| Objective: Depressive disorder is common non-motor symptom in Parkinson disease(PD)and associated with greater disability and lower quality of life in patients with PD.Newer-generation antidepressants have been used in routine clinical practice.However,available evidence on the comparative efficacy and safety of this intervention is inconclusive.Therefore we sought to systematically review and analyze the efficacy and tolerability of newer-generation antidepressants pharmacologic treatments in patients with PD.Methods: We did a systematic review and meta-analysis.We searched Pub Med,Embase,the Cochrane Central Register of Controlled Trials,Web of Science,CINAHL,Psyc INFO,Chinese Biological Medical Database,CBM,China National Knowledge Infrastructure(CNKI),Wan Fang Data,VIP Database for Chinese Technical Periodicals(VIP)and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until July 1,2020.We only included placebo-controlled trials in which newer-generation antidepressants are used for the treatment of PD patients with depressive disorder diagnosed according to standard operationalized criteria or depression assessed by depression rating scale(for example,HAMD≥13 or MADRS≥20,etc.).12 randomized controlled trials(RCTs)involving 9 antidepressants were included.The mean change score of depression rating scales from baseline to end point and the proportion of patients who drop out for any reason at the end of treatment were defined as primary outcomes.Secondary outcomes contained improvement in motor symptoms in PD,change score of anxiety rating scales from baseline to end point,cognitive function recovery,and adverse events.This study was registered with PROSPERO,number CRD42020198364.Results: In total 12 RCTS with 779 participants were included.Newer-generation antidepressants show a significant benefit in treatment in PD with depression(SMD-0.99,95% CI-1.57 to-0.41,P=0.0008,I~2=86%,8 trails),as well as in anxiety scores(SMD-0.60,95% CI-1.04 to-0.17,P=0.006,I~2=0%,2 trials),no significant difference was detected between newer-generation antidepressants treatment group and control group in the drop-out rates(RR 1.41,95% CI 0.96 to 2.05,P=0.08,I~2=50%,5 trials).But there was insufficient evidence for newer-generation antidepressants use in motor symptoms in PD(SMD-1.07,95% CI-2.27 to 0.13,P=0.08,I~2=95%,5 trials)neither in the cognitive function(SMD=0.57;95% CI,-0.33 to 1.47;P=0.21,I~2=86%,3 trials).In order to explore the relevant factors that affect the results of the primary efficacy outcome,a series of subgroup analyses and sensitivity analysis were conducted,we found that newer-generation antidepressants more effective in Asia group than in non-Asia group(P=0.04).Men may have better responses to newer-generation antidepressants than women(p=0.004).As for adverse events,newer-generation antidepressants therapy was in positively connection with the risk of nausea and vomiting(RR 2.50,95% CI 1.05 to5.94,P=0.04,I~2=0%,4 trails),diminished sexual desire(RR 2.34,95% CI1.13 to 4.86,P=0.02,I~2=0%,2 trials)and insomnia(RR 0.4,95% CI 0.21 to 0.77,P=0.006,I~2=36%,5 trials).Conclusion: According to the findings in this review,newer-generation antidepressants may be beneficial and safe in treating depression in patients with PD but shows less robust effects for the motor symptoms in PD.Further well-defined clinical studies should be performed to confirm these outcomes. |
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