Pharmacological Strategies for Targeting Residual Symptoms in Depression

Psychosocial Functioning ◽

Depressive Disorders ◽

Executive Dysfunction ◽

High Rate ◽

Residual Symptoms ◽

Increased Risk ◽

Symptom Remission ◽

Ultimate Objective ◽

Achieving full symptom remission in major depressive disorder (MDD) should be the ultimate objective in the treatment of depressed patients. However, antidepressant monotherapies have shown to have limited efficacy in the treatment of MDD, as evidenced by the relatively high rate of residual symptoms even among responders to antidepressant treatments. These symptoms, which include anxiety, irritability, insomnia, somnolence/fatigue, apathy, and cognitive and executive dysfunction, are associated with an increased risk of relapse and poor psychosocial functioning. Comprehensive clinical data are not yet available to guide management of these symptoms—whether residual or drug-related—in patients treated pharmacologically for depressive disorders. Suggested approaches to the management of residual symptoms include addressing treatment-emergent side effects and comorbid conditions, optimizing antidepressant dosing, and using augmentation therapies. In this chapter, we will review how best to assess residual symptoms and some of the preferred pharmacological strategies to address them.

Residual symptoms after remission of major depressive disorder with fluoxetine and risk of relapse

Depression and Anxiety ◽

10.1002/da.20768 ◽

2010 ◽

Vol 28 (2) ◽

pp. 137-144 ◽

Cited By ~ 47

Author(s):

Nadia Iovieno ◽

Adrienne van Nieuwenhuizen ◽

Alisabet Clain ◽

Lee Baer ◽

Andrew A. Nierenberg

Keyword(s):

Depressive Disorder ◽

Major Depressive ◽

Residual Symptoms ◽

The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals

10.1101/2020.06.23.20138271 ◽

2020 ◽

Author(s):

Rona J. Strawbridge ◽

Keira J. A. Johnston ◽

Mark E. S. Bailey ◽

Damiano Baldasarre ◽

Breda Cullen ◽

...

Keyword(s):

Bipolar Disorder ◽

Depressive Disorder ◽

Depressive Disorders ◽

Cardiometabolic Disease ◽

Metabolic Profiles ◽

Uk Biobank ◽

Major Depressive ◽

Increased Risk ◽

Chi Squared

AbstractUnderstanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researcher. We explored whether genetic variation could identify individuals with different metabolic profiles. Loci previously associated with schizophrenia, bipolar disorder and major depressive disorder were identified from literature and those overlapping loci genotyped on the Illumina CardioMetabo and Immuno chips (representing cardiometabolic processes and diseases) were selected. In the IMPROVE study (high cardiovascular risk) and UK Biobank (general population) multidimensional scaling was applied to genetic variants implicated in both mental and cardiometabolic illness. Visual inspection of the resulting plots used to identify distinct clusters. Differences between clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both cardiometabolic disease and schizophrenia (but not bipolar or major depressive disorders) identified three groups of individuals with distinct metabolic profiles. The grouping was replicated in UK Biobank, albeit with less distinction between metabolic profiles. This study provides proof of concept that common biology underlying mental and physical illness can identify subsets of individuals with different cardiometabolic profiles.

Predictors of Time to Relapse/Recurrence after Electroconvulsive Therapy in Patients with Major Depressive Disorder: A Population-Based Cohort Study

Depression Research and Treatment ◽

10.1155/2011/470985 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Axel Nordenskjöld ◽

Lars von Knorring ◽

Ingemar Engström

Keyword(s):

Depressive Disorder ◽

Electroconvulsive Therapy ◽

Substance Dependence ◽

Population Based ◽

Major Depressive ◽

Quality Register ◽

Increased Risk ◽

One Year ◽

Objective. The aim of the study is to define predictors of relapse/recurrence after electroconvulsive therapy, ECT, for patients with major depressive disorder.Methods. A study of all patients (n=486) treated by means of ECT for major depressive disorder was performed. The data were derived from a regional quality register in Sweden. Psychiatric hospitalisation or suicide was used as a marker for relapse/recurrence.Results. The relapse/recurrence rate within one year after ECT was 34%. Factors associated with increased risk of relapse/recurrence included comorbid substance dependence and treatment with benzodiazepines or antipsychotics during the follow-up period.Conclusions. Within the first years after ECT, relapses/recurrences leading to hospitalisation or suicide are common. Treatment with lithium might be beneficial, while benzodiazepines, antipsychotics, or continuation ECT does not seem to significantly reduce the risk of relapse/recurrence.

