Fluvoxamine and clomipramine in the treatment of cataplexy

Fluvoxamine 25-200 mg daily and clomipramine 25-200 mg daily were given for separate three week periods to 18 subjects with narcolepsy and cataplexy. Both drugs improved cataplexy but not narcolepsy. Fluvoxamine was less active than clomipramine, but both drugs abolished cataplexy in individual subjects. Gastrointestinal side effects prevented treatment with fluvoxamine in five subjects. All patients completed the clomipramine phase of the trial, but two men complained of delayed ejaculation. Fluvoxamine is a more potent inhibitor of 5-hydroxytryptamine (5-HT) reuptake in some systems, but not in others. It is therefore uncertain whether the greater anticataplectic effect of clomipramine is due to a greater inhibition of 5-HT reuptake or to other mechanisms.     

Treatment of Cataplexy with Clomipramine.

A new antodepressant drug, clomipramine hydrochloride, closely related to imipramine hydrochloride, was used to treat four patients suffering from cataplexy, sleep paralysis, and hypnagogic hallucinations. Attacks of cataplexy were associated with rapid-eye-movement (REM) electroencephalographic patterns. Cloripramine, in doses of 25 to 75 mg/day, completely stopped all attacks of cataplexy, sleep paralysis, and hypnagogic hallucinations within 48 hours of initial therapy. The patients have been free of symptoms for periods of 10 to 21 months. Side effects included impotence in the male patients, but no hematologic, cardiovascular, hepatic, or renal toxic effects were observed. Available evidence suggests that such drugs inhibit those brain stem systems that control the toxic components of REM sleep.     

Pharmacotherapy for cataplexy

A variety of medications representing several major drug classes improve cataplexy in patients with narcolepsy. These include aminergic reuptake inhibitors such as venlafaxine and clomipramine as well as sodium oxybate. This review is intended to familiarize readers with the safety and efficacy of these medications, thus enabling clinicians to optimize their management of cataplexy.     

Status cataplecticus induced by abrupt withdrawal of clomipramine

Introduction: Cataplexy is one of the main narcoleptic symptoms and is characterized by sudden loss of muscle tone triggered by emotional stimuli while consciousness is mantained. Clomipramine is an effective treatment of cataplexy. Cataplexy that occurs repeatedly for hours or days is referred to as status cataplecticus.Patients: We report three adults with narcolepsy in whom cataplexy was chronically and effectively treated with clomipramine (75-150 mg/day). For diverse reasons, these three patients had an abrupt withdrawal of clomipramine, and after 2-9 days patients showed an invalidant status cataplecticus characterized by a marked increase of the frequency, duration and severity of their cataplectic attacks that were now elicited by mild emotional stimuli. After introduction of anticataplectic agents (clomipramine in two patients and fluoxetine in one patient), status cataplecticus was resolved in less than a week.Conclusion: In patients with narcolepsy, abrupt withdrawal of chronic treatment with clomipramine may be associated with status cataplecticus. This condition may be resolved with the reintroduction of anticataplectic agents.     

NATURAL HISTORY, SYMPTOMS AND TREATMENT OF THE NARCOLEPTIC SYNDROME

This study describes the clinical features, natural history and treatment of 100 patients with narcolepsy. Over half had one or more affected relatives. Symptoms commenced in adolescence or early adult life in most patients, and remissions were uncommon. Narcolepsy occurred several times each day, often in unusual circumstances and sometimes with little warning. The mean total sleep time of narcoleptics was a little over 9 hours in each 24 hour period, as compared with under 8 in normal subjects. Cataplexy occurred in 93 patients, most commonly when subjects were tired. Attacks were similar in nature to physiological weakness with laughter, although other sudden sensory or emotional stimuli did not cause paralysis of voluntary movement nor loss of muscle tone in normal subjects. Half these patients had frequent dreams before the onset of proper sleep, and 62 had sleep paralysis. This was often frightening, with feelings of suffocation, accompanied by dreams, and of uncertain length. A minority of patients with narcolepsy had muscle aches and jerks before sleep, double vision or loss of focus during cataplexy, went sleep-walking by day, and had daytime hallucinations. Amphetamines had been given to 71 patients for periods of up to 33 years with adequate, but rarely complete, control of narcolepsy. Side effects were common and almost half these patients became tolerant, needing higher dosage to control symptoms. Three patients had a cerebrovascular accident whilst taking amphetamines. Imipramine or clomipramine had ben given in combination with amphetamines to 33 patients for periods of up to 6 years with considerable improvement in both cataplexy and sleep paralysis, and few side effects. Sustained or paroxysmal hypertension as a result of amphetamines or combined treatment did not occur.     

