{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:29:01Z","timestamp":1784734141386,"version":"3.55.0"},"reference-count":66,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Lamotrigine has been widely investigated in the treatment and prevention of the emergence of symptoms of depression in unipolar and bipolar depression. This work systematically appraises published and unpublished double-blind randomised controlled trials of lamotrigine to provide up-to-date guidance on the use of lamotrigine in the presence of depressive symptoms. Methods: Systematic searches identified 32 randomised controlled trials, of which 24 were included in the meta-analysis, involving 2257 patients and 2320 controls. Results: Evidence supports the use of lamotrigine in the acute phase of bipolar depression in monotherapy vs. placebo (SMD: 0.155; CI: 0.005\u20130.305) in the absence of significant heterogeneity and small study effects. In the prophylaxis of bipolar depression, lamotrigine reduced the risk of the emergence of depressive symptoms (RR: 0.78; CI: 0.63, 0.98) and prolonged the duration of symptoms survival (RR: 1.59; CI: 1.19, 2.11) compared to placebo, with no evidence of publication and small study bias. Lamotrigine was not found to be superior to lithium in the acute treatment and prophylaxis of bipolar depression. In the treatment of unipolar depressive episodes, with the inclusion in the analyses of three unpublished studies, lamotrigine was not superior to placebo in monotherapy and as adjunct treatment. There were no maintenance studies in unipolar depression. Conclusions: There is evidence supporting the use of lamotrigine in monotherapy as acute and prophylactic treatment of bipolar depression. Evidence of the use of lamotrigine in unipolar disorders is lacking. PROSPERO registration ID: CRD42025633709.<\/jats:p>","DOI":"10.3390\/ph18101590","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:42:03Z","timestamp":1761054123000},"page":"1590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of Lamotrigine in the Treatment of Unipolar and Bipolar Depression: Meta-Analysis of Acute and Maintenance Randomised Controlled Trials"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3831-2301","authenticated-orcid":false,"given":"Danilo","family":"Arnone","sequence":"first","affiliation":[{"name":"Centre for Affective Disorders, Psychological Medicine, Institute of Psychiatry, King\u2019s College London, London SE5 8AF, UK"},{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates"},{"name":"Division of Psychiatry, Department of Brain Sciences, Imperial College London, Burlington Danes, The Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"\u00d6stlundh","sequence":"additional","affiliation":[{"name":"University Library, \u00d6rebro University, SE-702 81 \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Mosa","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianne","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4608-7124","authenticated-orcid":false,"given":"Jonathan","family":"Oldershaw","sequence":"additional","affiliation":[{"name":"Royal Free London NHS Foundation Trust, London NW3 2QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7607-360X","authenticated-orcid":false,"given":"Tarik","family":"Qassem","sequence":"additional","affiliation":[{"name":"College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates"},{"name":"Maudsley Health, 201\u2013205 Al-Montazah Tower, Khalidiya, Abu Dhabi 20002, United Arab Emirates"},{"name":"Al Amal Psychiatric Hospital, Emirates Health Service, Dubai 50262, United Arab Emirates"},{"name":"South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan H.","family":"Young","sequence":"additional","affiliation":[{"name":"Centre for Affective Disorders, Psychological Medicine, Institute of Psychiatry, King\u2019s College London, London SE5 8AF, UK"},{"name":"Division of Psychiatry, Department of Brain Sciences, Imperial College London, Burlington Danes, The Hammersmith Hospital, Du Cane Road, London W12 0NN, UK"},{"name":"South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Costa, B., and Vale, N. (2023). Understanding Lamotrigine\u2019s Role in the CNS and Possible Future Evolution. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076050"},{"key":"ref_2","unstructured":"National Center for Biotechnology Information (2025, May 21). PubChem Compound Summary for CID 3878, Lamotrigine, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Lamotrigine."},{"key":"ref_3","unstructured":"(2025, May 21). European Medicine Agency. