Elevated plasma levels of clozapine after concomitant use of fluvoxamine

Selective serotonin reuptake inhibitors can be added to clozapine therapy in order to treat remaining negative symptoms and obsessive compulsive symptoms. The present case report describes a 44yearold man exhibiting extremely elevated plasma levels of clozapine after the addition of fluvoxamine, up to 4160 mcg/l. The elevated plasma levels of clozapine, which were discovered 6 months after the SSRI was added, is likely to be caused by a drugdrug interaction. Clozapine is a substrate of CYP 1A2 and is predominantly metabolised in the liver. Of the SSRIs, fluvoxamine is one of the most potent inhibitors of the isoenzyme CYP 1A2. This case serves to emphasise the need for continuous attention to drugdrug interactions, especially when they might be easily overlooked due to the lack of clear symptoms.     

Fluvoxamine, a selective serotonin reuptake inhibitor, exerts its antiallodynic effects on neuropathic pain in mice via 5-HT2A/2C receptors

There is an association between depression and chronic pain, and some antidepressants exert antinociceptive effects in humans and laboratory animals. We examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, on mechanical allodynia and its mechanism of action in the mouse chronic pain model, which was prepared by partially ligating the sciatic nerve. The antiallodynic effect was measured using the von Frey test. Fluvoxamine produced antiallodynic effects following both systemic and intrathecal administration. In 5-hydroxytryptamine (5-HT)-depleted mice, prepared by intracerebroventricular injection of 5,7-dihyroxytryptamine, the fluvoxamine-induced antiallodynic effect was significantly attenuated. The antiallodynic effects of systemic fluvoxamine were also reduced by both systemic and intrathecal administration of ketanserin, a 5-HT2A/2C receptor antagonist. In addition, fluvoxamine also induced antinociceptive effect in the acute paw pressure test, and this effect was antagonized by the 5-HT3 receptor antagonist granisetron. These results indicate that fluvoxamine exerts its antiallodynic effects on neuropathic pain via descending 5-HT fibers and spinal 5-HT2A or 5-HT2C receptors, and the antinociception on acute mechanical pain via 5-HT3 receptors.     

Serotonin mediated cluster headache, trigeminal neuralgia, glossopharyngeal neuralgia, and superior laryngeal neuralgia with SAD chronicity

Cluster headache is a rare and severe pain syndrome with elusive pathophysiology. Serotonin pathways within the brainstem may be implicated in cluster headache with seasonal affective disorder and a subset of cranial nerve neuralgias. We describe and chronicle a syndrome consisting of cluster headache, seasonal affective disorder, with associated trigeminal, glossopharyngeal, superior laryngeal neuralgias in an 11-year-old female. Pharmacologic interventions for this patient were examined in conjunction with current classification, location and function of serotonin receptors. Etiology is postulated as mixed cranial nerve excitation via endogenous 5-HT (agonist) activity of 5-HT₃ receptors within the nucleus tractus solitarius and trigeminal tract nucleus.     

The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment

RATIONALE: The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and ejaculation in men. In men with rapid ejaculation it was shown that, of the SSRIs, paroxetine exerted the strongest delay in ejaculation and fluvoxamine the weakest. OBJECTIVES: In the present study, we compared the acute and chronic effects of fluvoxamine and paroxetine on sexual behavior in the male rat in order to compare their differential inhibitory effects on sexual behavior. METHODS: During a 4-week period, 48 male Wistar rats, selected on the basis of their sexual performance, were repeatedly tested for sexual behavior. All male rats received vehicle (saline, n=12), fluvoxamine (30 mg/kg, n=12), or paroxetine (10 mg/kg, n=12) daily for 2 weeks. Sexual behavioral tests were performed on days 1 (acute), 7, and 14. RESULTS: After acute oral administration, fluvoxamine and paroxetine did not inhibit sexual behavior. After 7 days and 14 days treatment, fluvoxamine mildly inhibited certain parameters of sexual behavior but ejaculation was never delayed. In contrast, paroxetine, after 7 days and particularly after 14 days treatment, strongly inhibited sexual behavior, including ejaculation. CONCLUSIONS: These results strongly concur with clinical data, suggesting that paroxetine, but not fluvoxamine, delays ejaculation. Because fluvoxamine does not delay ejaculation it may serve as an optimal treatment for depressive illness when sexual side effects, such as a delayed ejaculation, are undesired. The mechanisms whereby paroxetine and fluvoxamine, both being selective serotonin uptake inhibitors, differentially inhibit sexual behavior are unclear.     

氟伏沙明与无抽搐电休克联合不同剂量阿立哌唑治疗强迫症的疗效及安全性评价

目的 评价氟伏沙明与无抽搐电休克(MECT)联合不同剂量阿立哌唑治疗强迫症的疗效及安全性。方法 选取2012年1月至2017年1月濮阳市精神卫生中心收治的强迫症病人200例,根据随机数字表法将其分为A、B、C、D、E五组,每组40例。A组病人使用氟伏沙明和MECT治疗,B、C、D、E组病人给予氟伏沙明和MECT治疗的同时,分别给予不同剂量的阿立哌唑治疗(剂量分别为2.5、5.0、7.5、10.0 mg/d)。12周后对其临床效果及安全性进行评价。结果 治疗后各组耶鲁布朗强迫量表(Y-BOCS)评分明显下降、生存质量综合评定(GQOLI-74)评分明显升高,与治疗前比较,均差异有统计学意义(P<0.05);A组、B组、C组Y-BOCS评分、GQOLI-74评分比较,差异有统计学意义(P<0.05); A组、B组、C组、D组、E 组总有效率分别为62.50%、87.50%、90.00%、65.00%、57.50%,差异有统计学意义(χ²=18.307,P=0.001);五组症状量表(TESS)评分、不良反应发生率比较,差异无统计学意义(P>0.05)。结论 氟伏沙明与MECT联合小剂量(2.5、5.0 mg/d)阿立哌唑治疗强迫症效果显著,且较安全。     

