Clinical predictors of incident somatic morbidity in a sample of depressed patients: A 16–30 years follow-up study

Background and objectives: We investigated the independent associations between various characteristics at trial entrance and subsequent development of somatic morbidity in patients participating trials on antidepressants.Methods338 in-patients diagnosed with major depression who had participated in trials on antidepressants conducted between 1983 and 1994 were followed for up to 30 years in Danish registers. By applying a Cox regression model with incident diagnoses of somatic disease as outcome, explanatory variables such as age at first episode, duration of index episode, bipolarity and scores on the Hamilton Depression Scale and subscales hereof, were investigated.ResultsCardiovascular diseases were associated with increasing number of previous depressive episodes at baseline (HR 1.06, 95% CI (1.00–1.11)). The risk of diabetes was associated with increasing duration of index episode (HR 1.01, 95% CI (1.00–1.01) as was respiratory disease (HR 1.00, 95% CI (1.00–1.01)). Diagnoses of infection were associated with increasing score on HAM-D6 (HR 1.11, CI 95 % (1.01–1.22)).ConclusionsThe association between number of previous depressive episodes and CVD is in line with previous results. The findings of associations between the psychometric measures and specific diseases should be interpreted with caution, as well as the associations between duration of episodes, higher severity and higher number of previous episodes, and increased risks of somatic morbidity, albeit these are in line with previous evidence. (AU)

The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine.

OBJECTIVE: To investigate to what extent the primary depression subtype atypical depression can predict differential outcome of the mono-amino-oxidase inhibitor (MAO-I) moclobemide and the tricyclic antidepressant clomipramine in the Danish University Antidepressant Group Study (DUAG). METHODS: In a randomised, double blind trial, a total of 117 patients with major depression were treated over 6 weeks with either 400 mg moclobemide or 150 mg clomipramine. A baseline principal component analysis (PCA) was performed to identify atypical symptoms on the combined depression scales (Hamilton Depression Scale (HAM-D(17)) and the Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was the subscale HAM-D(6) which contains the pure items of depression. RESULTS: PCA identified two items with loadings opposite to the other depression items within HAM-D(17) and QSAD, namely increased duration of sleep and increased appetite (atypical neurovegetative symptoms). Patients with a positive score at baseline on these items were classified as having atypical depression. In total 13 patients were classified as having atypical depression. Within this group of patients 8 received clomipramine and 5 patients received moclobemide. At endpoint the moclobemide treated patients had a significantly better response than the clomipramine treated (P=0.036), effect size 1.42, when using HAM-D(6) as outcome. However, in the 104 patients classified as having typical depression clomipramine was superior to moclobemide (P=0.034), effect size 0.47. LIMITATIONS: The number of patients with atypical neurovegetative symptoms was very small and no placebo arm was included. CONCLUSIONS: It is very important to screen for atypical depression (increased duration of sleep/increased appetite) in the acute therapy of patients with major depression. Our results add to the body of evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants in this sub-group of patients.

Do we agree about when patients are psychotic?

OBJECTIVE: To investigate into the use of the term 'psychotic' as defined by ICD-10 or by the concept of impaired reality testing, among psychiatric staff members. METHOD: Questionnaire investigation using 11 short case vignettes. RESULTS: Responses were received from 266 psychiatric staff members: psychiatrists, nursing staff and psychologists. When using ICD-10, patients were identified as psychotic with a sensitivity ranging from 90% to 55%. Specificity ranged from 60% to 75%. According to the concept of impaired reality testing, all three groups showed a sensitivity of about 60%, whereas specificity ranged from 65% to 50%. The combined use of the terms correlated significantly with responses regarding indication for legal detention for psychiatrists and nursing staff. CONCLUSION: In identifying a patient as 'psychotic' a broad concept of impaired reality testing was widely used particularly in cases with legal issues. Psychotic symptoms, however, were identified with high sensitivity and specificity.

