Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis

UNSTRUCTURED Generalised anxiety disorder (GAD) is the most common mental health condition based on weekly prevalence. Digital interventions (DIs) have been used as alternatives or as add-ons to conventional therapies to improve access, patient choice and clinical outcomes. Little is known about their comparative effectiveness for GAD. To address this, we conducted a systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs) comparing DIs with medication, non-digital interventions, non-therapeutic controls and no intervention. We included 21 RCTs with a total of 2,350 participants from GAD populations. Pooled outcomes using analysis of Covariance and rankograms based on the surface under the cumulative ranking curves (SUCRA) indicated that antidepressant medication and group therapy had a higher probability than DIs of being the ‘best’ intervention. Supported DIs were not necessarily “better” than unsupported (pure self-help) ones. Due to very wide confidence intervals, NMA results were inconclusive as to whether DIs are better than no intervention and non-therapeutic active controls, or whether they confer an additional benefit to standard therapy. Future research needs to compare DIs with one-to-one therapy and with manualised non-digital self-help and to include antidepressant medication as a treatment comparator and effect modifier.

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Systematic review and meta-analysis of the association between peripheral inflammatory cytokines and generalised anxiety disorder

BMJ Open ◽

10.1136/bmjopen-2018-027925 ◽

2019 ◽

Vol 9 (7) ◽

pp. e027925 ◽

Cited By ~ 10

Author(s):

Harry Costello ◽

Rebecca L Gould ◽

Esha Abrol ◽

Robert Howard

Keyword(s):

Systematic Review ◽

Anxiety Disorder ◽

Inflammatory Cytokines ◽

Data Extraction ◽

Meta Analysis ◽

Preliminary Evidence ◽

Generalised Anxiety Disorder ◽

Eligibility Criteria ◽

Markers Of Inflammation ◽

Small Effect Size

ObjectiveInflammation has been implicated in the aetiology of mental illness. We conducted the first systematic review and meta-analysis of the association between peripheral markers of inflammation and generalised anxiety disorder (GAD).DesignSystematic review and meta-analysis of studies measuring peripheral cytokine levels in people with GAD compared with controls.Data sourcesMEDLINE (1950–), EMBASE (1947–), PsycINFO (1872–) and Web of Science (1945–) databases up until January 2018.Eligibility criteriaPrimary, quantitative research studies of people with a diagnosis of GAD assessed using a standardised clinical interview that measured peripheral inflammatory markers.Data extraction and synthesisTwo independent reviewers extracted data and assessed study quality. Meta-analysis using a random-effects model was conducted for individual cytokines where data from three or more studies were available.Results14 of 1718 identified studies met the inclusion criteria, comprising 1188 patients with GAD and 10 623 controls. In total 16 cytokines were evaluated. Significantly raised levels of C reactive protein (CRP), interferon-γ and tumour necrosis factor-α were reported in patients with GAD compared with controls in two or more studies. Ten further proinflammatory cytokines were reported to be significantly raised in GAD in at least one study. However, 5 of 14 studies found no difference in the levels of at least one cytokine. Only CRP studies reported sufficient data for meta-analysis. CRP was significantly higher in people with GAD compared with controls, with a small effect size (Cohen’s d=0.38, 0.06–0.69), comparable with that reported in schizophrenia. However, heterogeneity was high (I2=75%), in keeping with meta-analyses of inflammation in other psychiatric conditions and reflecting differences in participant medication use, comorbid depression and cytokine sampling methodology.ConclusionThere is preliminary evidence to suggest an inflammatory response in GAD, but it remains unclear whether inflammatory cytokines play a role in the aetiology. GAD remains a poorly studied area of neuroinflammation compared with other mental disorders, and further longitudinal studies are required.

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