Therapeutic effects of escitalopram and reboxetine in seasonal affective disorder: A pooled analysis

The monoaminergic neurotransmitters serotonin and noradrenaline have both been implicated in the pathogenesis of seasonal affective disorder (SAD). However, the differential therapeutic value of selective serotonin reuptake inhibitors (SSRI) and selective noradrenaline reuptake inhibitors (NARI) in SAD has not been assessed until now. This study compares data from two open-label trials with similar methodology investigating the SSRI escitalopram and the NARI reboxetine. 20 SAD patients were treated with escitalopram (10-20 mg) and 15 patients received treatment with reboxetine (fixed dosage: 8 mg) over 6 weeks. Ratings included the structured interview guide for the Hamilton depression rating scale, SAD version (SIGH-SAD), the clinical global impression of severity (CGI-S) and improvement (CGI-I) and the UKU side effect rating scale. Treatment led to a significant reduction in SIGH-SAD score, CGI-S and CGI-I after one week in the reboxetine group and after two weeks in the escitalopram group. SIGH-SAD score was significantly lower in the reboxetine group at weeks 1, 2 and 4 but not at the end of the study. The response rate (SIGH-SAD <50% of baseline value) and the remission rate (SIGH-SAD <8) were not significantly different after 6 weeks of treatment, but the time to response and to remission was significantly shorter in the reboxetine group. The number and severity of side effects were higher in patients treated with reboxetine at all time points. Thus escitalopram and reboxetine were equally effective in treating SAD on all primary and secondary outcome measures. Reboxetine displayed a faster onset of action, but was associated with more pronounced side effects. Further studies comparing SSRI and NARI in SAD are warranted.     

Cost-effectiveness analysis of escitalopram: a new SSRI in the first-line treatment of major depressive disorder in Austria

SUMMARY

Objectives: To compare the cost-effectiveness of escitalopram, a new selective serotonin reuptake inhibitor (SSRI), with (generic) citalopram in the first-line treatment of major depressive disorder (MDD) in Austria.

Methods: A two-path decision analytic model with a 6-month horizon was adapted to the Austrian setting using Austrian clinical guidelines. All patients (aged ≥ 18?years) started at the primary care path and were referred to specialist care in the secondary care path in case of insufficient response. Model inputs included drug-specific probabilities from head-to-head trial data, literature and expert opinion. The main outcome measure was success (i.e., remission defined as Montgomery–Åsberg Depression Rating Scale (MADRS) score ≤ 12) and costs of treatment (i.e., drug costs and medical care). The analysis was performed from the Austrian societal and Social Healthcare Insurance System (SHIS) perspectives. The Human Capital approach was used to estimate the societal costs of lost productivity.

Results: Treatment with escitalopram yielded lower expected cost and greater effectiveness compared with citalopram. The expected success rate was higher for escitalopram (64.5%) compared to citalopram (59.1%). From the SHIS perspective, the total expected cost per successfully treated patient was lower (€115) for escitalopram (€608) compared with citalopram (€723). From the societal perspective, these expected costs were €3034 and €3269 respectively. Sensitivity analyses on unit costs and probabilities demonstrated the robustness of the results. From the societal perspective, escitalopram remained the dominant treatment option, even at a cost of €0 for (generic) citalopram.

Conclusion: Escitalopram is a cost-effective alternative compared to (generic) citalopram in the first-line treatment of MDD in Austria.     

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram

Background Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [¹²³I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram.Methods Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5), 10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)]. Midbrain SERT binding was measured with [¹²³I]ADAM and SPECT on two study days, once without study drug and once 6 h after single dose administration of the study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure (V3”) for specific binding to SERT in midbrain. Subsequently, SERT occupancy levels were calculated using the untreated baseline level for each subject. An E _max model was used to describe the relationship between S-citalopram concentrations and SERT occupancy values. Additionally, four subjects received placebo to determine test–retest variability.Results Single doses of 5, 10, or 20 mg escitalopram led to a mean SERT occupancy of 60±6, 64±6, and 75±5%, respectively. SERT occupancies for subjects treated with single doses of 10 and 20 mg citalopram were 65±10 and 70±6%, respectively. A statistically significant difference was found between SERT occupancies after application of 10 and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no statistically significant difference between the SERT occupancies of either 10 mg citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg escitalopram. E _max was slightly higher after administration of citalopram (84%) than escitalopram (79%). In the test–retest study, a mean SERT “occupancy” of 4% was found after administration of placebo, the intraclass correlation coefficient was 0.92, and the repeatability coefficient was 0.25.Conclusion SPECT and [¹²³I]ADAM were used to investigate SERT occupancies after single doses of escitalopram or citalopram. The test–retest study revealed good reproducibility of SERT quantification. Similar SERT occupancies were found after administration of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect evidence for a fractional blockade of SERT by the inactive R-citalopram.     