A double-blind randomized study of clomipramine versus maprotiline in patients with idiopathic pain syndromes

Seventy patients with idiopathic syndromes were treated with maprotiline, a noradrenaline reuptake inhibitor, or clomipramine, a serotonin reuptake inhibitor in a 6-week, double-blind, randomized, multicenter trial. Fifty-two patients completed the double-blind phase. Overall, 50% of the patients improved. Significant decreases were seen not only in the levels of pain but also in bodily discomfort, sadness an inner tension (determined by visual analogue scales, VAS). A decrease was also found in the frequency of sleep disturbances, intellectual and emotional inhibition, irritability, guilt feelings, retardation, sadness and suicidal ideas (observed ratings). Sixty-three percent of the subjects showed an overall improvement during treatment with clomipramine as compared to 36% during treatment with maprotiline (p less than 0.05). During clomipramine treatment significant decreases were seen on all the six VAS: sadness, bodily discomfort, inner tension, concentration difficulties, memory disturbances and pain. Bodily discomfort and pain were significantly reduced during maprotiline treatment. The effects produced by clomipramine were also significantly greater than the effects caused by maprotiline as concerns psychic anxiety and inhibition (VAS). The overall reduction in VAS was significantly greater with clomipramine when compared to maprotiline. The most important side effects were dry mouth (both drugs) and sweating (clomipramine). However, in the clomipramine group, 8 patients were excluded due to side effects as compared to 1 patient in the maprotiline group. Thus, the results indicate that antidepressants reduce not only pain but are also of clinical value in the treatment of patients with idiopathic pain syndromes. Drugs with pronounced effects on the serotonin reuptake are to be preferred.     

西酞普兰合并氯丙咪嗪治疗难治性强迫症

目的探讨西酞普兰以及西酞普兰合并氯丙咪嗪治疗难治性强迫症的疗效和不良反应。方法将16例难治性强迫症患者随机分为2组(n=8)，分别给予西酞普兰，西酞普兰合并氯丙咪嗪治疗。采用耶鲁布朗强迫症量表(YBOCS)和副反应量表(TESS)评定疗效和副反应。结果西酞普兰合并氯丙咪嗪组的所有病人的YBOCS减分率均大于35％，有6例出现副反应。西酞普兰组仅有一例患者的YBOCS减分率大于35％，有3例出现副反应。结论西酞普兰合并氯丙咪嗪治疗难治性强迫症的疗效优于单用西酞普兰，但副反应明显多于西酞普兰组。     

氟西汀治疗发作性睡病的猝倒发作

目的观察氟西汀(即百优解,fluoxetine)对发作性睡病(narcolepsy)猝倒(cataplexy)发作的治疗效果并探讨其剂量选择.方法随机选择入组之前6个月内未接受任何针对性治疗的发作性睡病患者30例.治疗开始前1周,由患者详细记录相关的临床表现和各种症状的出现频率,单独选用氟西汀20～40 mg/d,早餐后顿服.于用药的第1、2、4、6周根据患者猝倒发作次数的减少情况评价疗效.结果氟西汀对猝倒发作有良好的治疗作用,多数患者的有效治疗剂量在20～40 mg/d之间.治疗前后相比,患者的猝倒发作次数平均减少了78.83%(P ＜0.01).毒副作用少而轻且多数能在治疗过程中自行消失.结论氟西汀是治疗猝倒发作有效而安全的药物,完全可以替代三环类抗抑郁剂.     

