Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: what do we know and future vistas

References

• Exclusive: UK probes Novo’s Ozempic, weight-loss drug Saxenda over suicidal, self-harming thoughts. Reuters [Internet]. [updated 2023 Jul 26; cited 2024 Jan 29]. Available from: https://www.reuters.com/business/healthcare-pharmaceuticals/uk-probing-novos-ozempic-weight-loss-drug-saxenda-over-suicidal-self-harming-2023-07-26/
   Google Scholar
• EMA statement on ongoing review of GLP-1 receptor agonists [Internet]. [cited 2024 Jan 29]. Available from: https://www.ema.europa.eu/en/news/ema-statement-ongoing-review-glp-1-receptor-agonists
   Google Scholar
• Courcoulas AP, Daigle CR, Arterburn DE. Long term outcomes of metabolic/bariatric surgery in adults. BMJ. 2023;383:e071027. doi: 10.1136/bmj-2022-071027
   PubMedGoogle Scholar
• Ettaro R, Laudermilk L, Clark SD, et al. Behavioral assessment of rimonabant under acute and chronic conditions. Behav Brain Res. 2020;390:112697. doi: 10.1016/j.bbr.2020.112697
   PubMed Web of Science ®Google Scholar
• Thomas KH, Martin RM, Potokar J, et al. Reporting of drug induced depression and fatal and non-fatal suicidal behaviour in the UK from 1998 to 2011. BMC Pharmacol Toxicol. 2014;15(1):54. doi: 10.1186/2050-6511-15-54
   PubMedGoogle Scholar
• Christensen R, Kristensen PK, Bartels EM, et al. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370(9600):1706–1713. doi: 10.1016/S0140-6736(07)61721-8
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Paron E, Burrows M, et al. Psychiatric safety and weight loss efficacy of naltrexone/bupropion as add-on to antidepressant therapy in patients with obesity or overweight. J Affect Disord. 2021;289:167–176. doi: 10.1016/j.jad.2021.04.017
   PubMed Web of Science ®Google Scholar
• Shi Q, Wang Y, Hao Q, et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. Lancet. 2022;399(10321):259–269. doi: 10.1016/S0140-6736(21)01640-8
   PubMed Web of Science ®Google Scholar
• Frífrías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide Once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503–515. doi: 10.1056/NEJMoa2107519
   PubMed Web of Science ®Google Scholar
• Chen X, Zhao P, Wang W, et al. The antidepressant effects of GLP-1 receptor agonists: a systematic review and meta-analysis. Am J Geriatr Psychiatry. 2024;32(1):117–127. doi: 10.1016/j.jagp.2023.08.010
   PubMed Web of Science ®Google Scholar
• Cooper DH, Ramachandra R, Ceban F, et al. Glucagon-like peptide 1 (GLP-1) receptor agonists as a protective factor for incident depression in patients with diabetes mellitus: a systematic review. J Psychiatr Res. 2023;164:80–89. doi: 10.1016/j.jpsychires.2023.05.041
   PubMed Web of Science ®Google Scholar
• Mansur RB, Zugman A, Ahmed J, et al. Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders. Eur Neuropsychopharmacol. 2017;27(11):1153–1162. doi: 10.1016/j.euroneuro.2017.08.433
   PubMed Web of Science ®Google Scholar
• Cukierman-Yaffe T, Gerstein HC, Colhoun HM, et al. Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial. Lancet Neurol. 2020;19(7):582–590. doi: 10.1016/S1474-4422(20)30173-3
   PubMed Web of Science ®Google Scholar
• Victorino DB, Nejm M, Guimarães-Marques M, et al. Repurposing GLP-1 receptor agonists for Parkinson’s disease: current evidence and future opportunities. Pharmaceut Med. 2021;35(1):11–19. doi: 10.1007/s40290-020-00374-5
   PubMed Web of Science ®Google Scholar
• Leggio L, Hendershot CS, Farokhnia M, et al. GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders. Nat Med. 2023;29(12):2993–2995. doi: 10.1038/s41591-023-02634-8
   PubMedGoogle Scholar
• Chuong V, Farokhnia M, Khom S, et al. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023;8(12). Internet. Available from. doi: 10.1172/jci.insight.170671
   PubMed Web of Science ®Google Scholar
• Klausen MK, Jensen ME, Møller M, et al. Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight Internet. 2022;7(19). doi: 10.1172/jci.insight.159863
   PubMed Web of Science ®Google Scholar
• McGarry A, Rosanbalm S, Leinonen M, et al. Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2024;23(1):37–45. doi: 10.1016/S1474-4422(23)00378-2
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Mansur RB, Rosenblat JD, et al. The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the food and drug administration adverse event reporting system (FAERS). Expert Opin Drug Saf. 2023;23(1):47–55. doi: 10.1080/14740338.2023.2295397
   PubMed Web of Science ®Google Scholar
• Center for Drug Evaluation, Research. Update on FDA’s ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity [internet]. U.S. Food and Drug Administration. FDA; 2024 [cited 2024 Jan 29]. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type
   Google Scholar
• Wium-Andersen IK, Osler M, Jørgensen MB, et al. Diabetes, antidiabetic medications and risk of depression - a population-based cohort and nested case-control study. Psychoneuroendocrinology. 2022;140:105715. doi: 10.1016/j.psyneuen.2022.105715
   PubMed Web of Science ®Google Scholar
• Wang W, Volkow ND, Berger NA, et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med. 2024;30(1):168–176. doi: 10.1038/s41591-023-02672-2
