Treatment of cannabis dependence using escitalopram in combination with cognitive-behavior therapy: a double-blind placebo-controlled study

Background: Cannabis is the most frequently used illegal substance in the United States and Europe. There is a dramatic increase in the demand for treatment for cannabis dependence. Cannabis users frequently have co-morbid mood symptoms, especially depression and anxiety, and regular cannabis users may self-medicate for such symptoms. Objectives: We report a double-blind, placebo-controlled treatment study, for the prevention of cannabis use in cannabis-dependent individuals. Method: Regular cannabis-dependent users (n?=?52) were treated for 9 weeks with weekly cognitive-behavior and motivation-enhancement therapy sessions together with escitalopram 10?mg/day. Urine samples were collected to monitor delta-9 tetrahydrocannabinol (THC) during treatment and questionnaires were administered to assess anxiety and depression. Results: We observed a high rate of dropout (50%) during the 9-week treatment program. Fifty-two patients were included in the intention-to-treat analysis. Of these, ten (19%) remained abstinent after 9 weeks of treatment as indicated by negative urine samples for THC. Escitalopram provided no advantage over placebo in either abstinence rates from cannabis or anxiety and depression scores during the withdrawal and abstinent periods. Conclusions: Escitalopram treatment does not provide an additional benefit either for achieving abstinence, or for the treatment of the cannabis withdrawal syndrome. Due to limitations of our study, namely, a high dropout rate and effects of low abstinence rates on measures of anxiety, depression and withdrawal, it is premature to conclude that selective serotonin reuptake inhibitors are not effective for treatment of the cannabis withdrawal syndrome.     

Blunted autonomic reactivity to pharmacological panic challenge under long-term escitalopram treatment in healthy men

Background:

Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and, thereby, influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways, including central autonomic pathways. However, only a few studies have assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV).

Methods:

The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time- and frequency-domain HRV parameters, assessed at both baseline and immediately after CCK-4 application.

Results:

Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to heart rate (p < 0.001; _pη² = 0.499), SDNN (p < 0.001; _pη² = 576), RMSSD (p = 0.015; _pη² = 194), NN50% (p = 0.008; _pη² = 0.224), and LF% (p = 0.014; _pη² = 0.196), and moderate effects with respect HF% (p = 0.099; _pη² = 0.094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50, LF and HF than subjects in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4. Secondary analysis indicated no effect of the 5-HTTLPR polymorphism on CCK-4-induced autonomic response.

Conclusions:

Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.     

Quantitation of escitalopram and its metabolites by liquid chromatography‐tandem mass spectrometry in psychiatric patients: New metabolic ratio establishment

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC‐MS/MS to analyse quantitative assay of escitalopram (S‐CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S‐CT and its metabolites in the patients’ plasma. A new method with short sample preparation and analysis time was developed and validated using LC‐MS/MS to analyse quantitative assay of S‐CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S‐CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S‐CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S‐CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S‐CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S‐CT.     

艾司西酞普兰合并托吡酯治疗男性酒依赖伴焦虑抑郁及复饮

目的 探讨艾司西酞普兰合并托吡酯对男性酒依赖患者伴有焦虑抑郁的临床疗效、安全性及对复饮的影响。方法 采用了随机、对照的临床试验设计,把入组的患者分成艾司西酞普兰合并托吡酯治疗组(协同用药组)和单用艾司西酞普兰治疗组(单一用药组)。共治疗了12周,治疗前后分别采用了汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、用药后出现的不良反应量表(TESS)、可视渴求量表(VAS)等评估患者的临床效果及安全性。结果 2组HAMA、HAMD评分在治疗后4周末、8周末与治疗前比较差异有统计学意义(P<0.05)。随着治疗时间的延长2组VAS评分均逐渐下降,协同用药组渴求程度下降更为明显(P<0.05);协同用药组在随访6个月时复饮率低于单一用药组,差异有统计学意义(χ²=11.009,P=0.001<0.05);2组用药后不良反应发生率的差异无统计学意义(P>0.05)。结论 对伴焦虑抑郁症状的酒依赖患者,艾司西酞普兰合并托吡酯治疗焦虑、抑郁症状的疗效与单用艾司西酞普兰相当,但减少对酒的渴求优于单用艾司西酞普兰,且患者有更低的复饮率。2种治疗方案的不良反应相当。     

