Antidepressant therapy in patients with ischemic heart disease

Depressive disorders are common in patients with ischemic heart disease and have serious consequences in terms of the risk of further cardiac events and cardiac mortality. Among survivors of acute myocardial infarction, up to one fifth meet diagnostic criteria for major depression, and the presence of major depression carries a >5-fold increased risk for cardiac mortality within 6 months. This article reviews clinical trial data on the cardiac safety profiles of antidepressant agents with the aim of discussing clinical considerations in selecting the most appropriate treatment of comorbid depression in patients with ischemic heart disease. Tricyclic antidepressants are effective against depression but are associated with cardiovascular side effects including orthostatic hypotension, slowed cardiac conduction, antiarrhythmic activity, and increased heart rate. Selective serotonin reuptake inhibitors, by contrast, have benign cardiovascular profiles and are well tolerated in patients with cardiac disease. The safety of dual-acting serotonin and noradrenaline reuptake inhibitors has not been well studied. Intervention with a selective serotonin reuptake inhibitors has the potential to provide the depressed patient with ischemic heart disease relief from their depressive symptoms and may offer a potential improvement in their cardiovascular risk profile.     

抗抑郁药治疗肠易激综合征的研究进展

目前研究发现精神心理因素在肠易激综合征（IBS）的发病中起重要作用,抗抑郁药在治疗IBS中的作用已受到越来越多的关注。常用的抗抑郁药包括选择性5-羟色胺再摄取抑制剂（SSRIs）、三环类抗抑郁药（TCAs）、5-羟色胺和去甲。肾上腺素再摄取抑制剂（SNRIs）等。本文就近年抗抑郁药治疗IBS的研究进展作一综述。     

Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants

BACKGROUND: Serotonin plays a role in platelet aggregation. Because antidepressants influence blood serotonin levels, their use may be associated with an increased risk of abnormal bleeding. However, previous studies were inconclusive regarding this association. The aim of this study was to estimate the risk of abnormal bleeding associated with the use of antidepressants and to establish the relationship between serotonin reuptake inhibition and the risk of bleeding. METHODS: We used data collected from 1992 through 2000 to conduct a nested case-control study of a cohort of more than 64 000 new antidepressant users. Cases were identified as all patients hospitalized for a primary diagnosis of abnormal bleeding, and they were matched with controls for age and sex. We classified exposure according to the degree (high, intermediate, or low) of serotonin reuptake inhibition and performed logistic regression analysis to calculate odds ratios. RESULTS: There were 196 cases of abnormal bleeding. The risk of hospitalization increased with the use of inhibitors providing intermediate (odds ratio, 1.9; 95% confidence interval, 1.1-3.5) and high degrees of serotonin reuptake inhibition (odds ratio, 2.6; 95% confidence interval, 1.4-4.8). CONCLUSIONS: In a large population of new antidepressant users we found a significant association between degree of serotonin reuptake inhibition by antidepressants and risk of hospital admission for abnormal bleeding as the primary diagnosis. An increased risk of abnormal bleeding was strongly associated with the degree of serotonin reuptake inhibition.     

Depression and heart disease: therapeutic implications

The consequences of depression and coronary artery disease (CAD) were reviewed in the literature. The comorbidity of depression and CAD results in an increased cardiovascular mortality. We reviewed possible explanations for this increased morbidity, which include: toxicity of tricyclic antidepressants that can cause cardiac arrhythmias, abnormalities in platelet function leading to increased platelet aggregation due to abnormalities in serotonin in the platelet (an abnormality that possibly causes depression in the central nervous system), diffuse atherosclerosis causing central nervous system abnormalities including depression (vascular depression), as well as the possibility that depressed patients are less compliant with their medications and physician-directed health recommendations. Recent reports of selective serotonin reuptake inhibitors (SSRIs) causing a reduced cardiovascular mortality may be related to serotonin platelet abnormalities in depressed patients that are effectively treated by SSRIs (SADHART and ENRICHD trial). It is possible that these trials reveal a mechanism of depression that also effects platelet function and can be improved with SSRI therapy, suggesting a preferential therapeutic pathway for the treatment of depressed patients with CAD.     

Antidepressant use in painful rheumatic conditions

This article reviews the pharmacologic and clinical evidence supporting the use of antidepressant drugs for treating painful rheumatologic conditions. Clinical studies have shown that tricyclic antidepressants, even at low doses, have analgesic effects in rheumatologic conditions equivalent to those of serotonin and noradrenalin reuptake inhibitors, but are less well tolerated. Selective serotonin reuptake inhibitors may also have analgesic effects, but higher doses are required to achieve analgesia in conditions such as fibromyalgia and low back pain. Antidepressant drugs may be useful in painful rheumatologic conditions, but in some studies the analgesic effects of antidepressants may be associated with functional impairment, sleep disorders, and fatigue. Further studies are required to determine antidepressants' analgesic mechanism of action and the specific role they should play in the management of chronic painful rheumatologic conditions.     

Pharmacological treatment of fibromyalgia and other chronic musculoskeletal pain

The pharmacologic management of fibromyalgia is based on the emerging evidence that pain in this disorder is primarily related to central pain sensitization. There is strong evidence that tricyclic antidepressants are effective, and moderate evidence for the effectiveness of serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors. Recent work suggests that the anti-seizure medications pregabalin and gabepentin are also effective. The only analgesic demonstrated to be helpful is tramadol.     

Selective serotonin reuptake inhibitor use by patients with acute coronary syndromes

Background

Selective serotonin reuptake inhibitors are commonly used to treat anxiety, depression, and other conditions that commonly affect patients with coronary artery disease. Selective serotonin reuptake inhibitors inhibit platelet activation and may, therefore, affect outcomes in patients with acute coronary syndromes.

Methods

A retrospective study was performed of 1254 patients with acute coronary syndromes comparing in-hospital bleeding and cardiac event rates in 158 patients who received a selective serotonin reuptake inhibitor and a propensity score-matched group of patients who did not. All patients were treated with a glycoprotein IIb/IIIa inhibitor and almost all also received aspirin, clopidogrel, and heparin.

Results

Patients who received a selective serotonin reuptake inhibitor were significantly more likely to experience any bleeding (37.3% vs 26.6%, OR 1.65, 95% confidence interval (CI), 1.02-2.66, P =.04) and significantly less likely to experience recurrent myocardial ischemia, heart failure, or asymptomatic cardiac enzyme elevation while in the hospital (7.0% vs 13.9%, OR 0.46, 95% CI, 0.22-0.99, P =.04). No differences were observed in death, myocardial infarction during the hospitalization, urgent revascularization, or major bleeding. Bleeding and cardiac events were not affected by antidepressants other than selective serotonin reuptake inhibitors.

Conclusions

Selective serotonin reuptake inhibitor use during a hospitalization for an acute coronary syndrome is associated with reduced rates of recurrent ischemia, heart failure, or cardiac enzyme elevation at the expense of increased bleeding in patients receiving maximal conventional antiplatelet medications and heparin. Clinicians should be aware of this association when treating patients with an acute coronary syndrome.     

Depression and congestive heart failure

The prevalence rates of depression in congestive heart failure patients range from 24%-42%. Depression is a graded, independent risk factor for readmission to the hospital, functional decline, and mortality in patients with congestive heart failure. Physicians can assess depression by using the SIG E CAPS + mood mnemonic, or any of a number of easily administered and scored self-report inventories. Cognitive-behavior therapy is the preferred psychological treatment. Cognitive-behavior therapy emphasizes the reciprocal interactions among physiology, environmental events, thoughts, and behaviors, and how these may be altered to produce changes in mood and behavior. Pharmacologically, the selective serotonin reuptake inhibitors are recommended, whereas the tricyclic antidepressants are not recommended for depression in congestive heart failure patients. The combination of a selective serotonin reuptake inhibitor with cognitive-behavior therapy is often the most effective treatment.     

Treatment of depression in patients with congestive heart failure

Heart failure is common, and depression is common in heart failure patients, adding substantially to the burden of the disease. There is some evidence for the safe and at least modestly effective use of psychotherapy and antidepressants to treat depression in heart failure patients. Cognitive behavioral psychotherapy and selective serotonin reuptake inhibitors are first line treatments. The efficacy of depression treatment in altering cardiac outcomes in heart failure patients has yet to be established.     

A systematic review on the effectiveness of treatment with antidepressants in fibromyalgia syndrome

OBJECTIVE: To systematically review the efficacy of treatment of fibromyalgia syndrome (FMS) with antidepressants. METHODS: We screened Medline, PsychINFO, SCOPUS, and the Cochrane Library databases (through October 2007) and the reference sections of original studies, meta-analyses, and evidence-based guidelines and recommendations on antidepressants in FMS. Randomized controlled trials (RCTs) on the treatment of FMS with antidepressants were analyzed. Inclusion criteria, study characteristics, quality, and all outcome measures were investigated. RESULTS: Twenty-six of 167 studies were included. The main outcome variables reviewed were pain, fatigue, sleep, depressiveness, and quality of life. Amitriptyline, studied in 13 RCTs, was efficient in reducing pain with a moderate magnitude of benefit (pain reduction by a mean of 26%, improvement in quality of life by 30%). Selective serotonin reuptake inhibitors (SSRIs) were studied in 12 RCTs, which also showed positive results, except for 2 studies on citalopram and 1 on paroxetine. Three RCTs on the dual serotonin and noradrenaline reuptake inhibitors (SNRIs) duloxetine and milnacipran and 1 of the 2 RCTs using the monoamine oxidase inhibitor moclobemide reported a positive result. The longest study duration was 12 weeks. CONCLUSION: Amitriptyline 25-50 mg/day reduces pain, fatigue, and depressiveness in patients with FMS and improves sleep and quality of life. Most SSRIs and the SNRIs duloxetine and milnacipran are probably also effective. Short-term treatment of patients with FMS using amitriptyline or another of the antidepressants that were effective in RCTs can be recommended. Data on long-term efficacy are lacking.     

