Preventing Relapse After Successful ECT for Depression

Project title

PRASED – Preventing Relapse After successful ECT for depression

Project description

In the current research project, we assess the additional effect of lithium addition in preventing relapse following electroconvulsive therapy (ECT) for depression. 

Project duration

01/01/2019 - 01/12/2022

Promotor

Didier Schrijvers

Pascal Sienaert

PhD researcher

Jean-Baptiste Belge

Team

Violette Coppens, Eline Schellens, Ingrid Vanderplas, Sarah Debruyne

Contact

For more information please contact Didier Schrijvers:

Tel. n°: 015304189

E-mail: didier.schrijvers@uantwerpen.be

Summary

Although electroconvulsive therapy (ECT) is a very effective acute treatment for (unipolar as well as bipolar(1,2)) major depression, one of the major challenges in the treatment of mood disorders is to prevent relapse after successful treatment. Without continuation treatment, up to 50% of patients will relapse within 3 months after the last treatment and 6 months relapse rates are as high as 80% (3).

Several strategies have been used to decrease these relapse rates. The most commonly used strategy, pharmacological treatment with antidepressants, decrease 6-month relapse rates by 30% (4,5). Nevertheless, as nearly half of patients on antidepressants will relapse within one year after successful ECT, relapse prevention remains a major challenge (6,7). Other strategies are addition of lithium to antidepressant maintenance treatment or continuation of ECT after the acute course (M-ECT), alone or in combination with antidepressants and/or lithium.  These strategies decrease relapse rates to different extents.

In a large RCT, lithium in combination with Nortriptyline reduced 6-month-relapse rates to 32% (8). A recently published audit also found superior results of the combination of an antidepressant with lithium at six months (relapse rate of 16%) (9). Although it is advised to consider lithium combined with an antidepressant as a possible continuation treatment after ECT (10), its effectiveness remains understudied.

M-ECT is a course that begins after the end of the acute ECT course and is intended to prevent relapse of the treated episode occurrence of a new depressive episode (11). Continuation of ECT can be done either at a fixed schedule (slowly tapering of ECT according to a fixed schedule) or personalized (flexible ECT depending on change in the level of depression symptoms). Most studies have used a fixed M-ECT scheme, while clinical practice suggest that a flexible, symptom driven treatment scheme might be more effective in preventing relapse (12). This was confirmed in the recently published PRIDE-study (13). Only 13% of the patients receiving personalized ECT, an antidepressant and lithium had relapsed at six months. This study, however, was limited to elderly patients, who are known to respond better (14) and have a better long-term outcome than the non-elderly (15).

Our project is designed to validate results of the PRIDE-study, not limiting inclusions to older patients, as about half of the patients treated with ECT are non-elderly and relapse prevention in this patient group is as least as challenging. Besides that, we would like to assess the additional effect of lithium addition in preventing relapse with a flexible, symptom-driven and personalized ECT algorithm. After successful brief pulse ECT, patients will be randomized to receive either personalized M-ECT in combination with their ongoing (antidepressant) medication and lithium, or personalized M-ECT in combination with their ongoing (antidepressant) medication without lithium. There will be a follow-up period of one year.

This project enables us to validate the effectiveness of personalized M-ECT, and to assess the effectiveness of lithium as part of a relapse prevention strategy post-ECT. Improving relapse prevention is ‘the most pressing issue in the field’ (7), with an added value for the group of patients with depression that were treated with ECT. As this is only scarcely been investigated, it leaves the clinician without clear

guidance on the best treatment strategy after successful ECT. Although our main goal is a positive medical impact, reducing relapse rates eventually also has a socio-economic influence by reducing health care costs.

References

1. Dierckx B, Heijnen WT, van den Broek WW, Birkenh.ger TK. Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta-analysis. Bipolar Disord [Internet]. 2012 Mar [cited 2014 Nov 27];14(2):146–50.

2. Haq AU, Sitzmann AF, Goldman ML, Maixner DF, Mickey BJ. Response of depression to electroconvulsive therapy: a meta-analysis of clinical predictors. J Clin Psychiatry [Internet]. 2015 Oct;76(10):1374–84.

3. Jelovac A, Kolshus E, McLoughlin DM. Relapse following successful electroconvulsive therapy for major depression: a meta-analysis. Neuropsychopharmacology [Internet]. 2013 Nov [cited 2014 May 11];38(12):2467–74.

4. Sackeim H a, Haskett RF, Mulsant BH, Thase ME, Mann JJ, Pettinati HM, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA. 2001;285(10):1299–307.

5. van den Broek WW, Birkenh.ger TK, Mulder PGH, Bruijn JA, Moleman P. Imipramine is effective inpreventing relapse in electroconvulsive therapy-responsive depressed inpatients with prior pharmacotherapy treatment failure: a randomized, placebo-controlled trial. J Clin Psychiatry [Internet]. 2006 Feb;67(2):263–8.

6. Gueorguieva R, Chekroud AM, Krystal JH. Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis.The lancet Psychiatry [Internet]. 2017 Mar;4(3):230–7.

7. Lisanby SH. Electroconvulsive therapy for depression. N Engl J Med [Internet]. 2007 Nov 8 [cited 2014 Dec 8];357(19):1939–45.

8. Kellner CH, Knapp RG, Petrides G, Rummans TA, Husain MM, Rasmussen K, et al. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry[Internet]. 2006 Dec [cited 2014 May 11];63(12):1337–44.

9. Atiku L, Gorst-Unsworth C, Khan BU, Huq F, Gordon J. Improving Relapse Prevention After Successful Electroconvulsive Therapy For Patients With Severe Depression. J ECT [Internet]. 2015;31(1):34–6.

10. Rasmussen KG. Lithium for post-electroconvulsive therapy depressive relapse prevention: a consideration of the evidence. J ECT [Internet]. 2015 Jun;31(2):87–90.

11. Petrides G, Tobias KG, Kellner CH, Rudorfer M V. Continuation and maintenance electroconvulsive therapy for mood disorders: Review of the literature. Neuropsychobiology. 2011;64(3):129–40.

12. Lisanby SH, Sampson S, Husain MM, Petrides G, Knapp RG, McCall V, et al. Toward individualized post electroconvulsive therapy care: piloting the Symptom-Titrated, Algorithm-Based Longitudinal ECT (STABLE) intervention. J ECT [Internet]. 2008 Sep [cited 2014 May 11];24(3):179–82.

13. Kellner CH, Husain MM, Knapp RG, McCall WV, Petrides G, Rudorfer M V, et al. A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study. Am J Psychiatry [Internet]. 2016 Nov 1;173(11):1110–8.

14. van Diermen L, van den Ameele S, Kamperman AM, Sabbe BCG, Vermeulen T, Schrijvers D, et al. Prediction of electroconvulsive therapy response and remission in major depression: meta-analysis. Br J psychiatry [Internet]. 2018 Feb;212(2):71–80.

15. Rosen BH, Kung S, Lapid MI. Effect of Age on Psychiatric Rehospitalization Rates After Electroconvulsive Therapy for Patients With Depression. J ECT [Internet]. 2015 Aug 25;00(00):1.