Evidence Needed for Efficacy of Antidepressant Medications Among Patients With Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA) experience pain from inflammation, joint destruction, and neuropathy. Antidepressants may play a role among patients with RA and depression, fibromyalgia, or neuropathy to achieve desired outcomes. This commentary evaluated evidence for medications individually and identified important variables for future research. While we await the results of well-designed studies, a trial of duloxetine or milnacipran may be considered for patients with remnant pain and RA remission. Research is needed to evaluate the efficacy and safety of serotonin–norepinephrine reuptake inhibitors and tricyclic antidepressants in patients with RA and associated comorbid conditions.

Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials

<b><i>Introduction:</i></b> Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose. <b><i>Objective:</i></b> This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder. <b><i>Methods:</i></b> A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers’ product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031). <b><i>Results:</i></b> From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of –0.06 (–0.16 to 0.04) and –0.06 (–0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis. <b><i>Conclusion:</i></b> Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs.

Onset of Transient Sadness Following the Concomitant Use of a Triptan and Selective Serotonin Reuptake Inhibitor/Serotonin Norepinephrine Reuptake Inhibitors Therapy: A Case Report

Background: Migraine and depression have a bi-directional, positive association. The likelihood of these conditions being comorbidities is high, thus, the possibility of concomitant use of an antidepressant and a triptan is also increased. Case Presentation: We present a case of a 39-year-old female with a history of migraine with aura and depression who had brief episodes of exacerbated depressive symptoms following oral administration of sumatriptan 100 mg daily as needed while taking various selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) medications on different occasions. The patient experienced 30-minute episodes of sweating and subjective increase in temperature approximately 2–3 hours after administration of sumatriptan 100 mg. This was followed by a transient exacerbation of sadness described by the patient as unhappiness, hopelessness, and tearfulness, which lasted 1 to 2 hours. To date, there are no other published case reports that have described this particular presentation. Several studies have reported possible serotonin syndrome as a result of the combination. Current evidence and known pharmacological actions of SSRIs/SNRIs and triptans are not well-defined enough to explain how one can experience episodic worsening depression. Conclusion: This case illustrates that clinicians should consider other potential adverse effects of the combined use of triptans and SSRIs/SNRIs beyond serotonin syndrome.

Tapentadol: Use and Abuse

Tapentadol is a synthetic opioid analgesic that has been on the market in India since 2011. According to international studies, there is a low danger of abuse and diversion. Prescription opioid pain reliever abuse remains a major public health concern. Tapentadol, a prescription painkiller, differs from opioids such as oxycodone and morphine in that it has two modes of action: opioid receptor agonism and norepinephrine reuptake inhibition. Tapentadol has been on the market in India for eight and a half years. Our center was the topic of a single peer-reviewed research in 2017 that detailed two instances of abuse. Tapentadol is less likely to be diverted, abused, addicted, overdosed, or sold on the street than other prescribed opioids. This article reviews uses, pharmacological properties and abuse of tapentadol as it is the most serious issues like addiction, seeking behavior, withdrawal, and physical dependency .The main challenge with tapentadol use is controlling the ratio of MOR agonist to NRI. Finally, tapentadol provides both nociceptive and neuropathic pain relief, but there are concerns about abuse and reliance. Keywords: Tapentadol, Abuse, Opioid, Addiction.

New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations

Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic neuronal uptake of serotonin and norepinephrine and prolong the effects of the monoamines in the synaptic cleft within the central nervous system, leading to increased postsynaptic receptor activation and neuronal activities. Serotonin-norepinephrine reuptake inhibitors can have multiple clinical indications, including as the first-line agents for the management of depression and anxiety, and as analgesics in the treatment of chronic pain. The effects of reuptake inhibition of norepinephrine and serotonin are often dose-dependent and agent-dependent. There are five FDA-approved serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, levomilnacipran, milnacipran and sibutramine) currently being marketed in the United States. As the COVID-19 pandemic significantly increased the incidence and prevalence of anxiety and depression across the country, there are significantly increased prescriptions of these medications perioperatively. Thus, anesthesiologists are more likely than ever to have patients administered with these agents and scheduled for elective or emergency surgical procedures. A thorough understanding of these commonly prescribed serotonin-norepinephrine reuptake inhibitors and their interactions with commonly utilized anesthetic agents is paramount. There are two potentially increased risks related to the continuation of SNRIs through the perioperative period: intraoperative bleeding and serotonin syndrome. SNRIs have some off-label uses, more new indications, and ever-increasing new applications in perioperative practice. This article aims to review the commonly prescribed serotonin-norepinephrine reuptake inhibitors and the current clinical evidence regarding their considerations in perioperative anesthesia and analgesia.