CGP 12.103 A versus clomipramine in the treatment of depressed inpatients--results of a double-blind study

In a double-blind study, which was conducted as an interindividual comparison, 41 depressed inpatients were divided into two test groups according to a randomized list and received either the test substance CGP 12.103 A (19 patients) or the comparative substance clomipramine (22 patients). The study was conducted over a period of 28 days and the dosage of each substance, after being gradually increased, was stabilized at 150 mg. Except for a significantly varied distribution of syndrome patterns, the two treatment groups were comparable with regard to relevant criteria. Both treatment groups showed a significant improvement as assessed by both the degree of severity of depression and the Hamilton Depression Rating Scale; on each scale, however, the clomipramine treatment group exhibited a tendency toward better antidepressive efficacy. According to the self-evaluations of the patients, which were conducted with the help of v. Zerssen's Self-Rating Scale, this tendency was not significant. The Kusta activation parameter indicated a tendentially stronger manifestation in the case of clomipramine. In the final evaluation the onset of efficacy for the CGP 12.103 A group lay in the mean on treatment day 6, for the clomipramine group on treatment day 10. The physician's overall assessment of therapeutic effect found no differences between the two treatment groups on day 14 and on day 28. Expected side effects were observed in the CGP 12.103 A group in nine patients, in the clomipramine group in 14. All in all, the test substance CGP 12.103 A, the (-) or R-enantiomer of the antidepressant oxaprotiline, which itself is derived from maprotiline, showed no essential differences in its antidepressive efficacy compared with clomipramine.     

Increased antipanic efficacy in combined treatment with clomipramine and dixyrazine

A double-blind 12 week trial was undertaken to compare the effects of clomipramine + dixyrazine with clomipramine + placebo in the treatment of panic disorder with or without agoraphobia. Of 45 patients included (21 dixyrazine, 24 placebo), 16 dropped out (6 dixyrazine, 10 placebo). The number of panic attacks and the scores on the panic disorder subscale of the Hamilton Anxiety Rating Scale were significantly reduced in response to both treatment regimens, but the reduction was significantly greater in the dixyrazine group. The patients’ daily functioning was significantly more improved with the dixyrazine combination. The serum concentration of desmethylclomipramine monotherapy was significantly higher and the side effects significantly lower in the combined treatment with dixyrazine than with clomipramine monotherapy. Clomipramine combined with dixyrazine seems superior to clomipramine in the treatment of panic disorder.     

Controlled comparisons of clomipramine and fluoxetine in the treatment of obsessive-compulsive disorder. Behavioral and biological results

Treatment with fluoxetine hydrochloride was compared with treatment with clomipramine hydrochloride in two groups of patients with obsessive-compulsive disorder using two different experimental designs. In the first group of 11 patients with obsessive-compulsive disorder studied using a randomized, double-blind, crossover design, treatment with fluoxetine for 10 weeks was found to produce therapeutic effects similar to treatment with clomipramine for 10 weeks. There were significantly fewer total side effects reported during fluoxetine than clomipramine treatment. Drug tapering and placebo substitution in the 4-week crossover interval phase led to substantial relapses in obsessive-compulsive disorder symptoms and depression. Furthermore, responses to the second drug took as long to occur as responses to the first drug, although both drugs are thought to act by a common mechanism, serotonin uptake inhibition. A second group of 21 patients with obsessive-compulsive disorder that had been previously stabilized on clomipramine treatment with at least partial benefit were crossed over to fluoxetine treatment in a double-blind fashion. After 10 weeks of fluoxetine administration, most patients manifested behavioral rating scores of obsessive-compulsive disorder and depressive symptoms that were comparable with precrossover ratings completed during clomipramine treatment. A significant exacerbation in obsessive-compulsive disorder and depression ratings as well as a similar lag in therapeutic efficacy were also noted in this second cohort of patients with obsessive-compulsive disorder. Platelet 5-HT concentrations were reduced 95% during both clomipramine and fluoxetine treatment periods. These results suggest that fluoxetine may represent a viable alternative to clomipramine in the treatment of obsessive-compulsive disorder, although further studies with larger sample sizes are needed.     

