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Brain Behav. 2015 Aug;5(8):e00338. doi: 10.1002/brb3.338. Epub 2015 May 29.

Inflammation and depression: combined use of selective serotonin reuptake inhibitors and NSAIDs or paracetamol and psychiatric outcomes.

Author information

1
Department P, Research Unit, Aarhus University Hospital Risskov Risskov, Denmark ; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH Aarhus, Denmark.
2
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH Aarhus, Denmark ; National Centre for Register-based Research, Aarhus University Aarhus, Denmark.
3
National Centre for Register-based Research, Aarhus University Aarhus, Denmark.

Abstract

BACKGROUND:

Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol have been shown to yield the potential of adjunctive antidepressant treatment effects to selective serotonin reuptake inhibitors (SSRIs); however, when investigating treatment effects of concomitant use, simultaneous evaluation of potential adverse events is important. The objective was thus to investigate treatment effectiveness and safety aspects of concomitant SSRI use with NSAIDs or paracetamol.

METHODS:

Within a 25% random sample of the Danish population, we identified all incident SSRI users between 1997 and 2006 (N = 123,351). Effectiveness and safety measures were compared between periods of SSRI use only and periods of combined SSRI and NSAID or paracetamol use by applying Cox regression.

RESULTS:

Among 123,351 SSRI users (follow-up: 53,697.8 person-years), 21,666 (17.5%) used NSAIDs and 10,232 (8.3%) paracetamol concomitantly. Concomitant NSAID use increased the risk of any psychiatric contact [Hazard rate ratio (95%-confidence interval): 1.22 (1.07; 1.38)] and with depression [1.31 (1.11; 1.55)]. Low-dose acetylsalicylic acid reduced the risk of psychiatric contact in general [0.74 (0.56; 0.98)] and with depression [0.71 (0.50; 1.01)]. Ibuprofen reduced the risk of psychiatric contacts [0.76 (0.60; 0.98)]. Concerning safety, paracetamol was associated with increased mortality [3.18 (2.83; 3.58)], especially cardiovascular [2.51 (1.93; 3.28)]. Diclofenac [1.77 (1.22; 2.55)] and the selective COX-2 inhibitors [1.75 (1.21; 2.53)] increased mortality risks.

CONCLUSIONS:

Concomitant use of SSRIs and NSAIDs occurred frequently, and effectiveness and safety outcomes varied across individual NSAIDs. Especially low-dose acetylsalicylic acid may represent an adjunctive antidepressant treatment option. The increased mortality risk of concomitant use of paracetamol needs further investigation.

KEYWORDS:

Antidepressants; depression; epidemiology; mood disorders; pharmacoepidemiology; pharmacotherapy

PMID:
26357585
PMCID:
PMC4559013
DOI:
10.1002/brb3.338
[Indexed for MEDLINE]
Free PMC Article

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