Application of antidepressants in depression: A systematic review and meta-analysis

Abstract

Background: The type and quantities of antidepressants are increasing, but the efficacy and safety of first-line and emerging drugs vary between studies. In this article, we estimated the efficacy and safety of first-line and emerging antidepressants (anti-inflammatory drugs and ketamine).

Method: ystematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the depression, depressive symptoms, antidepressants, fluoxetine (Prozac), paroxetine, escitalopram, sertraline, fluvoxamine, venlafaxine, duloxetine, NSAIDs, anti-cytokine drugs or pioglitazone published before May 1st, 2019. Information on study characteristics, depression or depressive symptoms, antidepressants and the descriptive statistics (including efficacy and safety of antidepressants) was extracted independently by 2 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. The response and remission of antidepressants were used as clinical evaluation indicators, and the evaluation criteria were clinical depression scales. OR value of antidepressants as assessed by meta-analysis.

Results: The literature search retrieved 5529 potentially relevant articles of which 49 studies were finally included. We compared the efficacy of antidepressants (seven first-line antidepressants (fluoxetine, paroxetine, escitalopram, sertraline, fluvoxamine, venlafaxine, duloxetine), there kinds of anti-inflammatory drugs(NASIDs, cytokine-inhibitor, pioglitazone) and ketamine) by comparing the OR values.

Conclusion: The three drugs with the highest OR value in response were NASID (OR = 3.62(1.58, 8.32)), venlafaxin (OR = 3.50(1.83, 6.70)) and ketamine (OR = 3.28(1.89, 5.68)), while the highest OR value in remission were NASID (OR = 3.17(1.60, 6.29)), ketamine (OR = 2.99(1.58, 5.67)) and venlafaxin (OR = 2.55(1.72, 3.78)). Through reading the literature, we found 69 SNPs associated with depression. Major depression was a debilitating disorder that could ultimately lead to enormous societal and economical challenge [1]. The number of person which affected by depression was up to 16% of the population worldwide. More than 300 million individuals were estimated to suffer depression these days [1,2]. Therefore, it is apparent that safety and effective treatments for depression are necessary. In the 1930 s, the first drug for schizophrenia was discovered. This finding was a landmark for the emerging of biological psychiatry. In the 1950 s, pharmacologists had stumbled upon the antidepressant effect of imipramine. Since then, every 30 years, the use of antidepressants had made a pulsatile leap. Selective serotonin reuptake inhibitors (SSRIs) are the most widely-prescribed psychiatric drugs for the treatment of depression. However, the efficacy was variable and incomplete: 60%-70% of the patients do not experience remission, while 30%-40% do not show a significant response [3,4]. Nevertheless, SSRIs, SNRIs (selective serotonin-norepinephrine reuptake inhibitors, which can block norepinephrine at the same time) and NaSSAs (norepinephrine and selective serotonin receptor agonist), constituted the first-line clinical drugs. Nearly 30 years after the outbreak of SSRIs, antidepressants have ushered in a new chapter. It has been found that anti-inflammatory drugs could also have the small and moderate antidepressant effect and it's widely discussed [5]. More than 40 anti-inflammatory drugs have been certificated to have antidepressant effects in preclinical and clinical studies [6]. The antidepressant that has been approved for use recently is ketamine. There is no comprehensive comparison of the efficacy of all these drugs. In this review, we tried to estimate the efficacy and safety of first-line antidepressants, anti-inflammatory drugs and ketamine. On the other hand, with the development of GWAS, SNPs related to depression have been reported, and the corresponding mechanisms have been elaborated, respectively. However, patients with these SNPs have not been treated with individualized drugs according to the mechanisms. We hope to push this process forward through the summary of this article.

Methods: Search Strategy and Study Eligibility.

Keywords: Anti-inflammatory; Antidepressants; Depression; Ketamine; MDD; Meta-analysis; OR; SNPs.