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/referrals\/lamictal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/S2215-0366(23)00199-2","article-title":"Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: A systematic review and network meta-analysis","volume":"10","author":"Yildiz","year":"2023","journal-title":"Lancet Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1177\/0269881115581093","article-title":"Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines","volume":"29","author":"Cleare","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1177\/07067437241245384","article-title":"Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: R\u00e9seau canadien pour les traitements de l\u2019humeur et de l\u2019anxi\u00e9t\u00e9 (CANMAT) 2023: Mise \u00e0 jour des lignes directrices cliniques pour la prise en charge du trouble d\u00e9pressif majeur chez les adultes","volume":"69","author":"Lam","year":"2024","journal-title":"Can. J. Psychiatry Rev. Can. Psychiatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1192\/bjp.bp.107.048504","article-title":"Lamotrigine for treatment of bipolar depression: Independent meta-analysis and meta-regression of individual patient data from five randomised trials","volume":"194","author":"Geddes","year":"2009","journal-title":"Br. J. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/bdi.13452","article-title":"The efficacy of lamotrigine in bipolar disorder: A systematic review and meta-analysis","volume":"26","author":"Haenen","year":"2024","journal-title":"Bipolar Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1017\/S1092852916000523","article-title":"Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: A comprehensive meta-analysis of efficacy and safety outcomes in short-term trials","volume":"21","author":"Solmi","year":"2016","journal-title":"CNS Spectr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1177\/0269881119844199","article-title":"Lamotrigine augmentation in treatment-resistant unipolar depression: A comprehensive meta-analysis of efficacy and safety","volume":"33","author":"Goh","year":"2019","journal-title":"J. Psychopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13643-020-01542-z","article-title":"PRISMA-S: An extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews","volume":"10","author":"Rethlefsen","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_12","unstructured":"Higgins, J.P.T., and Cochrane Collaboration. (2020). Cochrane Handbook for Systematic Reviews of Interventions, Wiley-Blackwell. [2nd ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Schmitz, S., Adams, R., and Walsh, C. (2012). The use of continuous data versus binary data in MTC models: A case study in rheumatoid arthritis. BMC Med. Res. Methodol., 12.","DOI":"10.1186\/1471-2288-12-167"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/sim.2331","article-title":"Dichotomizing continuous predictors in multiple regression: A bad idea","volume":"25","author":"Royston","year":"2006","journal-title":"Stat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Arnone, D., Ramaraj, R., \u00d6stlundh, L., Arora, T., Javaid, S., Govender, R.D., Stip, E., and Young, A.H. (2025). Assessment of cognitive domains in major depressive disorders using the Cambridge Neuropsychological Test Automated Battery (CANTAB): Systematic review and meta-analysis of cross-sectional and longitudinal studies. Prog. Neuropsychopharmacol. Biol. Psychiatry, 138.","DOI":"10.1016\/j.pnpbp.2025.111301"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.euroneuro.2011.05.003","article-title":"Magnetic resonance imaging studies in unipolar depression: Systematic review and meta-regression analyses","volume":"22","author":"Arnone","year":"2012","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1192\/bjp.bp.108.059717","article-title":"Magnetic resonance imaging studies in bipolar disorder and schizophrenia: Meta-analysis","volume":"195","author":"Arnone","year":"2009","journal-title":"Br. J. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Arnone, D., Karmegam, S.R., \u00d6stlundh, L., Alkhyeli, F., Alhammadi, L., Alhammadi, S., Alkhoori, A., and Selvaraj, S. (2024). Risk of suicidal behavior in patients with major depression and bipolar disorder\u2014A systematic review and meta-analysis of registry-based studies. Neurosci. Biobehav. Rev., 159.","DOI":"10.1016\/j.neubiorev.2024.105594"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Arnone, D., Omar, O., Arora, T., \u00d6stlundh, L., Ramaraj, R., Javaid, S., Govender, R.D., Ali, B.R., Patrinos, G.P., and Young, A.H. (2023). Effectiveness of pharmacogenomic tests including CYP2D6 and CYP2C19 genomic variants for guiding the treatment of depressive disorders: Systematic review and meta-analysis of randomised controlled trials. Neurosci. Biobehav. Rev., 144.","DOI":"10.1016\/j.neubiorev.2022.104965"},{"key":"ref_22","unstructured":"Berman, H. (2025, May 21). Difference in Means Calculation. Available online: https:\/\/stattrek.com\/sampling\/difference-in-means."},{"key":"ref_23","unstructured":"Cochrane Collaboration (2025, May 21). Cochrane Handbook. Available online: https:\/\/www.cochrane.org\/authors\/handbooks-and-manuals\/handbook\/current."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control Clin. Trials."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/jrsm.1349","article-title":"Dealing with missing outcome data in meta-analysis","volume":"11","author":"Mavridis","year":"2020","journal-title":"Res. Synth. Methods."