{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:47:50Z","timestamp":1789469270587,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Major depressive disorder (MDD) has frequently been associated with inflammation; however, the relationship between antidepressant-related side effects and inflammatory markers remains unclear. This study investigated the associations of antidepressant side effects with the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-HDL ratio (MHR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), white blood cell (WBC) count, and C-reactive protein (CRP). Methods: The study included 60 patients aged 18\u201365 years who met DSM-5 criteria for MDD, had used antidepressants for at least one month, and developed side effects, together with 60 sociodemographically matched healthy controls. Complete blood count (CBC), CRP, and HDL levels were measured from venous blood samples, and NLR, MHR, MLR, and PLR were calculated. Patients completed the Udvalg Kliniske Unders\u00f8gelser (UKU) Side Effect Rating Scale, Clinical Global Impression Scale, Montgomery\u2013\u00c5sberg Depression Rating Scale (MADRS), and Hamilton Anxiety Scale (HAM-A). Only side effects considered medication-related according to the UKU causality assessment were included. Analyses were performed using SPSS 24.0. Results: Concentration problems correlated negatively with neutrophil levels and NLR. Sedation\/drowsiness correlated positively with MHR and MLR, and increased dreaming correlated positively with platelet levels. Weight gain correlated positively with neutrophil, lymphocyte, and WBC counts and negatively with PLR. Erectile dysfunction correlated negatively with PLR, orgasmic dysfunction with monocyte levels, vaginal dryness with neutrophil levels, and physical dependence with NLR. Conclusions: Antidepressant-related side effects showed several uncorrected associations with peripheral inflammatory markers, none of which survived correction for multiple comparisons (Benjamini\u2013Hochberg false discovery rate). As the first exploratory investigation of this relationship, these preliminary, hypothesis-generating findings may inform understanding of side-effect mechanisms and support future, adequately powered longitudinal studies aimed at enhancing treatment adherence and reducing relapse and chronicity.<\/jats:p>","DOI":"10.3390\/jcm15187160","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:31:57Z","timestamp":1789464717000},"page":"7160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Markers Associated with Antidepressant-Related Side Effects in Patients with Major Depressive Disorder: A Cross-Sectional Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2221-2894","authenticated-orcid":false,"given":"Ezgi","family":"\u00c7ankaya \u0130nan","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Defne State Hospital, 31000 Hatay, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Mahmut","family":"Bulut","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Dicle University, 21280 Diyarbak\u0131r, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6428-1097","authenticated-orcid":false,"given":"Bet\u00fcl","family":"Uyar","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, Dicle University, 21280 Diyarbak\u0131r, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-5, American Psychiatric Association.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_2","unstructured":"Sadock, B.J. (2015). Kaplan & Sadock\u2019s Synopsis of Psychiatry: Behavioral Sciences\/Clinical Psychiatry, Wolters Kluwer."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_4","unstructured":"World Health Organization (2011). Global Burden of Mental Disorders and the Need for a Comprehensive, Coordinated Response from Health and Social Sectors at the Country Level: Report by the Secretariat, World Health Organization."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.pnpbp.2010.07.030","article-title":"Beyond the serotonin hypothesis: Mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders","volume":"35","author":"Gardner","year":"2011","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_7","first-page":"2253","article-title":"Neutrophil\u2013lymphocyte ratio in patients with major depressive disorder undergoing no pharmacological therapy","volume":"11","author":"Demir","year":"2015","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5758","DOI":"10.2174\/0929867328666210922160116","article-title":"Neutrophil\/lymphocyte, platelet\/lymphocyte, and monocyte\/lymphocyte ratios in mood disorders","volume":"29","author":"Marazziti","year":"2022","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1176\/appi.focus.16407","article-title":"Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis","volume":"16","author":"Cipriani","year":"2018","journal-title":"Focus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e014912","DOI":"10.1136\/bmjopen-2016-014912","article-title":"Pharmacological and non-pharmacological treatments for major depressive disorder: Review of systematic reviews","volume":"7","author":"Gartlehner","year":"2017","journal-title":"BMJ Open"},{"key":"ref_11","first-page":"457","article-title":"Background and rationale for the sequenced treatment alternatives to relieve depression (STAR* D) study","volume":"26","author":"Fava","year":"2003","journal-title":"Psychiatr. