title: Inflammation and depression: combined use of selective serotonin reuptake inhibitors and NSAIDs or paracetamol and psychiatric outcomes.
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.
authors.affiliation: Department P, Research Unit, Aarhus University Hospital Risskov Risskov, Denmark ; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH Aarhus, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Köhler
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH Aarhus, Denmark ; National Centre for Register-based Research, Aarhus University Aarhus, Denmark.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Petersen
authors.affiliation: Department P, Research Unit, Aarhus University Hospital Risskov Risskov, Denmark ; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH Aarhus, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.affiliation: National Centre for Register-based Research, Aarhus University Aarhus, Denmark.
authors.forename: Christiane
authors.initials: C
authors.lastname: Gasse
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D003718:Denmark / Q000453:epidemiology; D003863:Depression / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000523:psychology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000082:Acetaminophen; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressants; depression; epidemiology; mood disorders; pharmacoepidemiology; pharmacotherapy