Escitalopram in major depressive disorder: clinical benefits and cost effectiveness versus citalopram

Objective. Escitalopram is the most selective of the serotonin reuptake inhibitors. Methods. We review all the clinical trials (three pivotal placebo-controlled trials with citalopram as an active reference, one long-term non-inferiority study and one head-to-head superiority study) that include citalopram as an active reference in major depressive disorder (MDD), and studies that evaluate the cost-effectiveness of the two drugs. Results. In two of the pivotal studies and in the long-term study, escitalopram was numerically better than citalopram in reducing Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline, with comparative tolerability. Meta-analyses of these studies showed statistically significant differences in favour of escitalopram in terms of reducing MADRS and increasing response. This effect was particularly apparent in patients with higher baseline MADRS scores. These trends were confirmed in a head-to-head study, which clearly demonstrated the superiority of escitalopram compared with citalopram on primary and secondary endpoints. The difference between treatments was clinically relevant. Cost-effectiveness analyses demonstrated that although escitalopram has a slightly higher unit cost than generic citalopram, expected direct medical and productivity- related costs were lower with escitalopram than citalopram. Conclusion. On the basis of these results, escitalopram was concluded to be more clinically effective and more cost-effective than citalopram for the treatment of MDD, with a similar tolerability profile.     

枣仁安神方联合艾司西酞普兰治疗冠心病伴焦虑症患者的疗效观察及与神经递质相关的机制探讨

目的观察自拟枣仁安神方联合艾司西酞普兰治疗冠心病(CHD)伴焦虑症患者的效果,以及对血清相关神经递质的影响,探讨自拟枣仁安神方的作用机制。方法选取驻马店市中心医院2016年4月—2018年3月期间收治的120例CHD伴焦虑症患者,随机分为对照组和治疗组,每组各60例。两组均给予CHD常规治疗方案,包括阿司匹林肠溶片、琥珀酸美托洛尔片、单硝酸异山梨酯、阿托伐他汀。对照组同时给予艾司西酞普兰,治疗组在对照组的基础上联合自拟枣仁安神方治疗,4周为1个疗程,连续3个疗程。在治疗前后对患者进行汉密尔顿焦虑量表(HAMA)评分、中医证候评分和心绞痛评分,评价CHD和焦虑症疗效,并检测血清5-羟色胺(5-HT)、髓过氧化物酶(MPO)、去甲肾上腺素(NE)和血浆神经肽(NPY)水平。结果治疗后,治疗组CHD和焦虑症有效率分别为91.67%、93.33%,高于对照组的78.33%、80.00%,差异显著(P0.05);治疗组HAMA评分、中医证候评分和心绞痛评分均低于对照组(P0.05);治疗组患者血清5-HT、NE、NPY水平高于对照组,MPO水平低于对照组(P0.05)。结论自拟枣仁安神方联合艾司西酞普兰治疗CHD伴焦虑症,能够改善患者CHD和焦虑症症状,提高疗效,通过调节5-HT、NE、NPY和MPO水平来发挥治疗作用。     

In vitro genotoxic and cytotoxic effects of doxepin and escitalopram on human peripheral lymphocytes

