow-up period was 29.8 months (range 0–67 months). A total of 33 incisional hernias were observed in the mesh group and 41 in the no-mesh group. There was no significant difference in the distribution of herniation time between the two groups ( p = 0.43). The two main predictive factors of herniation were age and weight. In conclusion, the use of an intraperitoneal polyglactin mesh does not prevent postoperative incisional hernias in obese patients.     

Effect on cellular and humoral immune responses of the AS03 adjuvant system in an A/H1N1/2009 influenza virus vaccine administered to adults during two randomized controlled trials

The influence of AS03_A, a tocopherol oil-in-water emulsion-based adjuvant system, on humoral and cell-mediated responses to A/California/7/2009 H1N1 pandemic vaccine was investigated. In two observer-blind studies, a total of 261 healthy adults aged 18 to 60 years were randomized to receive either AS03_A-adjuvanted H1N1 vaccine containing 3.75 μg hemagglutinin (HA) or nonadjuvanted H1N1 vaccine containing 15 or 3.75 μg HA on days 0 and 21. Hemagglutination inhibition (HI) antibody and T-cell responses were analyzed up to day 42. A first dose of AS03_A-adjuvanted vaccine (3.75 μg HA) or nonadjuvanted vaccine (15 μg HA) induced HI responses of similar magnitudes that exceeded licensure criteria (e.g., 94 to 100% with titers of ≥40). A lower response following 3.75 μg HA without adjuvant was observed (73% with titers of ≥40). Following a second dose, geometric mean HI titers at day 42 were higher for AS03_A-adjuvanted vaccine (636 and 637) relative to nonadjuvanted vaccine (341 for 15 μg HA and 150 for 3.75 μg HA). Over the 42-day period, the increase in frequency of A/H1N1/2009-specific CD4⁺ T cells was significantly higher in the adjuvanted group than in the nonadjuvanted group. There was no evidence of correlation between baseline CD4⁺ T-cell frequencies and day 21 HI antibody titers, while there was some correlation (R = 0.35) between day 21 CD4⁺ T-cell frequencies and day 42 HI titers. AS03_A adjuvant enhanced the humoral and CD4⁺ T-cell-mediated responses to A/H1N1/2009 vaccine. Baseline A/H1N1/2009-specific CD4⁺ T-cell frequencies did not predict post-dose 1 antibody responses, but there was some correlation between post-dose 1 CD4⁺ T-cell frequencies and post-dose 2 antibody responses.     

Six-month compliance with antidepressant medication in the treatment of major depressive disorder

The investigation of compliance in patients with major depressive disorder (in drop-outs versus completers and in first episode versus recurrent episode patients). A total of 85 outpatients with major depressive disorder were followed for 6 months. Different dimensions of compliance were investigated: drop-outs versus completers and their medication adherence (with electronic monitoring). General linear mixed models were applied to examine the time courses of adherence. Drop-out rates were higher in younger patients and in patients with a lower initial depression severity. The adherence during 6 months of treatment with selective serotonin reuptake inhibitors was above 80 in 70% of the patients. The adherence decreased by 2.5% per month and decreased more than three times more rapidly in drop-outs (from baseline to time of drop-out). A medical visit resulted in a temporary increase in pill intake. General linear mixed model analysis showed that the predicted outcome was worse in drop-outs than in completers and worse in recurrent episode patients than in first episode patients (the former showing a higher adherence). Adherence decreases with time during 6 months of treatment with antidepressants and is influenced by demographic and clinical variables. Completers show a higher adherence than drop-outs. The outcome was worse in recurrent episode patients than first episode patients although they had a higher adherence.