Using an experimental medicine model to explore combination effects of pharmacological and cognitive interventions for depression and anxiety.
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ABSTRACT:
SUBMITTER: Browning M
PROVIDER: S-EPMC3214161 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Gray's theory of personality postulates that fear and anxiety are distinct emotional systems with only the latter being sensitive to anxiolytic drugs. His work was mainly based on animal research, and translational studies validating his theory are scarce. Previous work in humans showed an influence of the benzodiazepine lorazepam on both systems, however, dependent on dosage (1 and 2 mg) and personality differences in negative emotionality. The present study aims to replicate these findings, and in addition tests the drug threshold effect by introducing a lower dosage of 0.5 mg lorazepam. Fifty healthy adults (23 males, agemean 22.40, SD ± 3.68) participated in an experimental threat-avoidance paradigm designed to dissociate risk assessment intensity (RAI, reflecting anxiety) and flight intensity (FI, reflecting fear) and completed two self-report questionnaires assessing facets of negative emotionality (Spielberger State Trait Anxiety Inventory and Fear Survey Schedule). In a randomized placebo-controlled within-subjects design, 0.5 and 1 mg of lorazepam were applied per os. Saccadic peak velocity was assessed by means of eye-tracking in order to control for sedating drug effects. Results showed the expected and specific anxiolytic effect of lorazepam on RAI, however, only in the 0.5 mg condition. FI was not influenced by lorazepam, and previous findings of interaction effects of lorazepam with self-reported negative emotionality could not be corroborated. Overall, this study demonstrates anxiolytic effects of lorazepam in dosages ≤1 mg in the absence of a drug effect on fear using a translational behavioural task. However, a putative moderating role of personality on defensive behaviour has to be clarified in future research.
| S-EPMC7303801 | biostudies-literature
Project description:OBJECTIVE:To review the effectiveness of non-pharmacological interventions in older adults with depression or anxiety and comorbidities affecting functioning. DESIGN:Systematic review and meta-analysis of randomized controlled trials, including searches of 10 databases (inception-Jul 2017). SETTING:Home/community. PARTICIPANTS:People aged 60 and over experiencing functional difficulties from physical or cognitive comorbidities and have symptoms or a diagnosis of depression and/or anxiety. INTERVENTIONS:Non-pharmacological interventions targeted at depression/anxiety. MEASUREMENTS:We extracted outcome data on depressive symptoms, quality of life, functioning, and service use. We used random effects meta-analysis to pool study data where possible. Two authors assessed the risk of bias using the Cochrane Risk of Bias tool. RESULTS:We identified 14 eligible trials including 2099 randomized participants and two subgroup analyses. Problem-solving therapy (PST) reduced short-term clinician-rated depressive symptoms (n = 5 trials, mean difference in Hamilton Depression Rating Scale score -4.94 [95% CI -7.90 to -1.98]) but not remission, with limited evidence for effects on functioning and quality of life. There was limited high-quality evidence for other intervention types. Collaborative care did not appear to affect depressive symptoms, functioning, or quality of life; and had mixed evidence for effects upon remission. No intervention consistently affected service use, but trials were limited by small sample sizes and short follow-up periods. No anxiety interventions were identified. CONCLUSION:PST may reduce depressive symptoms post-intervention in older people with depression and functional impairments. Collaborative care appears to have few effects in this population. Future research needs to assess cost-effectiveness, long-term outcomes, and anxiety interventions for this population.
| S-EPMC6398582 | biostudies-literature
Project description:Objectives: To assess the published randomized controlled trials (RCT) of non-pharmacological interventions systematically and to synthesize the evidence of these interventions for the management of anxiety and depression in adults with inflammatory bowel disease (IBD). Background: Anxiety and depression are common symptoms in adults with IBD and can have many negative outcomes on their quality of life (QOL). Non-pharmacological interventions for anxiety and depression are important to improve the adaptive strategies of adults with IBD. Previously published reviews of non-pharmacological interventions to mitigate anxiety and depression in those with IBD have resulted in inconclusive evidence. This review is aimed to fill that gap. Design: Systematic review and meta-analysis. Method: Using a PRISMA diagram, English-language RCT published were searched using combined keywords of inflammatory bowel disease, Crohn's disease, ulcerative colitis, randomized controlled trial, anxiety, and depression. The Cochrane risk of bias tool is utilized to assess the methodological quality of each study. A meta-analysis of RCTs was conducted using Comprehensive Meta-Analysis (CMA) software. Results: The final review included 10 studies. The overall risk of bias of the selected studies varied from low risk in three studies, some concerns in four of the studies, and high risk of bias in three of the studies. Interventions included cognitive-behavioral therapy, mindfulness-based therapy, breath-body- mind -workshop, guided imagery with relaxation, solution-focused therapy, yoga, and multicomponent interventions. The pooled evidence from all non-pharmacological interventions showed that these interventions significantly helped to reduce anxiety, depression, and disease specific quality of life (QOL) in adults with IBD compared to control groups. However, the effect sizes are small. The pooled standardized mean difference (SMD) was -0.28 (95% CI [-0.47, -0.09], p = 0.004) for anxiety, -0.22 (95% CI [-0.41, -0.03], p = 0.025) for depression and 0.20 (95% CI [0.004, 0.39], p = 0.046) for disease specific QOL. Conclusion: The addressed non-pharmacological interventions were multifaceted and demonstrated positive effects on anxiety and depression, and QOL in those with IBD. Healthcare providers can facilitate a discussion with adults with IBD about the availability of these interventions to mitigate their anxiety and depression and to improve their QOL.
