抗抑郁药物的药物经济学比较研究

目的:对抗抑郁药物进行药物经济学比较研究,从经济学角度探讨抗抑郁药的合理应用问题。方法:运用经济学原理和方法,对目前抗抑郁药的不同治疗方案以及同一品种的进口与国产药作了价格、药动学、疗效和不良反应等方面的比较。结果:各治疗方案、进口药与国产药在疗程和疗效方面都无显著差异,在价格上却有明显差异,不良反应方面也有差异。结论:抗抑郁新药取代老药是总趋势,但从经济承受能力考虑,老药还是应该占有一定的市场。     

新型抗抑郁药物的药物相互作用

新型抗抑郁药物的联合治疗及其与其他药物的联合应用可引起经细胞色素P450酶介导的多种药物的药动学改变,药物相互作用研究对临床合理用药具有重要意义。本文综述新型抗抑郁药物的药物相互作用,以期为临床用药提供参考。     

抗抑郁药的药代动力学与临床疗效的关系

介绍广泛用于临床的几类抗抑郁药的药动学特点与临床应用的关系。几类主要的抗抑郁药的药动学有实质性差别。同类药物成员之间的药动学差别通常较小，但选择性５－羟色胺（５－ＨＴ）重摄取抑制剂类例外。该类药物成员之间的药动学差别是有特异性的可变因素，对临床治疗有重要影响。     

我院门诊抗抑郁药应用分析

目的 了解我院门诊抗抑郁药使用情况,为临床合理用药提供参考.方法 以用药频率(DDDs)、限定日费用(DDC)等对我院2013～2015年门诊抗抑郁药的临床使用情况进行分析.结果 我院抗抑郁药总金额及总DDDs均呈逐年上升趋势,SNRIs、SSRIs为我院抗抑郁治疗主流药物,二者占抗抑郁药总DDDs的80％以上.结论 我院门诊抗抑郁药使用情况基本合理.新型抗抑郁药占据了抗抑郁病药销售金额与临床应用的主导地位.     

一种研制中的新型抗抑郁药——奈米非肽

奈米非肽是一种正在进行Ⅲ期临床试验的人工合成肽类抗抑郁药。本文概述了奈米非肽的药动学、药理作用机制以及临床试验情况。奈米非肽抗抑郁活性和安全性已得到临床证实。     

影响文拉法辛血药浓度相关因素的研究进展

文拉法辛为苯乙胺类抗抑郁药，具有抗抑郁谱广、药物起效快、生物利用度高、安全耐受性高、对5-HT选择吸收抑制效果好等优点，在治疗重度抑郁、广泛性焦虑障碍和抑郁共病方面占有重要地位，但该药药动学过程个体差异较大，且其血药浓度受患者个体、药物相互作用和基因多态性等多方面因素影响，导致治疗效果不理想或治疗无效。该文通过检索PubMed、Medline、Embase、CENTRAL、PsycNET、中国生物医学文献数据库、CNKI、维普、万方等数据库，搜索建库至2022年12月文拉法辛治疗药物监测的相关文献，旨在对影响文拉法辛血药浓度的因素进行综述，为该药在临床应用中的安全、有效提供参考。     

文拉法辛相关PK-PD关系及影响因素研究进展

文拉法辛（venlafaxine,VEN）是一种新型抗抑郁药物，能有效拮抗5-羟色胺（5-hydroxytryptamine,5-HT）和去甲肾上腺素（norepinephrine,NE）的再摄取，相比较其他抗抑郁药物，文拉法辛的药动学/药效学（pharmacokinetics-pharmacodynamics,PK-PD）更有规律可循且具有毒副作用较小、口服吸收快、生物利用度高等特点，本文综述了VEN的PK-PD模型化研究及其定量关系以及影响VEN体内过程的因素，包括性别、体质量、个体基因型、肝肾功能损伤、药物相互作用等相关因素。     

