Research

The research group investigates interventional therapies in psychiatry, such as VNS and NMDA antagonists, for the treatment of treatment-resistant depression (TRD). We are particularly interested in predictors of treatment response. The link between TRD and suicidal ideation is another focus of the group.

The working group is led by Dr. Reif-Leonhard, who also serves as the senior consultant in charge of the TRD inpatient unit, the corresponding outpatient clinic, and the VNS and (es)ketamine outpatient clinic. The working group investigates the effectiveness of interventional procedures, also in multicenter studies such as OASIS-D, ECHO (esketamine), and RESTORE-LIFE (VNS). In addition, biological predictors (neurophysiological and electrophysiological) of response to biological therapies are evaluated. EEG methods are primarily used here, for example in the multicenter P4D study; however, digital recording of neuropsychological parameters is also employed. The studies are closely integrated into clinical structures of the Department. Another focus of the working group is the relationship between TRD, contextual factors such as socioeconomic and health policy factors, and suicidal behavior. For example, a longitudinal study examined both the impact of the COVID-19 pandemic and urban factors on suicidality.

• Therapy-resistant depression

• Suicidality

• Esketamine

• Vagus nerve stimulation (VNS)

• Predictors

• EEG

• Neuropsychology

• Neurostimulation

• Epidemiology

• Clinical research

P4D

P4D is a multicenter study investigating response to conventional antidepressants. Our research group focuses specifically on EEG predictors and lipidomic biomarkers, although methylation analyses also play an important role in the overall study.

RESTORE-LIFE

Vagus nerve stimulation is a new, promising treatment option for patients with treatment-resistant depression. However, it is not yet known which patients are likely to benefit the most. For this reason, the multicenter RESTORE-LIFE study is investigating clinical variables that could predict treatment response.

Prädiktoren für das Ansprechen auf Esketamin

Esketamine is the first antidepressant in the class of NMDA antagonists/AMPA activators and is approved for treatment-resistant depression (TRD). However, it is not yet clear which patients respond particularly well to this therapy. We are therefore using neuropsychological emotion regulation tasks to investigate whether an early response to therapy can be predicted. We are also participating in two large epidemiological studies (ECHO, OASIS-D) that examine predictive clinical variables.

FraPPE - sozioökonomische und gesundheitspolitische Kontextfaktoren für suizidales Verhalten

As part of the FraPPE project, funded by the Federal Ministry of Health (BMG), suicides and suicide attempts were systematically recorded throughout the city of Frankfurt over a four-year period; this period also coincided with the onset of the COVID-19 pandemic, allowing for the assessment of its impact on suicidal behavior. Since granular data on patients is available, it is possible to analyze the effects of urban and socioeconomic contextual factors on suicidality.

Group Leader

Dr. Christine Reif-Leonhard, Leitende Oberärztin der Klinik
Reif-Leonhard@med.uni-frankfurt.de
Telefon: 069/6301 87312

Team Members

• Sana Arshad (clinician scientist)

• Jan Leonards (CS)

• Max Bayas (CS)

• Rebecca Stadtje (CS)

• Anja Lichtblau (Study Nurse)

• D. Ferdowssian, R. Joshi, Y. Gülegen (all cand. med.)

• K. Bechstedt, H. Dana, N. Neigefink, S. Kadakathalakal (student assistants)

FraPPE, BMG, 2017-2021

ECHO, J&J, 2023-ongoing

OASIS-D, J&J, 2021-2025

RESTORE-LIFE, LivaNova, 2019-ongoing

P4D, BMBF, 2023-ongoing

• Sana Arshad: Auswertung der Suizidpräventionshotlinedaten (FraPPE-Projekt und Uniklinik Frankfurt separat)
• Dorsa Ferdowssian: Effekt wiederholter Esketamininfusionen auf die Emotionserkennung bei Patienten mit therapieresistenter Depression
• Rachana Ferdowssian: Neuropsychiatrische Langzeitfolgen einer Coronainfektion 
• Yunus Gülegen: Auswirkung einer komorbiden PTBS auf EEG-Parameter bei TRD-Patienten (P4D-Projekt)
• Max Bayas: Populationsbasierte Prävalenz und Pharmakotherapie von TRD in Deutschland, Auswertung von umfangreichen Versicherten-Daten

1. M. Bayas, Auerbach J., …, Reif-Leonhard C. Population-based prevalence and pharmacotherapy sequences of Treatment Resistant Depression in Germany. Accepted for ENP, 2026
2. McAllister-Williams RH, Alva G,…Reif-Leonhard C…, Sackeim HA. The Use of Vagus Nerve Stimulation (VNS) in the Management of Patients with Difficult-to-Treat Major Depressive Disorder (MDD): An Expert Consensus Statement. Neuropsychiatr Dis Treat. 2026 Mar 18; doi: 10.2147/NDT.S554007.
3. Freudenberg F, Reif-Leonhard C, Dawson GR, McKernan RM, Reif A. All roads lead to glutamate: NMDA and AMPA receptors as targets for rapid-acting antidepressants. Pharmacol Res. 2025 Oct;220:107918. doi:10.1016/j.phrs.2025.107918.
4. Reif-Leonhard C, Lemke D, … Schlang C, Reif A. Effectiveness of a communal, multilevel, interdisciplinary suicide prevention program. Eur Psychiatry. 2025 Jul 16;68(1):e119. doi: 10.1192/j.eurpsy.2025.10056.
5. Reif-Leonhard C, Millard SN, Ferdowssian D.… Malik A. Effects of repeated intravenous esketamine administration on affective biases. World J Biol Psychiatry. 2025 Jan;26(1):60-73. doi: 10.1080/15622975.2024.2441304.
6. Zhao T, Schiweck C…,Reif-Leonhard C, … Edwin Thanarajah S. Transcutaneous vagus nerve stimulation improves emotional processing. J Affect Disord. 2025 Mar 1;372:96-105. doi: 10.1016/j.jad.2024.11.077
7. Freudenberg F, Reif-Leonhard C, Reif A. Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression. Eur Arch Psychiatry Clin Neurosci. 2025 Sep;275(6):1547-1557. doi: 10.1007/s00406-024-01875
8. Mueller JK, Ahrens KF, … Reif-Leonhard C. Prevalence of COVID-19 and Psychotropic Drug Treatment in Psychiatric In-patients in Germany in 2020: Results from a Nationwide Pilot Survey. Pharmacopsychiatry. 2023 Nov;56(6):227-238. doi: 10.1055/a-2177-3056.
9. Reif-Leonhard C, Lemke D, …Schlang C, Reif A. Changes in the pattern of suicides and suicide attempt admissions in relation to the COVID-19 pandemic. Eur Arch Psychiatry Clin Neurosci. 2023 Mar;273(2):357-365. doi: 10.1007/s00406-022-01448-y.