Clomipramine and obsessive compulsive disorder: a placebo-controlled double-blind study of 32 patients

Thirty-two nondepressed patients with obsessive compulsive disorder were randomly assigned to treatment with clomipramine (N = 16) or placebo (N = 16) in a 10-week double-blind study. Of the 15 patients who received at least 3 weeks of clomipramine treatment, 11 (73%) improved, 5 (33%) improved by more than 50%, and none worsened. Only 2 (12.5%) of the 16 placebo-treated patients improved, 1 (6%) by more than 50%; two (13%) worsened. Clomipramine treatment was associated with statistically significant improvement on several measures of obsessive compulsive symptoms. Side effects were more frequent and severe with clomipramine than with placebo. Although most patients tolerated clomipramine well, 3 discontinued treatment because of side effects.     

舍曲林与氯米帕明对强迫症患者生活质量的影响

目的:探讨舍曲林与氯米帕明对强迫症患者生活质量的影响.方法:应用舍曲林与氯米帕明分别治疗强迫症各30例,采用Yale-Brown强迫量表、生活质量综合评定问卷(GQOLI-74)分别于治疗前和治疗8周末进行疗效和生活质量评估.结果:舍曲林和氯米帕明对强迫症疗效相当,但舍曲林不良反应少,对患者生活质量的提高优于氯米帕明(P＜0.05).结论:舍曲林比氯米帕明能更好地改善强迫症患者的生活质量.     

氟西汀和氯米帕明治疗中性强迫症的对照研究

目的 评价氟西汀和氯米帕明对难治性强迫症的疗效。方法 符合CCMD－2－R强迫症诊断标准的难治性病人共60例,随机分为两组,分别用氟西汀和氯米帕明系统治疗8周。采用耶鲁布郎强迫量表（Y－BOCS）和药物副反应量表（TESS）评价疗效及主要副反应。结果 两药的总体疗效相当;氟西汀对强迫性行为见效快,疗效好,副作用小,尤其是心血管系统及抗胆碱能副反应少,远期效果优于氯米帕明。结论 氟西汀尤其适用于伴有心血管痢疾而又以强迫行为为主的难治性强迫症病人。     

帕罗西汀与氯米帕明治疗难治性强迫症对照研究

目的：观察帕罗西汀和氯米帕明对难治性强迫症的疗效和不良反应。方法：对难治性强迫症患者60例,随机分为两组,分别用帕罗西汀和氯米帕明治疗8周。采用强迫症量表（Y-BOCS）和副反应量表（TESS）评价疗效及不良反应。结果：两药的总体疗效相仿。帕罗西汀对强迫行为疗效较好,不良反应小,尤其是心血管系统及抗胆碱能不良反应少。结论：帕罗西汀尤适用于以强迫行为为主的难治性强迫症患者。     

Safety and efficacy of long-term use of sodium oxybate for narcolepsy with cataplexy in routine clinical practice

