Baseline In Depressive Symptoms Research Articles

Schema therapy versus treatment as usual for outpatients with difficult-to-treat depression: study protocol for a parallel group randomized clinical trial (DEPRE-ST)

BackgroundAbout one third of patients with depression are in a condition that can be termed as “difficult-to-treat”. Some evidence suggests that difficult-to-treat depression is associated with a higher frequency of childhood trauma and comorbid personality disorders or accentuated features. However, the condition is understudied, and the effects of psychotherapy for difficult-to-treat depression are currently uncertain. The aim of this trial is to investigate the beneficial and harmful effects of 30 sessions of individual schema therapy versus treatment as usual for difficult-to-treat depression in the Danish secondary, public mental health sector.MethodsIn this randomized, multi-centre, parallel-group, superiority clinical trial, 129 outpatients with difficult-to-treat depression will be randomized (1:1) to 30 sessions of individual schema therapy or treatment as usual; in this context mainly group-based, short-term cognitive behaviour or psychodynamic therapy. The primary outcome is the change from baseline in depressive symptoms 12 months after randomization, measured on the observer-rated 6-item Hamilton Rating Scale for Depression. The secondary outcomes are health-related quality of life assessed with the European Quality of Life 5 Dimensions 5 Level Version, functional impairment assessed with the Work and Social Adjustment Scale, psychological wellbeing assessed with the WHO-5 Well-being Index, and negative effects of treatment assessed with the Negative Effects Questionnaire. Exploratory outcomes are improvement on patient self-defined outcomes, personal recovery, anxiety symptoms, anger reactions, metacognitive beliefs about anger, and perseverative negative thinking. Outcomes will be assessed at 6, 12, and 24 months after randomization; the 12-month time-point being the primary time-point of interest. Outcome assessors performing the depression-rating, data managers, statisticians, the data safety and monitoring committee, and conclusion makers for the outcome article will be blinded to treatment allocation and results. To assess cost-effectiveness of the intervention, a health economic analysis will be performed.DiscussionThis trial will provide evidence on the beneficial and harmful effects, as well as the cost-effectiveness of schema therapy versus treatment as usual for outpatients with difficult-to-treat depression. The results can potentially improve treatment for a large and understudied patient group.Trial registrationClinicalTrials.gov NCT05833087. Registered on 15th April 2023 (approved without prompts for revision on 27th April 2023).

