Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial

Savitz, Jonathan; Preskorn, Sheldon; Teague, T. Kent; Drevets, Douglas A.; Yates, William R.; Drevets, Wayne

doi:10.1136/bmjopen-2011-000643

Cited by 69 publications

(46 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Contradictory to the above, aspirin treatment in the CMS group for about 28 days showed noteworthy antidepressant effect through the rise in sucrose preference, brain serotonin levels and decline in serum cortisol and immobility in the CMS group treated with aspirin. These findings are in agreement with the observations seen in previous studies which focus on the positive effect of aspirin in affective disorders [55,56].…”

Section: Discussionsupporting

confidence: 83%

Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats

Bhatt

Shukla

Raval

et al. 2016

Basic Clin Pharma Tox

View full text Add to dashboard Cite

A large number of current studies indicate that inflammatory mediators may contribute to depression in experimental models as well as in human beings. Nevertheless, the subject, whether anti-inflammatory treatments can prevent depression still remains controversial. In the present study, a chronic mild stress (CMS) model of male Sprague Dawley rats was used to investigate the role of anti-inflammatory drugs in the treatment of depression. All the animals in different groups, except the normal control group, were exposed to CMS procedure for 28 days and concurrently treated with aspirin (10 mg/kg, p.o.), dexamethasone (1 mg/kg p.o.) and amitriptyline (10 mg/kg p.o., reference standard), respectively. Amitriptyline was also used in combination with aspirin and dexamethasone to inspect any synergistic effects. Tests performed towards the end of the study included sucrose preference test, behavioural tests like forced swim test, elevated plus-maze, light/dark box, locomotor activity and biochemical estimations like serum cortisol and brain neurotransmitters. Disease control group (CMS-treated) produced significant depressive behaviour in rats. The animals treated with aspirin showed increased sucrose preference, decreased immobility time in forced swim test, decreased serum cortisol and increased brain serotonin levels signifying antidepressant action. In contrast, there was aggravation of depressive behaviour in rats treated with dexamethasone. Together, these findings suggest that aspirin can serve as a potential antidepressant both individually and as adjunctive agent in the treatment of depression. Inhibition of the inflammatory mediators during stress procedures or any other potential physiological and biochemical mechanisms may be involved in its antidepressant effect.Major depression is one of the most commonly diagnosed neuropsychiatric disorders, with a worldwide life-time prevalence of 17%. It is estimated that by 2020, major depression will be the second most disabling condition in the world. Despite considerable strides have been made over the years, treatment-resistant depression (TRD) remains a common condition which accounts for approximately 30% of the depressed population [1,2]. Historically, treatment options for depression and associated disorders have focused on the medications that modify the activity of monoamine neurotransmitter systems [3].Several studies support the role of inflammation and immune system deregulation in pathophysiology of depression [4,5]. Patients with major depression have been found to exhibit all of the vital features of inflammation, including elevation of inflammatory cytokines, acute phase proteins, chemokines, adhesion molecules and inflammatory mediators such as prostaglandins. Repeated administration of IL-1, TNF-a and IL-6 elicits depressive-like behaviour in animals [6][7][8]. The mechanisms contributing to pathogenesis of depression incorporate abnormal neurotransmitter metabolism, altered neuro-endocrine functions and distorted neural plasticity [9,10...

show abstract

Section: Discussionsupporting

confidence: 83%

Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats

Bhatt

Shukla

Raval

et al. 2016

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…Regarding the statistical power and sample size, meta-analysis of 96 antidepressant treatment studies found a calculated effect size of 0.81, with an 80% probability. Based on effect sizes, a sample size of 26 subjects per group was required [27,28]. Furthermore, meta-analysis studies for serum-derived IL-6 depression calculated effect sizes were 0.71 for IL-6.…”

Section: Discussionmentioning

confidence: 99%

The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

El-Haggar

Eissa

Mostafa

et al. 2018

Psychother Psychosom

View full text Add to dashboard Cite

Background: There is evidence for an association between major depressive disorder (MDD) and both inflammatory and phosphodiesterase (PDE) pathways. This study aimed to evaluate the adjunct role of the PDE inhibitor pentoxifylline (PTX), a compound with anti-inflammatory properties, in the treatment of adult patients with MDD. Methods: This was a prospective, 12-week, double-blind study of parallel groups. Eighty adult outpatients who met the DSM-IV criteria for MDD participated in the trial. Patients were required to have a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 18. Patients were allocated randomly: 40 received escitalopram 20 mg/day plus placebo while the other 40 received escitalopram 20 mg/day plus PTX (400 mg b.i.d.). Patients were assessed by a psychiatrist at baseline, and 4, 8, and 12 weeks after the medication had been started. The serum levels of TNF-α, IL-6, IL-10, BDNF, 8-OHdG, and serotonin were measured at baseline and after therapy. Results: After 8 and 12 weeks, the PTX group showed a statistically significantly greater improvement in HAM-D score compared to the control group (least squares mean difference [LSMD] –3.29, p = 0.000 and LSMD –3.49, p = 0.000, respectively). Moreover, the PTX group showed a statistically significantly greater reduction in the serum levels of TNF-α, IL-6, IL-10, and 8-OHdG along with a statistically significant increase in the levels of BDNF and serotonin in comparison with the control group after the treatment. Conclusion: The findings of this study suggest that PTX could be a promising adjunct to antidepressants in the treatment of MDD patients.

show abstract

“…In a treatment-intervention study of 70 patients with depression, administration of aspirin together with fluoxetine conferred a greater reduction of OS parameters compared with fluoxetine monotherapy [132]. Another randomized controlled clinical trial is currently underway to investigate the potential benefits of aspirin as an adjunctive treatment in bipolar depression [133]. …”

Section: Role Of Aspirin In Mood Disorders; Clinical Datamentioning

confidence: 99%

Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness

Berk

Dean

Drexhage

et al. 2013

BMC Med

177

105

View full text Add to dashboard Cite

There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor-α and interleukin (IL)--6, but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.

show abstract

Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial

Cited by 69 publications

References 98 publications

Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats

Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats

The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness

Contact Info

Product

Resources

About