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The article presents a study on the effectiveness and tolerability of venlafaxine in extensive metabolizer (EM) and poor metabolizer (PM) patients. Researchers analyzed blood samples for plasma concentrations of venlafaxine, O-desmethylvenlafaxine (ODV), total venlafaxine+ODV and ODV/venlafaxine ratio. They found that EMs had significantly more mean changes from baseline on 4 of 5 depression rating scales when compared with PMs. They concluded that venlafaxine treatment in EMs was linked to greater effectiveness in major depressive disorder (MDD).

Attrition rates are high during treatment for major depressive disorder (MDD), and patients who drop out are less likely to reach remission. This report evaluates the incidence, timing, and predictors of attrition during second-step medication treatment. Outpatients in the multisite Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study receiving a medication augmentation (n=563) or medication switch (n=723) for non-psychotic MDD after an unsatisfactory outcome with citalopram were evaluated to determine attrition rates and pretreatment sociodemographic or clinical predictors of attrition. Twenty percent of participants receiving a medication augmentation and 27% receiving a medication switch dropped out before 12 wk in the second treatment step. Remission rates were lower for dropouts [7% vs. 43% (medication augmentation) ; 12% vs. 31% (medication switch)]. For medication augmentation, Black and other non-Caucasian races, Hispanic ethnicity, younger age, family history of drug abuse, concurrent drug abuse, sociodemographic disadvantage, less symptom improvement with initial citalopram treatment, and greater symptom severity when beginning augmentation were associated with attrition. For medication switch, Black and other non-Caucasian races, younger age, more melancholic features, and lower exit doses but more severe side-effects with citalopram treatment were associated with attrition. Minority status, younger age, and greater difficulty with the first treatment step are risk factors for attrition in the second treatment step. Focus on patients with attrition risk factors for medication augmentation or switch strategies may enhance retention and improve outcomes. [ABSTRACT FROM AUTHOR]

The efficacy and safety of a selective NK1 antagonist, L-759274, was investigated in outpatients with diagnosis of major depressive disorder with melancholic features, following evidence obtained with the novel compound aprepitant that Substance P (NK1) antagonists may provide a unique mechanism of antidepressant activity. A randomized, double-blind placebo-controlled study was carried out. Patients, male or female, aged 18-60, scoring ≥ 25 points on total of first 17 items of 21-item Hamilton Depression Scale (HAMD), and scoring ≥4 (moderately ill) on Clinical Global Impressions-Severity Scale were randomized to oral L-759274 40 mg daily (n=66) or placebo (n=62) for 6 weeks. For patients receiving L-759274, improvement (mean decrease from baseline) in HAMD-17 total score was 10.7 points, compared with a mean 7.8 point improvement in patients receiving placebo (p<0.009). Mean scores for item I of HAMD-17 (depressed mood) also improved to a greater extent in the active group compared with the placebo group (0.3 points, p < 0.058). Compared with placebo, mean scores on Clinical Global Impressions-Improvement Scale improved significantly by the end of the trial (p = 0.009). L-759274 was generally safe and well-tolerated. The incidence of sexual side effects was on par with that observed in patients receiving placebo, and the incidences of gastrointestinal effects were E. Antidepressant actions have now been observed with two different highly selective NK1 antagonists (aprepitant and L-759274). NK1 antagonism is a replicated and generally extroverted antidepressant mechanism. [ABSTRACT FROM AUTHOR]

Presents information on a study which described the pharmacokinetics and safety of nefazodone (NFZ) in depressed children and adolescents. Pharmacokinetic characteristics of NFZ and three of its metabolites; Methodology; Results and discussion; Clinical implications and limitations of the study.

• Blood samples were obtained from adults with depression who were receiving outpatient treatment with venlafaxine to determine their metabolizer status by means of genotypic and phenotypic analysis.• Among 900 patients for whom both genotype and phenotype data were available, 3.9% were classified as CYP2D6 poor metabolizers under genotype analysis, but 27% were found to be phenotypic poor metabolizers.• Phenotypic conversion to poor metabolizer status is commonly associated with use of multiple medications, including antidepressants such as fluoxetine and paroxetine that inhibit CYP2D6 activity. Prescribers should be mindful of this phenomenon in patients taking multiple medications. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the serious adverse effects of combining fluoxetine and tricyclic antidepressants.