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4088\/JCP.v60n0203","article-title":"A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group","volume":"60","author":"Calabrese","year":"1999","journal-title":"J. Clin. Psychiatry"},{"key":"ref_29","unstructured":"GSK SR (2025, May 21). GW603\/SCAA2010. Available online: https:\/\/www.gsk-studyregister.com\/en\/trial-details\/?id=SCAA2010."},{"key":"ref_30","unstructured":"GSK SR (2025, May 21). SCA40910. Available online: https:\/\/www.gsk-studyregister.com\/en\/trial-details\/?id=SCA40910."},{"key":"ref_31","unstructured":"GSK SR (2025, May 21). SCA100223. Available online: https:\/\/www.gsk-studyregister.com\/en\/trial-details\/?id=SCA100223."},{"key":"ref_32","unstructured":"GSK SR (2025, May 21). SCA30924. Available online: https:\/\/www.gsk-studyregister.com\/en\/trial-details\/?id=SCA30924."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jad.2008.02.004","article-title":"A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression","volume":"111","author":"Suppes","year":"2008","journal-title":"J. Affect. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1017\/S1461145708009735","article-title":"Olanzapine\/fluoxetine combination vs. lamotrigine in the 6-month treatment of bipolar I depression","volume":"12","author":"Brown","year":"2009","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4088\/JCP.08m04152","article-title":"Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: A multicenter, double-blind, placebo-controlled trial","volume":"70","author":"Mulder","year":"2009","journal-title":"J. Clin. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/bdi.12013","article-title":"Lamotrigine as add-on treatment to lithium and divalproex: Lessons learned from a double-blind, placebo-controlled trial in rapid-cycling bipolar disorder","volume":"14","author":"Kemp","year":"2012","journal-title":"Bipolar Disord."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S2215-0366(15)00450-2","article-title":"Comparative evaluation of quetiapine plus lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in bipolar depression (CEQUEL): A 2 \u00d7 2 factorial randomised trial","volume":"3","author":"Geddes","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"841","DOI":"10.4088\/JCP.v61n1106","article-title":"A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group","volume":"61","author":"Calabrese","year":"2000","journal-title":"J. Clin. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.4088\/JCP.v64n0906","article-title":"A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder","volume":"64","author":"Calabrese","year":"2003","journal-title":"J. Clin. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1001\/archpsyc.60.4.392","article-title":"A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder","volume":"60","author":"Bowden","year":"2003","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1399-5618.2010.00836.x","article-title":"Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: An open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG-6)","volume":"12","author":"Licht","year":"2010","journal-title":"Bipolar Disord."},{"key":"ref_42","unstructured":"GSK SR (2025, May 21). SCAA2011. Available online: https:\/\/www.gsk-studyregister.com\/en\/trial-details\/?id=SCAA2011."},{"key":"ref_43","unstructured":"GSK SR (2025, May 21). SCA20022. Available online: https:\/\/www.gsk-studyregister.com\/en\/trial-details\/?id=SCA20022."},{"key":"ref_44","unstructured":"GSK SR (2025, May 21). SCA20025. Available online: https:\/\/www.gsk-studyregister.com\/en\/trial-details\/?id=SCA20025."},{"key":"ref_45","first-page":"187","article-title":"Efficacy and safety of antidepressant augmentation with lamotrigine in patients with treatment-resistant depression: A randomized, placebo-controlled, double-blind study","volume":"10","author":"Santos","year":"2008","journal-title":"Prim. Care Companion J. Clin. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"403","DOI":"10.4088\/JCP.v64n0407","article-title":"A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes","volume":"64","author":"Barbosa","year":"2003","journal-title":"J. Clin. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4088\/JCP.v63n0411","article-title":"Lamotrigine as adjunct to paroxetine in acute depression: A placebo-controlled, double-blind study","volume":"63","author":"Normann","year":"2002","journal-title":"J. Clin. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.4088\/JCP.09m05355gre","article-title":"A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression","volume":"72","author":"Barbee","year":"2011","journal-title":"J. Clin. