Top 50 Studies on Depression

The most cited studies that built our evidence base for depression

STUDY: Albesher AA et al, Cureus 2026;18(4)

STUDY TYPE: Bibliometric review

FUNDING: Independent

Background

Which studies actually shaped how psychiatrists treat depression? This bibliometric analysis set out to answer that question by identifying the 50 most-cited articles on major depressive disorder treatment published before 2019 (setting the date there gives time for articles to gain citations).

Results

The 50 articles accumulated between 96 and 1,837 citations each (median 210). Two studies dominated

1. A 2002 trial that laid the grounds for collaborative care between psychiatrists, care managers, and PCPs (1,837 citations).
2. The NIMH Collaborative Research Program (1,738 citations), which showed similar benefits with antidepressants, cognitive behavioral therapy, and a general “interpersonal” therapy approach.

Randomized controlled trials made up 64% of the top 50, with systematic reviews and meta-analyses accounting for another 32%. More than 90% qualified as Level 1 evidence.

They covered antidepressants, CBT, behavioral activation, mindfulness, light therapy, TMS, exercise, yoga, diet, curcumin, and probiotics. The CANMAT guidelines appeared multiple times, reflecting their standing as a primary reference for evidence-based practice.

Research skewed heavily toward North America. The United States contributed 48% of articles, Canada 24%, and the United Kingdom 10%.

The Full List

1. Unützer J, Katon W, Callahan CM, et al. Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA. 2002;288(22):2836-2845. PubMed

2. Elkin I, Shea MT, Watkins JT, et al. National Institute of Mental Health Treatment of Depression Collaborative Research Program: general effectiveness of treatments. Arch Gen Psychiatry. 1989;46(11):971-982. PubMed

3. Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. Can J Psychiatry. 2016;61(9):540-560. PubMed

4. Katon W, Robinson P, Von Korff M, et al. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry. 1996;53(10):924-932. PubMed

5. Jacka FN, O’Neil A, Opie R, et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med. 2017;15(1):23. PubMed

6. Lespérance F, Frasure-Smith N, Koszycki D, et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA. 2007;297(4):367-379. PubMed

7. Sotsky SM, Glass DR, Shea MT, et al. Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program. Am J Psychiatry. 1991;148(8):997-1008. PubMed

8. Shea MT, Elkin I, Imber SD, et al. Course of depressive symptoms over follow-up: findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Arch Gen Psychiatry. 1992;49(10):782-787. PubMed

9. Milev RV, Giacobbe P, Kennedy SH, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 4. Neurostimulation treatments. Can J Psychiatry. 2016;61(9):561-575. PubMed

10. Fava GA, Rafanelli C, Grandi S, Conti S, Belluardo P. Prevention of recurrent depression with cognitive behavioral therapy: preliminary findings. Arch Gen Psychiatry. 1998;55(9):816-820. PubMed

11. Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009;117 Suppl 1:S26-S43. PubMed

12. Mazzucchelli T, Kane R, Rees C. Behavioral activation treatments for depression in adults: a meta-analysis and review. Clin Psychol (New York). 2009;16(4):383-411. PubMed Search

13. Mynors-Wallis LM, Gath DH, Day A, Baker F. Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. BMJ. 2000;320(7226):26-30. PubMed

14. Segal ZV, Bieling P, Young T, et al. Antidepressant monotherapy vs sequential pharmacotherapy and mindfulness-based cognitive therapy, or placebo, for relapse prophylaxis in recurrent depression. Arch Gen Psychiatry. 2010;67(12):1256-1264. PubMed

15. Szegedi A, Jansen WT, van Willigenburg AP, van der Meulen E, Stassen HH, Thase ME. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry. 2009;70(3):344-353. PubMed

16. Gartlehner G, Hansen RA, Morgan LC, et al. Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis. Ann Intern Med. 2011;155(11):772-785. PubMed

17. Elkin I, Gibbons RD, Shea MT, Sotsky SM, Watkins JT, Pilkonis PA, Hedeker D. Initial severity and differential treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. J Consult Clin Psychol. 1995;63(5):841-847. PubMed

18. Trivedi MH, Rush AJ, Crismon ML, et al. Clinical results for patients with major depressive disorder in the Texas Medication Algorithm Project. Arch Gen Psychiatry. 2004;61(7):669-680. PubMed

19. van der Feltz-Cornelis CM, Nuyen J, Stoop C, et al. Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: a systematic review and meta-analysis. Gen Hosp Psychiatry. 2010;32(4):380-395. PubMed

20. Strong V, Waters R, Hibberd C, et al. Management of depression for people with cancer (SMaRT oncology 1): a randomised trial. Lancet. 2008;372(9632):40-48. PubMed

21. Parikh SV, Quilty LC, Ravitz P, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 2. Psychological treatments. Can J Psychiatry. 2016;61(9):524-539. PubMed

22. Ravindran AV, Balneaves LG, Faulkner G, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 5. Complementary and alternative medicine treatments. Can J Psychiatry. 2016;61(9):576-587. PubMed

23. Unützer J, Katon W, Williams JW Jr, et al. Improving primary care for depression in late life: the design of a multicenter randomized trial. Med Care. 2001;39(8):785-799. PubMed

24. Berman RM, Fava M, Thase ME, et al. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009;14(4):197-206. PubMed

25. Mohr DC, Hart SL, Julian L, Catledge C, Honos-Webb L, Vella L, Tasch ET. Telephone-administered psychotherapy for depression. Arch Gen Psychiatry. 2005;62(9):1007-1014. PubMed

