Escitalopram versus citalopram: the surprising role of the <Emphasis Type="Italic">R</Emphasis>-enantiomer

Rationale Citalopram is a racemate consisting of a 1:1 mixture of the R(–)- and S(+)-enantiomers. Non-clinical studies show that the serotonin reuptake inhibitory activity of citalopram is attributable to the S-enantiomer, escitalopram. A series of recent non-clinical and clinical studies comparing escitalopram and citalopram to placebo found that equivalent doses of these two drugs, i.e. containing the same amount of the S-enantiomer, showed better effect for escitalopram. These results suggested that the R-citalopram in citalopram inhibits the effect of the S-enantiomer.Objective To review the pharmacological and non-clinical literature that describes the inhibition of escitalopram by R-citalopram, as well as the implications of this inhibition for the clinical efficacy of escitalopram compared to citalopram.Methods The information in this review was gathered from published articles and abstracts.Results In appropriate neurochemical, functional, and behavioural non-clinical experiments, escitalopram shows greater efficacy and faster onset of action than comparable doses of citalopram. The lower efficacy of citalopram in these studies is apparently due to the inhibition of the effect of the S-enantiomer by the R-enantiomer, possibly via an allosteric interaction with the serotonin transporter. Data from randomised clinical trials consistently show better efficacy with escitalopram than with citalopram, including higher rates of response and remission, and faster time to symptom relief.Conclusion The R-enantiomer present in citalopram counteracts the activity of the S-enantiomer, thereby providing a possible basis for the pharmacological and clinical differences observed between citalopram and escitalopram.     

Mirtazapine (Remergil) for treatment resistant hyperemesis gravidarum: rescue of a twin pregnancy

Case report We present the case of a 25-year-old woman with treatment resistant hyperemesis gravidarum in the 15th week with a 13 kg loss of body weight. When the patient asked for termination of the pregnancy because of the unbearable symptoms, treatment with intravenous mirtazapine (Remergil) was started.Results Nausea and vomiting disappeared within hours, pregnancy termination was no longer desired. The patient was discharged two weeks later in good health and at 36 weeks gestation a cesarean section was performed. Post partum evaluation as well as 6-month post-partum revealed no dysmorphology or laboratory abnormalities in the children.     

Sex differences in response to oral amitriptyline in three animal models of depression in C57BL/6J mice

Rationale Knockout and transgenic mice provide a tool for assessing the mechanisms of action of antidepressants. The effectiveness of oral administration of the tricyclic antidepressant amitriptyline (AMI) was assessed in C57BL/6J (B6) mice, a common genetic background on which knockout and transgenic mice are maintained.Objectives We determined whether oral AMI would have antidepressant-like effects in B6 mice and whether these effects varied according to sex, duration of treatment, and the depression model utilized.Methods Male and female B6 mice were administered AMI (200 g/ml) in the drinking water as the sole source of fluid, along with 2% saccharin to increase palatability. Control mice were administered 2% saccharin alone. Mice were assessed for responsiveness to AMI in the tail suspension test (TST), the forced swim test (FST), and the learned helplessness (LH) paradigm.Results In the TST, AMI decreased immobility time regardless of sex or duration of treatment. AMI also decreased immobility time in the FST, but chronic treatment was necessary for full efficacy in both sexes. In the LH paradigm, both subchronic and chronic AMI treatment decreased escape latencies in female mice, but AMI was effective only after chronic treatment in males. The antidepressant-like effects of AMI could not be explained by differences in locomotor activity because activity levels were not altered by antidepressant treatment.Conclusions Overall, oral AMI administration provides a valid model for behavioral assessment of antidepressant-like effects in knockout and transgenic mice maintained on a B6 background, but the effectiveness of oral AMI varies depending on sex, duration of treatment, and the depression model used.     

Tryptophan depletion in SSRI-recovered depressed outpatients

RATIONALE: Recently, a number of studies have challenged the finding that acute tryptophan depletion (TD) increases depressive symptoms in medicated, formerly depressed patients. The present study examined the effects of acute nutritional TD on remitted depressed patients currently treated with selective serotonin reuptake inhibitors. In an attempt to clarify conflicting earlier findings, the effects of a number of clinical variables on outcome were also investigated. METHODS: Ten patients underwent TD in a double-blind, controlled, balanced crossover fashion. The control session followed the procedure of Krahn et al. (1996 Neuropsychopharmacology 15:325-328). Sessions were 5-8 days apart. RESULTS: TD was significantly related to increased scores on clinician-rated depression and anxiety scales, and on self-rated depression, anxiety, and somatic symptoms. The control challenge had no effect, despite the fact that the reductions in plasma tryptophan during the control session were unexpectedly high. Some evidence was found for a threshold in the relationship between reduction of plasma tryptophan and mood response. CONCLUSIONS: The mood effect of TD in medicated, formerly depressed patients was confirmed. A threshold may exist for mood effects following TD, implying that recent negative findings may have been caused by insufficient depletion. No other predicting or mediating factors were identified, although the variable "history of response pattern to medication" deserves further study.     

植物提取物抗抑郁作用研究进展

抑郁症是较常见的疾病,影响着不同肤色、种族、性别、年龄以及不同经济地位的人们。为寻找更有效的抗抑郁剂,从我国传统植物中,发展安全、有效的抗抑郁剂已经成为了研究热点。目前已经发现不少植物提取物具有抗抑郁作用,它们从不同的方面发挥抗抑郁作用。现就植物提取物的抗抑郁作用及可能的相关机制予以综述。     

Antidepressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression

RATIONALE: Epidemiological studies of smokers suggest that there is a link between nicotine and depression. Nonetheless, few studies have examined the potential use of nicotinic ligands in the treatment of depression. OBJECTIVES: The goal of this study was to evaluate the effects of SIB-1508Y, a novel subtype-selective ligand for high affinity nicotinic acetylcholine receptors (nAChRs), in the learned helplessness model of depression in rats. METHODS: In this model, exposure to inescapable foot-shock produces a lasting deficit in escape responses emitted in a subsequent conditioned avoidance procedure (learned helplessness). The effect of SIB-1508Y on learned helplessness was compared to the clinically used antidepressants, imipramine and fluoxetine, and the non-selective nAChR ligand, nicotine. RESULTS: Similarly to imipramine and fluoxetine, subchronic treatment (5 days) with SIB-1508Y reversed the escape deficit in the learned helplessness model in a dose dependent manner. The effect of SIB-1508Y on learned helplessness was still apparent 1 week following drug administration and was also maintained after 4 weeks of daily administration. In contrast, while nicotine was able to attenuate the learned helplessness deficit, this trend only reached statistical significance after chronic administration. The non-competitive ion channel blocker mecamylamine increased escape failures when administered alone and blocked the effects of SIB-1508Y but not imipramine. SIB- 1508Y also produced an increase in avoidance responding, which suggests an enhancement of learning. CONCLUSION: These results not only suggest a role for nAChRs in the development of a depressive-like syndrome, but also that subtype-selective nAChR agonists, such as SIB-1508Y, may offer a novel therapeutic approach to the treatment of depression.     

心脏病与抑郁障碍的认识及处理

抑郁障碍与心脏疾病的关系大致有5个方面:因果关系、反应关系、诱发关系伴发关系、药物因素。二者在不同的关系下,其处理方式亦有所不同。因果关系,治疗以心脏病为主;反应关系,心理治疗为主,必要时加用抗抑郁药;诱发、伴发关系,心脏病和抗抑郁治疗并重,辅以心理治疗;药物关系,抗抑郁药物减量。因此,为了给患者选择更恰当的治疗方式,有必要分清二者的5种关系。