Peripheral inflammatory effects of different interventions for treatment-resistant depression: A systematic review

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Background: Immune-related mechanisms are increasingly recognised as important in the pathophysiology of
depression, particularly treatment-resistant depression (TRD). Preliminary evidence suggests that people with
TRD may benefit from anti-inflammatory interventions; however, the relative anti-inflammatory effects of ther-
apies currently recommended for TRD have not been integrated in a specific evidence synthesis.
Methods: A systematic search was performed to identify articles published up to February 8, 2021. Results from
databases (Pubmed, Embase) and handsearches were reviewed to include any longitudinal study examining
circulating marker(s) of inflammation in humans before and after treatment with electroconvulsive therapy
(ECT), ketamine, bupropion, lithium, aripiprazole, or quetiapine. We undertook a narrative synthesis of results
and risk of bias assessment to incorporate and interpret the evidence.
Results: Of 57 included studies, 34 assessed the effects of ketamine and 12 of ECT, with other medications
examined in 5 studies each. Results were highly heterogeneous. Numerically, more frequent increases than
decreases in pro-inflammatory markers were reported after ketamine, quetiapine and lithium (although more
frequent significant decreases were observed for lithium). Findings for ECT and bupropion were even more
inconsistent. Two studies consistently reported inflammatory reductions (significant/non-significant) after
Conclusions: Treatment effects on inflammatory proteins are confounded by several factors: ketamine, in most
studies, was co-administered with other surgical procedures, while ketamine and ECT findings are also obscured
by variable post-procedure assessment timing. The evidence base for other treatments is scant. Greater exami-
nation is warranted to establish whether inflammatory biomarkers could be used to stratify TRD patients to a
‘most appropriate’ intervention
Original languageEnglish
Article number101014
JournalNeuroscience Applied
Publication statusPublished - 1 Nov 2022


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