Depression: treating the patient with comorbid cardiac disease

Depressed patients develop symptomatic and fatal ischemic heart disease at a higher rate than nondepressed patients, even after studies are controlled for known cardiovascular risk factors. Changes in sympathetic and parasympathetic tone appear to make depressed patients more vulnerable to ventricular fibrillation. Tricyclic antidepressants share the electrophysiologic profile of type 1A antiarrhythmic compounds and therefore may carry a risk of increased mortality when given to patients with ischemic heart disease. Serotonin reuptake inhibitors have shown no antiarrhythmic effect in depressed patients with serious cardiovascular disease, but studies to date have been small and short-term.     

选择性5-HT再摄取抑制剂与胃肠道损害的研究进展

选择性5-羟色胺再摄取抑制剂(SSRIs)是全世界最常见的处方药之一,目前临床上广泛用于抑郁症治疗,与三环类抗抑郁药(TCAs)药效相当,但比TCAs安全且耐受性好.然而,随着SSRIs使用人群的增加.一些病例报道和流行病学研究开始报道SSRJs治疗后出现胃肠道出血并发症.本文就SSRIs的临床应用与胃肠道出血的相关性...     

Triiodothyronine addition to paroxetine in the treatment of major depressive disorder

There is evidence that thyroid hormone T3 increases serotonergic neurotransmission. Therefore, T3 addition to antidepressants may improve treatment response in major depression. In nonrefractory depression, T3 addition to tricyclic antidepressants indeed accelerates treatment response. Current therapeutic practice favors selective serotonin reuptake inhibitors. This is the first study to investigate the efficacy of T3 addition to paroxetine in major depression. One hundred thirteen patients with major depressive disorder were randomly assigned to 8 wk of double-blind outpatient treatment with low-dose T3 (25 microg), high-dose T3 (25 microg twice daily), or placebo in addition to paroxetine 30 mg daily. A total of 106 patients started treatment and were included in the outcome analysis. Response rate after 8 wk (reduction of Hamilton Rating Scale for Depression score > or = 50%) was 46% in all three treatment arms (P = 0.99). T3 addition did not accelerate clinical response to paroxetine, nor was an effect of T3 found when only women were analyzed. Patients on T3 addition reported more adverse events than patients on placebo comedication. In conclusion, these results do not support a role for T3 addition to selective serotonin reuptake inhibitors in the treatment of nonrefractory major depressive disorder. On the contrary, more adverse reactions occurred in T3-treated patients.     

Antidepressant drug compliance: reduced risk of MI and mortality in depressed patients

Background

The long-term risk of myocardial infarction (MI) associated with use of antidepressants is uncertain, especially for nontricyclic antidepressants. The present study uses a national Veterans Affairs cohort to test whether antidepressants increase or decrease risk of MI and all-cause mortality.

Methods

US Department of Veterans Affairs patient records were analyzed to identify a cohort free of cardiovascular disease in fiscal years 1999 and 2000, aged 25-80 years, who had an International Classification of Diseases, Ninth Revision, Clinical Modification code indicating an episode of depression (n = 93,653). Incident MI and all-cause mortality were modeled in patients who received 12 weeks or more of antidepressant pharmacotherapy as compared with 0-11 weeks during follow-up. Age-adjusted Cox proportional hazard models were computed before and after adjusting for baseline sociodemographics and time-dependent covariates.

Results

Receipt of 12 or more weeks of continuous antidepressant therapy was associated with significantly reduced rates of incident MI across classes of antidepressants: selective serotonin reuptake inhibitor (SSRIs) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.44-0.52), serotonin-norepinephrine reuptake inhibitors (SNRIs) (HR 0.35; 95% CI, 0.32-0.40), tricyclic antidepressants (TCAs) (HR 0.39; 95% CI, 0.34-0.44), and “Other” (HR 0.41; 95% CI, 0.37-0.45). Risk of all-cause mortality also was decreased with receipt of 12 weeks of pharmacotherapy with all classes of antidepressants (SSRI, SNRI, TCA, Other), with HRs ranging from 0.50 to 0.66.

Conclusions

Across classes of antidepressants, 12 weeks of pharmacotherapy appears to be safe in terms of MI risk. Although the mechanism for this association remains uncertain, it is possible that compliance with pharmacotherapy for depression reflects compliance with cardiovascular medications. It also is possible that a direct drug effect or improved depressed mood may attenuate the risk of MI in depressed patients.     

Sexual disorder improvement: a target or a way in treatment of fibromyalgia. A case report and brief review

Abstract

Previous studies had shown the relation between fibromyalgia (FM) and sexual impairment as a symptom of established disease, which causes often serious problems in partners’ relationship. We described a middle-aged man with FM who was refractory to conventional treatments after an 8-year history of generalized chronic pain. He underwent multiple treatment modalities, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin?norepinephrine reuptake inhibitors, and nonpharmacological therapies, with no dramatic success. Psychiatric assessment revealed a homosexual tendency. He and his wife were informed about the problem. A change in sexual behavior caused a significant resolution of symptoms over a 6-month period, and he no longer receives medication for FM. This is the first case report to demonstrate the efficacy of sexual disorder improvement in the treatment of refractory FM.