   PubMedGoogle Scholar
• McIntyre RS, Kwan ATH, Rosenblat JD, et al. Psychotropic drug–related weight gain and its treatment. Am J Psychiatry. 2024;181(1):26–38. doi: 10.1176/appi.ajp.20230922
   PubMed Web of Science ®Google Scholar
• McElroy SL, Guerdjikova AI, Blom TJ, et al. Liraglutide in obese or overweight individuals with stable bipolar disorder. J Clin Psychopharmacol. 2024;44(2):89–95. InternetAvailable from doi: 10.1097/JCP.0000000000001803
   PubMed Web of Science ®Google Scholar
• Siskind D, Russell A, Gamble C, et al. Metabolic measures 12 months after a randomised controlled trial of treatment of clozapine associated obesity and diabetes with exenatide (CODEX). J Psychiatr Res. 2020;124:9–12. doi: 10.1016/j.jpsychires.2020.02.015
   PubMed Web of Science ®Google Scholar
• Mansur RB, Ahmed J, Cha DS, et al. Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: a pilot, open-label study. J Affect Disord. 2017;207:114–120. doi: 10.1016/j.jad.2016.09.056
   PubMed Web of Science ®Google Scholar
• O’Neil PM, Aroda VR, Astrup A, et al. Neuropsychiatric safety with liraglutide 3.0 mg for weight management: results from randomized controlled phase 2 and 3a trials. Diab Obes Metab. 2017;19(11):1529–1536. doi: 10.1111/dom.12963
   PubMed Web of Science ®Google Scholar
• Hill AB. The environment and disease: association or causation? 1965. J R Soc Med. 2015;108(1):32–37. doi: 10.1177/0141076814562718
   PubMed Web of Science ®Google Scholar
• Eren-Yazicioglu CY, Yigit A, Dogruoz RE, et al. Can GLP-1 Be a target for reward system related disorders? A qualitative synthesis and systematic review analysis of studies on palatable food, drugs of abuse, and alcohol. Front Behav Neurosci. 2020;14:614884. doi: 10.3389/fnbeh.2020.614884
   PubMed Web of Science ®Google Scholar
• Gillissie ES, Le GH, Rhee TG, et al. Evaluating anhedonia as a risk factor in suicidality: a meta-analysis. J Psychiatr Res. 2023;158:209–215. doi: 10.1016/j.jpsychires.2022.12.024
   PubMed Web of Science ®Google Scholar
• Lengvenyte A, Aouizerate B, Aubin V, et al. Violent suicide attempt history in elderly patients with bipolar disorder: the role of sex, abdominal obesity, and verbal memory: results from the FACE-BD cohort (Fonda Mental advanced center of expertise for bipolar disorders). J Affect Disord. 2022;296:265–276. doi: 10.1016/j.jad.2021.09.097
   PubMed Web of Science ®Google Scholar
• Jawad MY, Meshkat S, Tabassum A, et al. The bidirectional association of nonalcoholic fatty liver disease with depression, bipolar disorder, and schizophrenia. CNS Spectr. 2023;28(5):541–560. doi: 10.1017/S1092852922001043
   PubMed Web of Science ®Google Scholar
• Liu YK, Ling S, Lui LMW, et al. Prevalence of type 2 diabetes mellitus, impaired fasting glucose, general obesity, and abdominal obesity in patients with bipolar disorder: a systematic review and meta-analysis. J Affect Disord. 2022;300:449–461. doi: 10.1016/j.jad.2021.12.110
   PubMed Web of Science ®Google Scholar
• Haynes A, Kersbergen I, Sutin A, et al. Does perceived overweight increase risk of depressive symptoms and suicidality beyond objective weight status? A systematic review and meta-analysis. Clin Psychol Rev. 2019;73:101753. doi: 10.1016/j.cpr.2019.101753
   PubMed Web of Science ®Google Scholar
• Klinitzke G, Steinig J, Blüher M, et al. Obesity and suicide risk in adults—a systematic review. J Affect Disord. 2013;145(3):277–284. doi: 10.1016/j.jad.2012.07.010
   PubMed Web of Science ®Google Scholar
• Al Alshaikh L, Doherty AM. The relationship between diabetic ketoacidosis and suicidal or self-injurious behaviour: a systematic review. J Clin Transl Endocrinol. 2023;34:100325. doi: 10.1016/j.jcte.2023.100325
   PubMedGoogle Scholar
• Mann JJ, Michel CA, Auerbach RP. Improving suicide prevention through evidence-based strategies: a systematic review. Am J Psychiatry. 2021;178(7):611–624. doi: 10.1176/appi.ajp.2020.20060864
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Berk M, Brietzke E, et al. Bipolar disorders. Lancet. 2020;396(10265):1841–1856. doi: 10.1016/S0140-6736(20)31544-0
   PubMed Web of Science ®Google Scholar
• Bauer AM, Parker MM, Moffet HH, et al. Depressive symptoms and adherence to cardiometabolic therapies across phases of treatment among adults with diabetes: the diabetes study of northern california (DISTANCE). Patient Prefer Adherence. 2017;11:643–652. doi: 10.2147/PPA.S124181
   PubMed Web of Science ®Google Scholar
• Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606–613. doi: 10.1046/j.1525-1497.2001.016009606.x
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Patel MD, Masand PS, et al. The rapid mood screener (RMS): a novel and pragmatic screener for bipolar I disorder. Curr Med Res Opin. 2021 Jan;37(1):135–144. doi: 10.1080/03007995.2020.1860358. Epub 2021 Jan 6. PMID: 33300813.
   PubMed Web of Science ®Google Scholar
• Guo X, Lei M, Zhao J, et al. Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats. Front Pharmacol. 2023;14:1146960. doi: 10.3389/fphar.2023.1146960
   PubMed Web of Science ®Google Scholar