. 2022 Jul;129(7):925-944.

doi: 10.1007/s00702-022-02504-6. Epub 2022 May 7.

Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001-2017

Johanna Seifert^#¹, Hannah B Maier^#², Fabienne Führmann³, Stefan Bleich², Susanne Stübner^{4

5}, Marcel Sieberer^{6

7}, Xueqiong Bernegger^{4

8}, Waldemar Greil^{4

8}, Cornelius Schüle⁴, Sermin Toto², Renate Grohmann⁴, Matthias A Reinhard⁴

Affiliations

¹ Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany. seifert.johanna@mh-hannover.de.
² Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
³ Department of Psychiatry and Psychotherapy, KRH Psychiatrie GmbH, Wunstorf, Germany.
⁴ Department of Psychiatry and Psychotherapy, LMU University Hospital Munich, Munich, Germany.
⁵ Department of Forensic Psychiatry, Bezirksklinikum Ansbach, Ansbach, Germany.
⁶ Department of Psychiatry, Psychotherapy and Psychosomatics, St. Marien-Hospital Hamm gGmbH, Hamm, Germany.
⁷ Department of Psychiatry and Psychotherapy, University Witten/Herdecke, Witten, Germany.
⁸ Psychiatric Private Hospital, Sanatorium Kilchberg, Kilchberg, Switzerland.

^# Contributed equally.

PMID: 35524828
PMCID: PMC9217868
DOI: 10.1007/s00702-022-02504-6

Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001-2017

Johanna Seifert et al. J Neural Transm (Vienna). 2022 Jul.

. 2022 Jul;129(7):925-944.

doi: 10.1007/s00702-022-02504-6. Epub 2022 May 7.

Authors

Affiliations

¹ Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany. seifert.johanna@mh-hannover.de.
² Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
³ Department of Psychiatry and Psychotherapy, KRH Psychiatrie GmbH, Wunstorf, Germany.
⁴ Department of Psychiatry and Psychotherapy, LMU University Hospital Munich, Munich, Germany.
⁵ Department of Forensic Psychiatry, Bezirksklinikum Ansbach, Ansbach, Germany.
⁶ Department of Psychiatry, Psychotherapy and Psychosomatics, St. Marien-Hospital Hamm gGmbH, Hamm, Germany.
⁷ Department of Psychiatry and Psychotherapy, University Witten/Herdecke, Witten, Germany.
⁸ Psychiatric Private Hospital, Sanatorium Kilchberg, Kilchberg, Switzerland.

^# Contributed equally.

PMID: 35524828
PMCID: PMC9217868
DOI: 10.1007/s00702-022-02504-6

Abstract

The International Classification of Diseases (10^th Version) categorizes major depressive disorder (MDD) according to severity. Guidelines provide recommendations for the treatment of MDD according to severity. Aim of this study was to assess real-life utilization of psychotropic drugs based on severity of MDD in psychiatric inpatients. Drug utilization data from the program "Drug Safety in Psychiatry" (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) were analyzed according to the severity of MDD. From 2001 to 2017, 43,868 psychiatric inpatients with MDD were treated in participating hospitals. Most patients were treated with ≥ 1 antidepressant drug (ADD; 85.8% of patients with moderate MDD, 89.8% of patients with severe MDD, and 87.9% of patients with psychotic MDD). More severely depressed patients were more often treated with selective serotonin-norepinephrine reuptake inhibitors and mirtazapine and less often with selective serotonin reuptake inhibitors (p < 0.001 each). Use of antipsychotic drugs (APDs), especially second-generation APDs, increased significantly with severity (37.0%, 47.9%, 84.1%; p < 0.001 each). APD + ADD was the most used combination (32.8%, 43.6%, 74.4%), followed by two ADDs (26.3%, 29.3%, 24.9%). Use of lithium was minimal (3.3%, 6.1% ,7.1%). The number of psychotropic drugs increased with severity of MDD-patients with psychotic MDD had the highest utilization of psychotropic drugs (93.4%, 96.5%, 98.7%; p < 0.001). ADD monotherapy was observed to a lesser extent, even in patients with non-severe MDD (23.2%, 17.1%, 4.4%). Findings reveal substantial discrepancies between guideline recommendations and real-life drug utilization, indicating that guidelines may insufficiently consider clinical needs within the psychiatric inpatient setting.

