Depression is the fourth leading cause of disease burden worldwide and is expected to show a rising trend over the next 20 years. Depression is associated with a marked personal, social and economic morbidity, loss of functioning and productivity, and creates significant demands on service providers in terms of workload. Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs remain the mainstay of treatment. During the last 20 years, selective serotonin reuptake inhibitors (SSRIs) have progressively become the most commonly prescribed antidepressants. Sertraline, one of the first SSRIs introduced in the market, is a potent and specific inhibitor of serotonin uptake into the presynaptic terminal, with a modest activity as inhibitor of dopamine uptake. In the present review we assessed the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with all other antidepressants in the acute-phase treatment of major depression. Fifty-nine randomised controlled trials (about 10,000 participants) were included in the review. The review showed evidence of differences in efficacy, acceptability and tolerability between sertraline and other antidepressants, with meta-analyses highlighting a trend in favour of sertraline over other antidepressants, both in terms of efficacy and acceptability, in a homogeneous sample of clinical trials, using conservative statistical methods. The included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians, in particular, patients and their carers' attitudes to treatment, their ability to return to work and resume normal social functioning, were not reported in the included studies. Nevertheless, based on currently available evidence, results from this review suggest that sertraline might be a strong candidate as the initial choice of antidepressant in people with acute major depression.
This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.
The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness.
To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression.
MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data.
Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent.
Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects).
A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea.