Selective serotonin reuptake inhibitors yield additional antiplatelet protection in patients with congestive heart failure treated with antecedent aspirin

Clinical depression has been identified as an independent risk factor for increased mortality in patients with coronary artery disease. Enhanced platelet activity has been suggested as the mechanism responsible for this adverse association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelets in patients undergoing coronary stenting. We sought to determine whether concomitant therapy with SSRIs would yield additional anti-platelet benefit in patients with congestive heart failure (CHF) already treated with antecedent aspirin. A total of 88 patients with left ventricular ejection fraction (LVEF) <40% or CHF symptoms in the setting of preserved systolic function and NYHA Class II-IV were analyzed. Of these, 23 patients (26%) were chronic SSRI users (SSRI+), and 65 patients were free from SSRI therapy (SSRI-). All patients received aspirin (325 mg) for at least 1 month prior to platelet studies. Platelets were assessed by aggregometry, flow cytometry and a rapid analyzer. The SSRI+ group exhibited a substantial decrease in platelet activity when compared with SSRI- patients, as manifested by a significant reduction in ADP- (P=0.001), and collagen-induced (P=0.02) aggregation, and the expression of PECAM-1 (P=0.03), GPIb (P=0.03), GP IIb/IIIa antigen (P=0.02) and GP IIb/IIIa activity with PAC-1 antibody (P=0.04) and P-selectin (P=0.02). Therapy with SSRIs also resulted in the reduced formation of platelet-leukocyte microparticles (P=0.01). Epinephrine-induced aggregation in plasma, collagen-induced whole blood aggregation, closure time and expression of vitronectin receptor, CD63, CD107a, CD107b and CD151 did not differ between groups. In patients with CHF already on aspirin, SSRI therapy was associated with further inhibition of platelet function. This observation may help to explain some of the clinical benefits associated with SSRI therapy. Further clinical trials may help to elucidate the potential outcome benefits of SSRIs in other potential thrombotic circumstances.     

Deep brain stimulation electrode insertion and depression: Patterns of activity and modulation by analgesics

Background

An initial antidepressant effect when using deep brain stimulation (DBS) of the subcallosal area of the cingulate cortex (Cg25) to treat resistant depression that could be the result of electrode insertion has been described. We previously showed that electrode insertion into the infralimbic cortex (ILC; the Cg25 rodent correlate) provokes a temporally limited antidepressant-like effect that is counteracted by non-steroidal anti-inflammatory drugs, such as those routinely used for pain relief.

Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake

It has recently become more clearly understood that in human brain pathophysiology, neurosteroids play a role in anxiety disorders, premenstrual syndrome, postpartum depression, posttraumatic stress disorder, and depression. In the treatment of major depression, recent clinical studies indicate that the pharmacological profiles of fluoxetine and fluvoxamine are correlated with the ability of these drugs to increase the brain and cerebrospinal fluid content of allopregnanolone (Allo), a potent positive allosteric modulator of gamma-aminobutyric acid (GABA) action at GABA_A receptors. Thus, the neurosteroid-induced positive allosteric modulation of GABA action at GABA_A receptors is facilitated by fluoxetine or its congeners (i.e., paroxetine, fluvoxamine, sertraline), which may not block 5-HT reuptake at the doses currently prescribed in the clinic. However, these doses are effective in the treatment of premenstrual dysphoria, anxiety, and depression. In socially isolated mice, we tested the hypothesis that fluoxetine, norfluoxetine, and other specific serotonin reuptake inhibitor (SSRI) congeners stereoselectively upregulate neurosteroid content at doses insufficient to inhibit 5-HT reuptake; although they potentiate pentobarbital-induced sedation and exert antiaggressive action. Very importantly, the inhibition of 5-HT reuptake lacks stereospecificity and requires fluoxetine and norfluoxetine doses that are 50-fold greater than those required to increase brain Allo content, potentiate the action of pentobarbital, or antagonize isolation-induced aggression. Based on these findings, it could be inferred that the increase of brain Allo content elicited by fluoxetine and norfluoxetine, rather than the inhibition selective of 5-HT reuptake, may be operative in the fluoxetine-induced remission of the behavioral abnormalities associated with mood disorders. Therefore, the term “SSRI” may be misleading in defining the pharmacological profile of fluoxetine and its congeners. To this extent, the term “selective brain steroidogenic stimulants” (SBSSs) could be proposed.     

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial

Rationale

Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.

Objectives

We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.

Method

Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥ 20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50 mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100 mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥ 50% improvement in the MADRS) at week 8.

Results

Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n = 20) showed a higher rate of responders than the Continuing group (n = 21) (75% vs. 19%: p = 0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤ 10 in the MADRS) (60% vs. 14%: p = 0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p < 0.001).

Conclusions

Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.     

针灸结合选择性5-羟色胺再摄取抑制剂治疗抑郁症的临床疗效分析

目的 探究针灸结合选择性5-羟色胺再摄取抑制剂(SSRIs)在治疗抑郁症患者中的临床疗效.方法 选择本院在2019年1月—2020年1月间收治的83例抑郁症患者作为研究对象,对照组抑郁症患者给予SSRIs治疗,联合治疗组在对照组基础上加以针灸治疗,比较两组抑郁症患者的临床疗效,以及治疗前后焦虑(HAMA)和抑郁量表(H...