Depression In Routine Clinical Practice Research Articles

“I’m always going to be tired”: a qualitative exploration of adolescents’ experiences of fatigue in depression

Adolescent depression is a prevalent and disabling condition, but current psychological treatments are only moderately effective. One way to enhance outcomes is to further our understanding of adolescent depression and improve our capacity to target the most frequently reported and problematic symptoms. A common but often neglected symptom of depression is fatigue, which is associated with considerable impairment and has the potential to interfere with adolescents’ engagement in psychological therapies. Despite this, the experience of fatigue in adolescent depression and how we target it in treatment is currently poorly understood. Therefore, we aimed to explore adolescents’ experiences and understandings of fatigue in depression, recruiting from clinical and community settings. Semi-structured interviews were conducted with 19 UK-based adolescents aged 14–18 years old with elevated symptoms of depression. Using reflexive thematic analysis, three themes were generated. Fatigue is a complex concept explored adolescents’ understanding of fatigue as a dynamic, multifaceted symptom which had mental and physical components. Trapped in a cycle of fatigue considered the complex and reciprocal relationship between fatigue and other depressive symptoms, and the subsequent impact of limited energy on engagement with everyday activities. Finally, stigma as a barrier to help-seeking highlighted how adolescents were reluctant to seek help due to experienced stigma and the perception that fatigue was not a serious enough symptom. Findings from this study suggest that fatigue should be viewed as a psychological as well as somatic symptom of depression, with implications regarding the identification and treatment of fatigue in depression in routine clinical practice.

The clinical characterization of the adult patient with depression aimed at personalization of management.

Depression is widely acknowledged to be a heterogeneous entity, and the need to further characterize the individual patient who has received this diagnosis in order to personalize the management plan has been repeatedly emphasized. However, the research evidence that should guide this personalization is at present fragmentary, and the selection of treatment is usually based on the clinician's and/or the patient's preference and on safety issues, in a trial-and-error fashion, paying little attention to the particular features of the specific case. This may be one of the reasons why the majority of patients with a diagnosis of depression do not achieve remission with the first treatment they receive. The predominant pessimism about the actual feasibility of the personalization of treatment of depression in routine clinical practice has recently been tempered by some secondary analyses of databases from clinical trials, using approaches such as individual patient data meta-analysis and machine learning, which indicate that some variables may indeed contribute to the identification of patients who are likely to respond differently to various antidepressant drugs or to antidepressant medication vs. specific psychotherapies. The need to develop decision support tools guiding the personalization of treatment of depression has been recently reaffirmed, and the point made that these tools should be developed through large observational studies using a comprehensive battery of self-report and clinical measures. The present paper aims to describe systematically the salient domains that should be considered in this effort to personalize depression treatment. For each domain, the available research evidence is summarized, and the relevant assessment instruments are reviewed, with special attention to their suitability for use in routine clinical practice, also in view of their possible inclusion in the above-mentioned comprehensive battery of measures. The main unmet needs that research should address in this area are emphasized. Where the available evidence allows providing the clinician with specific advice that can already be used today to make the management of depression more personalized, this advice is highlighted. Indeed, some sections of the paper, such as those on neurocognition and on physical comorbidities, indicate that the modern management of depression is becoming increasingly complex, with several components other than simply the choice of an antidepressant and/or a psychotherapy, some of which can already be reliably personalized.

Scheduled Telephone Support for Internet Cognitive Behavioral Therapy for Depression in Patients at Risk for Dropout: Pragmatic Randomized Controlled Trial.

BackgroundTherapist-supported, internet-delivered cognitive behavioral therapy (iCBT) is efficient in the treatment of depression. However, the optimal mode and intensity of therapist support remain to be identified. Scheduled telephone support (STS) may improve adherence and outcomes but, as it is time- and resource-consuming, should be reserved for patients for whom the usual support may be insufficient.ObjectiveThis paper aims to reveal whether add-on STS for patients at risk of dropping out improves treatment adherence and symptoms in iCBT for depression.MethodsAmong patients participating in an ongoing large observational routine clinical practice study of iCBT for depression delivered nationwide by Helsinki University Hospital (HUS-iCBT), those demonstrating a ≥14-day delay in initiation of treatment received invitations to this subsidiary STS study. A total of 100 consenting patients were randomly allocated to either HUS-iCBT as usual (control group, n=50) or HUS-iCBT plus add-on STS (intervention group, n=50). Proportions of those reaching midtreatment and treatment end point served as the primary outcome; secondary outcomes were change in Beck Depression Inventory (BDI)–measured depressive symptoms and time spent in treatment.ResultsAdd-on STS raised the proportion of patients reaching midtreatment compared with HUS-iCBT as usual (29/50, 58% vs 18/50, 36%; P=.045) and treatment end point (12/50, 24% vs 3/50, 6%; P=.02). Change in BDI score also favored add-on STS (3.63 points vs 1.1 points; P=.049), whereas duration of treatment did not differ.ConclusionsAdd-on STS enhances adherence and symptom improvement of patients at risk of dropping out of iCBT for depression in routine clinical practice.Trial RegistrationInternational Standard Randomised Controlled Trial Number (ISRCTN) 55123131; http://www.isrctn.com/ISRCTN55123131.