117 Impact of Antipsychotic Treatment Switching in Patients with Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

CNS Spectrums ◽

10.1017/s1092852920000358 ◽

2020 ◽

Vol 25 (2) ◽

pp. 276-276

Author(s):

Rajeev Ayyagari ◽

Darren Thomason ◽

Fan Mu ◽

Michael Philbin ◽

Benjamin Carroll

Keyword(s):

Bipolar Disorder ◽

Side Effects ◽

Depressive Disorder ◽

Antipsychotic Treatment ◽

Disease Relapse ◽

Major Depressive ◽

Study Objective ◽

Increased Risk ◽

Abstract:Study Objective:To evaluate the risk of relapse for patients with schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) who switched antipsychotics compared with those who did not switch.Background:Antipsychotics are commonly used for maintenance treatment of SZ, BP, and MDD but can have significant side effects, such as extrapyramidal symptoms (EPS). Adherence to treatment is important for reducing the risk of relapse, but fear of side effects may prompt medication switching.Methods:Medicaid claims from 6 US states spanning 6 years were retrospectively analyzed for antipsychotic switching versus non-switching. For all patients with SZ, BD or MDD and for the subset of patients who also had ≥1 EPS diagnosis during the baseline period, times to the following outcomes, during a 2-year study period were analyzed: underlying disease relapse, psychiatric relapse, all-cause emergency room (ER) visit, all-cause inpatient (IP) admission and EPS diagnosis.Results:Switchers (N=10,548) had a shorter time to disease relapse, other psychiatric relapse, IP admissions, ER visits, and EPS diagnosis (all, log-rank P<0.001) than non-switchers (N=31,644). Switchers reached the median for IP admission (21.50 months) vs non-switchers (not reached) and for ER visits (switchers, 9.07 months; non-switchers, 13.35 months). For disease relapse, other psychiatric relapse, and EPS diagnosis, <50% of patients had an event during the 2-year study period. Comparisons in a subgroup of patients with ≥1 EPS diagnosis revealed similar outcomes.Conclusions:These results show that disease and other psychiatric relapse, all-cause ER visits, IP admissions, and EPS diagnosis occurred earlier for switchers than for non-switchers, suggesting that switching is associated with an increased risk of relapse in patients with SZ, BP and MDD.Funding Acknowledgements:This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report

Psychological Medicine ◽

10.1017/s0033291709006011 ◽

2009 ◽

Vol 40 (1) ◽

pp. 41-50 ◽

Cited By ~ 218

Author(s):

A. A. Nierenberg ◽

M. M. Husain ◽

M. H. Trivedi ◽

M. Fava ◽

D. Warden ◽

...

Keyword(s):

Depressive Symptoms ◽

Side Effects ◽

Self Report ◽

Major Depressive ◽

Residual Symptom ◽

Residual Symptoms ◽

Symptom Domains ◽

BackgroundMany patients with major depressive disorder (MDD) who experience full symptomatic remission after antidepressant treatment still have residual depressive symptoms. We describe the types and frequency of residual depressive symptoms and their relationship to subsequent depressive relapse after treatment with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.MethodParticipants in primary (n=18) and psychiatric (n=23) practice settings were openly treated with citalopram using measurement-based care for up to 14 weeks and follow-up for up to 1 year. We assessed 943 (32.8% of 2876) participants who met criteria for remission to determine the proportions with individual residual symptoms and any of the nine DSM-IV criterion symptom domains to define a major depressive episode. At each visit, the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16) and the self-report Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale were used to assessed depressive symptoms and side-effects respectively.ResultsMore than 90% of remitters had at least one residual depressive symptom (median=3). The most common were weight increase (71.3%) and mid-nocturnal insomnia (54.9%). The most common residual symptom domains were sleep disturbance (71.7%) and appetite/weight disturbance (35.9%). Those who remitted before 6 weeks had fewer residual symptoms at study exit than did later remitters. Residual sleep disturbance did not predict relapse during follow-up. Having a greater number of residual symptom domains was associated with a higher probability of relapse.ConclusionsPatients with remission of MDD after treatment with citalopram continue to experience selected residual depressive symptoms, which increase the risk of relapse.