26. Ell K, Xie B, Quon B, Quinn DI, Dwight-Johnson M, Lee PJ. Randomized controlled trial of collaborative care management of depression among low-income patients with cancer. J Clin Oncol. 2008;26(27):4488-4496. PubMed

27. MacQueen GM, Frey BN, Ismail Z, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 6. Special populations: youth, women, and the elderly. Can J Psychiatry. 2016;61(9):588-603. PubMed

28. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73(1):56-63. PubMed

29. Lam RW, Chan P, Wilkins-Ho M, Yatham LN. Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and metaanalysis. Can J Psychiatry. 2008;53(9):621-631. PubMed

30. Pinquart M, Duberstein PR, Lyness JM. Effects of psychotherapy and other behavioral interventions on clinically depressed older adults: a meta-analysis. Aging Ment Health. 2007;11(6):645-657. PubMed

31. Mota-Pereira J, Silverio J, Carvalho S, Ribeiro JC, Fonte D, Ramos J. Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011;45(8):1005-1011. PubMed

32. Hedrick SC, Chaney EF, Felker B, et al. Effectiveness of collaborative care depression treatment in Veterans’ Affairs primary care. J Gen Intern Med. 2003;18(1):9-16. PubMed

33. Fava GA, Rafanelli C, Grandi S, Canestrari R, Morphy MA. Six-year outcome for cognitive behavioral treatment of residual symptoms in major depression. Am J Psychiatry. 1998;155(10):1443-1445. PubMed

34. Hall-Flavin DK, Winner JG, Allen JD, et al. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 2013;23(10):535-548. PubMed

35. Emslie GJ, Ventura D, Korotzer A, Tourkodimitris S. Escitalopram in the treatment of adolescent depression: a randomized placebo-controlled multisite trial. J Am Acad Child Adolesc Psychiatry. 2009;48(7):721-729. PubMed

36. Panahi Y, Badeli R, Karami GR, Sahebkar A. Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder. Phytother Res. 2015;29(1):17-21. PubMed

37. Parikh SV, Segal ZV, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication. J Affect Disord. 2009;117 Suppl 1:S15-S25. PubMed

38. Qaseem A, Snow V, Denberg TD, Forciea MA, Owens DK. Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;149(10):725-733. PubMed

39. Trivedi MH, Rush AJ, Gaynes BN, et al. Maximizing the adequacy of medication treatment in controlled trials and clinical practice: STAR()D measurement-based care. Neuropsychopharmacology. 2007;32(12):2479-2489. PubMed

40. Gould RL, Coulson MC, Howard RJ. Cognitive behavioral therapy for depression in older people: a meta-analysis and meta-regression of randomized controlled trials. J Am Geriatr Soc. 2012;60(10):1817-1830. PubMed

41. Kennedy SH, Milev R, Giacobbe P, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. J Affect Disord. 2009;117 Suppl 1:S44-S53. PubMed

42. Tolahunase MR, Sagar R, Faiq M, Dada R. Yoga- and meditation-based lifestyle intervention increases neuroplasticity and reduces severity of major depressive disorder: a randomized controlled trial. Restor Neurol Neurosci. 2018;36(3):423-442. PubMed

43. Guidi J, Tomba E, Fava GA. The sequential integration of pharmacotherapy and psychotherapy in the treatment of major depressive disorder: a meta-analysis of the sequential model and a critical review of the literature. Am J Psychiatry. 2016;173(2):128-137. PubMed

44. Adler DA, Bungay KM, Wilson IB, et al. The impact of a pharmacist intervention on 6-month outcomes in depressed primary care patients. Gen Hosp Psychiatry. 2004;26(3):199-209. PubMed

45. Kasper S, de Swart H, Friis Andersen H. Escitalopram in the treatment of depressed elderly patients. Am J Geriatr Psychiatry. 2005;13(10):884-891. PubMed

46. Zou L, Yeung A, Li C, et al. Effects of meditative movements on major depressive disorder: a systematic review and meta-analysis of randomized controlled trials. J Clin Med. 2018;7(8):195. PubMed

47. Scott C, Tacchi MJ, Jones R, Scott J. Acute and one-year outcome of a randomised controlled trial of brief cognitive therapy for major depressive disorder in primary care. Br J Psychiatry. 1997;171:131-134. PubMed

48. Melville JL, Reed SD, Russo J, Croicu CA, Ludman E, LaRocco-Cockburn A, Katon W. Improving care for depression in obstetrics and gynecology: a randomized controlled trial. Obstet Gynecol. 2014;123(6):1237-1246. PubMed

49. Schramm E, van Calker D, Dykierek P, et al. An intensive treatment program of interpersonal psychotherapy plus pharmacotherapy for depressed inpatients: acute and long-term results. Am J Psychiatry. 2007;164(5):768-777. PubMed

50. Majeed M, Nagabhushanam K, Arumugam S, Majeed S, Ali F. Bacillus coagulans MTCC 5856 for the management of major depression with irritable bowel syndrome: a randomised, double-blind, placebo controlled, multi-centre, pilot clinical study. Food Nutr Res. 2018;62:1218. PubMed

Practice Implications

1. It’s nice to know where our ideas come from. I’ll plan a podcast to keep us up to date on these 50 findings.