Comparative efficacy and acceptability of antidepressant treatment in poststroke depression: a multiple-treatments meta-analysis

Abstract

ObjectiveThe aim of this study is to create a rank order of the comparative efficacy and acceptability (risk of all-cause discontinuation) of antidepressant treatment in poststroke depression (PSD) by integrating direct and indirect evidence.DesignMultiple-treatments meta-analysis of randomised controlled trials.ParticipantsPatients with depression following stroke.Interventions10 antidepressants and placebo in the acute treatment of PSD.Outcome measuresThe primary outcomes were the overall efficacy, defined as the mean change of the total depression score. The secondary outcome was the acceptability, defined as risk of all-cause discontinuation. These estimates as standardised mean differences or ORs with 95% CIs.ResultsWe identified 12 suitable trials, with data from 707 participants. All drugs were significantly more effective than placebo apart from sertraline, nefiracetam and fluoxetine. Most of the comparisons for acceptability revealed no significant differences except that paroxetine had significantly lower all-cause discontinuation than doxepin, citalopram and fluoxetine. Standardised mean differences compared with placebo for efficacy varied from −6.54 for the best drug (reboxetine) to 0.51 for the worst drug (nefiracetam). ORs compared with placebo for acceptability ranged from 0.09 for the best drug (paroxetine) to 3.42 for the worst drug (citalopram). For the efficacy rank, reboxetine, paroxetine, doxepin and duloxetine were among the most efficacious treatments, the cumulative probabilities of which were 100%, 85.7%, 83.2%, 62.4%, respectively. With respect to the acceptability rank, paroxetine, placebo, sertraline and nortriptyline were among the most acceptable treatments, the cumulative probabilities of which were 92.4%, 63.5%, 57.3%, 56.3%.ConclusionAfter weighing the efficacy and acceptability, we conclude that paroxetine might be the best choice when starting acute treatment for PSD, and fluoxetine might be the worst choice.Trial registration numberThis systematic review has been registered in the Prospective Register of Systematic Review Protocols (PROSPERO) public database (CRD42017054741; http://www.crd.york.ac.uk/PROSPERO).

Effectiveness of paroxetine in the treatment of poststroke depression

“…Previous systematic studies have addressed this topic to evaluate the efficacy of paroxetine for the treatment of patients with PSD. [ 16 – 18 ] However, they drew inconsistent conclusions based on their results. One study designed with multiple treatments by meta-analysis of randomized controlled trials to create a rank order of the comparative efficacy and acceptability of different medications in PSD.…”

“…One study designed with multiple treatments by meta-analysis of randomized controlled trials to create a rank order of the comparative efficacy and acceptability of different medications in PSD. [ 16 ] It found that paroxetine might be the best option for treating PSD after acute stroke, and fluoxetine might be the worst option. On the other hand, the other Cochrane systematic review failed to draw a positive conclusion of pharmacological agents, including paroxetine, and psychological therapies, because of the insufficient evidence.…”

Neuropsychiatric Complications after Stroke

“…94 Another network meta-analysis found doxepin, paroxetine, and nortriptyline to be significantly more effective than placebo, with paroxetine appearing to demonstrate the best balance between efficacy, acceptability, and tolerability, 95 a finding echoed by another meta-analysis. 96 A 2018 meta-analysis found sertraline to be associated with improvements in depressive symptoms as well as functional ability and neurologic deficits, though the effect disappeared when low-quality studies were excluded. 97 In one study, the serotonin and norepinephrine reuptake inhibitor (SNRI) duloxetine outperformed sertraline and citalopram for depressive symptom reduction at 4-and 8-week follow-up but not at the 12-week endpoint, suggesting a potential advantage for duloxetine in rapid symptom reduction.…”

Depression in the medically ill

“…Similar to psychotherapeutic interventions, antidepressants with efficacy in the general population have demonstrated efficacy in the medically ill, but with fewer supporting studies, smaller samples sizes and lower antidepressant effect sizes (Kennedy et al, 2016;Ostuzzi et al, 2018). Metaanalytic level data has demonstrated small-to-moderate antidepressant effect sizes of antidepressants for MDD in cancer (Ostuzzi et al, 2018), diabetes (Baumeister et al, 2014;Darwish et al, 2018), coronary heart disease (Ostuzzi et al, 2019), post-stroke (Robinson and Jorge, 2016;Sun et al, 2017), HIV (Eshun- Wilson et al, 2018), epilepsy (Elger et al, 2017;Maguire et al, 2014) and MS (Fiest et al, 2016). The benefits of antidepressants in heart failure and major neurocognitive disorder are unclear with mixed results (Das et al, 2019;Dudas et al, 2018).…”