Mirtazapine in drug-induced excessive sweating

Excessive sweating is a well-known side effect of a selective serotonin reuptake inhibitor treatment, but little is known about the impact of sweating on treatment discontinuation or the general quality of life of patients. In this case report, we present a patient suffering from excessive sweating induced by escitalopram. When mirtazapine was administered as an additional treatment, a dose-dependent reduction of drug-induced excessive sweating was observed. Taking into account the particular serotonin antagonistic properties of mirtazapine, its eventual influence on the regulation of body temperature and diaphoresis in the central nervous system is discussed.     

Mechanistic model of acute autoinhibitory feedback action after administration of SSRIs in rats: Application to escitalopram-induced effects on brain serotonin levels

This study presents the development and evaluation of a feedback turnover model that mimics drug-induced effects on brain extracellular levels of serotonin (5-HT) after acute administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram (S-citalopram) in rats. The extracellular 5-HT output in the hippocampus was continuously monitored by intracerebral microdialysis in conjunction with serial arterial blood sampling for evaluation of escitalopram pharmacokinetics. 5-HT levels were significantly increased following administration of 2.5, 5 and 10 mg/kg of escitalopram and the 5-HT levels gradually declined to its baseline value within 360 min. However, at 5 and 10 mg/kg, the response–time curves were almost identical. This might be explained by activation of serotonergic autoreceptors exerting negative feedback, leading to a reduced release of new 5-HT into the synapse. The dynamics of escitalopram-evoked changes of 5-HT response was characterized by a turnover model, which included an inhibitory feedback moderator component. Thus, the response acted linearly on the production of the moderator, which acted inversely on the production of response. The plasma kinetics served as input to an inhibitory function acting on the loss of response. Simultaneous fitting of the model after three constant rate infusions demonstrated the flexibility of the system. The efficacy (I_max) and potency (IC₅₀) of inhibition of reuptake were 0.9 ± 0.03 and 4.4 ± 1.4 ng/ml, respectively, corresponding to an EC₅₀ of escitalopram about 30 ng/ml. In conclusion, the model lends itself to ‘what–if’ predictions at different drug exposure scenarios, and has potential for extrapolation of the pharmacodynamics of SSRIs in man.     

艾司西酞普兰改善创伤后应激障碍症状及脑结构的磁共振研究

目的 探讨艾司西酞普兰对创伤后应激障碍(PTSD)核心症状、伴发症状及脑结构的影响.方法 收集符合美国精神障碍诊断与统计手册第四版诊断标准的12例PTSD患者,单独应用艾司西酞普兰治疗3个月.采用临床应用的PTSD诊断量表(CAPS)、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、威斯康星分类卡片(WCST)、韦氏记忆量表(WMS)对PTSD患者治疗前后进行评估.治疗前后,所有患者进行核磁共振扫描.采用基于体素的形态学分析(VBM)技术,用统计参数 图5(SPM5)软件包分析治疗前后脑灰质体积的差异.结果 PTSD患者经艾司西酞普兰治疗后CAPS、HAMD、HAMA、WCST、WMS评分均较治疗前明显下降(P＜0.05).磁共振结果显示,经艾司西酞普兰治疗后PTSD患者额叶、颞叶等部分脑区灰质体积明显恢复.结论 艾司西酞普兰能有效改善PTSD患者的核心症状,以及伴发的抑郁、焦虑及认知功能损害症状；并明显促进脑灰质体积的恢复.     

艾司西酞普兰与氟西汀治疗抑郁症的临床疗效对比

目的探讨艾司西酞普兰与氟西汀治疗抑郁症的临床疗效。方法本研究按照随机数字表法将60例患者随机分为研究组和对照组各30例,其中研究组患者采用艾司西酞普兰治疗,而对照组则采用氟西汀治疗,比较两组患者的临床疗效、HAMD评分及不良反应。结果研究组患者治疗2w后即起效,且HAMD评分明显低于对照组,且差异具有统计学意义(P0.05)。研究组的总有效率明显高于对照组,且差异具有统计学意义(P0.05)。研究组的不良反应发生率(36.67%)与对照组(40.00%)比较无明显差异(P0.05)。结论艾司西酞普兰在治疗抑郁症方面,与氟西汀相比临床疗效佳,起效快,安全性好,值得临床推广使用。     

艾司西酞普兰治疗后抑郁症患者功能磁共振影像学改变的研究进展

本文目的是探讨抑郁症患者接受艾司西酞普兰治疗前后大脑功能磁共振激活改变。功能磁共振研究显示,治疗前,抑郁症患者前额叶、扣带回和纹状体等脑区的活动存在异常,前扣带回、背外侧前额叶、丘脑异常激活可预测艾司西酞普兰的疗效。经艾司西酞普兰治疗后,患者部分脑区恢复正常,且脑区激活的改变与症状的改善具有相关性。本文对抑郁症患者治疗前和不同用药时间的脑功能活动以及脑功能活动改变与临床症状的相关性进行综述。