| S-EPMC7676293 | biostudies-literature
Project description:Social anxiety disorder is one of the most persistent and common anxiety disorders. Individually delivered psychological therapies are the most effective treatment options for adults with social anxiety disorder, but they are associated with high intervention costs. Therefore, the objective of this study was to assess the relative cost effectiveness of a variety of psychological and pharmacological interventions for adults with social anxiety disorder.A decision-analytic model was constructed to compare costs and quality adjusted life years (QALYs) of 28 interventions for social anxiety disorder from the perspective of the British National Health Service and personal social services. Efficacy data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published literature and national sources, supplemented by expert opinion.Individual cognitive therapy was the most cost-effective intervention for adults with social anxiety disorder, followed by generic individual cognitive behavioural therapy (CBT), phenelzine and book-based self-help without support. Other drugs, group-based psychological interventions and other individually delivered psychological interventions were less cost-effective. Results were influenced by limited evidence suggesting superiority of psychological interventions over drugs in retaining long-term effects. The analysis did not take into account side effects of drugs.Various forms of individually delivered CBT appear to be the most cost-effective options for the treatment of adults with social anxiety disorder. Consideration of side effects of drugs would only strengthen this conclusion, as it would improve even further the cost effectiveness of individually delivered CBT relative to phenelzine, which was the next most cost-effective option, due to the serious side effects associated with phenelzine. Further research needs to determine more accurately the long-term comparative benefits and harms of psychological and pharmacological interventions for social anxiety disorder and establish their relative cost effectiveness with greater certainty.
| S-EPMC4624770 | biostudies-literature
Project description: Not available
| S-EPMC8763347 | biostudies-literature
Project description:Palm grass (Curculigo recurvata) is an ethnomedicinally important herb reported to have significant medicinal values. The present study aimed to evaluate the antidepressant and anxiolytic activities of a methanol extract of C. recurvata rhizome (Me-RCR) through different approaches. The antidepressant and anxiolytic properties of Me-RCR were assessed by using elevated plus maze (EPM), hole-board (HBT), tail suspension (TST), and forced swimming (FST) tests in Swiss Albino mice. The in-depth antioxidative potential of Me-RCR was also evaluated through DPPH radical scavenging activity, ferric-reducing power capacity, total phenolic, flavonoid, flavonol, and antioxidant content analysis. Computational investigations were performed using computer-aided methods for screening the anxiolytic, antidepressant, and antioxidative activities of the selected lead molecules. Treatment with Me-RCR (200 and 400 mg/kg, b.w.) notably increased the number of open arm entries and the time spent in the EPM test. In the HBT, Me-RCR exhibited significant anxiolytic activity at a dose of 200 mg/kg, whereas similar activity was observed at 400 mg/kg in the EPM test. Me-RCR significantly decreased the immobility time in a dose-dependent manner in both TST and FST. The IC50 for DPPH and reducing power capacity assay were found to be 18.56 and 193 μg/mL, respectively. Promising outcomes were noted for the determination of total phenolics, flavonoids, flavonols, and antioxidant capacity. In the case of computer-aided studies, nyasicoside showed promising binding energy for antidepressant and anxiolytic activities, whereas isocurculigine demonstrated promising effects as an antioxidant. Overall, these findings suggest that Me-RCR could be a favourable therapeutic candidate for the treatment of mental and psychiatric disorders, as well as a good source of antioxidants.
