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Meta-Analysis
. 2018 Jan 22;1(1):CD008525.
doi: 10.1002/14651858.CD008525.pub3.

Antidepressants for depression in adults with HIV infection

Ingrid Eshun-Wilson  1 , Nandi Siegfried, Dickens H Akena, Dan J Stein, Ekwaro A Obuku, John A Joska
Affiliations
Meta-Analysis

Antidepressants for depression in adults with HIV infection

Ingrid Eshun-Wilson et al. Cochrane Database Syst Rev. .

Abstract

Background: Rates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population.

Objectives: To assess the efficacy of antidepressant therapy for treatment of depression in PLWH.

Search methods: We searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017.

Selection criteria: We included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria.

Data collection and analysis: Two review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach.

Main results: We included 10 studies with 709 participants in this review. Of the 10 studies, eight were conducted in high income countries (USA and Italy), seven were conducted prior to 2000 and seven had predominantly men. Seven studies assessed antidepressants versus placebo, two compared different antidepressant classes and one had three arms comparing two antidepressant classes with placebo.Antidepressant therapy may result in a greater improvement in depression compared to placebo. There was a moderate improvement in depression when assessed with the Hamilton Depression Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to 0.96; participants = 357; studies = 6; I2 = 62%, low quality evidence). However, there was no evidence of improvement when this was assessed with HAM-D score as a dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies = 5; I2 = 0%, low quality evidence) or Clinical Global Impression of Improvement (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I2 = 29%, low quality evidence). There was little to no difference in the proportion of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants = 306; studies = 4; I2 = 0%, moderate quality evidence).The methods of reporting adverse events varied substantially between studies, this resulted in very low quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21; participants = 167; studies = 2; I2 = 34%; very low quality evidence). Based on this, we were unable to determine if there was a difference in the proportion of participants experiencing adverse events in the antidepressant versus placebo arms. However, sexual dysfunction was reported commonly in people receiving selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic antidepressants (TCAs) frequently reported anticholinergic adverse effects such as dry mouth and constipation. There were no reported grade 3 or 4 adverse events in any study group.There was no evidence of a difference in follow-up CD4 count at study termination (MD -6.31 cells/mm3, 95% CI -72.76 to 60.14; participants = 176; studies = 3; I2 = 0%; low quality evidence). Only one study evaluated quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies = 1; very low quality evidence), due to the poor quality evidence we could not draw conclusions for this outcome.There were few studies comparing different antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to 4.47; participants = 14; studies = 1; very low quality evidence). There was some evidence that mirtazapine resulted in a greater improvement in depression compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies = 1; low quality evidence); however, this finding was not consistent for all measures of improvement in depression for this comparison.No studies reported on virological suppression or any other HIV specific outcomes.The studies included in this review had an overall unclear or high risk of bias due to under-reporting of study methods, high risk of attrition bias and inadequate sequence generation methods. Heterogeneity between studies and the limited number of participants, and events lead to downgrading of the quality of the evidence for several outcomes.

Authors' conclusions: This review demonstrates that antidepressant therapy may be more beneficial than placebo for the treatment of depression in PLWH. The low quality of the evidence contributing to this assessment and the lack of studies representing PLWH from generalized epidemics in low- to middle-income countries make the relevance of these finding in today's context limited. Future studies that evaluate the effectiveness of antidepressant therapy should be designed and conducted rigorously. Such studies should incorporate evaluation of stepped care models and health system strengthening interventions in the study design. In addition, outcomes related to HIV care and antiretroviral therapy should be reported.

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Conflict of interest statement

IEW: is supported by the Effective Health Care Research Consortium. This Consortium is funded by UK aid from the UK Government for the benefit of developing countries (Grant: 5242). The views expressed in this publication do not necessarily reflect UK government policy. She was also supported by a fellowship offered by the Effective Health Care Research Consortium. This Consortium is funded by UK aid from the UK Government for the benefit of developing countries (Grant: 5242). The views expressed in this publication do not necessarily reflect UK government policy. In 2009 she was further supported by South African Tuberculosis AIDS training, Fogarty international NIH grant (1U2RTW007370).

NS: none.

DA: none.

DJS: between 2011 and 2014, Dr Stein received research grants or consultancy honoraria (or both) from AMBRF, Biocodex, Cipla, Lundbeck, National Responsible Gambling Foundation, Novartis, Servier, and Sun. Prior to 2011, Dr Stein has received research grants or consultancy honoraria (or both) from Abbott, AMBRF, Astrazeneca, Biocodex, Eli‐Lilly, GlaxoSmithKline, Jazz Pharmaceuticals, Johnson & Johnson, Lundbeck, National Responsible Gambling Foundation, Novartis, Orion, Pfizer, Pharmacia, Roche, Servier, Solvay, Sumitomo, Sun, Takeda, Tikvah, and Wyeth. None of this past support influences Dr Stein's current work on this Cochrane Review.

EAO: none.

JJ: none.

Figures

1
1
Conceptual framework of factors influencing depression in people living with HIV
2
2
PRISMA diagram
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
5
5
Forest plot and risk of bias assessment: Selective serotonin reuptake inhibitors (SSRI) versus placebo, outcome: 1.1 HAM‐D score.
6
6
Forest plot and risk of bias assessment: Selective serotonin reuptake inhibitors (SSRI) versus placebo, outcome: 1.2 Dichotomized HAM‐D score (greater than 50% reduction).
7
7
Forest plot and risk of bias assessment: Antidepressant versus placebo, outcome: 1.3 CGI‐I (score = 1 or 2).
8
8
Forest plot and risk of bias assessment: Selective serotonin reuptake inhibitors (SSRI) versus placebo, outcome: 1.4 Study dropouts.
9
9
Forest plot of comparison: Antidepressant versus placebo, outcome: 1.5 Adverse effects.
10
10
Forest plot of comparison: Selective serotonin reuptake inhibitors (SSRI) versus placebo, outcome: 1.5 Follow‐up CD4 count.
11
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Forest plot of comparison: Antidepressant versus placebo, outcome: 1.7 Quality of life score.
12
12
Forest plot of comparison: Selective serotonin reuptake inhibitors (SSRI) versus tricyclic antidepressants (TCA), outcome: 2.1 HAM‐D score.
13
13
Forest plot of comparison: Selective serotonin reuptake inhibitors (SSRI) versus tricyclic antidepressants (TCA), outcome: 2.2 Dichotomized HAM‐D score (greater than 50% reduction).
14
14
Forest plot of comparison: Selective serotonin reuptake inhibitors (SSRI) versus tricyclic antidepressants (TCA), outcome: 2.3 CGI‐I (score of 1 or 2).
15
15
Forest plot of comparison: Selective serotonin reuptake inhibitors (SSRI) versus tricyclic antidepressants (TCA), outcome: 2.4 Study dropouts.
16
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Forest plot of comparison: 3 Selective serotonin reuptake inhibitors (SSRI) versus mirtazapine, outcome: 3.1 Improvement in depression: HAM‐D score: continuous (follow‐up score).
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Forest plot of comparison: 4 Subgroup analysis: HIV disease severity, outcome: 4.1 Improvement in depression: HAM‐D score: continuous (mean change).
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Forest plot of comparison: 5 Sensitivity analysis: low risk attrition, detection and performance bias, outcome: 5.1 Improvement in depression: HAM‐D score: continuous (mean change).
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