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.eurpsy.2015.12.003","article-title":"European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe","volume":"33","author":"Jobst","year":"2016","journal-title":"Eur. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S2215-0366(18)30133-0","article-title":"Antidepressants might work for people with major depression: Where do we go from here?","volume":"5","author":"Cipriani","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1176\/appi.ajp.163.1.28","article-title":"Evaluation of outcomes with citalopram for depression using measurement-based care in STAR* D: Implications for clinical practice","volume":"163","author":"Trivedi","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_15","first-page":"5","article-title":"Patient-rated versus clinician-rated side effects of drug treatment in schizophrenia. Clinical validation of a self-rating version of the UKU Side Effect Rating Scale (UKU-SERS-Pat)","volume":"55","author":"Lewander","year":"2001","journal-title":"Nord. J. Psychiatry"},{"key":"ref_16","first-page":"1","article-title":"The UKU side effect rating scale: A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients","volume":"76","author":"Ahlfors","year":"1987","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Guy, W. (1976). ECDEU Assessment Manual for Psychopharmacology.","DOI":"10.1037\/e591322011-001"},{"key":"ref_18","first-page":"185","article-title":"Montgomery-Asberg Depresyon De\u011ferlendirme \u00d6l\u00e7e\u011fi: De\u011ferlendiriciler aras\u0131 g\u00fcvenilirlik ve ge\u00e7erlik \u00e7al\u0131\u015fmas\u0131","volume":"12","author":"Demir","year":"2001","journal-title":"T\u00fcrk Psikiyatr. Derg."},{"key":"ref_19","first-page":"114","article-title":"Hamilton anksiyete de\u011ferlendirme \u00f6i\u00e7e\u011fi, de\u011ferlendiriciler aras\u0131 g\u00fcvenirlik ve ge\u00e7erlik \u00e7al\u0131\u015fmas\u0131","volume":"9","author":"Yazici","year":"1998","journal-title":"T\u00fcrk Psikiyatr. Derg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"177","DOI":"10.12991\/marupj.259895","article-title":"Antidepresan Kullanan Maj\u00f6r Depresyon Hastalar\u0131nda Yan Etkilerin ve Hasta Uyuncunun De\u011ferlendirilmesi","volume":"21","author":"SanCar","year":"2017","journal-title":"Marmara Pharm. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104041","DOI":"10.1016\/j.archger.2020.104041","article-title":"Elevated blood neutrophil to lymphocyte ratio in older adults with cognitive impairment","volume":"88","author":"Liu","year":"2020","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/ggi.14016","article-title":"Preoperative neutrophil-lymphocyte ratio, an independent risk factor for postoperative cognitive dysfunction in elderly patients with gastric cancer","volume":"20","author":"Yong","year":"2020","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/ana.25159","article-title":"Neutrophil hyperactivation correlates with Alzheimer\u2019s disease progression","volume":"83","author":"Dong","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s41252-022-00258-6","article-title":"New hematological parameters as inflammatory biomarkers: Systemic immune inflammation index, platerethritis, and platelet distribution width in patients with adult attention deficit hyperactivity disorder","volume":"6","author":"Ceyhun","year":"2022","journal-title":"Adv. Neurodev. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110581","DOI":"10.1016\/j.pnpbp.2022.110581","article-title":"Peripheral blood inflammatory markers in patients with attention deficit\/hyperactivity disorder (ADHD): A systematic review and meta-analysis","volume":"118","author":"Misiak","year":"2022","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"522","DOI":"10.24938\/kutfd.956479","article-title":"Sa\u011flikli Kadinlarda Fiziksel Aktivite D\u00fczeyine G\u00f6re Uyku Kalitesi Ve Monosit\/Y\u00fcksek Yo\u011funluklu Lipoprotein Oranin Kar\u015fila\u015ftirilmasi","volume":"23","year":"2021","journal-title":"K\u0131r\u0131kkale \u00dcniv. T\u0131p Fak\u00fcltesi Derg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e006071","DOI":"10.1136\/bmjopen-2014-006071","article-title":"Daytime napping, sleep duration and serum C reactive protein: A population-based cohort study","volume":"4","author":"Leng","year":"2014","journal-title":"BMJ Open"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"136692","DOI":"10.1016\/j.neulet.2022.136692","article-title":"Peripheral blood inflammatory cytokines are associated with rapid eye movement sleep behavior disorder in Parkinson\u2019s disease","volume":"782","author":"Wang","year":"2022","journal-title":"Neurosci. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2020858118","DOI":"10.1073\/pnas.2020858118","article-title":"Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder","volume":"118","author":"Farmen","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/ejh.13560","article-title":"The hematologic consequences of obesity","volume":"106","author":"Purdy","year":"2021","journal-title":"Eur. J. Haematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/j.1600-0609.2006.00658.x","article-title":"Leukocytosis in obese individuals: Possible link in patients with unexplained persistent neutrophilia","volume":"76","author":"Herishanu","year":"2006","journal-title":"Eur. J. Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1160\/TH12-09-0696","article-title":"Obesity with insulin resistance increase thrombosis in wild-type and bone marrow-transplanted Zucker Fatty rats","volume":"109","author":"Vera","year":"2013","journal-title":"Thromb. Haemost."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e14337","DOI":"10.1111\/and.14337","article-title":"A systematic review and meta-analysis of the relationship between erectile dysfunction and the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios","volume":"54","author":"Zhang","year":"2022","journal-title":"Andrologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.kjms.2015.11.002","article-title":"The relationship between platelet\u2013lymphocyte ratio and severity of erectile dysfunction","volume":"32","author":"Akbas","year":"2016","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41443-017-0007-1","article-title":"Relationship between erectile dysfunction and the neutrophil to lymphocyte and platelet to lymphocyte ratios","volume":"30","author":"Sambel","year":"2018","journal-title":"Int. J. Impot. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100401","DOI":"10.1016\/j.esxm.2021.100401","article-title":"The relationship between hematologic parameters and erectile dysfunction","volume":"9","author":"Liao","year":"2021","journal-title":"Sex. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1080\/13685538.2018.1427712","article-title":"Visceral adiposity index is associated with premature ejaculation inversely: A cross-sectional study","volume":"21","author":"Cakir","year":"2018","journal-title":"Aging Male"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100086","DOI":"10.1016\/j.cpnec.2021.100086","article-title":"Inflammation predicts sexual arousability in healthy women","volume":"8","author":"Clephane","year":"2021","journal-title":"Compr. Psychoneuroendocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s40264-022-01246-4","article-title":"Withdrawal Syndrome Following Discontinuation of 28 Antidepressants: Pharmacovigilance Analysis of 31,688 Reports from the WHO Spontaneous Reporting Database","volume":"45","author":"Gastaldon","year":"2022","journal-title":"Drug Saf."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"190","DOI":"10.9758\/cpn.2018.16.2.190","article-title":"Increased neutrophil-lymphocyte and platelet-lymphocyte ratios in male heroin addicts: A prospective controlled study","volume":"16","author":"Eren","year":"2018","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"32","DOI":"10.9758\/cpn.2020.18.1.32","article-title":"Elevated neutrophil to lymphocyte ratio in older adults with cocaine use disorder as a marker of chronic inflammation","volume":"18","author":"Soder","year":"2020","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.2147\/NDT.S213839","article-title":"The association between cortisol: C-reactive protein ratio and depressive fatigue is a function of CRP rather than cortisol","volume":"15","author":"Sharpley","year":"2019","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"769","DOI":"10.5665\/sleep.2646","article-title":"Extreme sleep durations and increased C-reactive protein: Effects of sex and ethnoracial group","volume":"36","author":"Grandner","year":"2013","journal-title":"Sleep"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1017\/S1041610214002683","article-title":"Low-grade inflammation differentiates between symptoms of apathy and depression in community-dwelling older individuals","volume":"27","author":"Eurelings","year":"2015","journal-title":"Int. Psychogeriatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.clinbiochem.2014.08.022","article-title":"Red blood cell distribution width and neutrophil\/lymphocyte ratio are positively correlated with disease activity in primary Sj\u00f6gren\u2019s syndrome","volume":"47","author":"Hu","year":"2014","journal-title":"Clin. Biochem."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7160\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:58:45Z","timestamp":1789466325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":45,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187160"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187160","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}