Low predictive power of clinical features for relapse prediction after antidepressant discontinuation in a naturalistic setting.
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ABSTRACT:
SUBMITTER: Berwian IM
PROVIDER: S-EPMC9249776 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The risk of relapsing into depression after stopping antidepressants is high, but no established predictors exist. Resting-state functional magnetic resonance imaging (rsfMRI) measures may help predict relapse and identify the mechanisms by which relapses occur. rsfMRI data were acquired from healthy controls and from patients with remitted major depressive disorder on antidepressants. Patients were assessed a second time either before or after discontinuation of the antidepressant, and followed up for six months to assess relapse. A seed-based functional connectivity analysis was conducted focusing on the left subgenual anterior cingulate cortex and left posterior cingulate cortex. Seeds in the amygdala and dorsolateral prefrontal cortex were explored. 44 healthy controls (age: 33.8 (10.5), 73% female) and 84 patients (age: 34.23 (10.8), 80% female) were included in the analysis. 29 patients went on to relapse and 38 remained well. The seed-based analysis showed that discontinuation resulted in an increased functional connectivity between the right dorsolateral prefrontal cortex and the parietal cortex in non-relapsers. In an exploratory analysis, this functional connectivity predicted relapse risk with a balanced accuracy of 0.86. Further seed-based analyses, however, failed to reveal differences in functional connectivity between patients and controls, between relapsers and non-relapsers before discontinuation and changes due to discontinuation independent of relapse. In conclusion, changes in the connectivity between the dorsolateral prefrontal cortex and the posterior default mode network were associated with and predictive of relapse after open-label antidepressant discontinuation. This finding requires replication in a larger dataset.
| S-EPMC7749105 | biostudies-literature
Project description: Not available
| S-EPMC10005929 | biostudies-literature
Project description:There is lack of research on effects of red wine on consciousness when drank in wine bars designed to enhance the pleasurableness of the wine drinking experience. Effects of a moderate dose of red wine (≈ 40.98 g of ethanol) on consciousness were examined in a naturalistic study taking place in a wine bar located in one of the most touristic areas of Lisbon, Portugal. One hundred two participants drank in one of three conditions: alone, in dyad, or in groups up to six people. Red wine increased pleasure and arousal, decreased the awareness of time, slowed the subjective passage of time, increased the attentional focus on the present moment, decreased body awareness, slowed thought speed, turned imagination more vivid, and made the environment become more fascinating. Red wine increased insightfulness and originality of thoughts, increased sensations of oneness with the environment, spiritual feelings, all-encompassing love, and profound peace. All changes in consciousness occurred regardless of volunteers drinking alone, in dyad or in group. Men and women did not report different changes in consciousness. Older age correlated with greater increases in pleasure. Younger age correlated with greater increases in fascination with the environment of the wine bar. Drinking wine in a contemporaneous Western environment designed to enhance the pleasurableness of the wine drinking experience may trigger changes in consciousness commonly associated with mystical-type states.
| S-EPMC8425548 | biostudies-literature
Project description:ImportanceNearly 1 in 3 patients with major depressive disorder who respond to antidepressants relapse within 6 months of treatment discontinuation. No predictors of relapse exist to guide clinical decision-making in this scenario.ObjectivesTo establish whether the decision to invest effort for rewards represents a persistent depression process after remission, predicts relapse after remission, and is affected by antidepressant discontinuation.Design, setting, and participantsThis longitudinal randomized observational prognostic study in a Swiss and German university setting collected data from July 1, 2015, to January 31, 2019, from 66 healthy controls and 123 patients in remission from major depressive disorder in response to antidepressants prior to and after discontinuation. Study recruitment took place until January 2018.ExposureDiscontinuation of antidepressants.Main outcomes and measuresRelapse during the 6 months after discontinuation. Choice and decision times on a task requiring participants to choose how much effort to exert for various amounts of reward and the mechanisms identified through parameters of a computational model.ResultsA total of 123 patients (mean [SD] age, 34.5 [11.2] years; 94 women [76%]) and 66 healthy controls (mean [SD] age, 34.6 [11.0] years; 49 women [74%]) were recruited. In the main subsample, mean (SD) decision times were slower for patients (n?=?74) compared with controls (n?=?34) (1.77 [0.38] seconds vs 1.61 [0.37] seconds; Cohen d?=?0.52; P?=?.02), particularly for those who later relapsed after discontinuation of antidepressants (n?=?21) compared with those who did not relapse (n?=?39) (1.95 [0.40] seconds vs 1.67 [0.34] seconds; Cohen d?=?0.77; P?<?.001). This slower decision time predicted relapse (accuracy?=?0.66; P?=?.007). Patients invested less effort than healthy controls for rewards (F1,98?=?33.970; P?<?.001). Computational modeling identified a mean (SD) deviation from standard drift-diffusion models that was more prominent for patients than controls (patients, 0.67 [1.56]; controls, -0.71 [1.93]; Cohen d?=?0.82; P?<?.001). Patients also showed higher mean (SD) effort sensitivity than controls (patients, 0.31 [0.92]; controls, -0.08 [1.03]; Cohen d?=?0.51; P?=?.05). Relapsers differed from nonrelapsers in terms of the evidence required to make a decision for the low-effort choice (mean [SD]: relapsers, 1.36 [0.35]; nonrelapsers, 1.17 [0.26]; Cohen d?=?0.65; P?=?.02). Group differences generally did not reach significance in the smaller replication sample (27 patients and 21 controls), but decision time prediction models from the main sample generalized to the replication sample (validation accuracy?=?0.71; P?=?.03).Conclusions and relevanceThis study found that the decision to invest effort was associated with prospective relapse risk after antidepressant discontinuation and may represent a persistent disease process in asymptomatic remitted major depressive disorder. Markers based on effort-related decision-making could potentially inform clinical decisions associated with antidepressant discontinuation.
