In continuation of a previous psychometric analysis of dose-response data for citalopram in depression, the corresponding study data for escitalopram is of interest, since escitalopram is the active enantiomer of citalopram and because citalopram was used as the active control. Revisiting those corresponding data, the psychometric properties of the Montgomery-Asberg Depression Scale (MADRS) and the Hamilton Depression Scale (HAMD) were investigated by focusing on the unidimensional HAMD6 and MADRS6. Effect sizes were calculated and compared for two dosages of escitalopram (10 mg and 20 mg daily) and between each of these two dosages and 40 mg citalopram daily. The results showed that the three depression scales MADRS6, MADRS10 and HAMD6 were psychometrically acceptable (coefficient of homogeneity of 0.40 or higher). In the severely depressed patients (MADRS10> or =30) a rather clear dose-response relationship for escitalopram was seen on all three scales after 6 and 8 wk of therapy. Thus, the effect size for 10 mg escitalopram ranged from 0.28 to 0.38 while the effect sizes for 20 mg escitalopram ranged from 0.57 to 0.77. This difference was statistically significant (p<0.01). The effect size for 40 mg citalopram ranged from 0.36 to 0.47, which is within the range found for 40 mg citalopram in our previous dose-response analysis of citalopram after 6 wk of therapy. The numerically largest difference between 20 mg escitalopram and 40 mg citalopram was seen after 8 wk of therapy for MADRS10 (effect size 0.71 vs. 0.37). An item analysis identified 'suicidal thoughts' to be the most discriminating item in this respect. These results for the severely depressed patients were confirmed by the patients self-reported quality of life evaluation. When all included patients were analysed, however, no clear dose-response relationship was seen. In conclusion, a dose-response relationship for escitalopram was seen in the severely depressed patients on all outcome scales after 6 and 8 wk of treatment. After 8 wk of treatment 20 mg escitalopram was superior to 40 mg citalopram, but not after 2 wk of treatment.

This psychometric re-examination of a citalopram dose-response trial has shown that the pure antidepressive or antianxiety effects can be observed after 6 weeks of therapy even in a dose of 10 mg daily. However, both 10 mg and 20 mg daily had lower effect sizes than 40 mg and 60 mg daily. At a dose level of 20 mg daily, side effects are more pronounced initially than at 10 mg daily; this should be taken into account clinically when evaluating the overall benefit of the drug. For a highly serotonin-specific drug such as citalopram, both wanted and unwanted effects are dose-related.

No abstract

The selective serotonin reuptake inhibitors (SSRIs) are believed to have a more benign cardiovascular safety profile than do the tricyclic antidepressants. The effects of the SSRI citalopram on cardiac conduction and repolarization have been extensively evaluated, both in prospective studies in volunteers and patients and in retrospective evaluations of all electrocardiographic (ECG) data from all clinical trials conducted from 1978 through 1996 (a total of 40 studies). A randomized, double-blind, placebo-controlled study was conducted in healthy volunteers (N = 23) to assess intraindividual variability of the QTc interval, as well as possible changes during treatment with placebo or citalopram, and its correlation to plasma drug levels. To document any dose-related changes, ECGs were performed at baseline and at the end of study in three randomized, double-blind, placebo- or active-controlled, fixed-dose trials in adult and elderly patients (N = 1,460) with major depression and/or dementia. Finally, more than 6,000 ECGs (N = 1,789 citalopram-treated patients) collected from all clinical trials conducted from 1978 through 1996 were reassessed in a standardized manner to identify any effects of citalopram on ECG parameters. Results of both prospective and retrospective analyses showed that the only effect of citalopram on ECG findings is a small reduction in heart rate (< or = 8 beats per minute). There were no significant effects on PQ, QRS, or QTc intervals, indicating that citalopram has no effect on cardiac conduction and repolarization during short- or long-term treatment.

The aim of the present study was to evaluate the influence of individual explanatory factors, such as sex, age, atopy, test time and presence of diseased skin, on clinical patch test results, by application of multivariate statistical analysis. The study population was 2166 consecutive patients patch tested with the standard series of the International Contact Dermatitis Research Group (ICDRG) by members of the Danish Contact Dermatitis Group (DCDG) over a period of 6 months. For the 8 test allergens most often found positive (nickel, fragrance-mix, cobalt, chromate, balsam of Peru, carba-mix, colophony, and formaldehyde), one or more individual factors were of significance for the risk of being sensitized, except for chromate and formaldehyde. It is concluded that patch test results can be compared only after stratification of the material or by multivariate analysis.

The study demonstrated two distinct processes of action on cognition between sertindole and haloperidol and the marked beneficial effects of sertindole, particularly in parameters that are regarded as schizophrenia-related cognitive disturbances.

Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole.

Although serotonin reuptake inhibitors (SRIs) are the medications of choice in the treatment of obsessive-compulsive disorder (OCD), only 50-60% of patients respond to a single trial of any of these agents. Improved knowledge of the predictors of response to treatment may have important clinical implications. Data from a large randomized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response. Demographic (age, sex), clinical (OCD severity and duration, depression severity, prior treatment) and trial variables (citalopram dose, treatment duration) were included. Subjects with longer duration of OCD, more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial. In contrast, subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders. Despite greater awareness of OCD in recent years, there is evidence that the disorder continues to be underdiagnosed and undertreated. The data here emphasize the crucial importance of early diagnosis and treatment of OCD, and of pharmacotherapy with appropriate dose and duration.