喹硫平与氟西汀治疗抑郁发作的对照研究

目的:评价喹硫平治疗抑郁发作的疗效与副作用。方法:将抑郁发作患者60例随机分为喹硫平组与氟西汀组各30例,进行对照治疗研究,以HAMD抑郁量表、治疗药物副反应量表(TESS)及临床评定标准分别评定疗效和副作用。结果:两组药物治疗后HAMD评分较治疗前有明显下降,两种药物的治愈率无明显差异(P>0.05)。喹硫平组副作用比氟西汀组少见(P<0.05)。结论:喹硫平治疗抑郁发作疗效确切、副作用轻微。     

氟西汀治疗脑卒中后并发抑郁症189例临床分析

目的观察氟西汀治疗脑卒中后抑郁症的临床疗效,探讨其发生的可能机制及治疗方法。方法将189例脑卒中后抑郁症患者随机分为治疗组（氟西汀治疗99例）和对照组（常规治疗90例）。观察抑郁症的临床表现和服用氟西汀的治疗效果,分析抑郁症的产生与卒中后脑血管损害部位、神经功能缺失程度、文化程度等之间的关系。结果治疗组治疗后汉密尔顿抑郁量表（HAMD）评分显著下降（P〈0.01）,对照组治疗后评分比较差异无统计学意义（P〉0.05）。大脑皮质下脑血管病患者抑郁症发生率更高;神经功能缺失程度与抑郁症有显著相关（r=0.857,P〈0.01）;日常生活依赖程度评分与HAMD呈显著负相关（r=-0.753,P〈0.01）。结论抗抑郁药物氟西汀治疗脑卒中后抑郁不仅对抑郁有明显效果,且可促进脑卒中后神经功能的恢复。     

Fluoxetine Monotherapy in Attention-Deficit/Hyperactivity Disorder and Comorbid Non-Bipolar Mood Disorders in Children and Adolescents

Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing comorbid non-bipolar mood disorders. Fluoxetine monotherapy is an established treatment for pediatric mood disorders; however its efficacy in ADHD and comorbid mood disorder is unknown. Therefore, we evaluated 30 children who met DSM-IV criteria for ADHD and comorbid non-bipolar mood disorders in a prospective, 6–12-week open-label, study of fluoxetine monotherapy. Fluoxetine was associated with significant decreases in the severity of depressive symptoms, and also, associated with significant decreases on subscales of inattention/overactivity and aggression/defiant symptoms—47% of participants were much or very much improved without observed adverse effects.     

Cortico-striatal cyclic AMP-phosphodiesterase-4 signalling and stereotypy in the deer mouse: Attenuation after chronic fluoxetine treatment

Motor stereotypies, described as repetitive, topographically invariant and seemingly purposeless behaviours, are common to several developmental and neuropsychiatric disorders. While drug induced stereotypy has been extensively studied, the neurobiology of spontaneous stereotypy is poorly understood. Deer mice present with naturalistic stereotypic behaviours that are selectively suppressed by fluoxetine. We studied basal cyclic adenosine monophosphate (cAMP) levels and phosphodiesterase (PDE) type 4 activity in prefrontal cortex and striatum of high, low and non-stereotypic deer mice, as well as response in high stereotypic mice to chronic fluoxetine treatment (20 mg/kg/day × 21 days intraperitoneally). Cortical cAMP levels were associated with stereotypic behaviour, being significantly elevated in low and high stereotypic mice compared to non-stereotypic animals, with a similar trend in the striatum. In both brain regions, there was a significant inverse correlation between PDE4 activity and stereotypic behaviour. In the prefrontal cortex, PDE4 activity was significantly reduced in both low and high stereotypic mice compared to their non-stereotypic controls, while in the striatum, only high stereotypic mice showed a significant reduction in PDE4 activity. Fluoxetine significantly attenuated stereotypies in high stereotypic animals, together with a reduction in cortical cAMP levels and PDE4 activity, without noteworthy effects in the striatum. Spontaneous stereotypy in deer mice is thus characterized by raised cAMP and reduced PDE4 enzyme activity, particularly in the prefrontal cortex, and is modified by chronic treatment with fluoxetine.     