Generalizability of pharmacologic and psychotherapy trial results for late-life unipolar depression

Objectives Despite evidence of low representativeness of clinical trial results for depression in adults, the generalizability of clinical trial results for late-life depression is unknown. This study sought to quantify the representativeness of pharmacologic and psychotherapy clinical trial results for late-life unipolar depression. Method Data were derived from the 2004–2005 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of 34,653 adults from the United States population. To assess the generalizability of clinical trial results for late-life depression, we applied a standard set of eligibility criteria representative of pharmacologic and psychotherapy clinical trials to all individuals aged 65 years and older in NESARC with a DSM-IV diagnosis of MDE and no lifetime history of mania/hypomania (n = 273) and in a subsample of individuals seeking help for depression (n = 78). Results More than four of ten respondents and about two of ten respondents would have been excluded by at least one exclusion criterion in a typical pharmacologic and psychotherapy efficacy trial, respectively. Similar results (i.e.41.1% and 25.9%, respectively) were found in the subsample of individuals seeking help for depression. Excess percentage of exclusion in typical pharmacologic studies was accounted for by the criterion “significant medical condition”. We also found that populations typically included in pharmacologic and psychotherapy clinical trials for late-life unipolar depression may substantially differ. Conclusion Psychotherapy trial results may be representative of most patients with late-life unipolar depression in routine clinical practice. By contrast, pharmacologic clinical trials may not be readily generalizable to community samples.

Once-a-Day Trazodone in the Treatment of Depression in Routine Clinical Practice

Objective: The aim of the study was to evaluate the efficacy, tolerability, and safety of once-a day trazodone tablets (Trittico Prolong® 300 mg) in patients with moderate to severe depression in routine clinical practice. Methods: Men and women ≥18 years old with Montgomery-Åsberg Depression Rating Scale (MADRS) scores > 21 and Clinical Global Impression – Severity (CGI/S) ≥4 were included in this post-authorization, non-interventional, observational prospective safety study, conducted in 8 psychiatric centers in the Czech ­Republic. The acute treatment phase lasted 5 weeks: 1 week of titration and 4 weeks of full-dose treatment. Patients had follow-up visits 9 and 21 weeks after commencing ­treatment. Results: Overall, 85 patients were enrolled in the study, of which 80 completed the acute treatment of 5 weeks. There were significant decreases in the overall MADRS score from the baseline mean value of 27.4–21.2 at week 1 (p < 0.001), and a further decrease to 7.9 at week 5 (p < 0.001). The severity of depression according to CGI/S gradually declined. Most patients reported improvement after 6 days of trazodone treatment. The most frequent adverse drug reactions (ADRs) reported were somnolence and fatigue. Conclusions: Trazodone, in the new extended-release formulation, had very good effects in clinical practice, both in previously untreated depressive episodes and in episodes not responsive to previous antidepressive therapy.

Burden of Depression among Working-Age Adults with Rheumatoid Arthritis.

Objective This study estimated the excess clinical, humanistic, and economic burden associated with depression among working-age adults with Rheumatoid Arthritis (RA). Methods A retrospective cross-sectional study was conducted among working-age (18 to 64 years) RA patients with depression (N = 647) and without depression (N = 2,015) using data from the nationally representative Medical Expenditure Panel Survey for the years 2009, 2011, 2013, and 2015. Results Overall, 25.8% had depression. In adjusted analyses, adults with RA and depression compared to those without depression were significantly more likely to have pain interference with normal work (severe pain: AOR = 2.22; 95% CI = 1.55, 3.18), functional limitations (AOR = 2.17; 95% CI = 1.61, 2.94), and lower mental health HRQoL scores. Adults with RA and depression had significantly higher annual healthcare expenditures ($14,752 versus 10,541, p < .001) and out-of-pocket spending burden. Adults with RA and depression were more likely to be unemployed and among employed adults, those with depression had a significantly higher number of missed work days annually and higher lost annual wages due to missed work days. Conclusions This study highlights the importance of effectively managing depression in routine clinical practice of RA patients to reduce pain and functional limitations, improve quality of life, and lower direct and indirect healthcare costs.

The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder.

