Outcome of a three-phase treatment algorithm for inpatients with melancholic depression

https://doi.org/10.1016/j.pnpbp.2018.03.002Get rights and content

Highlights

  • In the completers, the favorable outcome of the algorithm is shown by a 93% response rate and a 64% remission rate.

  • Feasibility of the algorithm was reasonable, with an overall dropout rate of 28%.

  • Both an index episode less than one year, and not having received previous adequate treatment predicted a greater chance of achieving remission.

Abstract

Background

In patients suffering from major depressive disorder, non-response to initial antidepressant monotherapy is relatively common. The use of treatment algorithms may optimize and enhance treatment outcome.

Methods

A single-center 3-phase treatment algorithm was evaluated for inpatients with major depressive disorder, i.e. phase I (n = 85): 7 weeks optimal antidepressant monotherapy (imipramine or venlafaxine); phase II (n = 39): 4 weeks subsequent plasma level-targeted dose lithium addition in case of insufficient improvement of antidepressant monotherapy; and phase III (n = 8): subsequent electroconvulsive therapy in case of insufficient improvement of antidepressant‑lithium treatment. Overall feasibility of the 3-phase algorithm was determined by the number of dropouts, and overall efficacy was evaluated using weekly scores on the 17-item Hamilton Rating Scale for Depression (HAM-D) during the treatment phases of the algorithm. This paper is based on an RCT comparing the two antidepressants in phase I and adding lithium in phase II.

Results

Of the 85 patients analyzed, overall dropout during the 3-phase treatment algorithm was 24 (28%) patients. When analyzing the 3-phase treatment algorithm on a modified intention-to-treat basis, 39 (46%) patients achieved complete remission (HAM-D score ≤ 7) by the end of the algorithm. Regarding response (HAM-D score reduction ≥50%): of the 85 patients, 60 (71%) were responders by the end of the algorithm.

Conclusion

The favorable outcome of the 3-phase treatment algorithm emphasizes the importance of pursuing stepwise antidepressant treatment in patients who are nonresponsive to the first antidepressant.

Clinical trial registration

This study protocol is registered at http://www.controlled-trials.com, “Pharmacological Treatment of Depression” (identifier: ISRCTN73221288).

Introduction

According to the WHO World Mental Health (WMH) surveys, mental disorders are common in the general population, with mood disorders being the second most prevalent class (anxiety disorders being the most prevalent class) (Kessler et al., 2009). Mood disorders place a considerable burden on individuals and the society. In the WMH surveys, the lifetime prevalence of any mood disorder in the general population was found to be approximately 12% (Kessler et al., 2009). Moreover, the adequacy of treatment of mood disorders, with regard to dose and duration, remains a challenge in clinical practice. About 30–40% of patients with major depressive disorder (MDD) are non-responders to initial antidepressant monotherapy and a substantial proportion of these patients develop chronic depressive symptoms (Adli et al., 2006). The use of treatment guidelines (also known as treatment algorithms) for the treatment of MDD optimizes and enhances treatment outcome by stepwise ordering of the different treatments and providing guidance on how best to implement the different treatments (Adli et al., 2006; Bauer et al., 2009; Linden et al., 1994; Birkenhäger et al., 2006; Trivedi et al., 2004; Yoshino et al., 2009).

The present study aimed to evaluate the overall feasibility and efficacy of a 3-phase treatment algorithm for inpatients with major depression: phase I optimal antidepressant monotherapy (imipramine or venlafaxine); phase II subsequent lithium addition in case of insufficient improvement of antidepressant monotherapy; phase III subsequent electroconvulsive therapy (ECT) in case of insufficient improvement of antidepressant‑lithium treatment. All three phases were carried out while the patients were hospitalized.

Phase I, II and III combined form the entire treatment algorithm under evaluation.

This paper is based on an RCT comparing the two antidepressants in phase I and adding lithium in phase II (Vermeiden et al., 2013, Vermeiden et al., 2017).

Section snippets

Sample

Recruitment took place at the inpatient depression unit of the Department of Psychiatry of the Erasmus Medical Center Rotterdam (EMCR), between March 2005 and March 2010. Patients suffering from uncomplicated MDD and patients suffering from treatment-resistant depression are treated at the depression unit. Included were all patients admitted to the depression unit, aged 18 years and older, diagnosed with single or recurrent MDD, both with and without psychotic features, and a baseline

Patient population

Between March 2005 and March 2010, 244 patients with MDD were admitted to the inpatient depression unit of the Department of Psychiatry of the EMCR; of these, 125 (51%) were excluded (Table 1). Of the remaining 119 eligible patients, 31 (26%) refused participation in an RCT or receiving double-blind medication.

Of the 244 patients, 88 (36%) were included in the 3-phase treatment algorithm; of these, 3 (1%) patients dropped out after randomization but before study medication was started, i.e.1

Discussion and comparison with previous reports

During the 5-year study period, 244 patients with MDD were admitted to the depression unit and 36% of them participated in the 3-phase algorithm. Twenty-six percent of the eligible patients refused to provide informed consent, despite receiving thorough information about the study procedures from the nursing staff. Most patients refused receiving double-blind medication. All patients who participated suffered from severe major depression, as evidenced by both the mean baseline 17-item HAM-D

Conclusion

The present results emphasize the importance of pursuing stepwise antidepressant treatment in patients not responding to the first antidepressant. In the completers, the favorable outcome of the algorithm is shown by a 93% response rate and a 64% remission rate. Adherence to the algorithm was reasonable, with an overall dropout rate of 28%. Both an index episode less than one year and not having received previous adequate treatment predicted a greater chance of achieving remission with the

Declaration of conflicting interest

Vermeiden M, Kamperman AM, Van Den Broek WW and Hoogendijk WJG have no conflict of interests and disclosures to declare. Birkenhäger TK received an unrestricted grant from Lundbeck BV and received speaker's fees from Lundbeck BV.

The data have not previously been presented. The Department of Psychiatry, Erasmus Medical Center Rotterdam, owns the preexisting data. All authors have access to all data. Vermeiden M (first author) can provide access to the full trial protocol and all data of the

Funding

Funding for this study was provided by the Department of Psychiatry of the Erasmus Medical Center Rotterdam, the Netherlands. Venlafaxine was provided by Wyeth Pharmaceuticals.

Ethical Statement

Our study protocol was approved by the Medical Ethics Committee of Erasmus MC Rotterdam. Our study was carried out in accordance with the Declaration of Helsinki (1964), as amended in Edinburgh (2000). All patients provided written informed consent prior to entering the study.

Acknowledgments

The authors thank the following for their support: Mrs. S. Verploegh for valuable assistance in data collection and Laraine Visser-Isles for English language editing.

References (29)

  • M. Bauer et al.

    Efficacy of an algorithm-guided treatment compared with treatment as usual, a randomized, controlled study of inpatients with depression

    J. Clin. Psychopharmacol.

    (2009)
  • M. Bauer et al.

    World Federation of Societies of biological psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders. Part 2: maintenance treatment of major depressive disorder-update 2015

    World J. Biol. Psychiatry

    (2015)
  • T.K. Birkenhäger et al.

    Outcome of a 4-step treatment algorithm for depressed inpatients

    J. Clin. Psychiatry

    (2006)
  • T.K. Birkenhager et al.

    Efficacy of imipramine in psychotic versus nonpsychotic depression

    J. Clin. Psychopharmacol.

    (2008)
  • View full text