A preclinical model of binge eating elicited by yo-yo dieting and stressful exposure to food: effect of sibutramine,fluoxetine, topiramate,and midazolam

Rationale  Preclinical models are needed to investigate the neurobiology and psychobiology of binge eating and to identify innovative pharmacotherapeutic strategies. Objectives  A modification of the model based on the combination of cyclic caloric restrictions and acute stress was developed to further increase its face validity and reliability and, for the first time, to assess its predictive value. Materials and methods  Four groups of female rats were employed: group 1 was normally fed and not stressed on the test day (25th); group 2 was fed normally but was exposed to an acute stress on day 25; group 3 was exposed to three cycles (4 days 66% of chow intake + 4 days food ad libitum) of yo-yo dieting but not stressed; and group 4 was exposed to cyclic yo-yo dieting and then stressed. All groups were fed highly palatable food (HPF) for 2 h on days 5–6 and 13–14. Acute stress was elicited by exposing rats to HPF, but preventing them from access to it for 15 min. Results  The combination of cyclic food restriction and stressful exposure to food markedly increased HPF intake. Sibutramine and fluoxetine inhibited food intake in all conditions. Topiramate selectively inhibited compulsive HPF intake in rats submitted to caloric restriction and stress. Midazolam increased HPF intake. Conclusions  Pharmacological results suggest that this model, in addition to face validity as an isomorphic model of human binge eating, is endowed with good predictive validity.     

Monoaminergic regulation of Sonic hedgehog signaling cascade expression in the adult rat hippocampus

Monoamines are implicated in the modulation of adult hippocampal neurogenesis in depression models and following chronic antidepressant treatment. Given the key role of Sonic hedgehog (Shh) in adult neurogenesis, we examined whether monoaminergic perturbations regulate the expression of Shh or its co-receptors Smoothened (Smo) and Patched (Ptc). Combined depletion of both serotonin and norepinephrine with para-chlorophenylalanine (PCPA) resulted in a significant decrease in Smo and Ptc mRNA within the dentate gyrus subfield of the hippocampus. However, selective depletion of serotonin, using the serotonergic neurotoxin 5,7-dihyrdroxytryptamine (5,7-DHT), or norepinephrine, using the noradrenergic neurotoxin DSP-4, did not alter expression of Shh and its co-receptors, Smo and Ptc. Acute treatment with the monoamine releasing agent, para-chloroamphetamine (PCA) significantly upregulated Smo mRNA within the dentate gyrus. However, acute or chronic treatment with pharmacological antidepressants that modulate monoaminergic neurotransmission did not regulate Shh cascade expression. These results indicate that robust changes in monoamine levels can regulate the expression of the Shh signaling cascade in the adult rodent brain.     

氟西汀治疗持续的躯体形式疼痛障碍的成本-效果分析

目的 初步探索氟西汀治疗持续的躯体形式疼痛障碍(PSPD)的成本-效果分析.方法 将80例PSPD患者随机分为氟西汀组和安慰剂组,每组各40例,分别服用氟西汀胶囊(20 ms/d)和安慰剂胶囊(1粒/d)8周,研究者和患者双肓.调查入组前后直接医疗成本,计算两组患者入组前后共4个月的成本与效果比值.结果 (1)氟西汀组有效率为40%,安慰剂组有效率为8%.(2)氟西汀组和安慰剂组成本与效果比值分别为0.53万元(5345元)和1.83万元(18 345元).(3)敏感度分析,氟西汀组和安慰剂组的成本与效果比值分别为0.40万元(4033元)和1.22万元(12 188元).结论 应用氟西汀治疗PSPD的成本与效果比值较低,具有较好的药物经济学价值.     

