Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS.

BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. METHODS: Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n = 21) or placebo (n = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire. RESULTS: Included women were aged 31 (6) years (mean (s.d.)) and had body mass index (BMI) 35.8 (6.5) kg/m2 and waist 102 (12) cm. Escitalopram was associated with increased waist (median (quartiles) change 1 (0; 3) cm), P = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test), all P < 0.05 vs changes during placebo. Escitalopram had no significant effect on measures of insulin sensitivity, insulin secretion, fasting lipids, mental health or HRQoL. CONCLUSION: Waist circumference and cortisol levels increased during treatment with escitalopram in women with PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged.

Explanatory models of depression and treatment adherence to antidepressant medication: a qualitative interview study.

BACKGROUND: Adherence to antidepressant medication is a challenging clinical issue, which reduces treatment efficacy: 30-60% of all patients commencing treatment with antidepressants are estimated to stop taking the medication within the first 12 weeks. Patients' personal beliefs about depression and antidepressants are regarded as central influences on adherence. OBJECTIVES: The aim was to gain detailed insight into patients' personal accounts of depression and use of antidepressant medication and to relate these accounts to the patients' self-reported level of adherence. METHODS: In-depth, qualitative interviews of 16 depressed patients one, four, eight and twelve months after hospital discharge supplemented by diagnostic interviews and self-report measures. Kleinman's notion of "explanatory model" was used as the theoretical perspective on the patients' illness narratives. Interview transcripts were analysed thematically with "explanatory models" as the starting point. RESULTS: Patients had ambiguous experiences of depression and antidepressants. Patients explained their illness and the medical treatment in experience-near terms. Explanations of the reasons for depression were psychosocial and biology and medicine were not central. However, taking antidepressant medication was a meaningful part of being admitted to hospital, and the adoption of the rhetoric and practices of biomedicine strengthened patients' sense of control and hope for recovery. If medicine was ineffective, the explanatory models legitimised alternative strategies towards recovery, including non-adherence. CONCLUSIONS: The patients' reasons for adhering to antidepressants included a range of diverse psychosocial issues, and could be regarded as a central part of their common sense illness management.

[Risk of affective disorder in multiple sclerosis]. / Risiko for affektiv lidelse ved multipel sklerose.

An increased risk for depression has been found in multiple sclerosis (MS). The purpose of the present study has been to give suggestions to guidelines for diagnosis and treatment of depression in MS in Denmark based on the international literature and recommendations. The method was a review of the relevant literature. The study recommends assessment of all MS patients for depression. Treatment of depression with serotonin reuptake inhibitors and/or cognitive behavioural therapy is recommended, depending on the severity of the illness. Caution is recommended in patients receiving beta interferon treatment.

[Treatment of psychotic depression]. / Behandling af psykotisk depression.

Psychotic depression is frequent among hospitalized patients diagnosed with major depression. Patients diagnosed with this type of depression display a number of specific characteristics. They have a higher risk of suicidal behaviour, they have a prolonged and more severe clinical picture and subsequently they have an increased risk of relapse. Studies show that monotherapy with antidepressants is more effective than antipsychotic monotherapy. Electroconvulsive therapy remains the most effective treatment, while tricyclic antidepressants in monotherapy are also effective. An antipsychotic drug can be added if no effect of monotherapeutic antidepressant treatment is observed within two to four weeks.

Implementation of a rational pharmacotherapy intervention for inpatients at a psychiatric department.

The objective of the study was to develop, implement and evaluate two treatment algorithms for schizophrenia and depression at a psychiatric hospital department. The treatment algorithms were based on available literature and developed in collaboration between psychiatrists, clinical pharmacologists and a clinical pharmacist. The treatment algorithms were introduced at a meeting for all psychiatrists, reinforced by the project psychiatrists in the daily routine and used for educational purposes of young doctors and medical students. A quantitative pre-post evaluation was conducted using data from medical charts, and qualitative information was collected by interviews. In general, no significant differences were found when comparing outcomes from 104 charts from the baseline period with 96 charts from the post-intervention period. Most of the patients (65% in the post-intervention period) admitted during the data collection periods did not receive any medication changes. Of the patients undergoing medication changes in the post-intervention period, 56% followed the algorithms, and 70% of the patients admitted to the psychiatric hospital department for the first time had their medications changed according to the algorithms. All of the 10 interviewed doctors found the algorithms useful. The treatment algorithms were successfully implemented with a high degree of satisfaction among the interviewed doctors. The majority of patients admitted to the psychiatric hospital department for the first time had their medications changed according to the algorithms.

[Acute pharmacological treatment of depression]. / Akut farmakologisk behandling af depression.

Depression is one of the most economically burdensome diseases with serious consequences for patients as well as their families. Many depressed patients are not treated because they neither contact a doctor nor are diagnosed correctly. Today, it is generally accepted that depression is not just one disease but is composed of subgroups, each requiring its own specific treatment. In mild to moderate depression SSRIs or other newer antidepressants can be used but in cases of severe melancholic or psychotic depression TCAs or ECT are the treatments of choice.

[Medical treatment of depression during pregnancy and breastfeeding]. / Medikamentel behandling af depression under graviditet eller amning.

Medical treatment of depression during pregnancy and breastfeeding often involves concern by both the patient and the doctor because of the fear of adverse reactions or malformations of the child. This article gives an updated review on how antidepressants, lithium, antipsychotics and ECT can be used during pregnancy and breastfeeding, and presents a treatment algorithm which is used at Odense University Hospital.

[Depression and ischemic heart disease]. / Depression og iskaemisk hjertesygdom.