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. METHOD: Prospective evaluation of the impact of depression according to the ICD-10 criteria for depression. Cox proportional hazards regression was used to evaluate the independent impact of depression after controlling for significant univariate clinical predictors in the data set. Consenting out-patients (n = 49) who meet the criteria for COPD between September 1997 and September 1998. There were no age limits (range: 53-90 years). The sample was 67% female. Survival status at follow-up after a mean of 803 days was measured. RESULTS: At follow-up, 16 patients had died. Depression significantly reduced the mortality risk at follow-up (hazard ratio, 0.30; 95% confidence interval, 0.10-0.93; P = 0.037). The impact of depression remained after control for forced expiratory volume during the first second (FEV1), the only multivariate significant predictor of mortality in the data set (hazard ratio, 0.27; 95% confidence interval, 0.09-0.84; P = 0.024). CONCLUSION: Depression in out-patients suffering from COPD appears to be an independent protector for mortality. Additional studies in larger samples are needed to replicate this finding and to determine possible underlying pathogenetic mechanisms.

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. METHOD: A total of 210 previous participants in multicentre antidepressant drug trials, carried out in a randomized double-blind design, were followed prospectively through a maximum of 10 years. Patients with a drug or alcohol abuse were excluded. The association between suicide and the pretreatment psychopathological profile was analysed using survival statistics. RESULTS: The suicide rate for non-melancholic depressed patients was significantly higher than for melancholic depressed patients. Comorbid personality disorder was independently associated with an increased suicide rate [relative hazard 3.41(CI: 1.15-10.10)]. CONCLUSION: The study indicates that the non-melancholic aspect of depression, and especially comorbid personality disorder, is associated with an increased suicidal vulnerability.

Gender and depression: a study of severity and symptomatology of depressive disorders (ICD-10) in general practice.

OBJECTIVE: Gender differences in severity and symptomatology of depression in a large and representative sample of depressive patients from general practice were examined. METHOD: During a 2-year study period, 31 Danish general practitioners consecutively assessed patients, aged >18, for depression. A total of 1033 patients (692 female, 341 male) fulfilled ICD-10 criteria for depressive disorders. Gender differences were examined with regard to severity and symptomatology of depression. RESULTS: The severity of depression was similar for men and women with the following distribution: 22% mild, 56% moderate and 23% severe depressive episodes. The mean number of symptoms presented was 6.6 of 10 for both genders. There were no gender differences in prevalence of single depressive symptoms. CONCLUSION: No gender differences in the severity or symptomatology of depression were found in a highly representative sample of patients with depressive disorders.

Age-related adverse drug reactions to clomipramine.

OBJECTIVE: The aim of this study was to determine whether age itself is a significant factor in predicting adverse drug reactions in depressed inpatients treated with clomipramine. METHOD: The study involved 150 hospitalized, depressed patients treated with 150 mg clomipramine per day. Changes in orthostatic blood pressure during treatment as well as the patients' complaint about side-effects was examined with regard to age. The sample was divided into younger (<56) and older (56-70) groups. RESULTS: No significant differences between younger and older subjects were found on any of the 44 side-effects recorded. However, older depressed patients suffer from more pronounced orthostatic hypotension than younger patients. CONCLUSION: Older depressed patients who have been treated with clomipramine suffer from more severe orthostatic hypotension than younger patients. However, with the right precautions it is safe to treat older patient up to the age of 70 years with a tricyclic antidepressant.

ICD-10 criteria for depression in general practice.

BACKGROUND: The rate of recognition of depressive disorder in general practice is reported to be low. Current classification systems, i.e. ICD-10 and DSM-III-R, and DSM-IV with operational diagnostic criteria, have led to greater agreement concerning the diagnosis of depressive disorder. The aim of this study was to assess the applicability and validity of the ICD-10 criteria for depression in general practice in Denmark. METHODS: After a 1-day training course in the ICD-10 criteria for depression, ten general practitioners, during an 8-week period assessed all patients aged 18 or older for depressive symptoms in accordance with the ICD-10 criteria. RESULTS: Among a total of 3505 consultations, 116 patients (3.3%) met the criteria for a depressive episode. Of these, 80 (68.8%) accepted to be reinterviewed by a psychiatrist, who confirmed the diagnosis of depressive disorder in 57 of the 80 patients (71.3%). LIMITATIONS: The number of 'false negative' cases are unknown in the study. CONCLUSION: The ICD-10 criteria for depression seem to be appropriate and valid in general practice.

Differences in symptomatology and diagnostic profile in younger and elderly depressed inpatients.