Keywords: Antidepressant drugs; Antipsychotic drugs; Major depressive disorder; Pharmacotherapy; Pharmacovigilance; Psychiatric inpatients.

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Conflict of interest statement

JS took part in an educational event sponsored by Otsuka/Lundbeck. HM participated in an educational event sponsored by Livanova. ST is a member of the advisory board for Otsuka and Janssen-Cilag and has received speaker´s honoraria from Janssen-Cilag, Lundbeck/Otsuka, Recordati Pharma GmbH, and Servier. XB is currently working as Senior Manager for Takeda GmbH. All other authors state that they have no conflicts of interest to declare.

Figures

**Fig. 1**
Utilization of main groups of psychotropic drugs depending on severity of major depressive disorder. Any psychotropic drug: overall: X²(2,43,868) = 331.8, p< 0.001, V= 0.06; moderate vs. severe: X²(1,38,278) = 186.9, p< 0.001, ϕ = 0.07; moderate vs. psychotic: X²(1,17,906) = 229.8, p< 0.001, ϕ = 0.11; severe vs. psychotic: X²(1,31,552) = 73.9, p< 0.001, ϕ = 0.05. Antidepressant drugs: overall: X²(2,43,868) = 132.5, p< 0.001, V= 0.04; moderate vs. severe: X²(1,38,278) = 131.5, p< 0.001, ϕ = 0.06; moderate vs. psychotic: X²(1,17,906) = 145, p< 0.001, ϕ = 0.03; severe vs. psychotic: X²(1,31,552) = 167.6, p< 0.001, ϕ = 0.02. Antipsychotic drugs: overall: X²(2,43,868) = 3473.6, p< 0.001, V= 0.20; moderate vs. severe: X²(1,38,278) = 402.0, p< 0.001, ϕ = 0.10; moderate vs. psychotic: X²(1,17,906) = 3415.8, p< 0.001, ϕ = 0.44; severe vs. psychotic: X²(1,31,552) = 2429.1, p< 0.001, ϕ = 0.28. Tranquilizing drugs: overall: X²(2,43,868) = 796.3, p< 0.001, V= 0.10; moderate vs. severe: X²(1,38,278) = 183.9, p< 0.001, ϕ = 0.07; moderate vs. psychotic: X²(1,17,906) = 797.5, p< 0.001, ϕ = 0.21; severe vs. psychotic: X²(1,31,552) = 421.7, p< 0.001, ϕ = 0.12. Hypnotic drugs: overall: X²(2,43,868) = 22.9, p< 0.001, V= 0.02; moderate vs. severe: X²(1,38,278) = 18.6, p< 0.001, ϕ = 0.02; moderate vs. psychotic: X²(1,17,906) = 0.1, p= 0.86, ϕ < 0.01; severe vs. psychotic: X²(1,31,552) = 8.9, p< 0.05, ϕ = 0.02. Antiepileptic drugs: overall: X²(2,43,868) = 51.7, p< 0.001, V= 0.02; moderate vs. severe: X²(1,38,278) = 44.1, p< 0.001, ϕ = 0.03; moderate vs. psychotic: X²(1,17,906) = 0.5, p= 0.42, ϕ = 0.01; severe vs. psychotic: X²(1,31,552) = 17.0, p< 0.001, ϕ = 0.02. Lithium: overall: X²(2,43,868) = 161.5, p< 0.001, V= 0.04; moderate vs. severe: X²(1,38,278) = 132.9, p< 0.001, ϕ = 0.06; moderate vs. psychotic: X²(1,17,906) = 129.6, p< 0.001, ϕ = 0.09; severe vs. psychotic: X²(1,31,552) = 7.8, p< 0.05, ϕ = 0.02

