PMID- 30977111
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20200412
IS  - 1469-493X (Electronic)
IS  - 1361-6137 (Linking)
VI  - 4
IP  - 4
DP  - 2019 Apr 12
TI  - Adjuvant therapy with antidepressants for the management of inflammatory bowel 
      disease.
PG  - CD012680
LID - 10.1002/14651858.CD012680.pub2 [doi]
LID - CD012680
AB  - BACKGROUND: Symptoms of anxiety and depression are common in inflammatory bowel 
      disease (IBD). Antidepressants are taken by approximately 30% of people with IBD. 
      However, there are no current guidelines on treating co-morbid anxiety and 
      depression in people with IBD with antidepressants, nor are there clear data on 
      the role of antidepressants in managing physical symptoms of IBD. OBJECTIVES: The 
      objectives were to assess the efficacy and safety of antidepressants for treating 
      anxiety and depression in IBD, and to assess the effects of antidepressants on 
      quality of life (QoL) and managing disease activity in IBD. SEARCH METHODS: We 
      searched MEDLINE; Embase, CINAHL, PsycINFO, CENTRAL, and the Cochrane IBD Group 
      Specialized Register from inception to 23 August 2018. Reference lists, trials 
      registers, conference proceedings and grey literature were also searched. 
      SELECTION CRITERIA: Randomised controlled trials (RCTs) and observational studies 
      comparing any type of antidepressant to placebo, no treatment or an active 
      therapy for IBD were included. DATA COLLECTION AND ANALYSIS: Two authors 
      independently screened search results, extracted data and assessed bias using the 
      Cochrane risk of bias tool. We used the Newcastle-Ottawa Scale to assess quality 
      of observational studies. GRADE was used to evaluate the certainty of the 
      evidence supporting the outcomes. Primary outcomes included anxiety and 
      depression. Anxiety was assessed using the Hospital Anxiety and Depression Scale 
      (HADS) or the Hamilton Anxiety Rating Scale (HARS). Depression was assessed using 
      HADS or the Beck Depression Inventory. Secondary outcomes included adverse events 
      (AEs), serious AEs, withdrawal due to AEs, quality of life (QoL), clinical 
      remission, relapse, pain, hospital admissions, surgery, and need for steroid 
      treatment. QoL was assessed using the WHO-QOL-BREF questionnaire. We calculated 
      the risk ratio (RR) and corresponding 95% confidence intervals (CI) for 
      dichotomous outcomes. For continuous outcomes, we calculated the mean difference 
      (MD) with 95% CI. A fixed-effect model was used for analysis. MAIN RESULTS: We 
      included four studies (188 participants). Two studies were double-blind RCTs, one 
      was a non-randomised controlled trial, and one was an observational retrospective 
      case-matched study. The age of participants ranged from 27 to 37.8 years. In 
      three studies participants had quiescent IBD and in one study participants had 
      active or quiescent IBD. Participants in one study had co-morbid anxiety or 
      depression. One study used duloxetine (60 mg daily), one study used fluoxetine 
      (20 mg daily), one study used tianeptine (36 mg daily), and one study used 
      various antidepressants in clinical ranges. Three studies had placebo controls 
      and one study had a no treatment control group. One RCT was rated as low risk of 
      bias and the other was rated as high risk of bias (incomplete outcome data). The 
      non-randomised controlled trial was rated as high risk of bias (random sequence 
      generation, allocation concealment, blinding). The observational study was rated 
      as high methodological quality, but is still considered to be at high risk of 
      bias given its observational design.The effect of antidepressants on anxiety and 
      depression is uncertain. At 12 weeks, the mean anxiety score in antidepressant 
      participants was 6.11 + 3 compared to 8.5 + 3.45 in placebo participants (MD 
      -2.39, 95% -4.30 to -0.48, 44 participants, low certainty evidence). At 12 
      months, the mean anxiety score in antidepressant participants was 3.8 + 2.5 
      compared to 4.2 + 4.9 in placebo participants (MD -0.40, 95% -3.47 to 2.67, 26 
      participants; low certainty evidence). At 12 weeks, the mean depression score in 
      antidepressant participants was 7.47 + 2.42 compared to 10.5 + 3.57 in placebo 