| S-EPMC8546422 | biostudies-literature
Project description:There is increased interest in the development of cognitive training targeting working memory (WM) to alleviate anxiety symptoms, but the effectiveness of such an approach is unclear. Improved understanding of the effect of cognitive training on anxiety may facilitate the development of more effective cognitive training treatment for anxiety disorders. This study uses an experimental approach to examine the interplay of WM and anxiety following WM training. Previous studies show that increased demand on WM reduces concurrent anxiety evoked by threat of shock (induced anxiety). However, improving WM pharmacologically or via exercise prevents this anxiolytic effect. Conceivably, improving WM frees up cognitive resources to process threat information, thereby increasing anxiety. The present study tested the hypothesis that practicing a high load WM (i.e., increased demand) task would improve WM, and thus, free cognitive resources to process threat of shock, resulting in more anxiety (i.e., greater startle) during a subsequent WM task. Participants were randomly assigned to two training groups. The active-training group (N = 20) was trained on a 1- (low load) & 3-back (high load) WM task, whereas the control-training group (N = 20) performed a 0-back WM task. The experimental phase, similar in both groups, consisted of a 1- & 3-back WM task performed during both threat of shock and safety. As predicted, active training improved WM accuracy and increased anxiety during the experimental 3-back WM task. Therefore, improving WM efficiency can increase anxiety, possibly by freeing WM resources to process threat information.
| S-EPMC7437543 | biostudies-literature
Project description:BackgroundDepression occurs frequently in patients with coronary artery disease (CAD) and is associated with a poor prognosis.ObjectivesTo determine the effects of psychological and pharmacological interventions for depression in CAD patients with comorbid depression.Search strategyCENTRAL, DARE, HTA and EED on The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, ISRCTN Register and CardioSource Registry were searched. Reference lists of included randomised controlled trials (RCTs) were examined and primary authors contacted. No language restrictions were applied.Selection criteriaRCTs investigating psychological and pharmacological interventions for depression in adults with CAD and comorbid depression were included. Primary outcomes were depression, mortality and cardiac events. Secondary outcomes were healthcare costs and health-related quality of life (QoL).Data collection and analysisTwo reviewers independently examined the identified papers for inclusion and extracted data from included studies. Random effects model meta-analyses were performed to compute overall estimates of treatment outcomes.Main resultsThe database search identified 3,253 references. Sixteen trials fulfilled the inclusion criteria. Psychological interventions show a small beneficial effect on depression compared to usual care (range of SMD of depression scores across trials and time frames: -0.81;0.12). Based on one trial per outcome, no beneficial effects on mortality rates, cardiac events, cardiovascular hospitalizations and QoL were found, except for the psychosocial dimension of QoL. Furthermore, no differences on treatment outcomes were found between the varying psychological approaches. The review provides evidence of a small beneficial effect of pharmacological interventions with selective serotonin reuptake inhibitors (SSRIs) compared to placebo on depression outcomes (pooled SMD of short term depression change scores: -0.24 [-0.38,-0.09]; pooled OR of short term depression remission: 1.80 [1.18,2.74]). Based on one to three trials per outcome, no beneficial effects regarding mortality, cardiac events and QoL were found. Hospitalization rates (pooled OR of three trials: 0.58 [0.39,0.85] and emergency room visits (OR of one trial: 0.58 [0.34,1.00]) were reduced in trials of pharmacological interventions compared to placebo. No evidence of a superior effect of Paroxetine (SSRI) versus Nortriptyline (TCA) regarding depression outcomes was found in one trial.Authors' conclusionsPsychological interventions and pharmacological interventions with SSRIs may have a small yet clinically meaningful effect on depression outcomes in CAD patients. No beneficial effects on the reduction of mortality rates and cardiac events were found. Overall, however, the evidence is sparse due to the low number of high quality trials per outcome and the heterogeneity of examined populations and interventions.
| S-EPMC7389312 | biostudies-literature
Project description:BackgroundAnxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy.MethodsIn this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12.ResultsThe percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline.ConclusionsBoth cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.)
| S-EPMC2702984 | biostudies-literature
Project description:To mimic human mood disorders, traditional chronic stresses and social defeat stress have been developed and widely applied. However, these active stresses do not mimic the emotional flaws induced by stresses, and their input levels vary greatly. Also, emotional stresses resulting from social unobtainability remain largely elusive due to the lack of useful animal models. In this study, we developed a mouse model named "opposite sex contact and isolation" (OSCI) and found that OSCI induced significant social avoidance, anhedonia, and anxiety. These behavioral defects developed differently after 7 days of OSCI. The social avoidance behavior was self-curable while anxiety gradually worsened but was alleviated by re-pairing with the same female partner. Corresponding to the behavior changes, the plasma corticosterone and phosphorylated cAMP response element binding protein levels were decreased in the nucleus accumbens of the mice that experienced isolation. Together, this study has developed a novel strategy for depression/anxiety modeling and shows that OSCI may be a useful tool for studying the lovelorn/lovesick type of depression.
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