Depression

Research and further reading

A few key papers behind how this condition is understood and treated today. Links open the abstract on PubMed, a free public database from the U.S. National Library of Medicine.

• Depression

  Malhi et al. · The Lancet · 2018

  This broad clinical review explains that major depression can present in many ways, often recurs, and usually requires treatment tailored to the individual.

• Acute and longer term outcomes in depressed outpatients requiring one or several treatment steps: a STAR D report

  Rush et al. · The American Journal of Psychiatry · 2006

  Many patients improved after trying additional treatment steps, but the chance of remission decreased and relapse risk increased when several treatments were needed.

• Benefits from antidepressants: synthesis of 6 week patient level outcomes from double blind placebo controlled randomized trials of fluoxetine and venlafaxine

  Gibbons et al. · Archives of General Psychiatry · 2012

  Using patient level data from many trials, fluoxetine and venlafaxine improved depression more than placebo in adults, young people, and older adults.

• Antidepressant drug effects and depression severity: a patient level meta analysis

  Fournier et al. · JAMA · 2010

  The advantage of antidepressants over placebo grew with depression severity and was substantial for very severe depression, while it was small for mild or moderate symptoms.

• Atypical antipsychotic augmentation in major depressive disorder: a meta analysis of placebo controlled randomized trials

  Nelson et al. · The American Journal of Psychiatry · 2009

  Across placebo controlled trials, adding an atypical antipsychotic helped more patients reach response and remission when their antidepressant alone had not done enough. The benefit had to be weighed against a higher burden of side effects.

• Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta analyses of randomized, placebo controlled trials

  Crossley et al. · The Journal of Clinical Psychiatry · 2007

  Two combined analyses of randomized trials found lithium significantly more effective than placebo as an add on to antidepressants for depression. Evidence that lithium speeds up the onset of benefit was more modest.

• Zuranolone for the Treatment of Postpartum Depression

  Deligiannidis et al. · The American Journal of Psychiatry · 2023

  In 196 women with severe postpartum depression, a 14 day course of zuranolone 50 mg daily improved depressive symptoms more than placebo at day 15, with benefits sustained through day 45.

• Esketamine Monotherapy in Adults With Treatment Resistant Depression: A Randomized Clinical Trial

  Janik et al. · JAMA Psychiatry · 2025

  In 378 adults with treatment resistant depression, esketamine nasal spray 56 mg and 84 mg twice weekly improved depressive symptoms more than placebo over 4 weeks, with effects seen within 24 hours of the first dose.

• Esketamine Combined With SSRI or SNRI for Treatment Resistant Depression

  Del Casale et al. · JAMA Psychiatry · 2025

  In a large real world study of people with treatment resistant depression using esketamine, pairing it with an SNRI antidepressant was linked to fewer relapses, hospital stays, and deaths over five years than pairing it with an SSRI, while the SSRI pairing had slightly fewer suicide attempts.

• Esketamine Nasal Spray versus Quetiapine for Treatment Resistant Depression

  Reif et al. · N Engl J Med · 2023

  In a randomized trial of adults with treatment resistant depression, esketamine nasal spray combined with an SSRI or SNRI led to higher remission at eight weeks and fewer relapses through week thirty two than extended release quetiapine added to the same antidepressants.