本刊“医药专论”专题预告

本刊2012年第7期"医药专论"将聚焦抗抑郁药物的临床应用。抗抑郁药物的种类繁多,临床应用广泛,目前新型抗抑郁药物的研发和临床应用研究已取得很大进展。如何选择抗抑郁药物并同时客观评价药物的疗效以指导临床实践尤为重要,由复旦大学附属中山医院心理医学科季建林教授撰写的抗抑郁药物治疗的起效与疗效评价从循证医学的角度评估不同抗抑郁药物治疗急性期抑郁症的疗效,并探讨难治性抑郁症的治疗策略及疗效评估。妊娠期焦虑和抑郁的治疗需权衡抗抑郁药物     

败血症对抗菌药物药动学的影响机制及其对个体化用药的指导意义

败血症会改变内环境,从而影响药物药动学行为。本综述从药动学角度出发,总结分析败血症中相关病理生理因素对药物体内吸收,分布,代谢,排泄等药动学环节的影响,并且结合各类抗菌药物自身药动学特点,总结其在败血症患者体内药动学变化及剂量调节相关信息。为败血症治疗中预测抗菌药物药动学行为,合理解释治疗药物监测结果,优化治疗方案提供参考。氨基糖苷类、糖肽类、β-内酰胺类等抗菌药物在败血症患者间或个体内存在较大药动学差异及血药浓度波动,需要个体化剂量调节。万古霉素在败血症无器官衰竭时表观分布容积和清除率增大,需要考虑高于常规给药剂量,具体优化剂量方案尚未定论。     

盐酸安非他酮治疗抑郁与焦虑障碍的临床观察

目的研究安非他酮治疗抑郁症和焦虑症的临床疗效。方法将30例抑郁症患者和20例焦虑症患者分别给予安非他酮治疗,疗程6周。采用汉密顿抑郁量表(HAMD)评定临床疗效。结果治疗30例抑郁症中,痊愈率可达80%;对双相情感障碍抑郁发作更有效,10例中9例痊愈,且无转躁现象,而其他三环抚抑郁药和新型抗抑郁药常诱发躁狂发作。结论安非他酮是治疗抑郁症和焦虑症的有效药物,甚至优于其他新型抗抑郁药物。临床发现新型抗抑郁药如5-HT再摄取抑制剂和SNRI类如文拉法辛等所致恶心、头胀、紧张、嗜睡等副反应较常见,一定程度上影响其临床应用。盐酸安非他酮治疗应用中发现其抗抑郁和抗焦虑作用与上述新型抗抑郁药相似,且不良反应用较少。可作为首选药物。     

Sex differences in pharmacokinetics of antidepressants

INTRODUCTION: Sex differences have been identified in antidepressant treatment; however, it remains unclear to what extent pharmacokinetics contributes to these differences. As current antidepressant pharmacotherapy is less than optimal, understanding the role of sex in pharmacokinetics may substantially contribute to a gender-based optimized treatment. AREAS COVERED: An unrestricted PubMed literature search on antidepressant pharmacokinetics and sex was performed. Sex differences in absorption, distribution, metabolism and elimination of antidepressants, as well as the interaction of sex with age, genetic polymorphisms and gonadal hormones are discussed. We also provide an overview of how each antidepressant presents a particular sex-differentiated pharmacokinetic profile. Most antidepressants present to some extent pharmacokinetic sex differences, which often are further accentuated by gonadal hormones. In most cases, women, particularly elderly women, are expected to have higher exposure to antidepressants when dosed in a similar way as men. EXPERT OPINION: Although the available pharmacokinetic evidence indicates that women should receive lower doses of antidepressants and men should receive higher doses, current guidelines do not recommend dose adjustment, because these sex differences are considered to be clinically insignificant. Unless we understand the link between pharmacokinetics and pharmacodynamics of antidepressants, it will be difficult to determine whether sex differences are of clinical importance or not. Thus, further systematic and particularly focused research is needed on sex differences in pharmacokinetics.     