Antidepressants are drugs used for the treatment of many psychiatric conditions including depression. There are findings suggesting that these drugs might have genotoxic, carcinogenic, and/or mutagenic effects. Therefore, the present in vitro study is intended to investigate potential genotoxic and cytotoxic effects of the antidepressants escitalopram (selective serotonin reuptake inhibitor) and doxepin (Tricyclic antidepressant) on human peripheral lymphocytes cytokinesis-block micronucleus (CBMN), sister chromatid exchange (SCE), and single cell gel electrophoresis (alkaline comet assay) were used for the purpose of the study. In the study, four different concentrations of both drugs (1, 2.5, 5, and 10?µg/mL) were administered to human peripheral lymphocytes for 24?h. The tested concentrations of both drugs were found to exhibit no cytotoxic and mitotic inhibitory effects. SCE increase caused by 5 and 10?µg/mL of escitalopram was found statistically significant, while no statistically significant increase was observed in DNA damage and micronucleus (MN) formation. Moreover, the increase caused by doxepin in MN formation was not found statistically significant. Besides, 10?µg/mL of doxepin was demonstrated to significantly increase arbitrary unit and SCE formation. These findings suggest that the investigated concentrations of escitalopram and doxepin were non-cytotoxic but potentially genotoxic at higher concentrations.     

Higher serotonin transporter availability in early‐onset obsessive–compulsive disorder patients undergoing escitalopram treatment: A [11C]DASB PET study

Objective

Early‐onset obsessive–compulsive disorder (EOCD) and late‐onset obsessive–compulsive disorder (LOCD) are distinct subtypes of obsessive–compulsive disorder (OCD). OCD patients are treated with serotonin reuptake inhibitors, but the difference in serotonin transporter (SERT) availability between medicated EOCD and LOCD is unexplored yet.

Methods

Six EOCD and 6 LOCD patients were enrolled. They underwent serial [¹¹C]DASB positron emission tomography scans during maintenance therapy with escitalopram, and their plasma concentration of escitalopram was measured simultaneously with the scan. Then, the drug‐free binding potential of SERT was calculated by pharmacokinetic–pharmacodynamic modelling.

Results

In comparison with LOCD patients, SERT availability was significantly higher in the putamen of EOCD patients (U = 4, p = .026), but not in the caudate nucleus (U = 14, p = .589), thalamus (U = 16, p = .818), and dorsal raphe nucleus (U = 7, p = .093). Binding potential of putamen showed a negative correlation (r = ?.580, p = .048) with age of onset of the disease, but not with the Yale–Brown Obsessive Compulsive Scale scores.

Conclusions

These findings indicate that the earlier the age of onset of OCD, the less serotonergic pathology there is and that this difference remains even after long‐term serotonin reuptake inhibitor treatment. Clinically, it might suggest that nonserotonergic treatments would be a better option for EOCD patients.     

Pharmacotherapy for the treatment of depression in patients with alzheimer’s disease: a treatment-resistant depressive disorder

Introduction: Pharmacotherapy for the treatment of depressive disorders in Alzheimer’s Disease (AD) represents a clinical challenge. pharmacological options are often attempted after a period of watchful waiting (8–12 weeks). monoaminergic antidepressant drugs have shown only modest or null clinical benefits, maybe because the etiology of depressive symptoms in ad patients is fundamentally different from that of nondemented subjects.

Areas covered: The following article looks at the selective serotonin reuptake inhibitor sertraline, which is one of the most frequently studied antidepressant medications in randomized controlled trials (RCTs). It also discusses many other pharmacological approaches that have proven to be inadequate (antipsychotics, acetylcholinesterase inhibitors, anticonvulsants, hormone replacement therapy) and new drug classes (mainly affecting glutamate transmission) that are being studied for treating depression in AD. It also gives discussion to the phase II RCT on the alternative drug S47445 and the potential effect on cognition of the multimodal antidepressant vortioxetine in older depressed patients. Finally, it discusses the N-methyl-D-aspartate antagonist ketamine.

Expert opinion: The present RCT methodologies are too disparate to draw firm conclusions. Future studies are required to identify effective and multimodal pharmacological treatments that efficiently treat depression in AD. Genotyping may boost antidepressant treatment success.