Precision psychiatry: Anti-inflammatory medication in Immuno-metabolic depression

Depression is a major driver of disability and related health-care costs.
Available treatment options are far from optimal, with only ~60% response.
Developing effective treatments requires new treatment targets to depression
pathophysiology. As the role of (neuro)inflammation in depression is emerging,
augmentation of antidepressant treatments with anti-inflammatory drugs such as
celecoxib has shown encouraging preliminary results.
However, inflammation is not present in all depressed patients.
Depression is heterogeneous: patients express diverse and sometimes opposing
symptoms and biological profiles. We recently introduced the concept of
ImmunoMetabolic Depression (IMD), characterized by the clustering of
inflammatory/metabolic dysregulations and atypical, energy-related symptoms
(hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis), and
present in 30% of cases. Converging evidence suggests that in this subgroup of
depression cases, inflammation may exert a crucial pathobiological mechanism,
representing therefore an actionable therapeutic target. We will apply IMD as a
tool to personalize treatment, by matching depressed subjects with IMD with a
targeted anti-inflammatory add-on treatment. We expect that this personalized
intervention in subjects with IMD, through a reduction of inflammation, lowers
depressive symptoms and associated physical fatigue, while increasing
functioning compared to placebo.

This study has been transitioned to CTIS with ID 2024-513907-15-01 check the CTIS register for the current data.

Among patients under treatment for depression, we will select 140 persons with
IMD. In this specific group of patients, we will test whether celecoxib add-on
(400 mg/d) is more effective than placebo in the treatment of depression
through a 12-week double-blind, randomized (1:1), placebo-controlled trial.

12-week double-blind placebo-controlled randomized clinical trial

celecoxib add-on (400 mg/d) vs placebo

The first part of the study consists of online questionnaires and a
video-interview (1.5h) followed by finger prick blood collection, taking ~1
minutes (phase 1). Only individuals meeting all inclusion criteria are
randomized (phase 2) and will have 4 face-to-face meetings at baseline (T0, 2
hrs) and after 2 weeks (T1 ~1 hrs), 6 weeks (T3, 1,5 hrs) and 12 weeks (T6, 1,5
hrs). Face-to-face meetings will include diagnostic interviews, blood pressure
and weight assessment and questionnaires, and a blood draw. Optional components
include additional blood collection for DNA (baseline), additional blood
collection for PMBC (baseline, 12 weeks) and stool sampling (baseline, 12
weeks).At 12 weeks, we additionally perform drug accountability. Online
questionnaires are filled out in week 4, 8 and 10 (T2, T4, T5, 15 minutes
each). Study medication taken twice daily for 12 weeks from T0 to T6.
Celecoxib is a Non-Steroidal Anti Inflammatory Drug (NSAID), commonly used in
the treatment of arthritis. NSAIDs in general have been linked to
cardiovascular and gastrointestinal side effects, but celecoxib has a
favourable safety profile over traditional NSAIDs and has less gastrointestinal
events than other NSAIDs. Previous RCTs on MDD reported no major adverse events
for celecoxib 400 mg/day on top of antidepressants [10]. Since we will exclude
(1) persons with contraindications for use of celecoxib as well as persons aged
>65 year, and (2) celecoxib will be administered for a limited time, the risk
of serious adverse events is expected to be low. We assume a moderate risk for
the risk classification.