Public health impact of subthreshold depression comparable to major depression

Subthreshold depression is a clinically relevant condition and is associated with functional impairment, increased economic costs, help-seeking, and excess mortality. The strength of these associations have been found to be lower than in major depression. However, the impact at a population level of excess economic costs and excess mortality have been found to be comparable to the impact of major depression, because the prevalence of subthreshold is higher than the prevalence of major depression.


  • Cuijpers P, Vogelzangs N, Twisk J, Kleiboer A, Li J, Penninx BW (2013). Differential mortality rates in major and subthreshold depression? A meta-analysis of studies that measured both. British Journal of Psychiatry, 202, 22-27.
  • Cuijpers P, De Graaf R, Van Dorsselaer S (2004). Minor depression: risk profiles, functional disability, health care use and risk of developing major depression. Journal of Affective Disorders,79, 71-79.
  • Cuijpers P, Smit F, Oostenbrink J, de Graaf R, ten Have M, Beekman A (2007). Economic costs of minor depression: A population-based study. Acta Psychiatrica Scandinavica, 115, 229-236.

Combined treatment of depression is better

The combination of psychotherapy and pharmacotherapy is more effective then either psychotherapy or pharmacotherapy alone, also in severe and chronic depression and at longer follow. At the short term, psychotherapy and pharmacotherapy have comparable effects, but at the longer-term psychotherapy probably has better effects that pharmacotherapy, certainly when the use of antidepressants is stopped at some point. Drop-out is also lower for combined treatment compared with pharmacotherapy and the drop-out is also lower in psychotherapy compared with pharmacotherapy.


  • Cuijpers P, Noma H, Karyotaki E, Vinkers CH, Cipriani A, Furukawa TA (2020). A network meta-analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry, 19, 92–107.
  • Cuijpers P, Sijbrandij M, Koole SL, Andersson G, Beekman AT, Reynolds III CF (2014). Adding psychotherapy to antidepressant medication in depression and anxiety disorders: A meta-analysis. World Psychiatry, 13, 56-67.
  • Cuijpers P, Sijbrandij M, Koole SL, Andersson G, Beekman AT, Reynolds III CF (2013). The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta-analysis of direct comparisons. World Psychiatry, 12, 137–148.
  • Karyotaki E. Smit Y, Holdt Henningsen K, Huibers MJH, Robayse J, de Beurs D, Cuijpers P (2016). Combining pharmacotherapy and psychotherapy or monotherapy for major depression? A meta-analysis on the long-term effects. Journal of Affective Disorders, 194(1), 144-152.
  • Karyotaki E, Smit Y, de Beurs DP, Henningsen KH, Robays J, Huibers MJH, Weitz E, Cuijpers P (2016). The long-term efficacy of acute phase psychotherapy for depression: a meta-analysis of randomized trials. Depression & Anxiety, 33(5), 370-383.
  • Cuijpers P, Hollon SD, van Straten A, Bockting C, Berking M, Andersson G (2013). Does cognitive behaviour therapy have an enduring effect that is superior to keeping patients on continuation pharmacotherapy? A meta-analysis. BMJ Open, 2013: 3, doi: 10.1136/bmjopen-2012-002542

How do psychotherapies work?

Although hundreds of randomized trials have shown that psychotherapies work for most mental disorders, it is not clear how they work. Trials are designed to show if a treatment works, but not how it works. In order to show how therapies work, many different types of studies but they miss the certaintly of randomized trials. At this moment there is no therapy from which we know how it works. It is also unknown whether the 'common factors' such as the alliance between therapist and client are a core working mechanism of therapies.


  • Cuijpers P, Reijnders M, Huibers MJH (2019). The role of common factors in psychotherapy outcome. Annual Review of Clinical Psychology, 15, 207–231.
  • Cuijpers P, Cristea IA, Karyotakia E, Reijnders M, Hollon SD (2019). Component studies of psychological treatments of adult depression: A systematic review and meta-analysis. Psychotherapy Research, 29, 15-29.

Excess mortality in depression

It is now well-established that depressive disorders are associated with excess mortality. Patients with depression die earlier than other people. This excess mortality is higher in men and also exists in subthreshold depression. We found no difference in excess mortality rates in people from the community and patient with comorbid general medical disorders, such as heart disease, cancer or diabetes.

