Research reportLong-term response to successful acute pharmacological treatment of psychotic depression☆
Introduction
Although 20% of patients with an episode of major depressive disorder met criteria for psychotic depression (Coryell et al., 1984, Johnson et al., 1991, Wheeler Vega et al., 2000, Ohayon and Schatzberg, 2002) we found in a meta-analysis (up to 2004) only 10 randomized, double-blind trials (RCTs) studying its treatment. In this meta-analysis the combination of an antidepressant and an antipsychotic was found significantly more effective than an antipsychotic alone (3 studies;188 patients) but not significantly more effective than an antidepressant alone (2 studies; 77 patients) (Wijkstra et al., 2005, Wijkstra et al., 2006).
After having achieved response in psychotic depression, relapse rates are probably high (Rothschild and Duval, 2003). There are no double-blind studies on how to continue treatment after response. After response to antidepressant monotherapy, continuation with the same medication may be effective (Zanardi et al., 1997). However, it is unclear how to continue treatment after response to the combination of an antidepressant with an antipsychotic and for how long (Keck et al., 2000). As most relapses in psychotic depression appear to occur in the first 4 months after remission (Sackeim et al., 1990, Sackeim et al., 2001, Birkenhäger et al., 2005), continuation treatment should be at least 4 months.
In a recent 7 week RCT comparing imipramine, venlafaxine and venlafaxine + quetiapine (Wijkstra et al., 2010) we found that significantly more patients responded to venlafaxine + quetiapine (27/41; 65.9%) than to venlafaxine alone (13/39; 33.3%), while the difference between venlafaxine + quetiapine and imipramine (22/42; 52.4%) or between imipramine and venlafaxine was not statistically significant. Overall, tolerability was good. Weight increase was highest with venlafaxine + quetiapine.
In this paper we report the results of a 4 month open continuation treatment of those patients who completed the acute trial as responder, with focus on the question as to what extent response and remission rates as well as tolerability were maintained during follow-up and whether this differed between treatment conditions.
Section snippets
Patients and study design
The protocol of the acute trial has been described elsewhere (Wijkstra et al., 2010). In short, 122 patients with psychotic depression (SCID I, DSM-IV criteria) were randomized to a 7 week double-blind treatment with imipramine (plasma levels of 200–300 ng/ml), venlafaxine (375 mg/day) or venlafaxine + quetiapine (375 mg/day/600 mg/day). The present report concerns a 4 month follow-up among those patients who had achieved response (≥ 50% decrease and a final score ≤ 14 on the Hamilton Rating Scale for
Patient disposition
After the acute trial (week 7) there were 59 out of 122 (48.4%) patients who had completed the trial as responders: 20 in the imipramine group, 13 in the venlafaxine group and 26 in the venlafaxine + quetiapine group. Characteristics at baseline (week 0) and at week 7 of these 59 patients are summarized in Table 1. Although not statistically different, the groups showed differences in duration of the depressive episode and in hallucinations.
Six patients (10.2%) dropped out during follow-up: in
Discussion
The major finding of this study is that almost all patients (86.4%; 51/59) who had completed the acute double-blind trial as responders, remained responder after follow-up of another 15 weeks during which almost all of them (88.7%;47/53) continued the same medication. Relapse rate during these 4 months (3.8%; 2/53) was low and comparable with 0% relapse rates in previous studies (4 months continuation treatment with fluoxetine and perphenazine (Rothschild and Duval, 2003), and 6 months
Role of funding source
The study was supported by grants from AstraZeneca and Wyeth Pharmaceuticals, both of which also provided the study medication. They had the opportunity to review the manuscript. AstraZeneca and Wyeth had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Conflicts of interest
J. Wijkstra
—Grants: AstraZeneca, Wyeth
—Honoraria/Speaker's fees: AstraZeneca, Wyeth
H. Burger
—Grants: Stanley Medical Research Institute
W.W. van den Broek
—Grants: Hersenstichting
—Honoraria/Speaker's fees: Servier, Wyeth
R.J. Verkes
—Grants: ZonMw, Astra Zeneca, Eli Lilly, Pfizer, Wyeth, Organon, NWO
—Honoraria/Speaker's fees: Astra Zeneca, Eli Lilly, Lundbeck, Wyeth, Organon, BMS
—Advisory boards: Eli Lilly, Servier, Organon, Lareb
T.K. Birkenhäger
—Grants: Wyeth
—Honoraria/Speaker's fees: Wyeth,
Acknowledgments
The authors thank the following for their support:
J.P. Selten, R. van Ojen, .I Klijn: independent psychiatrist for medication
G. Hugenholtz, H. Wassens, C. Stuivenberg, T. Gerbranda: central distribution of medication
F. Ververs: laboratory (plasma levels imipramine)
E.A. Wijnia, K. Nijssen, J.W. van de Maaskant, Julius Center
J. Verploegh, J. Leijtens: research nurses
F. Kruisdijk, psychiatrist, Symfora, Amersfoort
M.F. de Vries, L.J. Vos, I. Sommer, C. Schubart, UMC Utrecht
N.P.J.T. van Schayk, I.
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This study protocol was registered at: http://www.controlled-trials.com/isrctn/trial ISRCTN36607067.