Sex differences in antidepressant response in recent antidepressant clinical trials

Some previous reports suggest that women respond differently than men to antidepressant treatment. Much of this literature compares men and women's response to tricyclics to that of newer antidepressants (SSRIs, SNRI), or only examines one particular antidepressant. This study compares men and women's responses to 6 newer antidepressants. A total of 15 randomized, placebo-controlled trials that included 323 depressed patients were examined for sex differences in antidepressant treatment response. Women had a significantly greater response than men to SSRI antidepressants. A similar trend was seen for those assigned to an SNRI antidepressant, although not to the same extent as with SSRI antidepressants. Although these gender differences in treatment response are not large enough to suggest that gender should guide the clinical use of SSRI and SNRI antidepressants, the results do have implications for the design and interpretation of antidepressant clinical trials. These findings also raise the possibility that antidepressants may work somewhat differently in men and women.     

Involvement of the endocannabinoid system in the ability of long-term tricyclic antidepressant treatment to suppress stress-induced activation of the hypothalamic-pituitary-adrenal axis.

The efficacy of antidepressants has been linked in part to their ability to reduce activity of the hypothalamic-pituitary-adrenal (HPA) axis; however, the mechanism by which antidepressants regulate the HPA axis is largely unknown. Given that recent research has demonstrated that endocannabinoids can regulate the HPA axis and exhibit antidepressant potential, we examined the hypothesis that the endocannabinoid system is regulated by long-term antidepressant treatment. Three-week administration of the tricyclic antidepressant desipramine (10 mg/kg/day) resulted in a significant increase in the density of the cannabinoid CB(1) receptor in the hippocampus and hypothalamus, without significantly altering endocannabinoid content in any brain structure examined. Furthermore, chronic desipramine treatment resulted in a reduction in both secretion of corticosterone and the induction of the immediate early gene c-fos in the medial dorsal parvocellular region of the paraventricular nucleus of the hypothalamus (PVN) following a 5 min exposure to swim stress. Acute treatment with the CB(1) receptor antagonist, AM251 (1 mg/kg), before exposure to swim stress, completely occluded the ability of desipramine to reduce both corticosterone secretion and induction of c-fos expression in the PVN. Collectively, these data demonstrate that CB(1) receptor density in the hippocampus and hypothalamus is increased by chronic tricyclic antidepressant treatment, and suggest that this upregulation could contribute to the ability of tricyclic antidepressants to suppress stress-induced activation of the HPA axis.     

The use of tricyclic antidepressants and selective serotonin reuptake inhibitors in women who are breastfeeding

Postpartum depression is a well-recognized psychiatric condition that has gained increased attention over the past decade due to several nationally publicized tragedies. Medical management of this condition in women who are breastfeeding provides a unique challenge to health care professionals who may seek to maintain a fine balance between limiting the infant's exposure to hormone-altering drugs and maintaining the benefits of breastfeeding. No controlled trials have examined antidepressant therapy in nursing women; however, numerous case reports and case series have been published. Relatively few serious adverse effects have been reported. Although tricyclic antidepressants have been the treatment of choice in the past, selective serotonin reuptake inhibitors are gaining popularity due to their superior safety profiles. Of all the agents reviewed in the literature, sertraline was the most prescribed, and no adverse effects were reported. Therefore, this agent would be a good first choice for treatment-naive women. For treatment of postpartum depression in women with a history of successfully treated depression, the most practical approach may be to continue therapy with the previously effective agent. Treatment should be maintained at the lowest effective dosage to minimize infant exposure. Both mother and child should be closely monitored; in addition, collaboration between the prescribing physician and the child's pediatrician is essential.     