Profiles of Psychosocial and Clinical Functioning in Adolescence and Risk for Later Depression

10.31234/osf.io/umc2x ◽

2019 ◽

Author(s):

Thomas M Olino ◽

Daniel Klein ◽

John Seeley

Keyword(s):

Psychosocial Functioning ◽

Adolescent Depression ◽

Depressive Disorders ◽

Self Report ◽

Initial Assessment ◽

Predictive Utility ◽

Regression Methods ◽

History Of ◽

History Of Depression

Background: Most studies examining predictors of onset of depression focus on variable centered regression methods that focus on effects of multiple predictors. In contrast, person-centered approaches develop profiles of factors and these profiles can be examined as predictors of onset. Here, we developed profiles of adolescent psychosocial and clinical functioning among adolescents without a history of major depression. Methods: Data come from a subsample of participants from the Oregon Adolescent Depression Project who completed self-report measures of functioning in adolescence and completed diagnostic and self-report measures at follow-up assessments up to approximately 15 years after baseline. Results: We identified four profiles of psychosocial and clinical functioning: Thriving; Average Functioning; Externalizing Vulnerability and Family Stress; and Internalizing Vulnerability at the baseline assessment of participants without a history of depression at the initial assessment in mid- adolescence. Classes differed in the likelihood of onset and course of depressive disorders, experience of later anxiety and substance use disorders, and psychosocial functioning in adulthood. Moreover, the predictive utility of these classes was maintained when controlling for multiple other established risk factors for depressive disorders. Conclusions: This work highlights the utility of examining multiple factors simultaneously to understand risk for depression.

Psychological interventions as an alternative and add-on to antidepressant medication to prevent depressive relapse: systematic review and meta-analysis

The British Journal of Psychiatry ◽

10.1192/bjp.2020.198 ◽

2020 ◽

pp. 1-8

Author(s):

Josefien Johanna Froukje Breedvelt ◽

Maria Elisabeth Brouwer ◽

Mathias Harrer ◽

Maria Semkovska ◽

David Daniel Ebert ◽

...

Keyword(s):

Psychological Intervention ◽

Meta Analysis ◽

Antidepressant Medication ◽

Cochrane Library ◽

Psychological Interventions ◽

Relapse Risk ◽

Increased Risk ◽

Antidepressant Use ◽

Randomised Controlled ◽

Background After remission, antidepressants are often taken long term to prevent depressive relapse or recurrence. Whether psychological interventions can be a viable alternative or addition to antidepressants remains unclear. Aims To compare the effectiveness of psychological interventions as an alternative (including delivered when tapering antidepressants) or addition to antidepressants alone for preventing depressive relapse. Method Embase, PubMed, the Cochrane Library and PsycINFO were searched from inception until 13 October 2019. Randomised controlled trials (RCTs) with previously depressed patients in (partial) remission where preventive psychological interventions with or without antidepressants (including tapering) were compared with antidepressant control were included. Data were extracted independently from published trials. A random-effects meta-analysis on time to relapse (hazard ratio, HR) and risk of relapse (risk ratio, RR) at the last point of follow-up was conducted. PROSPERO ID: CRD42017055301. Results Among 11 included trials (n = 1559), we did not observe an increased risk of relapse for participants receiving a psychological intervention while tapering antidepressants versus antidepressants alone (RR = 1.02, 95% CI 0.84–1.25; P = 0.85). Psychological interventions added to antidepressants significantly reduced the risk of relapse (RR = 0.85, 95% CI 0.74–0.97; P = 0.01) compared with antidepressants alone. Conclusions This study found no evidence to suggest that adding a psychological intervention to tapering increases the risk of relapse when compared with antidepressants alone. Adding a psychological intervention to antidepressant use reduces relapse risk significantly versus antidepressants alone. As neither strategy is routinely implemented these findings are relevant for patients, clinicians and guideline developers.

