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. 2024 Jun 24:15:1415505.
doi: 10.3389/fpsyt.2024.1415505. eCollection 2024.

Baseline monocyte count predicts symptom improvement during intravenous ketamine therapy in treatment-resistant depression: a single-arm open-label observational study

Bruno Pedraz-Petrozzi  1   2   3 , Moritz Spangemacher  1   3   4 , Anton Deicher  1 , Lena Drews  4 , Julie Defert  4 , Ana Yaiza Silva-Colmenero  4 , Paul Wein  5 , Elena Riedinger  5 , Gerhard Gründer  3   4 , Maria Gilles  1   2   3 , Alexander Sartorius  1   3   5 , Jonathan R Reinwald  1   3   5   6
Affiliations

Baseline monocyte count predicts symptom improvement during intravenous ketamine therapy in treatment-resistant depression: a single-arm open-label observational study

Bruno Pedraz-Petrozzi et al. Front Psychiatry. .

Abstract

Background: Neuroinflammatory processes in depression are associated with treatment resistance to conventional antidepressants. Ketamine is an effective new therapeutic option for treatment-resistant depression (TRD). Its well-established immunomodulatory properties are hypothesized to mediate its antidepressant effect. In this context, higher levels of inflammation may predict a better treatment response. However, conclusive evidence for this hypothesis is lacking. We thus investigated whether standard peripheral inflammatory cell markers and C-reactive protein (CRP) levels could predict symptom improvement during intravenous ketamine therapy in TRD patients.

Methods: 27 participants with TRD were treated with six weight-adjusted intravenous ketamine infusions (0.5 mg/kg bodyweight) over three weeks. Baseline assessments included CRP, absolute monocyte count (AMC), and absolute neutrophil count (ANC). Depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline (D1), after the first (D3) and before the last ketamine infusion (D18). Raters were blinded for the baseline laboratory assessments.

Results: 13 participants responded to ketamine treatment, and 8 participants partially responded. Baseline AMC showed a strong negative correlation with MADRS change at D3 (r=-0.57, p=0.002) and at D18 (r =-0.48, p=0.010), indicating that a high baseline AMC was associated with greater symptom improvement. A generalized linear model confirmed the association of baseline AMC with symptom improvement during ketamine treatment when additionally accounting for age, sex, and body mass index. Specifically, baseline AMC demonstrated predictive value to discriminate responders and partial responders from non-responders, but lacked discriminative ability between partial responders and responders. Baseline ANC correlated with the MADRS changes at D3 (r=-0.39, p=0.046), while CRP values did not correlate at all.

Conclusions: Our prospective single-arm open-label observational study demonstrated that baseline AMC reliably predicted symptom improvement during intravenous ketamine treatment in TRD patients. AMC could therefore serve as a simple and easily accessible marker for symptom improvement during ketamine therapy in daily clinical practice. Future studies with larger sample sizes and a more detailed longitudinal assessment of AMC subtypes are needed to better understand the specific relationship between monocytes and the neuromodulatory effects of ketamine.

Keywords: immunity; inflammation; ketamine; monocyte; neutrophil; prediction; treatment response; treatment-resistant depression.

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Conflict of interest statement

Gerhard Gründer has served as a consultant for Boehringer Ingelheim, Institute for Quality and Efficiency in Health Care (IQWiG), Janssen-Cilag, Lundbeck, MindMed, Otsuka, Recordati, Roche, ROVI, Sage, and Takeda. He has served on the speakers’ bureau of Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Recordati, and ROVI. He has received grant support from Beckley Psytech and Boehringer Ingelheim. He is co-founder and/or shareholder of Mind and Brain Institute GmbH, OVID Health Systems GmbH and MIND Foundation gGmbH. Jonathan Reinwald has received speaker fees from Egetis Therapeutics. Moritz Spangemacher has received speaker fees from MIND Foundation gGmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest.

Figures

Figure 1
Figure 1
Repeated measures analysis of variance for MADRS and BDI-II scores and comparison of MADRS change between responders, partial responders and non-responders.The MADRS (A) and BDI-II scores (B) are illustrated as mean ± standard error of the mean at D1, D3 and D18. The bar plots in (C) illustrate the change in MADRS score (mean ± standard error of the mean) compared to baseline for D3 (orange, left) and D18 (blue, right) in non-responders, partial responders and responders.BDI-II = Beck Depression Inventory, MADRS = Montgomery-Åsberg Depression Rating Scale, D1 = baseline or day 1, D3 = day 3, D18 = day 18, NR = non-responders, ns = not significant, PR = partial responders, R = responders. * = p < 0.05, **** = p < 0.0001.
Figure 2
Figure 2
Correlations between absolute changes in MADRS scores (D3-D1 and D18-D1) and baseline logAMC (cells/L) in TRD patients treated with intravenous ketamine for three weeks. MADRS [D3-D1]: Pearson’s r=-0.57, p=0.002; MADRS [D18-D1]: Pearson’s r =-0.48, p=0.010. AMC, absolute monocyte count; D1, baseline or day 1; D3, day 3; D18, day 18; MADRS, Montgomery-Åsberg Depression Rating Scale; TRD, treatment-resistant depression. AMC was logarithmically transformed due to non-normal distribution.
Figure 3
Figure 3
Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) values for the prediction of treatment response. The ROC curves illustrate the ability of logAMC to discriminate between non-responders and partial responders (A), partial responders and responders (B), and non-responders and responders (C) for D3 (top) and D18 (bottom), respectively. logAMC, log-transformed absolute monocyte count.
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