Psilocybin-Assisted Therapy Found to Improve Depression, Offer Other Benefits

Back to table of contents Previous article Next article Clinical & ResearchFull AccessPsilocybin-Assisted Therapy Found to Improve Depression, Offer Other BenefitsRichard KarelRichard KarelSearch for more papers by this authorPublished Online:23 May 2022https://doi.org/10.1176/appi.pn.2022.06.6.30AbstractA small study involving 24 participants found that psilocybin therapy was safe and effective up to one year following administration. More research using larger sample sizes is needed to further clarify efficacy and safety.A study on the safety and efficacy of psilocybin-assisted therapy in a therapeutic setting in 24 participants with major depressive disorder found that the hallucinogen provided rapid and substantial antidepressant effects lasting up to one year with no serious adverse effects. The long-term efficacy and safety of such treatment, however, are not known.The study, conducted by researchers at the Johns Hopkins Center for Psychedelic and Consciousness Research (CPCR) in the Department of Psychiatry and Behavioral Sciences in Baltimore, was published in February in the Journal of Psychopharmacology and augments research previously published in JAMA Psychiatry.The 24 participants were randomized to either an immediate or eight-week delayed treatment protocol, involving a combination of psilocybin sessions and supportive psychotherapy. Each participant received two doses of psilocybin and were followed for up to a year.The types of features that the researchers asked about in their study on psilocybin-assisted therapy, such as personal meaning and spiritual significance, did not predict patients’ magnitude of depression, says Natalie Gukasyan, M.D.Lead author Natalie Gukasyan, M.D., an assistant professor of psychiatry and behavioral sciences at Hopkins and medical director of the CPCR, and colleagues reported “large decreases from baseline using the standardized Hamilton Depression Rating Scale (GRID-HAMD) scores at one, three, six, and 12-month follow-up.” The principal investigator was Roland Griffiths, Ph.D., director of the CPCR.At 12 months, 75% of the 24 participants achieved “treatment response”—defined as a reduction of 50% or greater in GRID-HAMD score from baseline; 58% of the participants achieved remission—defined as a GRID-HAMD score less than or equal to 7. Self-reported measures, including the Quick Inventory of Depressive Symptomatology (QIDS) and the Beck Depression Inventory II (BDI-II), were consistent with the GRID-HAMD outcomes.One intriguing finding was that “participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months but did not predict improvement in depression.”The researchers employed the 30-item revised Mystical Experience Questionnaire (MEQ30) to evaluate spiritual and mystical experience. The instrument was developed from a survey of mystical-type experiences associated with the use of psilocybin. In a study explaining the MEQ30 published in 2015 in the Journal of Psychopharmacology, mystical experiences were defined as having a number of dimensions, including unity, sacredness, noetic quality (in this context, a sense of revelation hard to verbalize), ineffability, positive mood, and transcendence of time and space—with the authors emphasizing that a totality of these dimensions must occur to qualify as a complete mystical experience. The authors of that study further noted that “mystical experience is not conceptually limited to religious experience or practice. ...”The finding of a divergence between remission or improvement in major depression and self-reported well-being “is a somewhat counterintuitive part of our results,” Gukasyan commented. The research team was focused on determining which acute drug effects were helpful in predicting depression, she noted. Many studies of psilocybin-assisted therapy—including those whose participants had symptoms of anxiety and depression secondary to a terminal cancer diagnosis—have found that subjective ratings such as mystical experience were correlated with longer-term changes from baseline in depressive symptoms, Gukasyan said.“The important thing to understand about well-being scores is that they are not changes from baseline, but rather absolute scores taken at follow-up time points derived from a questionnaire that asks where participants continue to experience persisting changes in their well-being that they attribute to the psilocybin therapy,” Gukasyan added. “Taken together, these results suggest that the types of features we asked about—personal meaning, spiritual significance, mystical experience, and so on—did not help us predict magnitude of depression.”The finding may indicate that there are quality of life elements that are improved in people with major depression after psilocybin therapy that are not captured by depression severity scores in the GRID-HAMD and similar measures, she observed. This is an area that needs further exploration using instruments that better measure how well-being changes from baseline following psilocybin therapy, she said.Psychiatrist Charles Grob, M.D., a professor of psychiatry and biobehavioral sciences and pediatrics at the David Geffen School of Medicine at UCLA, has studied the therapeutic utility of psychedelic drugs for decades. The new Hopkins study “furthers the growing interest in the potential safety and utility of the psychedelic treatment model as an alternative—albeit novel—psycho-spiritual therapy and will likely catalyze future studies that examine even longer post-treatment time spans in order to measure the full durability of psilocybin treatment,” Grob told Psychiatric News.The divergence between self-reported findings of enhanced personal meaning and spirituality versus antidepressant measures requires further study to better understand the significance of the data, Grob said. ■ Resources“Efficacy and Safety of Psilocybin-Assisted Treatment for Major Depressive Disorder: Prospective 12-Month Follow-Up”“Psilocybin Treatment for Major Depression Effective for Up to a Year for Most Patients, Study Shows””Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder”“Validation of the Revised Mystical Experience Questionnaire in Experimental Sessions With Psilocybin” ISSUES NewArchived

Goal Management Training and Computerized Cognitive Training in Depression-a 2-Year Follow-Up of a Randomized Controlled Trial.

Objective: Information on the long-term effects of cognitive remediation (CR) in major depressive disorder (MDD) is lacking. The present study reports 2-year follow-up data from a previously published randomized controlled trial (RCT) from our research group, comparing Goal Management Training (GMT), a strategy-based CR intervention, to drill-and-practice computerized cognitive training (CCT). In previous work, we found comparable improvements in executive function (EF), in addition to reductions in depressive symptoms, following both GMT and CCT at 6-month follow-up.Methods: Forty-two participants of the RCT, all diagnosed with MDD, were invited to complete rating-scales pertaining daily-life EF, rumination, and depressive symptoms. Explorative analyses compared the 2-year follow-up with previously published baseline and 6-month follow-up data, using non-parametric statistics. Similarly, GMT and CCT were compared at the 2-year follow-up, and completers were compared with non-completers.Results: Twenty participants completed the study. Overall, completers (n = 20) and non-completers (n = 22) were similar. There were no significant differences between GMT (n = 11) and CCT (n = 9) for any outcome 2 years post-treatment. Reduction compared to baseline in depressive symptoms and rumination, but not in daily-life EFs, emerged for GMT only.Conclusions: Findings suggest long-term improvements in mental health following GMT, while improvements in everyday EFs might require additional treatment or maintenance to sustain. Caution is warranted in the interpretation due to the small sample size and high attrition rates.

