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Psychomotor Retardation and the Prognosis of Antidepressant Treatment in Patients with Unipolar Psychotic Depression

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Psychomotor Retardation and the Prognosis of Antidepressant Treatment in Patients with Unipolar Psychotic Depression Journal of Psychiatric Research 130 (2020) 321–326 Contents lists available at ScienceDirect Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/jpsychires Psychomotor Retardation and the prognosis of antidepressant treatment in patients with unipolar Psychotic Depression Joost G.E. Janzing a,*, Tom K. Birkenhager¨ b, Walter W. van den Broek b, Leonie M.T. Breteler c, Willem A. Nolen d, Robbert-Jan Verkes a a Department of Psychiatry, Department of Psychiatry, Radboudumc, Nijmegen, the Netherlands b Department of Psychiatry Erasmus University Medical Centre, Rotterdam, the Netherlands c Department of Psychiatry, St. Antonius-Mesos Hospital, Utrecht, the Netherlands d Department of Psychiatry, University Medical Center Groningen, the Netherlands ARTICLE INFO ABSTRACT Keywords: Background: Psychomotor Retardation is a key symptom of Major Depressive Disorder. According to the literature Antidepressive agents its presence may affect the prognosis of treatment. Aim of the present study is to investigate the prognostic role of Affective disorders Psychomotor Retardation in patients with unipolar Psychotic Depression who are under antidepressant Psychotic treatment. Depression Methods: The Salpetriere Retardation Rating Scale was administered at baseline and after 6 weeks to 122 patients Drug therapy Psychomotor retardation with unipolar Psychotic Depression who were randomly allocated to treatment with imipramine, venlafaxine or venlafaxine plus quetiapine. We studied the effects of Psychomotor Retardation on both depression and psychosis related outcome measures. Results: 73% of the patients had Psychomotor Retardation at baseline against 35% after six weeks of treatment. The presence of Psychomotor Retardation predicted lower depression remission rates in addition to a higher persistence of delusions. After six weeks of treatment, venlafaxine was associated with higher levels of Psy­ chomotor Retardation compared to imipramine and venlafaxine plus quetiapine. Conclusions: Our data confirm that Psychomotor Retardation is a severity marker of unipolar Psychotic Depression. It is highly prevalent and predicts lower effectivity of antidepressant psychopharmacological treatment. 1. Introduction 2017). Possibly related to its association with depression severity, literature Psychomotor Retardation is a key symptom of Major Depressive suggests that the presence of Psychomotor Retardation could inform Disorder (MDD) (American Psychiatric Association, 2013). It is char­ treatment choice: patients with Psychomotor Retardation responded acterized by slowness in both cognitive and motor processing and can be poorly to Selective Serotonin Reuptake Inhibitors (SSRIs) (Schrijvers observed in speech, thinking and body movements (Schrijvers et al., et al., 2008; Ulbricht et al., 2018). More positive results were found for 2008). In patients with unipolar depression prevalences of 60–70% have Tricyclic Antidepressants (TCAs), other dual acting antidepressants and been established (Novick et al., 2005). combinations of serotonergic and noradrenergic agents (Sobin and Psychomotor Retardation is a severity marker of depression. It is Sackeim, 1997; Schrijvers et al., 2008). Psychomotor Retardation pre­ associated with several characteristics indicating a severe course of dicted a higher treatment response in patients selected for Electrocon­ depression including an early age of onset, a longer duration of illness, a vulsive Therapy (Hickie et al., 1996; van Diermen et al., 2019; Heijnen higher number of depressive episodes and increased rates of suicide et al., 2019). attempts (Calugi et al., 2011). In addition, Psychomotor Retardation is Although Psychomotor Retardation is very common in Psychotic the primary symptom delineating the more severe melancholic subtype Depression, with a reported prevalence of up to 75% (Parker et al., from non-melancholic depression (Parker, 2000; Parker and McCraw, 1991), little research has been conducted to its role in the * Corresponding author. Department of Psychiatry, (961), Radboudumc, PO Box 9101, 6500 HB, Nijmegen, the Netherlands. E-mail address: [email protected] (J.G.E. Janzing). https://doi.org/10.1016/j.jpsychires.2020.07.020 Received 14 March 2020; Received in revised form 12 July 2020; Accepted 17 July 2020 Available online 9 August 2020 0022-3956/© 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). J.G.E. Janzing et al. Journal of Psychiatric Research 130 (2020) 321–326 pharmacological treatment of patients with Psychotic Depression. on a five point likert scale ranging from 0 (normal) to 4 (severe distur­ Additional research is important to conclude if Psychomotor Retarda­ bance) and refer to motor function, speech and objective and subjective tion influencesthe outcome of pharmacological treatment, as is the case mental activity (Dantchev and Widlocher, 1998). For the Dutch version in non- Psychotic Depression. The main aim of this study is to evaluate good internal consistency was confirmed. Interrater reliability was suf­ the role of Psychomotor Retardation as a predictor of treatment ficientto good. Convergent validity was indicated by a high association response, taking different outcome measures into account. Based on the between the SRRS score and the retardation items of the Comprehensive associations with severity in patients with non-psychotic MDD (Calugi Psychopathological Rating Scale (de Weme et al., 1996). et al., 2011), we hypothesize that the presence of Psychomotor Retar­ Measures of Psychomotor Retardation: dation predicts a lower response to pharmacological treatment. a. The SRRS-6 score, is the sum score of the first six SRRS items. This 2. Methods subscale includes only objective (assessor observed) items, while the complete SRRS scale also relies on the subjective experiences of We used data from a multicentre, double-blind randomized patients which might be biased by depression (Brebion et al., 1997; controlled trial comparing the efficacy of imipramine (Tricyclic Anti­ Lampe et al., 2001; Smith et al., 1994). depressant), venlafaxine (Serotonin-Noradrenaline Reuptake Inhibitor) b. Clinical Psychomotor Retardation, defined as a total SRRS score and venlafaxine plus quetiapine (2nd generation antipsychotic agent) in above the cut-off of 20 points (Widlocher, 1983). patients with unipolar Psychotic Depression. The complete description c. HAM-D retardation (HAM-D item 8; score 0 or 1 coded as absent; of the study can be found elsewhere (Wijkstra et al., 2010). Here, we score ≥2 coded as present). This dichotomized score reflects pres­ present a summary of the methods. ence or absence of psychomotor retardation, not severity. In the present study the HAM-D retardation score was only used for cross- 2.1. Patients validation of the SRRS based scores. Hospitalized patients aged 18–65 years were included if they met 2.4. Outcome measures DSM-IV-TR criteria (American Psychiatric Association, 2000) for uni­ polar major depressive episode with psychotic features and a score ≥18 Outcome of pharmacological treatment was measured after 7 weeks. on the Hamilton Rating Scale for Depression (HAM-D; 17 item version; The primary outcome measure is response, definedas a HAM-D score of Hamilton, 1960) both at the screening visit and at the day prior to start ≤14 and a ≥50% decrease from baseline. The maximum score of 14 in of medication. Exclusion criteria were: an acute indication for electro­ this definition was also applied in the primary study (Wijkstra et al., convulsive therapy (ECT); mental retardation; alcohol or substance 2010) and was chosen to preclude moderate to severe depression in abuse or dependence within 3 months of enrolment; any serious somatic patients who reached response. Secondary outcome measures were: a) illness; somatic medication affecting mood; contraindications for study treatment remission defined as HAM-D ≤7; b) the presence of halluci­ medication; adequate previous treatment of the current episode with nations and c) the presence of delusions. Assessments of hallucinations imipramine (≥4 weeks with adequate plasma levels (200–300 μg/l)) or and delusions were based on psychiatric interview and clinical obser­ venlafaxine (≥4 weeks ≥ 300 mg ⁄ day). vations (scored 1 if present and 0 if absent). Administration of HAM-D, SRRS and other measures was discussed 2.2. Study design at regular meetings with the researchers from all participating sites. Inter-rater reliability as indicated by the intraclass correlation coeffi­ The study was approved by the ethical review board of the University cient and based on three patients and eight raters was 0.93 (95% CI: Medical Centre Utrecht, and by the local review boards of the partici­ 0.74; 1.00) for the HAM-D. pating centres, and performed according to the rules of Good Clinical Practice. All patients, or their legal relatives in case of incapacity, gave written informed consent prior to enrolment. 2.5. Statistical analysis The diagnosis of unipolar Psychotic Depression was confirmedusing the Structured Clinical Interview for DSM-IV Axis I disorders (First, Univariate associations were expressed as Pearson’s correlation co­ 1999). Baseline assessments also included a psychiatric history, a efficients. For testing of changes in categorical and dimensional mea­ medical history and a physical examination including vital signs and sures we used chi-square tests and paired t-tests respectively. routine
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