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Depression may be neurotoxic

Professor Philip Gorwood, of the University Paris Descartes, Hospital Sainte-Anne, presented a Lundbeck Institute seminar on the neurotoxicity of depressive episodes . Neurotoxicity is clinically and therapeutically relevant. We should treat depression faster, better and longer.

To improve the long-term prognosis of a major depressive episode, we should:

  • treat faster - reduce the duration of untreated illness
  • treat better - focus on the quality of remission, do not tolerate partial response
  • treat longer - prevent relapse and recurrence

Better response is achieved with shorter duration of untreated depression - so early treatment is important.1 The duration of depression before recovery may predict the amount of time the patient will be symptom free over the next 10 years.2

Don’t wait and see - lost chances

The ‘wait and see’ approach does not benefit patients. Delayed treatment may hamper full recovery that means a lot to patients,3 who want to feel as ‘good’ as they were before.

The STAR*D study used a series of trials over up to four treatment steps to define the tolerability and effectiveness of various options.4 Remission rates decreased in each step - and so we need effective first-line treatment.

Depression is associated with several cognitive deficits including impaired executive function, memory and processing speed.5 Even in remission, capacity for delayed recall declines steadily with the number of previous depressive episodes.6

Neurotoxicity is clinically relevant. Depressed patients have a smaller hippocampus than controls, and this may be due to repeated periods of MDD.7,8,9 Grey matter density in the hippocampus of MDD patients is declined.10

An old study, but the best of its type, looked at 22 years of data on the nation of Denmark to understand the rate of depression recurrence.11 The rate increased with the number of previous episodes - highlighting that depression is progressive. We need to prevent relapse and recurrence.

Partial remission is the enemy - tell your patients

Don’t let your patients stop treatment if they have not reached full remission. Stopping early reduces the chances of full recovery.

Share this information with patients. Armed with a better understanding of the importance of treatment for long-term recovery, they will have the incentive to make their own decision to commit to treatment.

For further detail on this topic please go to the feature on Lundbeck Institute Campus http://institute.progress.im/en/content/depression-may-be-neurotoxic


  1. de Diego-Adeliño J et al. A short duration of untreated illness (DUI) improves response outcomes in first-depressive episodes. J Affect Disord. 2010;120(1-3):221-5.
  2. Furukawa TA et al. How many well vs. unwell days can you expect over 10 years, once you become depressed? Acta Psychiatr Scand. 2009;119(4):290-7.
  3. Ciudad A et al. Early response and remission as predictors of a good outcome of a major depressive episode at 12-month follow-up: a prospective, longitudinal, observational study. J Clin Psychiatry. 2012;73(2):185-91.
  4. Rush AJ et al. STAR*D: revising conventional wisdom. CNS Drugs. 2009;23(8):627-47.
  5. Millan MJ et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov. 2012;11(2):141-68.
  6. Gorwood P et al. Toxic effects of depression on brain function: impairment of delayed recall and the cumulative length of depressive disorder in a large sample of depressed outpatients. Am J Psychiatry. 2008;165(6):731-9.
  7. Videbech P et al. Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry. 2004;161(11):1957-66.
  8. Stockmeier CA et al. Cellular changes in the postmortem hippocampus in major depression. Biol Psychiatry. 2004;56(9):640-50.
  9. Sheline YI, et al. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci. 1999;19(12):5034-43.
  10. Frodl TS, et al. Depression-related variation in brain morphology over 3 years: effects of stress? Arch Gen Psychiatry. 2008;65(10):1156-65.
  11. Kessing LV et al. Recurrence in affective disorder. I. Case register study. Br J Psychiatry. 1998;172:23‑8.
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