Kurt Bjerregaard Stage

Anxiety and depression in patients with chronic obstructive pulmonary disease (COPD). A review

A review of the literature revealed high comorbidity of chronic obstructive pulmonary disease (COPD) and states of anxiety and depression, indicative of excess, psychiatric morbidity in COPD. The existing studies point to a prevalence of clinical significant symptoms of depression and anxiety amounting to around 50%. The prevalence of panic disorder and major depression in COPD patients is correspondingly markedly increased compared to the general population. Pathogenetic mechanisms remain unclear but both psychological and organic factors seem to play a role. The clinical and social implications are severe and the concurrent psychiatric disorders may lead to increased morbidity and impaired quality of life. Furthermore, the risk of missing the proper diagnosis and treatment of a concurrent psychiatric complication is evident when COPD patients are treated in medical clinics. Until now only few intervention studies have been conducted, but results suggest that treatment of concurrent psychiatric disorder leads to improvement in the physical as well as the psychological state of the patient. Panic anxiety as well as generalized anxiety in COPD patients is most safely treated with newer antidepressants. Depression is treated with antidepressants according to usual clinical guidelines. There is a need for further intervention studies to determine the overall effect of antidepressants in the treatment of anxiety and depression in this group of patients.

Moclobemide and nortriptyline in elderly depressed patients. A randomized, multicentre trial against placebo

Moclobemide and nortriptyline were compared with placebo in a double-blind randomized multinational (Canada, Denmark and UK) trial comprising 109 patients of > 60 years of age with major depression (DSM-III-R). Patients were randomized to 7 weeks of treatment with doses of 400 mg/day moclobemide, 75 mg/day nortriptyline or placebo. It was necessary to adjust nortriptyline dosage in < 20% of patients to maintain serum levels within the postulated therapeutic window of 50-170 ng/ml. At end of treatment, the remission rates were 23% for moclobemide, 33% for nortriptyline and 11% for placebo. Anticholinergic and orthostatic events occurred more often with patients on nortriptyline than either moclobemide or placebo.

Depression and chronic obstructive pulmonary disease (COPD). Impact on survival

Objective:  To determine if the presence of depression in patients suffering from chronic obstructive pulmonary disease (COPD) would have an independent impact on mortality.

Comorbid personality disorder predicts suicide after major depression: a 10-year follow-up

Objective:  To identify psychopathological predictors for suicide in a population of major depressed Diagnostic Statistical Manual‐III (DSM‐III) in‐patients.

The Major Depression Rating Scale (MDS). Inter-rater reliability and validity across different settings in randomized moclobemide trials

The Major Depression Rating Scale (MDS) has been derived from the Hamilton Depression Scale and the Melancholia Scale. The MDS contains the nine DSM-IV items for major depression which all have anchoring scores from 0 to 4; hence, the theoretical score range is up to 36. The Major Depression Rating Scale has in this study been psychometrically analysed in randomized moclobemide trials. The results showed that the MDS had higher internal validity than the Hamilton Depression Scale. Thus, the homogeneity of the items was higher; factor analysis identified only one general depression factor (after 4 weeks of treatment explaining more than 50% of the variance). The inter-rater reliability of the two scales was of the same high level. The ability to measure changes (external validity) was tested in randomized clinical trials with moclobemide versus tricyclics (clomipramine and notriptyline) performed in Denmark in the psychiatric setting as well as in the general practice. The results showed that in the psychiatric setting tricyclics were superior to moclobemide with effect sizes ranging between 0.43 and 0.53. The highest effect size was obtained with the Melancholia Scale and the Major Depression Rating Scale, while the Hamilton Depression Scale was below 0.50. In the general practice setting no difference was found between moclobemide and clomipramine. In conclusion, the Major Depression Rating Scale has been found to have a more homogeneous factor structure than the Hamilton Depression Scale, but still with the same level of reliability and external validity. However, studies are needed to standardize the scale, especially in the general practice setting.

Measurement of depression in patients with chronic obstructive pulmonary disease (COPD).

Objective: To estimate the validity of the Hamilton Depression Scale (HDS) in a population of patients with chronic obstructive pulmonary disease (COPD). Methods: Forty-nine patients with moderate to severe COPD were examined using the ICD-10 criteria for depression. The mean age of the patients was 71 years and 33 (64%) were women. Forty-six (94%) of the patients were also evaluated using the 17-item HDS including the six-item Hamilton Depression subscale (HDSS). Internal and external validity were measured using factor analysis, Cronbach Coefficient alpha, Loevinger coefficient of homogeneity, correlation analysis and ROC-curves. Results: Twenty-three (47%) of the patients were depressed according to the ICD-10 criteria for depression. The HDSS but not the HDS showed a good internal validity. An acceptable external validity was furthermore shown for the HDSS. Conclusion: The HDSS can be recommended as a suitable depression rating scale for COPD patients.