Prefrontal Transcranial Magnetic Stimulation (TMS) therapy repeated daily over 4-6 weeks (20-30 sessions) is US Food and Drug Administration (FDA) approved for treating Major Depressive Disorder in adults who have not responded to prior antidepressant medications. In 2011, leading TMS clinical providers and researchers created the Clinical TMS Society (cTMSs) (www.clinicaltmssociety.org, Greenwich, CT, USA), incorporated in 2013. This consensus review was written by cTMSs leaders, informed by membership polls, and approved by the governing board. It summarizes current evidence for the safety and efficacy of the use of TMS therapy for treating depression in routine clinical practice. Authors systematically reviewed the published TMS antidepressant therapy clinical trials. Studies were then assessed and graded on their strength of evidence using the Levels of Evidence framework published by the University of Oxford Centre for Evidence Based Medicine. The authors then summarize essentials for using TMS therapy in routine clinical practice settings derived from discussions and polls of cTMSs members. Finally, each summary clinical recommendation is presented with the substantiating peer-reviewed, published evidence supporting that recommendation. When the current published clinical trial evidence was insufficient or incomplete, expert opinion was included when sufficient consensus was available from experienced clinician users among the membership of the cTMSs, who were polled at the Annual Meetings in 2014 and 2015. Daily left prefrontal TMS has substantial evidence of efficacy and safety for treating the acute phase of depression in patients who are treatment resistant or intolerant. Following the clinical recommendations in this document should result in continued safe and effective use of this exciting new treatment modality.

Antidepressant augmentation with metyrapone for treatment-resistant depression (the ADD study): a double-blind, randomised, placebo-controlled trial

Many patients with major depressive disorder have treatment-resistant depression, defined as no adequate response to two consecutive courses of antidepressants. Some evidence suggests that antiglucocorticoid augmentation of antidepressants might be efficacious in patients with major depressive disorder. We aimed to test the proof of concept of metyrapone for the augmentation of serotonergic antidepressants in the clinically relevant population of patients with treatment-resistant depression. This double-blind, randomised, placebo-controlled trial recruited patients from seven UK National Health Service (NHS) Mental Health Trusts from three areas (northeast England, northwest England, and the Leeds and Bradford area). Eligible patients were aged 18-65 years with treatment-resistant depression (Hamilton Depression Rating Scale 17-item score of ≥18 and a Massachusetts General Hospital Treatment-Resistant Depression staging score of 2-10) and taking a single-agent or combination antidepressant treatment that included a serotonergic drug. Patients were randomly assigned (1:1) through a centralised web-based system to metyrapone (500 mg twice daily) or placebo, in addition to their existing antidepressant regimen, for 21 days. Permuted block randomisation was done with a block size of two or four, stratified by centre and primary or secondary care setting. The primary outcome was improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score 5 weeks after randomisation, analysed in the modified intention-to-treat population of all randomly assigned patients that completed the MADRS assessment at week 5. The study has an International Standard Randomised Controlled Trial Number (ISRCTN45338259) and is registered with the EU Clinical Trial register, number 2009-015165-31. Between Feb 8, 2011, and Dec 10, 2012, 165 patients were recruited and randomly assigned (83 to metyrapone and 82 to placebo), with 143 (87%) completing the primary outcome assessment (69 [83%] in the metyrapone and 74 [90%] in the placebo group). At 5 weeks, MADRS score did not significantly differ between groups (21·7 points [95% CI 19·2-24·4] in the metyrapone group vs 22·6 points [20·1-24·8] in the placebo group; adjusted mean difference of -0·51 points [95% CI -3·48 to 2·46]; p=0·74). 12 serious adverse events were reported in four (5%) of 83 patients in the metyrapone group and six (7%) of 82 patients in the placebo group, none of which were related to study treatment. 134 adverse events occurred in 58 (70%) patients in the metyrapone group compared with 95 events in 45 (55%) patients in the placebo group, of which 11 (8%) events in the metyrapone group and four (4%) in the placebo group were judged by principle investigators at the time of occurrence to be probably related to the study drug. Metyrapone augmentation of antidepressants is not efficacious in a broadly representative population of patients with treatment-resistant depression within the NHS and therefore is not an option for patients with treatment-resistant depression in routine clinical practice at this time. Further research is needed to clarify if such augmentation might benefit subpopulations with demonstrable hypothalamic-pituitary-adrenal axis abnormalities. Efficacy and Mechanism Evaluation (EME) programme, a UK Medical Research Council and National Institute for Health Research partnership.

Expectations among patients and health professionals regarding Web-based interventions for depression in primary care: a qualitative study.