Antidepressive Effect of Antipsychotics in the Treatment of Schizophrenia: Meta-Regression Analysis of Randomized Placebo-Controlled Trials.

BackgroundAntipsychotics improve the positive symptoms of schizophrenia. However, little is known about the extent of antidepressive effects of antipsychotics and their correlation with effects on other symptom domains in schizophrenia. The aim was to investigate whether antidepressive effects of antipsychotics have a significant correlation with the effects on specific symptom domains of schizophrenia.MethodsElectronic databases were searched to identify eligible studies that reported antidepressive effects of antipsychotics for the treatment of adult patients with schizophrenia in double-blind, randomized placebo-controlled trials (RCTs). Mean change from baseline in depressive symptoms was meta-analyzed, and the correlation with the effects on other symptom domains was examined through meta-regression analysis.ResultsThirty-five RCTs (13 890 patients) were included in this meta-analysis. Overall, antipsychotics showed greater efficacy than placebo in reducing depressive symptoms, with small to medium effect sizes (standardized mean difference = −0.27, 95% confidence interval −0.32 to −0.22, P < .001). All the antipsychotics, except for chlorpromazine, haloperidol, and ziprasidone, were associated with significantly greater decreases in depressive symptoms compared with placebo (standardized mean difference = −0.19 to −0.40). A higher antidepressive effect was significantly correlated with a higher improvement in Positive and Negative Syndrome Scale/Brief Psychiatric Rating Scale total, positive, and negative, and Positive and Negative Syndrome Scale-general psychopathology symptoms (β = .618, P < .001; β = .476, P < .001; β = .689, P < .001; β = .603, P < .001, respectively).ConclusionsSecond-generation antipsychotics (except for ziprasidone) were associated with small to medium effects sizes on improvement in depressive symptoms among adult patients with schizophrenia. The antidepressive effect of antipsychotics was significantly correlated with improvement in other symptom domains, with the highest correlation observed for improvement in negative symptoms.PROSPERO registration numberCRD42019133015

Cognitive-behavioral treatment with behavioral activation for smokers with depressive symptomatology: study protocol of a randomized controlled trial

BackgroundSmoking is an important risk factor for mental health-related problems. Numerous studies have supported a bi-directional association between cigarette smoking and depression. Despite the advances in understanding the comorbidity between both problems, the most effective psychological treatment that simultaneously targets smoking and depressive symptomatology remains unclear. The objective of this study is to assess the effectiveness of a cognitive-behavioral intervention for smoking cessation with components of behavioral activation for managing depressed mood.MethodA single blind, three-arm, superiority randomized controlled trial is proposed. Participants will be smokers over 18 years old, who smoke at least 8 cigarettes per day. Participants will be randomized to one of three conditions, using a 2:2:1 allocation ratio: 1) standard cognitive-behavioral smoking cessation treatment; 2) standard cognitive-behavioral smoking cessation treatment plus behavioral activation; or 3) a three-month delayed treatment control group. The primary outcome measures will be biochemically verified point-prevalence abstinence (carbon monoxide in expired air) and significant change from baseline in depressive symptoms to the end of treatment, and at the 3-, 6-, and 12-month follow-up.DiscussionThis study aims to assess the efficacy of a cognitive-behavioral intervention with behavioral activation components for smoking cessation and depressive symptoms, compared to a standard cognitive-behavioral intervention to quit smoking. As the relation between depressive symptoms, even at subclinical levels, and quitting smoking difficulties is well known, we expect that such intervention will allow obtaining higher abstinence rates, lower relapse rates, and mood improvement.Trial registrationClinicalTrials.gov: NCT02844595. Retrospectively registered 19th July, 2016. The study started in January 2016, and the recruitment is ongoing.

Association between oncologists’ dispositional affect and depressive symptoms in their patients with metastatic cancer.