Depression is an independent risk factor for ischemic heart disease and is related to increased cardiovascular mortality. Post myocardial infarction depression is related to less compliance with medical treatment, less participation in cardiac rehabilitation, less modification of life style factors and increased mortality. So far, routine treatment with selective serotonin re-uptake inhibitors is not warranted as the evidence is insufficient. Improved cooperation between general practice, cardiologists and psychiatrists is necessary in order to identify and treat this group of 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-Asberg 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 < or = 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.

Depression in COPD--management and quality of life considerations.

Depression is common in COPD patients. Around 40% are affected by severe depressive symptoms or clinical depression. It is not easy to diagnose depression in COPD patients because of overlapping symptoms between COPD and depression. However, the six-item Hamilton Depression Subscale appears to be a useful screening tool. Quality of life is strongly impaired in COPD patients and patients' quality of life emerges to be more correlated with the presence of depressive symptoms than with the severity of COPD. Nortriptyline and imipramine are effective in the treatment of depression, but little is known about the usefulness of newer antidepressants. In patients with milder depression, pulmonary rehabilitation as well as cognitive-behavioral therapy are effective. Little is known about the long-term outcome in COPD patients with co-morbid depression. Preliminary data suggest that co-morbid depression may be an independent protector for mortality.

Orthostatic side effects of clomipramine and moclobemide during treatment for depression.

From a clinical point of view, orthostatic hypotension is a significant side effect during antidepressant treatment, particularly in the case of tricyclic antidepressants (TCAs). This prospective, randomized clinical trial evaluated the effects of clomipramine and moclobemide on orthostatic blood pressure during treatment for depression. One hundred and fifteen depressed inpatients, age up to 70 years, were randomized to treatment with either moclobemide (400 mg/day) or clomipramine (150 mg/day) after 1 week of placebo treatment. Orthostatic blood pressure was measured weekly over the 6-week study period. Clomipramine, but not moclobemide, caused a statistically significant fall in systolic (F = 9.37, P = 0.0037) and diastolic orthostatic blood pressure (F = 3.74, P = 0.0017). In the clomipramine-treated group of patients, we found no correlation between subjective complaints of orthostatic dizziness and the size of systolic orthostatic blood pressure. In conclusion, this study indicates that moclobemide does not induce orthostatic side effects, which is a significant problem in treatment with TCAs. However, the choice of antidepressants depends on other factors as well, e.g. the therapeutic efficacy.

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.

Gender differences in severity, symptomatology and distribution of melancholia in major depression.

BACKGROUND: Studies of gender differences in the clinical presentation of depression have provided divergent results. This study aimed at analyzing gender differences in severity, symptomatology and distribution of melancholia in major depression. SAMPLING AND METHODS: The study comprised 930 in- and out-patients (652 women, 278 men) from 6 randomized controlled trials. All patients fulfilled DSM-III or DSM-III-R criteria for major depression. The 17-item Hamilton Depression Scale (HDS) was applied to all patients. A multi-axial evaluation was completed using the Newcastle 1 Depression Rating Scale from 1965 for melancholia (N1) in a subsample of patients (n = 439). A factor analysis on the HDS was performed. Non-parametric statistical tests were used and only gender differences greater than 20% were considered clinically relevant. RESULTS: The median on the HDS total score was 22 and the median number of symptoms was 13 for both men and women. Presentation of specific symptoms was similar for men and women. The factor analysis revealed no gender differences, and neither did analyses on symptoms of Axes II and IV. According to the N1, 80% of the men and 66% of the women suffered from melancholic depression (p = 0.004). CONCLUSIONS: In a large and broad sample of in- and out-patients with major depression, the severity and symptomatology of depression were similar for men and women. Melancholic depression was significantly more frequent among male than female patients. Inclusion and exclusion criteria in the randomized controlled trials provided a selected group of patients, which limited the generalisability of the results to an exclusive subgroup of patients treated for depression in routine clinical practice.

Are gender differences important for the clinical effects of antidepressants?

OBJECTIVE: Gender differences in antidepressant treatment response, side effects, dropout rates, and plasma concentrations were examined in patients with major and predominantly melancholic depression. METHOD: The study included a subgroup of 292 inpatients (96 men, 196 women) from three Danish double-blind, randomized, controlled trials. All patients completed a 5-week treatment period and fulfilled the DSM-III or DSM-III-R criteria for major depression. Clomipramine (150 mg/day) was the reference treatment, and comparable treatments were citalopram (40 mg/day), paroxetine (30 mg/day), and moclobemide (400 mg/day). Assessments were performed by using the 17-item Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. In a subgroup of 110 patients, weekly measurements of clomipramine plasma concentrations were obtained. Nonparametric statistical tests and multiple linear and logistic regression models were used for statistical evaluations. RESULTS: Both genders had similar remission rates (Hamilton depression scale score <8) when treated with clomipramine and had significantly higher remission rates with clomipramine than with the comparable treatments. The plasma concentrations of clomipramine were significantly higher for female than for male patients. No gender differences were found in posttreatment Hamilton depression scale scores, nor did the therapeutic effects of treatment depend on gender. Rates of dropout and side effects were similar for men and women. No relationship between plasma concentrations, gender, and therapeutic outcome was found. CONCLUSIONS: In a group of patients with major and predominantly melancholic depression, differentiation according to gender was not important in treatment with common antidepressants. Women appeared to have higher plasma concentrations of tricyclic antidepressants than men. The consequences of this difference for clinical effects are unclear. Gender-specific recommendations for dosing of tricyclic antidepressants may be considered.

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 randomized trial of sertraline as a cessation aid for smokers with a history of major depression.

OBJECTIVE: Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated. METHOD: The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits. RESULTS: Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed. CONCLUSIONS: Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.