BackgroundOne-quarter of the world’s population will suffer from depression symptoms at some point in their lives. Mental health services in developed countries are overburdened. Therefore, cost-effective interventions that provide mental health care solutions such as Web-based psychotherapy programs have been proposed.ObjectiveThe intent of the study was to identify expectations regarding Web-based psychotherapy for the treatment of depression in primary care among patients and health professionals that might facilitate or hinder its effects.MethodsThe expectations of untreated patients and health professionals were examined by means of interviews and focus groups. There were 43 participants (20 patients with mild and moderate levels of depression, 11 primary care physicians, and 12 managers; 22 of them for interviews and 21 for groups). A thematic content analysis from the grounded theory for interviews, and an analysis of the discursive positions of participants based on the sociological model for groups were performed. Interpretations were achieved by agreement between three independent analysts.ResultsAll participants showed a good general acceptance of Web-based psychotherapy, appreciating possible advantages and improvements. Patients, physicians, and managers shared the same conceptualization of their expectations, although highlighting different aspects. Patients focused on the need for individualized and personalized interaction, while professionals highlighted the need for the standardization of the program. Physicians were concerned with extra workload, while managers were worried about optimizing cost-effectiveness.ConclusionsExpectations of the different participants can conflict with each other. Finding a balanced position among them is needed if we are to harmoniously implement effective Web-based interventions for depression in routine clinical practice.

Safety and effectiveness of controlled-release paroxetine in routine clinical practice: results of a postmarketing surveillance study of patients with depression.

ObjectiveSelective serotonin reuptake inhibitors are commonly used in the pharmacotherapy of depression. However, adverse events can lead to their early discontinuation. This study evaluated the safety and effectiveness of paroxetine controlled-release (CR) tablets in Japanese patients with depression/depressive state (hereafter referred to as depression) in routine clinical practice in Japan.Patients and methodsThis was an open-label, noninterventional, prospective, postmarketing surveillance study. A total of 3,213 patients aged 12–92 years with depression were prescribed paroxetine CR for 8 weeks at the physician’s discretion. Safety was evaluated on the basis of the reporting of adverse drug reactions. Effectiveness was evaluated on the basis of the physician’s assessment using the Clinical Global Impression-Global Improvement (CGI-GI) and the Clinical Global Impression-Severity of Illness (CGI-SI) scales, as well as on the basis of the patients’ self-reported satisfaction. The primary effectiveness outcome was the improvement rate based on the physician’s assessment using the CGI-GI.ResultsThe incidence of adverse drug reactions was 11.2% (359/3,213; 95% confidence interval [CI]: 10.1%–12.3%). The common adverse drug reactions that accounted for 1.0% or more of the incidence were nausea (3.5%) and somnolence (2.7%). The proportion of patients who continued paroxetine CR at week 8 was 80.2% (2,577/3,213; 95% CI: 78.8%–81.6%). The improvement rate at week 8 (last observation carried forward) was 72.8% (2,132/2,927; 95% CI: 71.2%–74.4%). The proportion of patients with CGI-SI scores of moderately or severely ill decreased from 63.6% at baseline to 17.9% at week 8. The proportion of patients who were satisfied with paroxetine CR treatment was 69.8% (2,040/2,921; 95% CI: 68.1%–71.5%).ConclusionThe results of this study suggest that paroxetine CR is a well-tolerated and efficacious treatment for depression in routine clinical practice.

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 subjects in pharmacological treatment trials of depression representative of patients in routine clinical practice?

The methods used to evaluate the efficacy of antidepressants differ from treatment for depression in routine clinical practice. The rigorous inclusion/exclusion criteria used to select subjects for participation in efficacy studies potentially limit the generalizability of these trials' results. It is unknown how much impact these criteria have on the representativeness of subjects in efficacy trials. This study estimated the proportion of depressed patients treated in routine clinical practice who would meet standard inclusion/exclusion criteria for an efficacy trial. A total of 803 individuals, aged 16--65 years, who were seen at intake at an outpatient practice underwent a thorough diagnostic evaluation, including the administration of semistructured diagnostic interviews; 346 patients had current major depression. Common inclusion/exclusion criteria used in efficacy studies of antidepressants were applied to the depressed patients to determine how many would have qualified for an efficacy trial. Approximately one-sixth of the 346 depressed patients would have been excluded from an efficacy trial because they had a bipolar or psychotic subtype of depression. The presence of a comorbid anxiety or substance use disorder, insufficient severity of depressive symptoms, or current suicidal ideation would have excluded 86.0% (N=252) of the remaining 293 outpatients with nonpsychotic unipolar major depressive disorder from an antidepressant efficacy trial. Subjects treated in antidepressant trials represent a minority of patients treated for major depression in routine clinical practice. These results show that antidepressant efficacy trials tend to evaluate a subset of depressed individuals with a specific clinical profile.