New drug candidates for depression – a nationwide population‐based study

Kessing, Lars Vedel; Rytgaard, Helene Charlotte; Gerds, Thomas Alexander; Berk, Michael; Ekstrøm, Claus Thorn; Andersen, Per Kragh

doi:10.1111/acps.12957

Cited by 65 publications

(90 citation statements)

References 48 publications

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“…Epidemiological studies suggest that people taking aspirin or statins might be less likely to have concurrent depression [26][27][28][29][30], although the evidence is inconsistent, with some negative reports [31]. While there are positive randomised controlled trials of statins for the treatment of depression [32][33][34], and meta-analytic evidence for their effectiveness [35], no studies have investigated their therapeutic potential among youth.…”

Section: Introductionmentioning

confidence: 99%

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

Berk

Mohebbi

Dean

et al. 2020

BMC Med

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Background: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and antiinflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years). Methods: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15-25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. Results: At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (− 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (− 4.2, 95% CI (− 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. Conclusions: The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.

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Section: Introductionmentioning

confidence: 99%

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

Berk

Mohebbi

Dean

et al. 2020

BMC Med

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“…As the majority of aspirin is used at low dose, the observed protective effect of aspirin on the studied disorders is likely driven by COX-1 inhibition. The null association of high-dose aspirin may on the other hand be due to additional inhibition of COX-2 [25]. In contrast, although non-aspirin NSAIDs have mixed selectivity, they are mostly selective for COX-2 inhibition or non-selective, possibly leading to the observed harmful effect of non-aspirin NSAIDs on these psychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

“…A recent meta-analysis of 26 relatively small randomized clinical trials suggested that NSAIDs play an antidepressant role in patients with major depressive disorder and are reasonably safe [ 24 ]. Preclinical studies indicate that the use of aspirin is associated with a lower risk of depression in the general population [ 25 ], and among patients with stroke [ 26 ] or osteoarthritis [ 27 ]. There is, however, a lack of evidence in this regard among cancer patients and on psychiatric disorders other than depression.…”

Section: Introductionmentioning

confidence: 99%

Aspirin and other non-steroidal anti-inflammatory drugs and depression, anxiety, and stress-related disorders following a cancer diagnosis: a nationwide register-based cohort study

Sjölander

et al. 2020

BMC Med

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Background Cancer patients have a highly increased risk of psychiatric disorders following diagnosis, compared with cancer-free individuals. Inflammation is involved in the development of both cancer and psychiatric disorders. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the subsequent risk of psychiatric disorders after cancer diagnosis is however unknown. Methods We performed a cohort study of all patients diagnosed with a first primary malignancy between July 2006 and December 2013 in Sweden. Cox proportional hazards models were used to assess the association of NSAID use during the year before cancer diagnosis with the risk of depression, anxiety, and stress-related disorders during the first year after cancer diagnosis. Results Among 316,904 patients identified, 5613 patients received a diagnosis of depression, anxiety, or stress-related disorders during the year after cancer diagnosis. Compared with no use of NSAIDs, the use of aspirin alone was associated with a lower rate of depression, anxiety, and stress-related disorders (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 to 0.97), whereas the use of non-aspirin NSAIDs alone was associated with a higher rate (HR, 1.24; 95% CI, 1.15 to 1.32), after adjustment for sociodemographic factors, comorbidity, indications for NSAID use, and cancer characteristics. The association of aspirin with reduced rate of depression, anxiety, and stress-related disorders was strongest for current use (HR, 0.84; 95% CI, 0.75 to 0.93), low-dose use (HR, 0.88; 95% CI, 0.80 to 0.98), long-term use (HR, 0.84; 95% CI, 0.76 to 0.94), and among patients with cardiovascular disease (HR, 0.81; 95% CI, 0.68 to 0.95) or breast cancer (HR, 0.74; 95% CI, 0.56 to 0.98). Conclusion Pre-diagnostic use of aspirin was associated with a decreased risk of depression, anxiety, and stress-related disorders during the first year following cancer diagnosis.

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“…Thus, we also detected the expression of inflammatory response-related genes, including COX-2, IL-1β, PGE2, and MCP-1. Cyclooxygenase enzymes are critical for the synthesis of prostaglandins and participate in the inflammatory response process [24]. A previous study found that COX-2 directly affects the function of the CNS serotonergic system via the inflammatory process, and a higher level of serotonin in the frontal and temporoparietal cortices was observed after administration of rofecoxib, a selective inhibi-tor of COX-2 [37], restoring the basic function of the CNS system.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA alleviates the damage of neurocytes by targeting GLUT1 in ischaemia reperfusion model (in vivo and in vitro experiments)

Wang

Tong

Wang

et al. 2020

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Stroke is partial or complete brain dysfunction combined with acute cerebral circulatory disorders, and it affects millions of individuals around the world each year. A total of 70-80% of patients experience ischaemic stroke caused by disturbances in cerebral circulation, leading to cerebral ischaemia, neuronal apoptosis, and necrosis. Tanshinone IIA is a natural compound extracted from Salvia miltiorrhiza and has been proven to assist in recovery from cerebral ischaemia reperfusion injury. GLUT1 is ubiquitously expressed in all types of tissues in the human body and has important physiological functions due to its glucose uptake ability. This experiment was performed to detect the effect of GLUT1 in promoting the therapeutic effect of tanshinone IIA. Here, we found that tanshinone IIA treatment increased the viability of neurons and promoted the recovery of brain function, and that the concentration of glucose in serum and cultured medium was also increased. We noticed that these effects might be mediated by an increased glucose uptake ability. In addition, we further found that the PI3K/mTOR/HER3 signalling pathway played an important role in regulating these effects. Thus, we thought that overexpression of GLUT1 might be an important target in the treatment of cerebral ischaemia-reperfusion.

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New drug candidates for depression – a nationwide population‐based study

Abstract: The findings support the potential of agents acting on inflammation and the stress response system in depression as well as the potential of population-based registers to systematically identify drugs with repurposing potential.

Cited by 65 publications

References 48 publications

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

Aspirin and other non-steroidal anti-inflammatory drugs and depression, anxiety, and stress-related disorders following a cancer diagnosis: a nationwide register-based cohort study

Tanshinone IIA alleviates the damage of neurocytes by targeting GLUT1 in ischaemia reperfusion model (in vivo and in vitro experiments)

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