A systematic review of the antidepressant effects of glucagon-like peptide 1 (GLP-1) functional agonists: Further link between metabolism and psychopathology: Special Section on “Translational and Neuroscience Studies in Affective Disorders”. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

Marco Pozzi, Faizan Mazhar, Gabriëlla G.A.M. Peeters, Chiara Vantaggiato, Maria Nobile, Emilio Clementi, Sonia Radice, Carla Carnovale

Research output: Contribution to journalArticle

Abstract

Introduction: An increasing amount of preclinical and clinical evidence links together metabolic regulations and psychopathological mechanisms, in particular linking mood disorders with changes in Glycogen Synthase Kinase 3 beta and 5′Adenosine Monophosphate-activated Protein Kinase expression and activity. New hypoglycemic drugs, including thiazolidinediones and glucagon-like peptide 1 (GLP-1) functional agonists, which work by these mechanisms, have also been described as potential antidepressants. The putative role of thiazolidinediones in depression has been already supported, but no clear evidence exists yet for GLP-1 functional agonists. We conducted a systematic review and meta-analysis of the literature to describe the effect of GLP-1 functional agonists on depression rating scales and either support or confute a potential antidepressant role. Methods: We searched the PubMed and Scopus databases for terms related to DPP-4 inhibitors and GLP-1 receptor agonists, and depression, including symptoms and rating scales with acronyms and full names. We included longitudinal interventional and observational studies on GLP-1 functional agonists used for depression symptoms. We applied a random effects meta-analysis on standardized mean differences before-after treatment, comparing GLP-1 functional agonists versus control treatments. Results: Literature searches found 815 papers, 8 of which were eligible for meta-analysis. Both control treatments (-0.67, 95%C.I. -0.99 – -0.36, Z = 4.24, p < 0.0001) and GLP-1 functional agonists (-1.28, 95%C.I. -2.34 – -0.21, Z = 2.35, p = 0.02) resulted in a significant reduction of depression rating scores, although GLP-1 functional agonists tended to be superior. When a selection was made, including only studies conducted on diabetic patients that did not exclude depressed patients, the effect of GLP-1 functional agonists (-2.09, 95%C.I. -2.28 – -1.91, Z = 22.5, p < 0.00001) was significantly superior to that of control treatments (-0.57, 95%C.I. -0.66 – -0.49, Z = 13.6, p < 0.00001). Discussion: Results of this meta-analysis must be carefully considered, since the amount of studies available was low and heterogeneity was high. If further trials will confirm this hypothesis, GLP-1 functional agonists may be considered as antidepressants, either as adjuncts or in mono-therapy, with a peculiar value for preventing the adverse metabolic effects of long-term antipsychotic therapies used in rehabilitation.

Original languageEnglish
Pages (from-to)774-778
Number of pages5
JournalJournal of Affective Disorders
Volume257
DOIs
Publication statusPublished - Oct 1 2019

Fingerprint

Glucagon-Like Peptide 1
Neurosciences
Anxiety Disorders
Psychopathology
Mood Disorders
Antidepressive Agents
Research
Meta-Analysis
Depression
Thiazolidinediones
Therapeutics
Hypoglycemic Agents
PubMed
Protein Kinases
Antipsychotic Agents
Names
Observational Studies
Longitudinal Studies
Rehabilitation
Databases

Keywords

  • Antidepressants
  • Antipsychotics
  • DPP-4
  • GLP-1
  • Hypoglycemic agents

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

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title = "A systematic review of the antidepressant effects of glucagon-like peptide 1 (GLP-1) functional agonists: Further link between metabolism and psychopathology: Special Section on “Translational and Neuroscience Studies in Affective Disorders”. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.",
abstract = "Introduction: An increasing amount of preclinical and clinical evidence links together metabolic regulations and psychopathological mechanisms, in particular linking mood disorders with changes in Glycogen Synthase Kinase 3 beta and 5′Adenosine Monophosphate-activated Protein Kinase expression and activity. New hypoglycemic drugs, including thiazolidinediones and glucagon-like peptide 1 (GLP-1) functional agonists, which work by these mechanisms, have also been described as potential antidepressants. The putative role of thiazolidinediones in depression has been already supported, but no clear evidence exists yet for GLP-1 functional agonists. We conducted a systematic review and meta-analysis of the literature to describe the effect of GLP-1 functional agonists on depression rating scales and either support or confute a potential antidepressant role. Methods: We searched the PubMed and Scopus databases for terms related to DPP-4 inhibitors and GLP-1 receptor agonists, and depression, including symptoms and rating scales with acronyms and full names. We included longitudinal interventional and observational studies on GLP-1 functional agonists used for depression symptoms. We applied a random effects meta-analysis on standardized mean differences before-after treatment, comparing GLP-1 functional agonists versus control treatments. Results: Literature searches found 815 papers, 8 of which were eligible for meta-analysis. Both control treatments (-0.67, 95{\%}C.I. -0.99 – -0.36, Z = 4.24, p < 0.0001) and GLP-1 functional agonists (-1.28, 95{\%}C.I. -2.34 – -0.21, Z = 2.35, p = 0.02) resulted in a significant reduction of depression rating scores, although GLP-1 functional agonists tended to be superior. When a selection was made, including only studies conducted on diabetic patients that did not exclude depressed patients, the effect of GLP-1 functional agonists (-2.09, 95{\%}C.I. -2.28 – -1.91, Z = 22.5, p < 0.00001) was significantly superior to that of control treatments (-0.57, 95{\%}C.I. -0.66 – -0.49, Z = 13.6, p < 0.00001). Discussion: Results of this meta-analysis must be carefully considered, since the amount of studies available was low and heterogeneity was high. If further trials will confirm this hypothesis, GLP-1 functional agonists may be considered as antidepressants, either as adjuncts or in mono-therapy, with a peculiar value for preventing the adverse metabolic effects of long-term antipsychotic therapies used in rehabilitation.",
keywords = "Antidepressants, Antipsychotics, DPP-4, GLP-1, Hypoglycemic agents",
author = "Marco Pozzi and Faizan Mazhar and Peeters, {Gabri{\"e}lla G.A.M.} and Chiara Vantaggiato and Maria Nobile and Emilio Clementi and Sonia Radice and Carla Carnovale",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.jad.2019.05.044",
language = "English",
volume = "257",
pages = "774--778",
journal = "Journal of Affective Disorders",
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TY - JOUR