围绝经期妇女重度抑郁症综合康复治疗的临床疗效分析

目的探讨围绝经期妇女重度抑郁症综合康复治疗的临床疗效。方法对26例围绝经期重度抑郁症妇女给予服用尼尔雌醇、氟西汀、解郁汤及心理治疗,采用汉密尔顿抑郁量表（HAMD）和自评抑郁量表（SDS）评分进行治疗前后对比观察和治疗效果评价,同时检测血清雌二醇（E2）、血清促卵泡素（FSH）含量变化。结果经过8周的综合康复治疗后,患者E2水平明显增高（P〈0．01）,FSH含量显著降低（P〈0．01）,HAMD和SDS评分明显降低（P〈0．01）。26例患者经治疗后,治愈16例（61．5％）,显效6例（23．1％）,有效4例（15．4％）,总有效率为100％。结论综合康复治疗围绝经期妇女重度抑郁症疗效好、副作用小,是安全有效的治疗方法。     

艾司西酞普兰和氟西汀治疗首发抑郁症临床疗效及认知功能影响的比较

目的 比较艾司西酞普兰和氟西汀对抑郁症治疗的临床疗效及对抑郁症患者认知功能的影响.方法 将60例抑郁症患者随机分为艾司西酞普兰组(30例)和氟西汀组(30例),进行临床对照试验,两组药物治疗量分别为10～20 mg/d,20～40 mg/d,疗程8周.采用汉密尔顿抑郁量表17项(HAMD17)、临床整体量表-疗效总评估量表(CGI-SI)为疗效指标,以词汇流畅性测验和威斯康星卡片分类测验(WCST)评定患者认知功能,不良反应症状量表(TESS)为不良反应指标.结果 第1周艾司西酞普兰组有效率为20.00% 显著高于氟西汀组有效率(3.33%)(χ2=4.04,P <0.05).第8周治疗结束时艾司西酞普兰组有效率为73.33%,氟西汀组有效率为70.00%,两组疗效差异无统计学意义(χ2=0.08,P >0.05);在治疗第8周时与基线评分相比,两组在词汇流畅性测验和WCST的总测验次数、持续错误数和随机错误数中的评分均有改善,差异具有显著性( t =1.70～6.00, P <0.05),在WCST的正确数和分类数的评分改善不明显,差异无统计学意义( t =0.29～0.66, 均P >0.05).两组之间在词汇流畅性测验和WCST各项改善间的比较,差异无统计学意义( t =0.02～0.49,均P >0.05);两组与药物相关的不良反应出现频率的差异无统计学意义(χ2=0.07,P >0.05).结论 艾司西酞普兰和氟西汀治疗抑郁症疗效相当,均能部分缓解抑郁伴发的认知功能障碍,且副作用较小、安全性好,但艾司西酞普兰起效更快,有利于迅速缓解患者症状.     

Enhanced reactivity of 5-HT1A receptors in the rat dorsal periaqueductal gray matter after chronic treatment with fluoxetine and sertraline: evidence from the elevated T-maze

Behavioral evidence indicates that sensitization of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal gray (DPAG) may underlie the therapeutic effect of serotonin reuptake inhibitors (SRIs) in panic disorder. These results were obtained from studies using animal models that associate escape behavior with panic attacks, such as the elevated T-maze. In this test, chronic administration of the non-selective SRI imipramine enhances the inhibitory effect on escape caused by the intra-DPAG injection of the 5-HT1A receptor agonist 8-OH-DPAT. We here evaluated the generality of this finding by investigating the effect of chronic administration of two selective SRIs (SSRIs), fluoxetine and sertraline, on the reactivity of the rat DPAG 5-HT1A receptors. The results showed that both SSRIs inhibited escape behavior in the elevated T-maze, suggestive of a panicolytic-like effect. Whereas intra-DPAG injection of a low dose of 8-OH-DPAT (0.4nmol) had no effect on escape in control animals, it significantly enhanced the inhibitory effect caused by the SSRIs on this response. Microinjection of 8-OH-DPAT in SSRI-treated rats also inhibited the acquisition of inhibitory avoidance, another defensive response measured by the elevated T-maze. The results indicate that chronic administration of fluoxetine and sertraline sensitizes 5-HT1A receptors in the DPAG. Overall, they support the view that facilitation of 5-HT1A receptor-mediated neurotransmission in the DPAG is implicated in the therapeutic effect of SRIs on panic disorder.