214 Background: While caring for patients with metastatic cancer can be emotional, relationships between the emotions of oncologists and their patients have not been examined. As patients and oncologists read emotional cues in encounters, emotions of one or both may impact the other. We explored associations between dispositional affect, tendencies to emotionally respond to situations in certain ways, in oncologists and depressive symptoms in their patients with newly diagnosed metastatic lung and gastrointestinal (GI) cancers. Methods: As part of an ongoing trial of early palliative care, participants were assessed at baseline for depressive symptoms (Patient Health Questionnaire-9, PHQ9) within 8 weeks of diagnosis with metastatic lung and GI cancers. Oncologists providing care for these patients completed the Positive and Negative Affect Scale (PANAS), a validated measure of dispositional affect with positive and negative dimensions. Associations between patient depressive symptoms and oncologists' positive and negative dispositional affect were tested with linear regression models. Results: Sixteen of the 18 oncologists with patients in the trial completed the PANAS. Among 323 participants with baseline assessments, 277 (86%) had oncologists who completed the PANAS. Mean age=64.6, 129 (46%) were female, 159 (57%) had GI and 118 (43%) lung cancer, and mean PHQ9 score=6.5. Positive and negative dispositional affect were not associated with oncologists’ sex, years from training, hours in clinic, and cancer specialization. Patient depressive symptoms were significantly higher if their oncologists reported greater negative dispositional affect (p=.04). The relationship remained significant adjusting for patient age, sex, cancer type, ECOG PS, smoking, and number of oncology visits (β=.13, t=2.1, p=.04). PHQ9 scores were not associated with oncologists’ positive dispositional affect. Conclusions: Depressive symptoms in patients with metastatic lung and GI cancers appear to be associated with their oncologists’ negative dispositional affect. Determining the direction of the association may lead to new ways of improving patients and/or oncologists moods.

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study

BackgroundAn adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised serotonergic brain signaling. Here, we modeled a biphasic ovarian sex hormone fluctuation using a gonadotropin-releasing hormone agonist (GnRHa) and evaluated if emergence of depressive symptoms was associated with change in cerebral serotonin transporter (SERT) binding following intervention. MethodsA double-blind, randomized, placebo-controlled study included 63 healthy female volunteers (mean age 24.3 ± 4.9 years) with regular menstrual cycles between 23 and 35 days. Participants were randomized to active (goserelin [GnRHa] 3.6 mg implant) or placebo intervention. Sixty women completed follow-up and entered the analyses. Primary outcome measures were changes from baseline in depressive symptoms assessed on the 17-item Hamilton Depression Rating Scale and SERT binding as imaged by [11C]DASB positron emission tomography. Outcome measures were acquired at baseline in the follicular phase (cycle day 6.6 ± 2.2) and at follow-up (16.2 ± 2.6 days after intervention start). ResultsSex hormone manipulation with GnRHa significantly triggered subclinical depressive symptoms within-group (p = .003) and relative to placebo (p = .02), which were positively associated with net decreases in estradiol levels (p = .02) from baseline within the GnRHa group. Depressive symptoms were associated with increases in neocortical SERT binding in the GnRHa group relative to placebo (p = .003). ConclusionsOur data imply both serotonergic signaling and estradiol in the mechanisms by which sex-steroid hormone fluctuations provoke depressive symptoms and thus provide a rationale for future preventive strategies in high-risk groups.

A double-blind, placebo-controlled study of selegiline transdermal system in depressed adolescents.

A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12-17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features. Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156). Two hundred and fifteen (69.8%) subjects completed the study and 17 (5.5%) reported discontinuation because of adverse events (AEs). The primary efficacy outcome measure was the mean change from baseline to end of study (week 12 last observation carried forward [LOCF]) in the Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary outcome measures included end-point Clinical Global Impressions - Severity (CGI-S) and Clinical Global Impressions - Improvement (CGI-I). Patients on STS or placebo had a significant decline from baseline (p<0.001) on their CDRS-R total score with mean reductions±SD as follows: STS 21.4±16.6; placebo 21.5±16.5. Both groups had similar response rates (58.6% vs. 59.3%) defined as CGI-I of 1 or 2 at study end. However, these between-group efficacy findings were without statistical significance. The overall incidence of reported AEs was 62.5% for STS-treated patients and 57.7% for placebo-treated patients. Most commonly reported AEs in STS or placebo groups were application site reactions (STS=24.3%; placebo=21.8%), headache (STS=17.1%; placebo=16.7%), and nausea (STS=7.2%; placebo=7.7%). Treatment groups did not differ on any laboratory parameters, vital signs, or electrocardiogram (ECG) findings. No suspected hypertensive crises were reported in the trial. These data demonstrated that the STS was safe and well tolerated in this adolescent sample. However, both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms (CDRS-R total score) over the length of the study, without statistical superiority by either group.