Psychiatry should not become hostage to placebo: An alternative interpretation of antidepressant–placebo differences in the treatment response in depression

BackgroundIt is widely believed that in randomized controlled trials of antidepressants the difference between drug and placebo response rates is rather small (around 20%), leading to a common perception that antidepressants have limited efficacy.AimThe aim of the present paper was to present an alternative calculation and interpretation of antidepressant–placebo difference in the treatment response to antidepressant in drug trials which may shed a new light on the efficacy of antidepressants.IssuesWe have previously highlighted several controversial points concerning the calculation of antidepressant and placebo response rates in randomised controlled trials, which may influence views concerning the efficacy of drugs, and demonstrated several factors which may lead to overestimation of the placebo effect and underestimation of antidepressant efficacy. The traditional interpretation of antidepressant–placebo difference in randomized controlled trials on major depression has been also challenged previously from at least five points of view but all leading to a conclusion that currently prevailing opinions concerning relative placebo and antidepressant response rates overestimate placebo response, and thereby underestimate efficacy of antidepressant drugs. In our present paper we propose another method for calculating placebo and antidepressant response rates which may shed new light on an overlooked aspect of the efficacy of these drugs.ConclusionsWe contend that opinions on the effectiveness of antidepressants should be reconsidered, and comparisons with placebo should be more carefully applied. Interpretation of the placebo response is of crucial importance for establishing the efficacy of antidepressive medications, and psychiatry should not become the hostage of placebo.     

Neonatal complications after intrauterine exposure to SSRI antidepressants

(1) Newborns exposed to selective serotonin reuptake inhibitor (SSRI) antidepressants towards the end of pregnancy sometimes show signs of agitation, altered muscle tone, and breathing and suction problems. Similar symptoms can occur after exposure to tricyclic antidepressants. (2) These neonatal symptoms have been noted with all five SSRI antidepressants available in France, namely citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. (3) An estimated 20% to 30% of newborns exposed to an SSRI towards the end of pregnancy are affected. (4) The symptoms are variously attributed to withdrawal or to the drug itself. (5) In practice, doctors should be aware of this risk when considering antidepressant treatment for women in the third trimester of pregnancy. There is no consensus on the treatment of affected newborns, but close monitoring is mandatory.     

Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile.

BACKGROUND: Depression has emerged as a contrastive area of gender differences in psychiatry, as epidemiological data has consistently shown depression is twice as common in women as men. The pharmacodynamic effect of antidepressants may also show gender differences, as suggested by reports of better response of young women to non-tricyclic antidepressants. METHODS: The antidepressive effect of an SSRI (fluoxetine) and a tetracyclic antidepressant with selective norepinephrine reuptake inhibitory effect (maprotiline) was compared in a 6-week, double-blind trial of 105 depressed patients. RESULTS: No significant difference was observed in the change of HAMD17 total score from baseline to week 6 between fluoxetine- and maprotiline-treated patients. A significant difference was observed in females (fluoxetine, -17.8; maprotiline, -13.9; P=0.017) between treatment groups, but not in males. Amongst females, the difference was significant in women aged <44 years (fluoxetine, -18.4; maprotiline, -12.9; P=0.023) but not > or =44 years. CONCLUSIONS: Females in their reproductive period are more responsive to SSRI (fluoxetine) than norepinephrinergic tetracyclic antidepressant (maprotiline) treatment. Normal cyclical ovulation, and estrogen release may have a clinically relevant pharmacodynamic interaction with serotonergic antidepressants.     

