Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study.

Autor:	Aldossary KM; Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia., Ali LS; Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman, Jordan.; Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Abdallah MS; Department of Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City (USC), Sadat City, Menoufia, Egypt.; Department of PharmD, Faculty of Pharmacy, Jadara University, Irbid, Jordan., Bahaa MM; Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt., Elmasry TA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt., Elberri EI; Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt., Kotkata FA; Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt., El Sabaa RM; Department of Clinical Pharmacy, Faculty of Pharmacy, Menoufia University, Shebin El-Kom, Menoufia, Egypt., Elmorsi YM; Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt., Kamel MM; Psychiatry Department, Faculty of Medicine, Tanta University, Egypt., Negm WA; Pharmacognosy Department, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt., Elberri AI; Genetic Engineering and Molecular Biology Division, Department of Zoology, Faculty of Science, Menoufia University, Shebin El-Kom, Menoufia, Egypt., Hamouda AO; Department of Biochemistry and Pharmacology, Faculty of Pharmacy, Horus University, New Damietta, Egypt., AlRasheed HA; Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia., Salahuddin MM; Department of Biochemistry and Pharmacology, Faculty of Pharmacy, Horus University, New Damietta, Egypt., Yasser M; Department of Pharmaceutics, Faculty of Pharmacy, Port Said University, Port Said, Egypt.; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Horus University, New Damietta, Egypt., Hamouda MA; Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 May 24; Vol. 15, pp. 1381523. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1381523
Abstrakt:	Background: Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression. Aim: To investigate the mechanistic pathways of high dose atorvastatin in MDD. Patients and Methods: This trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured. Results: The atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine ( p = 0.03, and p = 0.005), respectively. Conclusion: These results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3. Clinical Trial Registration: clinicaltrials.gov, identifier NCT05792540. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Aldossary, Ali, Abdallah, Bahaa, Elmasry, Elberri, Kotkata, El Sabaa, Elmorsi, Kamel, Negm, Elberri, Hamouda, AlRasheed, Salahuddin, Yasser and Hamouda.)
Databáze:	MEDLINE
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