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/YIC.0b013e328014823d","article-title":"Lithium versus lamotrigine augmentation in treatment resistant unipolar depression: A randomized, open-label study","volume":"22","author":"Schindler","year":"2007","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/JCP.0000000000001424","article-title":"A Single-Blind Randomized Comparison of Lithium and Lamotrigine as Maintenance Treatments for Managing Bipolar II Disorder","volume":"41","author":"Parker","year":"2021","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0006-3223(01)01206-9","article-title":"Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders","volume":"51","author":"Obrocea","year":"2002","journal-title":"Biol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.4088\/JCP.v67n0703","article-title":"A 7-week, randomized, double-blind trial of olanzapine\/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression","volume":"67","author":"Brown","year":"2006","journal-title":"J. Clin. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8","DOI":"10.64719\/pb.4604","article-title":"Sequential Multiple Assignment Randomized Treatment (SMART) for Bipolar Disorder at Any Phase of Illness and at least Mild Symptom Severity","volume":"50","author":"Gao","year":"2020","journal-title":"Psychopharmacol. Bull."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1176\/appi.ajp.163.2.210","article-title":"Treatment-resistant bipolar depression: A STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone","volume":"163","author":"Nierenberg","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jad.2006.05.023","article-title":"Randomized, double-blind pilot trial comparing lamotrigine versus citalopram for the treatment of bipolar depression","volume":"96","author":"Schaffer","year":"2006","journal-title":"J. Affect. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/j.1600-0447.2007.00993.x","article-title":"Tranylcypromine vs. lamotrigine in the treatment of refractory bipolar depression: A failed but clinically useful study","volume":"115","author":"Nolen","year":"2007","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1600-0447.2009.01537.x","article-title":"Efficacy and safety of two treatment algorithms in bipolar depression consisting of a combination of lithium, lamotrigine or placebo and paroxetine","volume":"122","author":"Mulder","year":"2010","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.64719\/pb.4303","article-title":"Lamotrigine adjunctive therapy to lithium and divalproex in depressed patients with rapid cycling bipolar disorder and a recent substance use disorder: A 12-week, double-blind, placebo-controlled pilot study","volume":"43","author":"Wang","year":"2010","journal-title":"Psychopharmacol. Bull."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1399-5618.2011.00887.x","article-title":"Long-term outcome of bipolar depressed patients receiving lamotrigine as add-on to lithium with the possibility of the addition of paroxetine in nonresponders: A randomized, placebo-controlled trial with a novel design","volume":"13","author":"Mulder","year":"2011","journal-title":"Bipolar Disord."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/j.1600-0447.2012.01890.x","article-title":"Lamotrigine vs. lamotrigine plus divalproex in randomized, placebo-controlled maintenance treatment for bipolar depression","volume":"126","author":"Bowden","year":"2012","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_61","unstructured":"Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences, Lawrence Erlbaum Associates, Publishers. [2nd ed.]."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11349","DOI":"10.4088\/JCP.20f13681","article-title":"Mean Difference, Standardized Mean Difference (SMD), and Their Use in Meta-Analysis: As Simple as It Gets","volume":"81","author":"Andrade","year":"2020","journal-title":"J. Clin. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1503\/jpn.120065","article-title":"Publication bias: What are the challenges and can they be overcome?","volume":"37","author":"Joober","year":"2012","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.jclinepi.2010.02.009","article-title":"Unpublished data can be of value in systematic reviews of adverse effects: Methodological overview","volume":"63","author":"Golder","year":"2010","journal-title":"J. Clin. Epidemiol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Stip, E., Rizvi, T.A., Mustafa, F., Javaid, S., Aburuz, S., Ahmed, N.N., Abdel Aziz, K., Arnone, D., Subbarayan, A., and Al Mugaddam, F. (2020). The Large Action of Chlorpromazine: Translational and Transdisciplinary Considerations in the Face of COVID-19. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.577678"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/npp.2017.166","article-title":"Effect of Citalopram on Emotion Processing in Humans: A Combined 5-HT1A [11C]CUMI-101 PET and Functional MRI Study","volume":"43","author":"Selvaraj","year":"2018","journal-title":"Neuropsychopharmacology"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/10\/1590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T04:10:44Z","timestamp":1761192644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/10\/1590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":66,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ph18101590"],"URL":"https:\/\/doi.org\/10.3390\/ph18101590","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]}}}