| S-EPMC7042923 | biostudies-literature
Project description:Objectives To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy.Design Systematic review and meta-analyses of relapse prevention trials.Data sources PubMed, Cochrane, Embase, and clinical trial registers (from inception to July 2016).Study selection Eligible studies included patients with anxiety disorder who responded to antidepressants, randomised patients double blind to either continuing antidepressants or switching to placebo, and compared relapse rates or time to relapse.Data extraction Two independent raters selected studies and extracted data. Random effect models were used to estimate odds ratios for relapse, hazard ratios for time to relapse, and relapse prevalence per group. The effect of various categorical and continuous variables was explored with subgroup analyses and meta-regression analyses respectively. Bias was assessed using the Cochrane tool.Results The meta-analysis included 28 studies (n=5233) examining relapse with a maximum follow-up of one year. Across studies, risk of bias was considered low. Discontinuation increased the odds of relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89). Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies).Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients' preferences.
| S-EPMC5596392 | biostudies-literature
Project description:OBJECTIVE:To determine whether infants exposed in utero to serotonin reuptake inhibitor (SRI) antidepressants or a DSM-IV-TR-defined mood disorder have significantly more neonatal discontinuation signs compared to an unexposed group of infants at 2-4 weeks after birth. METHODS:This secondary analysis was derived from 2 observational studies with enrollment from July 2000 to December 2011 in Cleveland, Ohio, and Pittsburgh, Pennsylvania. Mothers (n = 214) belonged to one of 3 groups based on exposure status during pregnancy: (1) Comparison-women who did not take psychotropics during pregnancy and had no major mood disorder; (2) SRI-exposed-women with a mood disorder who were taking an SRI but no benzodiazepines; and (3) Mood Disorder-women with depression or bipolar disorder who did not take psychotropic medications. The infants were examined for signs according to the Finnegan Scale by evaluators blind to maternal exposure status. RESULTS:The rates of sign presence (defined as a score ? 2 on the Finnegan Scale) in the SRI, Mood Disorder, and Comparison groups were similar at 34.1%, 35.1%, and 30.4%, respectively. Women in the SRI group had a significantly higher preterm birth rate (24.4%) compared to the other 2 groups (7.4% and 8.9% in the Mood Disorder and Comparison groups, respectively; P = .012). Preterm newborns had a significantly higher sign rate compared to full-term newborns (54% vs 31%, P = .020). We observed a significant relationship between Finnegan signs and preterm birth. CONCLUSIONS:The presence of neonatal signs at 2-4 weeks was more closely associated with prematurity than with in utero SRI or mood disorder exposure. TRIAL REGISTRATION:ClinicalTrials.gov identifiers: NCT00279370 and NCT00585702.
| S-EPMC7087396 | biostudies-literature
Project description:The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker's goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption) of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance.
