Efficacy, safety, and tolerability of serotonin-norepinephrine reuptake inhibitors in controlling ADHD symptoms: a systematic review and meta-analysis

The aim of this study is to assess the effectiveness of serotonin-norepinephrine reuptake inhibitors (SNRIs) in managing ADHD symptoms compared to placebo, stimulants, or compared as pre- and post-treatment. Clinical trials assessing the potency of SNRIs in treating ADHD patients were imported from PubMed, Web of Science, and Scopus (until February 2023). Data were extracted by two independent researchers. Random- and fixed- effect meta-analysis was performed to pool the data. Publication bias and study heterogeneity were assessed. The Cochrane Collaboration tool was utilized to determine the risk of bias. The certainty of outcomes was evaluated by the Grade criteria. Of the initial 830 studies, 13 were finally imported after two screening stages which two separate researchers carried out. The pooled standardized mean difference (95% CI) of reducing the score of different ADHD questionnaires (showing reduction in total inattentive and hyperactivity/impulsivity symptoms) by SNRIs, venlafaxine, and duloxetine were − 2.20 [− 3.00, − 1.40], − 1.86 [− 2.69, − 1.02], − 2.65 [− 3.35, − 1.96], respectively. While the most reported side effects were nausea, abdominal pain, and sedation, all studies reported that side effects were not serious and were well tolerated. Outcomes for the effectiveness of venlafaxine and duloxetine got high and moderate certainty, respectively. Duloxetine and venlafaxine can be administered to treat symptoms of ADHD while being well tolerated. It seems that duloxetine is more potent in reducing ADHD symptoms. It can also be concluded that venlafaxine is more effective in females, and is more effective on inattentive symptoms of ADHD rather than hyperactive symptoms.