T1 - A systematic review of the antidepressant effects of glucagon-like peptide 1 (GLP-1) functional agonists

T2 - Further link between metabolism and psychopathology: Special Section on “Translational and Neuroscience Studies in Affective Disorders”. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

AU - Pozzi, Marco

AU - Mazhar, Faizan

AU - Peeters, Gabriëlla G.A.M.

AU - Vantaggiato, Chiara

AU - Nobile, Maria

AU - Clementi, Emilio

AU - Radice, Sonia

AU - Carnovale, Carla

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Introduction: An increasing amount of preclinical and clinical evidence links together metabolic regulations and psychopathological mechanisms, in particular linking mood disorders with changes in Glycogen Synthase Kinase 3 beta and 5′Adenosine Monophosphate-activated Protein Kinase expression and activity. New hypoglycemic drugs, including thiazolidinediones and glucagon-like peptide 1 (GLP-1) functional agonists, which work by these mechanisms, have also been described as potential antidepressants. The putative role of thiazolidinediones in depression has been already supported, but no clear evidence exists yet for GLP-1 functional agonists. We conducted a systematic review and meta-analysis of the literature to describe the effect of GLP-1 functional agonists on depression rating scales and either support or confute a potential antidepressant role. Methods: We searched the PubMed and Scopus databases for terms related to DPP-4 inhibitors and GLP-1 receptor agonists, and depression, including symptoms and rating scales with acronyms and full names. We included longitudinal interventional and observational studies on GLP-1 functional agonists used for depression symptoms. We applied a random effects meta-analysis on standardized mean differences before-after treatment, comparing GLP-1 functional agonists versus control treatments. Results: Literature searches found 815 papers, 8 of which were eligible for meta-analysis. Both control treatments (-0.67, 95%C.I. -0.99 – -0.36, Z = 4.24, p < 0.0001) and GLP-1 functional agonists (-1.28, 95%C.I. -2.34 – -0.21, Z = 2.35, p = 0.02) resulted in a significant reduction of depression rating scores, although GLP-1 functional agonists tended to be superior. When a selection was made, including only studies conducted on diabetic patients that did not exclude depressed patients, the effect of GLP-1 functional agonists (-2.09, 95%C.I. -2.28 – -1.91, Z = 22.5, p < 0.00001) was significantly superior to that of control treatments (-0.57, 95%C.I. -0.66 – -0.49, Z = 13.6, p < 0.00001). Discussion: Results of this meta-analysis must be carefully considered, since the amount of studies available was low and heterogeneity was high. If further trials will confirm this hypothesis, GLP-1 functional agonists may be considered as antidepressants, either as adjuncts or in mono-therapy, with a peculiar value for preventing the adverse metabolic effects of long-term antipsychotic therapies used in rehabilitation.

AB - Introduction: An increasing amount of preclinical and clinical evidence links together metabolic regulations and psychopathological mechanisms, in particular linking mood disorders with changes in Glycogen Synthase Kinase 3 beta and 5′Adenosine Monophosphate-activated Protein Kinase expression and activity. New hypoglycemic drugs, including thiazolidinediones and glucagon-like peptide 1 (GLP-1) functional agonists, which work by these mechanisms, have also been described as potential antidepressants. The putative role of thiazolidinediones in depression has been already supported, but no clear evidence exists yet for GLP-1 functional agonists. We conducted a systematic review and meta-analysis of the literature to describe the effect of GLP-1 functional agonists on depression rating scales and either support or confute a potential antidepressant role. Methods: We searched the PubMed and Scopus databases for terms related to DPP-4 inhibitors and GLP-1 receptor agonists, and depression, including symptoms and rating scales with acronyms and full names. We included longitudinal interventional and observational studies on GLP-1 functional agonists used for depression symptoms. We applied a random effects meta-analysis on standardized mean differences before-after treatment, comparing GLP-1 functional agonists versus control treatments. Results: Literature searches found 815 papers, 8 of which were eligible for meta-analysis. Both control treatments (-0.67, 95%C.I. -0.99 – -0.36, Z = 4.24, p < 0.0001) and GLP-1 functional agonists (-1.28, 95%C.I. -2.34 – -0.21, Z = 2.35, p = 0.02) resulted in a significant reduction of depression rating scores, although GLP-1 functional agonists tended to be superior. When a selection was made, including only studies conducted on diabetic patients that did not exclude depressed patients, the effect of GLP-1 functional agonists (-2.09, 95%C.I. -2.28 – -1.91, Z = 22.5, p < 0.00001) was significantly superior to that of control treatments (-0.57, 95%C.I. -0.66 – -0.49, Z = 13.6, p < 0.00001). Discussion: Results of this meta-analysis must be carefully considered, since the amount of studies available was low and heterogeneity was high. If further trials will confirm this hypothesis, GLP-1 functional agonists may be considered as antidepressants, either as adjuncts or in mono-therapy, with a peculiar value for preventing the adverse metabolic effects of long-term antipsychotic therapies used in rehabilitation.

KW - Antidepressants

KW - Antipsychotics

KW - DPP-4

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KW - Hypoglycemic agents

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