Treatment of postherpetic neuralgia: an update

Postherpetic neuralgia (PHN) is a chronic pain syndrome that is often refractory to treatment and can last for years, causing physical and social disability, psychological distress, and increased use of the healthcare system. In this paper we provide an update on recent developments in the treatment of PHN. We emphasise the results of recent studies that provide an evidence-based approach for treating PHN that was not available until very recently. In randomised, controlled clinical trials, the topical lidocaine patch, gabapentin, and controlled release oxycodone have been shown to provide superior pain relief in patients with PHN when compared with placebo. It has also recently been demonstrated that the tricyclic antidepressant nortriptyline provides equivalent analgesic benefit when compared with amitriptyline, but is better tolerated. Based on these results, nortriptyline can now be considered the preferred antidepressant for the treatment of PHN, although desipramine may be used if the patient experiences unacceptable sedation from nortriptyline. The topical lidocaine patch, gabapentin and controlled release oxycodone all appear to be as effective as tricyclic antidepressants in the treatment of patients with PHN, and the results of these recent studies suggest that each of these treatments should be considered early in the course of treatment. Additional controlled trials are needed to compare the efficacy and tolerability of these 4 treatments- tricyclic antidepressants, gabapentin, the topical lidocaine patch and controlled release opioid analgesics--used singly and in various combinations in the treatment of patients with PHN.     

A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test

Rationale and objective This paper describes a new procedure for detecting effective antidepressant treatments. The procedure uses the swim-test susceptible (Susceptible) rat which has been selectively bred to show decreased struggling behavior in a swim test after exposure to a mild stressor. The ability of treatments to block this decrease in swim-test activity was assessed as a method for detecting effective antidepressants. Results In both male and female Susceptible rats, chronic (14-day) treatment with different antidepressant drugs delivered via osmotic minipump [i.e., three tricyclics (desmethylimipramine, imipramine, amitriptyline), two selective serotonin reuptake inhibitors (fluoxetine and sertraline), a monoamine oxidase inhibitor (phenelzine), and two atypical antidepressants (venlafaxine and bupropion)] all prevented the stress-induced decrease in swim-test struggling normally shown by these rats. Electroconvulsive shock had a similar effect. Unlike antidepressant drugs, 14-day treatment with various nonantidepressant drugs [i.e., a stimulant (amphetamine), an anxiolytic (chlordiazepoxide), an antihistamine (chlorpheniramine), and an anticholinergic (scopolamine)] did not have this effect. Antidepressant drug treatment for 1 day (i.e., acute treatment) was also ineffective in this test. The procedure described above requires use of the Susceptible rat—swim test resistant rats (i.e., rats selectively bred to be resistant to decreased swim-test activity after exposure to stressful conditions) showed no significant differences in swim-test behavior between stress and nonstress conditions after 14-day drug treatment, and randomly bred Sprague–Dawley rats did not show a decrease in swim-test activity following exposure to the mild stressor that is the basis for the test. Conclusion These results suggest that the procedure described here, which uses a rat subject that has been bred for vulnerability to stressful conditions, may be a selective screening technique for effective antidepressant treatments.     

The approaches in the discovery of antidepressants using affective disorder models]

With the recent appearance of SSRI and SNRI, medication options with respect to depression have broadened. However, patients displaying clear improvement with existing antidepressants still do not exceed about 60 percent of total patients. New types of therapeutic agent development are currently required. Conditions for the determination of new antidepressants are: 1) instantaneous medications displaying a high level of antidepressant action in the early stages of treatment and 2) medications displaying efficacy with respect to patients that are therapy-resistant. However, drug discovery using new animal models is critical as part of drug development of these types of antidepressants in addition to models used in the past such as the forced swim test. We adopted two animal models (olfactory bulbectomy model and conditioned fear stress (CFS) model) developed for pharmacological evaluation of antidepressants. It has been well known that olfactory bulbectomied rats display extreme emotional response (aggressiveness and anxiety). However the improvement of this response occurs following chronic but not acute antidepressant treatment. Thus, we used this model to evaluate the period of the manifestation of antidepressant action. Mice exhibited a marked suppression of motility when they were returned to the same environment in which they had previously received an electric foot shock. Thus, it is suggested that the CFS stress model may be a useful model for therapy-resistant depression due to the fact that motor suppression is not readily attenuated by antidepressant treatment. In this report, we provide an overview of the approaches in the discovery of new antidepressants using these affective disorder models.