      participants (MD -3.03, 95% CI -4.83 to -1.23, 44 participants; low certainty 
      evidence). At 12 months, the mean depression score in antidepressant participants 
      was 2.9 + 2.8 compared to 3.1 + 3.4 in placebo participants (MD -0.20, 95% -2.62 
      to 2.22, 26 participants; low certainty evidence).The effect of antidepressants 
      on AEs is uncertain. Fifty-seven per cent (8/14) of antidepressant participants 
      group reported AEs versus 25% (3/12) of placebo participants (RR 2.29, 95% CI 
      0.78 to 6.73, low certainty evidence). Commonly reported AEs include nausea, 
      headache, dizziness, drowsiness, sexual problems, insomnia, fatigue, low 
      mood/anxiety, dry mouth, muscle spasms and hot flushes. None of the included 
      studies reported any serious AEs. None of the included studies reported on 
      pain.One study (44 participants) reported on QoL at 12 weeks and another study 
      (26 participants) reported on QoL at 12 months. Physical, Psychological, Social 
      and Environmental QoL were improved at 12 weeks compared to placebo (all low 
      certainty evidence). There were no group differences in QoL at 12 months (all low 
      certainty evidence). The effect of antidepressants on maintenance of clinical 
      remission and endoscopic relapse is uncertain. At 12 months, 64% (9/14) of 
      participants in the antidepressant group maintained clinical remission compared 
      to 67% (8/12) of placebo participants (RR 0.96, 95% CI 0.55 to 1.69; low 
      certainty evidence). At 12 months, none (0/30) of participants in the 
      antidepressant group had endoscopic relapse compared to 10% (3/30) of placebo 
      participants (RR 0.14, 95% CI 0.01 to 2.65; very low certainty evidence). 
      AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are 
      uncertain and no firm conclusions regarding the efficacy and safety of 
      antidepressants in IBD can be drawn. Future studies should employ RCT designs, 
      with a longer follow-up and develop solutions to address attrition. Inclusion of 
      objective markers of disease activity is strongly recommended as is testing 
      antidepressants from different classes, as at present it is unclear if any 
      antidepressant (or class thereof) has differential efficacy.
FAU - Mikocka-Walus, Antonina
AU  - Mikocka-Walus A
AD  - School of Psychology, Deakin University Geelong, 221 Burwood Highway, Burwood, 
      VIC, Victoria, Australia, 3025.
FAU - Prady, Stephanie L
AU  - Prady SL
FAU - Pollok, Justyna
AU  - Pollok J
FAU - Esterman, Adrian J
AU  - Esterman AJ
FAU - Gordon, Andrea L
AU  - Gordon AL
FAU - Knowles, Simon
AU  - Knowles S
FAU - Andrews, Jane M
AU  - Andrews JM
LA  - eng
PT  - Journal Article
PT  - Systematic Review
DEP - 20190412
PL  - England
TA  - Cochrane Database Syst Rev
JT  - The Cochrane database of systematic reviews
JID - 100909747
RN  - 0 (Antidepressive Agents)
SB  - IM
UOF - doi: 10.1002/14651858.CD012680
MH  - Antidepressive Agents/*therapeutic use
MH  - Anxiety/drug therapy
MH  - Case-Control Studies
MH  - Depression/*drug therapy
MH  - Humans
MH  - Inflammatory Bowel Diseases/*psychology
MH  - Quality of Life
MH  - Randomized Controlled Trials as Topic
PMC - PMC6459769
COIS- Antonina Mikocka-Walus: None known. Stephanie L. Prady: None known Justyna 
      Pollok: None known. Adrian Esterman: None known. Andrea Gordon: None known. Simon 
      R. Knowles: He has served as a consultant for AbbVie and Shire - these activities 
      are outside the submitted work. Jane M. Andrews: She has served as a consultant 
      for AbbVie, Abbott, Allergan, Bayer, Celgene, Ferring, Janssen, Pfizer, Takeda, 
      MSD, Shire - these activities are outside the submitted work. Antonina 
      Mikocka-Walus, Andrea Gordon, Adrian Esterman and Jane Andrews are co-authors of 
      a trial that was included in this systematic review (Mikocka-Walus 2016c). Data 
      extraction and risk of bias assessment for this study were carried out by Justyna 
      Pollok, Stephanie Prady and Simon Knowles.
EDAT- 2019/04/13 06:00
MHDA- 2019/05/29 06:00
PMCR- 2020/04/12
CRDT- 2019/04/13 06:00
PHST- 2019/04/13 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2019/04/13 06:00 [entrez]
PHST- 2020/04/12 00:00 [pmc-release]
AID - CD012680.pub2 [pii]
AID - 10.1002/14651858.CD012680.pub2 [doi]
PST - epublish
SO  - Cochrane Database Syst Rev. 2019 Apr 12;4(4):CD012680. doi: 
      10.1002/14651858.CD012680.pub2.