  • Liu NH, Daumit GL, Dua T, Aquila R, Charlson F, Cuijpers P, Druss B, Dudek K, Freeman M, Fujii C, Gaebel W, Hegerl U, Levav I, Laursen TM, Ma H, Maj M, Medina-Mora ME, Nordentoft M, Prabhakaran D, Pratt K, Prince M, Rangaswamy T, Shiers D, Susser E, Thornicroft G, Wahlbeck K, Wassie AF, Whitefield H, Saxena S (2017). Excess mortality in persons with severe mental disorders: a multilevel intervention framework and priorities for clinical practice, policy and research agendas. World Psychiatry, 16, 30-40.
  • Cuijpers P, Vogelzangs N, Twisk J, Kleiboer A, Li J, Penninx B (2014). Comprehensive meta-analysis of excess mortality in depression in the general community versus patients with specific illnesses. Am J Psychiatry, 171, 453–462.
  • Cuijpers P, Vogelzangs N, Twisk J, Kleiboer A, Li J, Penninx BW (2014). Is excess mortality higher in depressed men than in depressed women? A meta-analytic comparison. Journal of Affective Disorders, 161, 47-54.
  • Cuijpers P, Vogelzangs N, Twisk J, Kleiboer A, Li J, Penninx BW (2013). Differential mortality rates in major and subthreshold depression? A meta-analysis of studies that measured both. British Journal of Psychiatry, 202, 22-27.
  • Cuijpers P, Schoevers RA (2004). Increased mortality in depressive disorders: A review. Current Psychiatry Reports, 6, 430-7.
  • Cuijpers P, Smit F (2002). Excess mortality in depression: a meta-analysis of community studies. Journal of Affective Disorders, 72, 227-236.

Treatment format not associated with the effects of depression treatments

The effects of psychotherapies for depression are effective when used in individual, group, telephone, and in internet-based format and guided self-help. There are no significant differences between treatment formats, as long as human support is given to the patient. In guided self-help and internet-based treatments the drop-out is higher than in other formats. When nu human support is given, the effects are significantly smaller.

  • Cuijpers P, Noma H, Karyotaki E, Cipriani A, Furukawa T (2019). Individual, group, telephone, self-help and internet-based cognitive behavior therapy for adult depression; A network meta-analysis of delivery methods. JAMA Psychiatry, 76, 700-707.
  • Carlbring P, Andersson G, Cuijpers P, Riper H, Hedman E (2018). Internet-based vs. face-to-face cognitive behavior therapy for psychiatric and somatic disorders: An updated systematic review and meta-analysis. Cognitive Behavior Therapy, 47, 1-18.
  • Andersson, G., Cuijpers, P., Carlbring, P., Riper, H., & Hedman, E. (2014). Internet-based vs. face-to-face cognitive behaviour therapy for psychiatric and somatic disorders: a systematic review and meta-analysis. World Psychiatry, 13, 288-295.
  • Cuijpers P, Donker T, van Straten A, Li J, Andersson G (2010). Is guided self-help as effective as face-to-face psychotherapy for depression and anxiety disorders? A systematic review and meta-analysis of comparative outcome studies. Psychological Medicine, 40, 1943-1957.

Preventive interventions significantly reduce incidence of major depression

Psychological interventions can reduce the incidence of new cases of major depressive disorder in people who do not currently meet criteria for major depression. That is certainly the case for people with subthreshold depression.

  • Buntrock C, Ebert DD, Lehr D, Smit F, Riper H, Berking M, Cuijpers P (2016). Effect of a web-based guided self-help intervention for prevention of major depression in adults with sub-threshold depression: A randomized clinical trial. JAMA, 315, 1854-1863.
  • Van Zoonen K, Buntrock C, Ebert DD, Smit F, Reynolds CF, Beekman ATF, Cuijpers P (2014). Preventing the onset of major depressive disorder: A meta-analytic review of psychological interventions. International Journal of Epidemiology, 43, 318–329.
  • Cuijpers P, van Straten A, Smit F, Mihalopoulos C, Beekman A (2008). Preventing the onset of depressive disorders: A meta-analytic review of psychological interventions. American Journal of Psychiatry, 165, 1272-1280.
  • Cuijpers P (2003). Examining the effects of prevention programs on the incidence of new cases of mental disorders: The lack of statistical power. American Journal of Psychiatry, 160, 1385-1391.
  • Reins JA, Buntrock C, Zimmermann J, Grund S, Harrer M, Lehr D, Baumeister H, Weisel K, Domhardt M, Imamura K, Kawakami N, Spek V, Nobis S, Snoek F, Cuijpers P, Klein JP, Moritz S, Ebert DD (2020). Efficacy and moderators of internet-based interventions in adults with subthreshold depression; An individual participants data meta-analysis of randomized controlled trials. Psychotherapy and Psychosomatics, epub ahead of print.
  • Dias A, Azariah F, Anderson SJ, Sequeira M, Cohen A, Morse J, Cuijpers P, Patel V, Reynolds CF (2019). Preventing major depression in older adults living in low- and middle-income countries: a randomized controlled trial. JAMA Psychiatry, 76, 13-20.
  • López L, Smit F, Cuijpers P, Otero P, Blanco V, Torres A, Vázquez FL (2019). Problem-solving intervention to prevent depression in non-professional caregivers: A randomized controlled trial with 8 years of follow-up. Psychological Medicine, 24, 1-8
  • Van ’t Veer-Tazelaar PA, van Marwijk HWJ, van Oppen P, van Hout HPJ, van der Horst HE, Cuijpers P, Smit F, Beekman ATF (2009). Stepped-care prevention of anxiety and depression in late life: a randomized controlled trial. Archives of General Psychiatry, 66, 297-304.