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
KW - GLP-1
KW - Hypoglycemic agents
UR - http://www.scopus.com/inward/record.url?scp=85070957913&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070957913&partnerID=8YFLogxK
U2 - 10.1016/j.jad.2019.05.044
DO - 10.1016/j.jad.2019.05.044
M3 - Article
C2 - 31153593
AN - SCOPUS:85070957913
VL - 257
SP - 774
EP - 778
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
SN - 0165-0327
ER -