A three-year follow-up on the efficacy of psychosocial interventions for patients with mild dementia and their caregivers: the multicentre, rater-blinded, randomised Danish Alzheimer Intervention Study (DAISY)

ObjectivesTo examine the long-term efficacy at the 36-month follow-up of an early psychosocial counselling and support programme lasting 8–12 months for community-dwelling patients with mild Alzheimer's disease and their caregivers.DesignMulticentre,...

Association between depression and hospital outcomes among older men

Studies that have investigated the relation between depression and the type, nature, extent and outcome of general hospital admissions have been limited by their retrospective designs and focus on specific clinical populations. We explored this relation prospectively in a large, community-based sample of older men. A cohort of 5411 men aged 69 years and older enrolled in the Health in Men Study was assessed at baseline for depressive symptoms, defined as a score of 7 or higher on the 15-item Geriatric Depression Scale. Participants were followed for 2 years for occurrence and number of hospital admissions, type of hospital admission, length of hospital stay and inpatient death as recorded in the Western Australian Data Linkage System. Of 339 men with depressive symptoms, 152 (44.8%) had at least 1 emergency hospital admission, compared with 1164 of 5072 (22.9%) nondepressed men (p < 0.001). In multivariate analyses, the presence of depressive symptoms was a significant independent predictor of hospital admission (hazard ratio 1.67, 95% confidence interval [CI] 1.38-2.01), number of hospital admissions (incidence rate ratio [IRR] 1.22, 95% CI 1.07-1.39) and total length of hospital stay (IRR 1.65, 95% CI 1.36-2.01). Participants with depressive symptoms were at higher risk of hospital admission for nonpsychiatric conditions and were more likely to have longer hospital stays and worse hospital outcomes, compared with nondepressed participants. These results highlight the potential to target this high-risk group to reduce the burden of health care costs in an aging population.

Vilazodone

Vilazodone, a novel antidepressant agent that combines selective serotonin reuptake inhibitor (SSRI) activity and serotonin 5-HT(1A) receptor partial agonist activity in a single molecule, is indicated for the treatment of major depressive disorder (MDD) in the US. It is administered orally, once daily, with food. At the recommended dosage of 40 mg/day, vilazodone was effective in the short-term treatment of MDD in adults, as evidenced by significant improvements versus placebo on multiple measures of depression, including the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-item Hamilton Rating Scale for Depression (HAM-D-17), in two pivotal, 8-week, randomized, double-blind, phase III studies. Significant differences between vilazodone and placebo on the MADRS and HAM-D-17 were seen after 1 week of treatment (first efficacy timepoint) in one of the two studies. Long-term treatment with vilazodone 40 mg/day was associated with an improvement from baseline in depressive symptoms in a 52-week, noncompar-ative, phase III study. Vilazodone was generally well tolerated in the short- and long-term treatment of MDD, with diarrhoea and nausea being the most frequently occurring treatment-emergent adverse events. Vilazodone had a minimal impact on sexual functioning in the three phase III studies.

Double-Blind, Randomized, Placebo-Controlled Trials of Ethyl-Eicosapentanoate in the Treatment of Bipolar Depression and Rapid Cycling Bipolar Disorder

The results of pilot trials suggest that omega-3 fatty acids may have efficacy in the treatment of mood symptoms in bipolar disorder. We conducted a 4-month, randomized, placebo-controlled, adjunctive trial of ethyl-eicosapentanoate (EPA) 6 g/day in the treatment of bipolar depression and rapid cycling bipolar disorder. Subjects were receiving mood-stabilizing medications at therapeutic doses or plasma concentrations. The measures of efficacy were early study discontinuation, changes from baseline in depressive symptoms (Inventory for Depressive Symptomology total score) and in manic symptoms (Young Mania Rating Scale total score), and manic exacerbations ("switches"). We also measured side effects and bleeding time, a biomarker of drug action. Overall, there were no significant differences on any outcome measure between the EPA and placebo groups. This study did not find overall evidence of efficacy for adjunctive treatment with EPA 6 g/day in outpatients with bipolar depression or rapid cycling bipolar disorder.