Abstract
We aimed to compare the safety of antidepressants for the treatment of persistent depressive disorder (PDD) with each other and with placebo. We conducted a systematic electronic search and included randomized controlled trials that investigated antidepressants for the treatment of PDD in adults. Outcomes were the incidence of experiencing any adverse event, specific adverse events and related treatment discontinuations. We analyzed the data using traditional and network meta-analyses. Thirty-four studies that comprised 4,769 patients and examined 20 individual agents in nine substance classes were included. Almost all analyzed substance classes were associated with higher discontinuation rates than placebo including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), antipsychotics, and the serotonin antagonist and reuptake inhibitor (SARI) trazodone. The odds of experiencing any adverse event were significantly higher for TCAs and serotonin noradrenaline reuptake inhibitors (SNRIs) compared to placebo. Pairwise comparisons among the substance classes revealed that more patients receiving TCAs or SNRIs experienced any adverse event and that more patients receiving TCAs or the SARI trazodone discontinued treatment. The complementary treatment with acetyl-l-carnitine showed lower rates of experiencing any adverse event and related discontinuations than all other comparators. TCAs were primarily associated with (anti-)cholinergic and sedating adverse events. SSRIs primarily showed gastrointestinal adverse events. Patients treated with the antipsychotic amisulpride were more likely to manifest weight gain and endocrine adverse events. The comparative evidence for further agents was insufficient or lacking. The identified safety differences may be used to inform the selection among the antidepressants.
Highlights
During their lifetime, approximately 3% to 6% of the adults in Western countries suffer from a form of depression that persists for at least two years [1,2]
The findings suggest that almost all substance classes led to higher discontinuation rates due to adverse events than placebo including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), antipsychotics and the serotonin antagonist and reuptake inhibitor (SARI) trazodone
The odds of developing any adverse event were highest for TCAs and serotonin noradrenaline reuptake inhibitors (SNRIs) and lowest for acetyl-l-carnitine compared to other substance classes
Summary
Approximately 3% to 6% of the adults in Western countries suffer from a form of depression that persists for at least two years [1,2]. In the DSM-5, the new diagnostic category of persistent depressive disorder (PDD) was introduced subsuming those subtypes [4]. Systematic reviews, meta-analyses and clinical guidelines show evidence for the efficacy of pharmacological interventions in the treatment of PDD [5,6,7,8,9,10,11]. When the evidence regarding efficacy does not warrant recommending a particular treatment, the issue of adverse events becomes more important as a basis for clinical decision-making [11,15,16,17]
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