A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care

The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22–40 on the Montgomery–Åsberg Depression Rating Scale, MADRS) in Denmark. A three-path decision analytic model with a 6-month horizon was used. All patients started at the primary care path and were referred to outpatient or inpatient secondary care in the case of insufficient response to treatment. Model inputs included drug-specific probabilities derived from systematic literature review, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS≤12 and treatment costs. Analyses were conducted from healthcare system and societal perspectives. The human capital approach was used to estimate societal cost of lost productivity. Costs were reported in 2004 DDK. The expected overall 6-month remission rate was higher for escitalopram (64.1%) than citalopram (58.9%). From both perspectives, the total expected cost per successfully treated patient was lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for citalopram (DKK 25,778 healthcare, DKK 87,786 societal). Remission rates and costs were similar for escitalopram and venlafaxine. Robustness of the findings was verified in multivariate sensitivity analyses. For patients in primary care, escitalopram appears to be a cost-effective alternative to (generic) citalopram, with greater clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.

Moclobemide versus clomipramine in depressed patients in general practice. A randomized, double-blind, parallel, multicenter study.

In a double-blind, randomized, controlled, multicenter clinical trial in general practice, lasting 7 weeks, a fixed dose of moclobemide (400 mg daily) was compared with a fixed dose of clomipramine (150 mg daily). A total of 147 patients with DSM-III-R major depression were included in the study. After a 1-week drug-free washout period, patients were stratified, according to total scores on the Hamilton Rating Scale for Depression (HAM-D), into two groups--HAM-D total scores, 11 to 15 points, and HAM-D total scores, 16 points or more. A comparison of the therapeutic effect of the two treatments was based on HAM-D total scores and the classification of patients into therapeutic response categories defined on the basis of total rating score, complete response, HAM-D < or = 7 points; partial response, HAM-D, 8 to 15 points; or no response, HAM-D > or = 16 points. The Newcastle Diagnostic Rating Scale (1965) was used to classify the patients into two groups, endogenous and nonendogenous. Adverse events were registered by use of the UKU side effect scale. Clinical global assessments of severity, efficacy, and tolerance were completed during the active treatment period. Compliance to treatment was based on levels of the drugs in plasma and the number of returned capsules. One hundred forty-two patients were evaluated for clinical effects. The results of the efficacy analyses showed therapeutic equivalence between moclobemide and clomipramine. There were no differences in the outcome of the two treatment groups or the two diagnostic groups (endogenous and nonendogenous).(ABSTRACT TRUNCATED AT 250 WORDS)

Are in-patient depressives more often of the melancholic subtype?

In contrast to out‐patients, hospitalized depressed patients have been reported to respond better to tricyclic antidepressants (TCAs) than to selective serotonin reuptake inhibitors (SSRIs) and moclobemide. This may be due to differences in the type of patients included in the trials. The hypothesis that hospitalized depressed patients have a different symptom profile to out‐patients was tested by comparing 352 patients from three in‐patient studies with 581 patients from three out‐patient studies conducted in Denmark during the period 1980–1992. All patients had major depression and were evaluated using the Hamilton Depression Scale. The full version of the Newcastle Diagnostic Rating Scale (1965) was applied to 443 of the patients. In‐patients were characterized by higher scores on the items ‘depressed mood’, ‘suicidal impulses’,‘work and interest (reduced)’, ‘retardation’, ‘distinct quality of depression’, ‘weight loss’, ‘feeling of guilt’ and‘nihilistic delusions’, and by lower scores on the items ‘somatic complaints’, ‘hypochondriasis’, ‘psychological stressors’ and‘anxiety’. In total, 76% of the in‐patients and 40% of the out‐patients had melancholic/endogenous depression. These findings may explain why TCAs are superior to SSRIs and moclobemide in hospitalized patients, since other data indicate that TCAs seem to be the most effective treatment for the melancholic/endogenous subtype.

Clinical Relevance of Serum Nortriptyline and 10-Hydroxy-Nortriptyline Measurements in the Depressed Elderly: A Multicenter Pharmacokinetic and Pharmacodynamic Study

In a recent placebo-controlled multicenter study, 38 patients, ranging in age between 62 and 88 years (median, 71) were treated with nortriptyline (NT) for up to 7 weeks. NT was administered in a divided dose of 75 mg daily and serum NT (se NT), and its 10-hydroxy-metabolites (se OH-NT) were determined at various intervals. Several clinical measures of efficacy, including the 17-item Hamilton Rating Scale for Depression, were evaluated weekly as well as side effects (anticholinergic) and electrocardiogram (ECG) changes. Eighty-one percent of patients had NT levels in the previously defined therapeutic range of 50 to 170 ng/ml, with steady state reached between 1 and 3 weeks. There was little individual variation in drug kinetics and metabolism over the study period. In general se OH-NT levels were not greater than those of se NT.Pharmacodynamic analyses showed that patients with moderate to severe anticholinergic side effects [CSE(+)] had significantly higher NT levels than those with mild or no symptoms [CSE(−)]. Furthermore, repeated-measures ANOVA modeled over time showed a highly significant decrease in clinical measures in both CSE groups of patients and also a highly significant group–time interaction. Higher se OH-NT levels were associated with less anticholinergic side effects. No ECG changes were observed.