**Fig. 2**
Utilization of subgroups of antidepressant drugs depending on severity of major depressive disorder. **SSRI**: selective serotonin reuptake inhibitor; overall: X²(2,43,868) = 110.1, p< 0.001, V= 0.04; moderate vs. severe: X²(1,38,278) = 60.6, p< 0.001, ϕ = 0.04; moderate vs. psychotic: X²(1,17,906) = 94.8, p< 0.001, ϕ = 0.07; severe vs. psychotic: X²(1,31,552) = 24.9, p< 0.001, ϕ = 0.03. NaSSA: noradrenergic and specific serotonergic antidepressant: overall: X²(2,43,868) = 86.4, p< 0.001, V= 0.03; moderate vs. severe: X²(1,38,278) = 85.1, p< 0.001, ϕ = 0.05; moderate vs. psychotic: X²(1,17,906) = 29.7, p< 0.001, ϕ = 0.04; severe vs. psychotic: X²(1,31,552) = 1.1, p= 0.30, ϕ = 0.01. SSNRI: selective serotonin-norepinephrine reuptake inhibitor: overall: X²(2,43,868) = 85.4, p< 0.001, V= 0.03; moderate vs. severe: X²(1,38,278) = 82.1, p< 0.001, ϕ = 0.05; moderate vs. psychotic: X²(1,17,906) = 35.9, p< 0.001, ϕ = 0.04; severe vs. psychotic: X²(1,31,552) = 0.1, p= 0.76, ϕ < 0.01. TCA: tricyclic antidepressant: overall: X²(2,43,868) = 97.9, p< 0.001, V= 0.03; moderate vs. severe: X²(1,38,278) = 97.4, p< 0.001, ϕ = 0.05; moderate vs. psychotic: X²(1,17,906) = 18.4, p< 0.001, ϕ = 0.03; severe vs. psychotic: X²(1,31,552) = 7.9, p< 0.05, ϕ = 0.02. MAO-I: monoamine oxidase inhibitor: overall: X²(2,43,868) = 85.4, p< 0.001, V= 0.03; moderate vs. severe: X²(1,38,278) = 66.2, p< 0.001, ϕ = 0.04; moderate vs. psychotic: X²(1,17,906) = 81.9, p< 0.001, ϕ = 0.07; severe vs. psychotic: X²(1,31,552) = 6.9, p< 0.05, ϕ = 0.01

**Fig. 3**
Utilization of subgroups of antipsychotic drugs (APD) depending on severity of major depressive disorder. Second-generation APD: X²(2,43,868) = 4605.1, p< 0.001, V= 0.23; moderate vs. severe: X²(1,38,278) = 249.4, p< 0.001, ϕ = 0.08; moderate vs. psychotic: X²(1,17,906) = 4110.3, p< 0.001, ϕ = 0.48; severe vs. psychotic: X²(1,31,552) = 3514.2, p< 0.001, ϕ = 0.33. High-potency (hp) first-generation APDs: overall: X²(2,43,868) = 612.3, p< 0.001, V= 0.08; moderate vs. severe: X²(1,38,278) = 17.7, p< 0.001, ϕ = 0.02; moderate vs. psychotic: X²(1,17,906) = 440.3, p< 0.001, ϕ = 0.16; severe vs. psychotic: X²(1,31,552) = 455.9, p< 0.001, ϕ = 0.12. Low-potency (lp) first-generation APDs: overall: X²(2,43,868) = 147.9, p< 0.001, V= 0.04; moderate vs. severe: X²(1,38,278) = 146.8, p< 0.001, ϕ = 0.06; moderate vs. psychotic: X²(1,17,906) = 26.4, p< 0.001, ϕ = 0.04; severe vs. psychotic: X²(1,31,552) = 13.0, p< 0.001, ϕ = 0.02

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Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001-2017

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Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001-2017

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