| S-EPMC4244599 | biostudies-literature
Project description:BackgroundAmong patients with Alzheimer's disease who have had a response to antipsychotic medication for psychosis or agitation-aggression, the risk of a recurrence of symptoms after discontinuation of the medication has not been established.MethodsPatients with Alzheimer's disease and psychosis or agitation-aggression received open-label treatment with risperidone for 16 weeks. Those who had a response to risperidone therapy were then randomly assigned, in a double-blind fashion, to one of three regimens: continued risperidone therapy for 32 weeks (group 1), risperidone therapy for 16 weeks followed by placebo for 16 weeks (group 2), or placebo for 32 weeks (group 3). The primary outcome was the time to relapse of psychosis or agitation.ResultsA total of 180 patients received open-label risperidone (mean dose, 0.97 mg daily). The severity of psychosis and agitation were reduced, although there was a mild increase in extrapyramidal signs; 112 patients met the criteria for response to treatment, of whom 110 underwent randomization. In the first 16 weeks after randomization, the rate of relapse was higher in the group that received placebo than in the groups that received risperidone (60% [24 of 40 patients in group 3] vs. 33% [23 of 70 in groups 1 and 2]; P=0.004; hazard ratio with placebo, 1.94; 95% confidence interval [CI], 1.09 to 3.45; P=0.02). During the next 16 weeks, the rate of relapse was higher in the group that was switched from risperidone to placebo than in the group that continued to receive risperidone (48% [13 of 27 patients in group 2] vs. 15% [2 of 13 in group 1]; P=0.02; hazard ratio, 4.88; 95% CI, 1.08 to 21.98; P=0.02). The rates of adverse events and death after randomization did not differ significantly among the groups, although comparisons were based on small numbers of patients, especially during the final 16 weeks.ConclusionsIn patients with Alzheimer's disease who had psychosis or agitation that had responded to risperidone therapy for 4 to 8 months, discontinuation of risperidone was associated with an increased risk of relapse. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00417482.).
| S-EPMC3490406 | biostudies-literature
Project description:BackgroundConditional power of network meta-analysis (NMA) can support the planning of randomized controlled trials (RCTs) assessing medical interventions. Conditional power is the probability that updating existing inconclusive evidence in NMA with additional trial(s) will result in conclusive evidence, given assumptions regarding trial design, anticipated effect sizes, or event probabilities.MethodsThe present work aimed to estimate conditional power for potential future trials on antidepressant treatments. Existing evidence was based on a published network of 502 RCTs conducted between 1979-2018 assessing acute antidepressant treatment in major depressive disorder (MDD). Primary outcomes were efficacy in terms of the symptom change on the Hamilton Depression Scale (HAMD) and tolerability in terms of the dropout rate due to adverse events. The network compares 21 antidepressants consisting of 231 relative treatment comparisons, 164 (efficacy) and 127 (tolerability) of which are currently assumed to have inconclusive evidence.ResultsRequired sample sizes to achieve new conclusive evidence with at least 80% conditional power were estimated to range between N = 894 - 4190 (efficacy) and N = 521 - 1246 (tolerability). Otherwise, sample sizes ranging between N = 49 - 485 (efficacy) and N = 40 - 320 (tolerability) may require stopping for futility based on a boundary at 20% conditional power. Optimizing trial designs by considering multiple trials that contribute both direct and indirect evidence, anticipating alternative effect sizes or alternative event probabilities, may increase conditional power but required sample sizes remain high. Antidepressants having the greatest conditional power associated with smallest required sample sizes were identified as those on which current evidence is low, i.e., clomipramine, levomilnacipran, milnacipran, nefazodone, and vilazodone, with respect to both outcomes.ConclusionsThe present results suggest that conditional power to achieve new conclusive evidence in ongoing or future trials on antidepressant treatments is low. Limiting the use of the presented conditional power analysis are primarily due to the estimated large sample sizes which would be required in future trials as well as due to the well-known small effect sizes in antidepressant treatments. These findings may inform researchers and decision-makers regarding the clinical relevance and justification of research in ongoing or future antidepressant RCTs in MDD.
| S-EPMC7934491 | biostudies-literature
Project description:Saliency-based models of visual attention postulate that, when a scene is freely viewed, attention is predominantly allocated to those elements that stand out in terms of their physical properties. However, eye-tracking studies have shown that saliency models fail to predict gaze behavior accurately when social information is included in an image. Notably, gaze pattern analyses revealed that depictions of human beings are heavily prioritized independent of their low-level physical saliency. What remains unknown, however, is whether the prioritization of such social features is a reflexive or a voluntary process. To investigate the early stages of social attention in more detail, participants viewed photographs of naturalistic scenes with and without social features (i.e., human heads or bodies) for 200 ms while their eye movements were being recorded. We observed significantly more first eye movements to regions containing social features than would be expected from a chance level distribution of saccades. Additionally, a generalized linear mixed model analysis revealed that the social content of a region better predicted first saccade direction than its saliency suggesting that social features partially override the impact of low-level physical saliency on gaze patterns. Given the brief image presentation time that precluded visual exploration, our results provide compelling evidence for a reflexive component in social attention. Moreover, the present study emphasizes the importance of considering social influences for a more coherent understanding of human attentional selection.
| S-EPMC5526566 | biostudies-other