九味镇心颗粒联合氟伏沙明治疗老年期抑郁症的疗效观察

目的探讨九味镇心颗粒联合氟伏沙明治疗老年期抑郁症的临床效果。方法选取2017年1月—2018年9月成都市第三人民医院收治的88例老年期抑郁症患者,随机分为对照组和治疗组,每组各44例。对照组口服马来酸氟伏沙明片,100 mg/次,1次/d。治疗组在对照组基础上口服九味镇心颗粒,1袋/次,3次/d。两组连续治疗8周。观察两组的临床疗效,比较两组治疗前后17项汉密尔顿抑郁量表(HDRS-17)评分、汉密顿焦虑量表(HAMA)评分、匹兹堡睡眠质量指数(PSQI)评分、自杀意念自评量表(SIOSS)评分、家庭负担访谈问卷(FEIS)评分及36项健康调查简表(SF-36)评分变化。结果对照组和治疗组的总有效率分别是81.8%、95.5%,两组比较差异具有统计学意义(P0.05)。治疗后,两组HDRS-17评分、HAMA评分和PSQI评分较治疗前均显著降低,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组这些评分显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组SIOSS中各因子(绝望、乐观、睡眠、掩饰)评分及总分均显著降低,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组SIOSS评分显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组FEIS中各因子评分及总分较治疗前均显著升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组FEIS中各因子评分及总分均高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组SF-36中PCS评分、MCS评分及总分均较治疗前显著增加,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组PCS评分、MCS评分及总分均显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论九味镇心颗粒联合氟伏沙明治疗老年期抑郁症具有较好的临床疗效,能明显缓解患者病情,改善睡眠,降低自杀风险,减轻照料者的家庭负担,提高生活质量,具有一定的临床推广应用价值。     

疏肝解郁胶囊配合氟伏沙明治疗老年期抑郁症研究

目的:研究探讨疏肝解郁胶囊配合氟伏沙明治疗老年期抑郁症的临床疗效。方法:选取2012年2月²013年6月在我院进行检查且确诊为老年期抑郁症的68例患者,随机分为观察组和对照组各34例,观察组予疏肝解郁胶囊联合氟伏沙明治疗;对照组给予氟伏沙明治疗,疗程均为6周。用药后第2、4、6周末对患者进行随访,并用汉密尔顿抑郁量表(HAMD)和不良反应量表(TESS)进行疗效评定。结果:观察组总有效率为88.2%,对照组总有效率为85.3%,两组疗效比较差异无显著性;但观察组不良反应比对照组轻,差异有统计学意义,P<0.05。结论:疏肝解郁胶囊配合氟伏沙明与单纯应用氟伏沙明治疗老年期抑郁症的临床疗效相当,但疏肝解郁胶囊能提高患者对氟伏沙明的耐受性,减轻不良反应。     

Fear-potentiated startle response is remarkably similar in two laboratories

The fear-potentiated startle response paradigm is used to investigate anxiolytic properties of drugs. The first objective of the present study was to further investigate the predictive validity of this paradigm. The anxiolytics chlordiazepoxide (2.5–10 mg/kg IP) and oxazepam (1–10 mg/kg PO) and the putative anxiolytic flesinoxan (1–10 mg/kg PO) decreased startle potentiation dose-dependently, indicating an anxiolytic effect. The antidepressant fluvoxamine (5–20 mg/kg PO) did not affect startle potentiation. Ideally, anxiolytic drugs attenuate startle potentiation without affecting control startle levels, although some studies report altered control startle amplitudes. The second objective was to investigate whether different effects on control startle amplitudes are related to different startle devices. Therefore, the drugs were tested in two laboratories. Results showed no significant differences between laboratories, indicating that equipment is not a critical factor in the drug-induced alteration of control startle levels. In an additional experiment, it was shown that flesinoxan (10 mg/kg PO) did not affect strychnine-induced startle potentiation, supporting the idea that the attenuating effect of flesinoxan on the fear-potentiated startle response is due to its anxiolytic properties. Thus, the fear-potentiated startle response paradigm appears a valid and reliable model for anxiolytic properties of drugs.     

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia

The effect of fluvoxamine on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was investigated in 11 schizophrenic patients with prevailingly negative or depressive symptoms. Additional fluvoxamine, at the dose of 100 mg/day, was administered for 4 weeks to patients stabilized on risperidone (3-6 mg/day). Mean plasma concentrations of risperidone, 9-OH-risperidone and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) were not significantly modified following co-administration with fluvoxamine. After 4 weeks, fluvoxamine dosage was increased to 200 mg/day in five patients and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the six patients who were still receiving the initial fluvoxamine dose, while concentrations increased slightly but significantly (by a mean 26% over pretreatment; P < 0.05) in the subgroup of five subjects treated with a final dose of 200 mg/day. Fluvoxamine co-administration with risperidone was well tolerated and no patient developed extrapyramidal side effects. These findings indicate that fluvoxamine at dosages up to 100 mg/day is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of fluvoxamine may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of fluvoxamine on CYP2D6-and/or CYP3A4-mediated 9-hydroxylation of risperidone.