BackgroundSodium oxybate is licensed in Europe for the treatment of narcolepsy with cataplexy in adults. The aim of this study was to assess the efficacy and safety of sodium oxybate in clinical practice in patients with narcolepsy and cataplexy refractory to other treatments.Materials and methodsThis was a retrospective single centre study including patients with severe narcolepsy with cataplexy refractory to other treatments, who were initiated on sodium oxybate between 2009 and 2015. Patients were allowed to be on other stimulants or/and anti-cataplectic agents. Epworth sleepiness scale (ESS) and weekly cataplexy events were recorded. Side effects (SEs) were recorded at every follow-up visit.Results90 patients were prescribed sodium oxybate, with a total of 3116 patient-months of drug exposure. ESS and weekly cataplexy events were significantly reduced by sodium oxybate for all patients (ΔESS = 4.3 ± 4.4 and Δcataplexy = 21.8 ± 18.5 events/week; p < 0.0001, respectively). The required maintenance dose could not be predicted based upon gender, body mass index, or clinical factors. 60% of patients were able to reduce or come off other medications. Half of the patients experienced at least one SE, and 26.6% had to stop treatment due to limiting SEs. Nausea, mood swings and enuresis were the most commonly reported SEs. SEs that led to drug discontinuation, particularly psychosis, were associated with increasing age and were observed early after the initiation of the drug.ConclusionsSodium oxybate provides a good clinical efficacy and acceptable safety profile in routine clinical practice for the treatment of patients suffering from narcolepsy with cataplexy. A quarter of patients experience SEs requiring withdrawal of the drug with older patients being more vulnerable to the more serious SEs.     

Clomipramine: an antiobsessive drug

In the past decade, various investigators have attempted to find new pharmacological agents for the treatment of obsessive disorders. Of these, the drug which has attracted attention and has been most promising is clomipramine. This paper attempts to review the usefulness of clomipramine in the treatment of obsessive disorder. Accidentally, it was discovered that clomipramine was effective in alleviating obsessive symptoms in depressed patients by a Spanish psychiatrist, Lopez-Ibor. Initial studies carried out mainly on patients with major depression reported that obsessive symptomatology benefited with clomipramine therapy. A number of uncontrolled and controlled studies confirmed the efficacy of this drug in obsessive neurosis. The drug improves the obsessive symptoms. Discontinuation of the drug is followed by a relapse. The efficacy, dosage, duration and side effects of treatment with clomipramine are discussed in this paper.     

舍曲林与氯丙咪嗪治疗强迫症的对照研究

目的比较舍曲林与氯丙咪嗪治疗强迫症的疗效和不良反应。方法应用舍曲林和氯丙咪嗪治疗强迫症各30例，应用Yale-Brown强迫量表、汉密顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)及临床4级标准评定疗效。结果舍曲林与氯丙咪嗪治疗后Yale-Brown强迫量表分值、HAMD、HAMA分值均显著下降，两组间减分比较，差异无显著性，舍曲林不良反应发生率明显少于氯丙咪嗪。结论舍曲林治疗强迫症疗效与氯丙咪嗪相当，不良反应较轻，值得推广。     

Exacerbation of cataplexy following gradual withdrawal of antidepressants: manifestation of probable protracted rebound cataplexy

BackgroundA double-blind, placebo-controlled sodium oxybate trial provided a unique opportunity to compare changes in cataplexy following gradual withdrawal from antidepressants in narcolepsy patients.MethodsOf 228 enrolled patients, 71 discontinued antidepressant therapy. Data from 57 patients were available for analysis: 37 patients discontinued tricyclic antidepressants (TCAs) and 20 discontinued selective serotonin reuptake inhibitors (SSRIs). The trial included a 21-day withdrawal phase followed by 18-day washout and 14-day single-blind treatment phases. Two additional weeks were permitted for withdrawal from fluoxetine due to its long half-life. Weekly cataplexy attacks were recorded throughout the trial. No historical data on the frequency of cataplexy prior to treatment with antidepressants was available.ResultsAmong the patients who were and were not withdrawn from antidepressants treatment, the median frequency of baseline weekly cataplexy was similar (17.5 vs. 14.0, respectively). As expected, significant between-group differences emerged by the end of the washout period (52.04 vs. 15.25, respectively; p < 0.05); however, the frequency of cataplexy events became similar again by the end of the trial (16.5 vs. 17.5, respectively).ConclusionsPatients gradually withdrawn from antidepressants experienced a significant increase in cataplexy, but eventually returned to their baseline frequency, comparable to previously untreated control patients. Compared to SSRIs, discontinuation from TCAs was associated with a greater increase in cataplexy attacks.