Retraction Note: The Antidiabetic Metformin as an Adjunct to Antidepressants in Patients with Major Depressive Disorder: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Abdallah, Mahmoud S.; Mosalam, Esraa M.; Zidan, Abdel‐Aziz A.; Elattar, Khaled S.; Zaki, Shimaa A.; Ramadan, Ahmed Nabil; Ebeid, Abla M.

doi:10.1007/s13311-022-01291-y

Cited by 3 publications

(2 citation statements)

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“…In a recent placebo-controlled study of patients with treatment-resistant bipolar depression, those treated with metformin showed a significant improvement in depressive symptoms and global functioning 39 . A double-blind placebo-controlled study in patients with major depressive disorder demonstrated that 12 weeks of metformin treatment improved the antidepressant effects of fluoxetine compared with placebo 40 . A Swedish population-based study also observed an 80% reduction in psychiatric hospitalizations, and a 73% reduction in self-harm in bipolar disorder patients with exposed to metformin compared to those not exposed to metformin 41 .…”

Section: Discussionmentioning

confidence: 99%

Metformin is Protective Against the Development of Mood Disorders

et al. 2022

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Introduction Mood disorders are a major cause of disability, and current treatment options are inadequate for reducing the burden on a global scale. The aim of this project was to identify drugs suitable for repurposing to treat mood disorders. Methods This mixed-method study utilized gene expression signature technology and pharmacoepidemiology to investigate drugs that may be suitable for repurposing to treat mood disorders. Results The transcriptional effects of a combination of drugs commonly used to treat mood disorders included regulation of the steroid and terpenoid backbone biosynthesis pathways, suggesting a mechanism involving cholesterol biosynthesis, and effects on the thyroid hormone signaling pathway. Connectivity Map analysis highlighted metformin, an FDA-approved treatment for type 2 diabetes, as a drug having global transcriptional effects similar to the mood disorder drug combination investigated. In a retrospective cohort study, we found evidence that metformin is protective against the onset of mood disorders. Discussion These results provide proof-of-principle of combining gene expression signature technology with pharmacoepidemiology to identify potential novel drugs for treating mood disorders. Importantly, metformin may have utility in the treatment of mood disorders, warranting future randomized controlled trials to test its efficacy.

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Section: Discussionmentioning

confidence: 99%

Metformin is Protective Against the Development of Mood Disorders

et al. 2022

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“…The combination of metformin (glucose lowering, insulinsensitizing) and fluoxetine (selective serotonin reuptake inhibitor) was superior to placebo plus fluoxetine on the HAMD in a phase 1/2 trial (NCT04088448) 105 . Finally, transdermal estradiol plus inter mittent micronized progesterone (NCT01308 814) was more efficacious than placebo in preventing the development of clinically significant depressive symptoms among ini tially euthymic perimenopausal and early postmenopausal women in a phase 2/3 study 106 .…”

Section: Major Depressive Disordermentioning

confidence: 99%

The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de‐risk trial programmes of novel agents

et al. 2023

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Despite considerable progress in pharmacotherapy over the past seven decades, many mental disorders remain insufficiently treated. This situation is in part due to the limited knowledge of the pathophysiology of these disorders and the lack of biological markers to stratify and individualize patient selection, but also to a still restricted number of mechanisms of action being targeted in monotherapy or combination/augmentation treatment, as well as to a variety of challenges threatening the successful development and testing of new drugs. In this paper, we first provide an overview of the most promising drugs with innovative mechanisms of action that are undergoing phase 2 or 3 testing for schizophrenia, bipolar disorder, major depressive disorder, anxiety and trauma‐related disorders, substance use disorders, and dementia. Promising repurposing of established medications for new psychiatric indications, as well as variations in the modulation of dopamine, noradrenaline and serotonin receptor functioning, are also considered. We then critically discuss the clinical trial parameters that need to be considered in depth when developing and testing new pharmacological agents for the treatment of mental disorders. Hurdles and perils threatening success of new drug development and testing include inadequacy and imprecision of inclusion/exclusion criteria and ratings, sub‐optimally suited clinical trial participants, multiple factors contributing to a large/increasing placebo effect, and problems with statistical analyses. This information should be considered in order to de‐risk trial programmes of novel agents or known agents for novel psychiatric indications, increasing their chances of success.

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