BACKGROUND: Depression is the most prevalent psychiatric disorder in the elderly and several studies indicate that 10-15% of persons over 65 years suffer from significant depressive symptoms. Despite the high prevalence, most cases of depression in the elderly remain unrecognized and untreated, maybe because of a different pattern of symptoms across age groups. The objective of the study was to compare symptomatology and diagnostic profile between younger and elderly DSM-III and DSM-III-R major depressed inpatients and to advise an appropriate depression scale for the elderly. METHODS: The study covers 461 depressed inpatients evaluated with the Hamilton Depression Scale and the Newcastle 1965 Scale. To find differences between younger and elderly patients, the symptomatology was analyzed stepwise by principal component analyses, latent structure analyses and single item analyses. RESULTS: No clinically significant differences in symptomatology between younger and elderly depressed patients were found. The DSM-IV concept of Major Depression and the ICD-10 criteria for depression was not influenced by patients' age. LIMITATIONS: All patients were hospitalized and mainly endogenously depressed and generalization of the results to other populations should be made with caution. Only pretreatment data was analyzed. CONCLUSIONS: The DSM-IV concept of Major Depression and the ICD-10 criteria for depression can be used without modification for age.

Interrater reliability of a Danish version of the Morgan Russell scale for assessment of anorexia nervosa.

OBJECTIVE: To study the interrater reliability of a Danish version of the Morgan Russell scale for assessment of patients with anorexia nervosa, and subsequently to clarify the existing rating instructions. METHOD: Ten patients undergoing treatment for anorexia nervosa at a regional center participated and had their interview videotaped. Two interviews were reserved for a training phase only. The group of raters comprised eight clinicians, and measures of interrater reliability were computed using intraclass correlation coefficient (ICC). RESULTS: The ICC for the total score was good (0.79), while reliability for the single items varied from poor to excellent (0.14-0.99). Internal consistency as expressed by Cronbach's coefficient alpha was acceptable (0.74). DISCUSSION: The Morgan Russell scale stands out as an easily applied and reliable measure of severity of anorexia nervosa, though the rating instructions need clarification in some items.

Are in-patient depressives more often of the melancholic subtype? Danish University Antidepressant Group.

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.

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

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.

[Treatment of depression an the elderly]. / Behandling af depression hos aeldre.

The risk of depressive symptoms and disorders increases 2-3-fold after the age of 65. Research on the treatment of depression in the elderly is a new field of which our knowledge is still scanty. Patients over 75 years of age, patients with intercurrent physical disorders, and elderly patients with depression and concomitant organic brain disorders are seldom included in controlled clinical studies. Only by an active approach to treatment can depression-related mortality be reduced. The risk of death is three times greater in elderly patients with depression than in age-matched healthy controls, and not solely due to suicide. Both the risk of cardiac death and that of death following apoplexy are considerably increased in patients with depression.

Depression after smoking cessation: case reports.

BACKGROUND: Cigarette smokers with a history of major depression are at risk for developing depressive mood when they attempt cessation. Whether cessation can also provoke more severe depressions, however, has not been well documented. METHOD: Six case reports of severe depressive episodes after smoking cessation are described. RESULTS: Four cases occurred among smokers with a history of major depression but who were not depressed at the time of cessation. Two cases involved smokers with no previous history of major depression. Variability in both the timing and the outcome of the postcessation depressions was observed. CONCLUSION: The risk that depressive states may emerge or be exacerbated after smoking cessation, particularly in patients with a history of major depression, must be kept in mind in the treatment of nicotine dependence.

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)

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.

[Insufficient effect of nortriptyline in a rapid metabolizer of sparteine]. / Manglende effekt af nortriptylin hos en hurtig omdanner af spartein.

A 61-year old woman suffering from depression was treated with 150 mg nortriptyline daily for eight weeks by her general practitioner. In spite of this dose, her S-nortriptyline was only 100 nmol/1 (recommended range: 225-600 nmol/1), and she remained depressed and was admitted to hospital. A sparteine test gave a metabolic ratio of 0.06, hence the patient was classified as a very rapid extensive metabolizer. Her nortriptyline dose was increased to 250 mg/day and the S-nortriptyline rose to 528 nmol/l. After eight weeks of sufficient nortriptyline treatment, the patient was still depressed. The patient recovered completely after a series of five electroconvulsive treatments.