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. 2024 May 24:15:1381523.
doi: 10.3389/fphar.2024.1381523. eCollection 2024.

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

Khlood Mohammad Aldossary  1 , Lashin Saad Ali  2   3 , Mahmoud S Abdallah  4   5 , Mostafa M Bahaa  6 , Thanaa A Elmasry  7 , Eman I Elberri  8 , Fedaa A Kotkata  8 , Ramy M El Sabaa  9 , Yasmine M Elmorsi  8 , Mostafa M Kamel  10 , Walaa A Negm  11 , Aya Ibrahim Elberri  12 , Amir O Hamouda  13 , Hayam Ali AlRasheed  1 , Muhammed M Salahuddin  13 , Mohamed Yasser  14   15 , Manal A Hamouda  9
Affiliations

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

Khlood Mohammad Aldossary et al. Front Pharmacol. .

Erratum in

Abstract

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.

Keywords: NLRP-3; STAT-3; atorvastatin; major depressive disorder; neuroinflammation.

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Conflict of interest statement

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.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram showing flow chart of the patient participation.
See this image and copyright information in PMC

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