The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals

Scientific Reports ◽

10.1038/s41598-020-79964-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rona J. Strawbridge ◽

Keira J. A. Johnston ◽

Mark E. S. Bailey ◽

Damiano Baldassarre ◽

Breda Cullen ◽

...

Keyword(s):

Bipolar Disorder ◽

Depressive Disorder ◽

European Ancestry ◽

Cardiometabolic Disease ◽

Metabolic Profiles ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Major Depressive ◽

Increased Risk

AbstractUnderstanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.

ECG-guided PICC insertion using a new silicon catheter with a conductive tip: A retrospective clinical study

The Journal of Vascular Access ◽

10.1177/11297298211002572 ◽

2021 ◽

pp. 112972982110025

Author(s):

Yu-Xia Yin ◽

Wei Gao ◽

Sheng-Yu Feng ◽

Deng-Xu Wang ◽

Min Wan ◽

...

Keyword(s):

Clinical Study ◽

Daily Practice ◽

Patient Characteristics ◽

Mobile App ◽

High Rate ◽

Exit Site Infection ◽

Increased Risk ◽

Retrospective Clinical Study ◽

Operation Rate ◽

Catheter Tip

Objective: Safety and efficacy of ECG-guided PICC insertion using a new silicon catheter with a conductive tip was evaluated in daily practice. Methods: A retrospective study was conducted on 1659 patients who accepted successful tip-conductive PICC placement and clinically followed-up until the catheter removal between January 2018 and April 2019. Baseline of patient characteristics, catheter placement characteristics, date of dressing changes as well as records of catheter-related complications were extracted from a special designed mobile APP. Results: The first-attempt success (success of placing catheter tip to the ideal position by primary indwelling operation) rate of PICC placement was 99.3%. The average duration of PICC placement was 128.7 ± 39.5 days and 1535 patients (92.5%) reached the therapy end-point without any complications and removed the catheter normally. The cumulative rates of total complications were 7.5%, including exit site infection (2.5%), phlebitis (0.9%), DVT (1.0%), catheter malposition (1.1%), catheter breakage (0.1%), and liquid extravasation (1.8%). In multivariable logistic regression analyses, hyperlipidemia, diabetes mellitus, lung cancer, stomach cancer, and lymphoma were significantly associated with increased risk of complications, as the independent risk factors. Conclusions: This retrospective clinical study demonstrates that ECG-guided insertion of a new tip-conductive PICC is associated with a high rate of first-attempt success and low rate of catheter related complications.

Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284821997352 ◽

2021 ◽

Vol 14 ◽

pp. 175628482199735

Author(s):

Steven Deitelzweig ◽

Allison Keshishian ◽

Amiee Kang ◽

Amol D. Dhamane ◽

Xuemei Luo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Proportional Hazards ◽

Bleeding Event ◽

Cox Proportional Hazards ◽

High Rate ◽

Gi Bleeding ◽

Increased Risk ◽

Gi Bleed

Background: Gastrointestinal (GI) bleeding is the most common type of major bleeding associated with oral anticoagulant (OAC) treatment. Patients with major bleeding are at an increased risk of a stroke if an OAC is not reinitiated. Methods: Non-valvular atrial fibrillation (NVAF) patients initiating OACs were identified from the Centers for Medicare and Medicaid Services ( CMS) Medicare data and four US commercial claims databases. Patients who had a major GI bleeding event (hospitalization with primary diagnosis of GI bleeding) while on an OAC were selected. A control cohort of patients without a major GI bleed during OAC treatment was matched to major GI bleeding patients using propensity scores. Stroke/systemic embolism (SE), major bleeding, and mortality (in the CMS population) were examined using Cox proportional hazards models with robust sandwich estimates. Results: A total of 15,888 patients with major GI bleeding and 833,052 patients without major GI bleeding were included in the study. Within 90 days of the major GI bleed, 58% of patients discontinued the initial OAC treatment. Patients with a major GI bleed had a higher risk of stroke/SE [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.42–1.74], major bleeding (HR: 2.79, 95% CI: 2.64–2.95), and all-cause mortality (HR: 1.29, 95% CI: 1.23–1.36) than patients without a major GI bleed. Conclusion: Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.