Neuroleptic malignant syndrome in an adolescent receiving olanzapine-lithium combination therapy

A 16-year-old boy developed fever, generalized rigidity, leukocytosis, and increased serum transaminase and creatine kinase levels while receiving treatment with olanzapine and lithium. When both drugs were discontinued, his fever and rigidity subsided and biochemical irregularities spontaneously returned to normal, without any complications. Classic neuroleptic malignant syndrome (NMS) was diagnosed. Concomitant administration of lithium with olanzapine may place patients at risk for NMS. Clinicians need to be aware of this rare but potentially fatal side effect in patients of all ages, and especially in adolescents receiving both drugs.     

Extrapyramidal symptoms and signs in first-episode, antipsychotic exposed and non-exposed patients with schizophrenia or related psychotic illness

Movement disorders in first-episode psychosis are increasingly recognized; however, the prevalence and clinical correlates are uncertain. We compared antipsychotic exposed (< 12 weeks) with nonexposed first-episode patients, and report prevalence as well as clinical and demographic variables associated with extrapyramidal dysfunction. Data are baseline assessments from a multicentre, international drug trial of first-episode psychosis (n = 535). Analysis included the Extrapyramidal Symptom Rating Scale, Premorbid Adjustment Scale, and the Positive and Negative Syndrome Scale. Of non-exposed patients, 28.1% (n = 47/167) had at least one mild sign of extrapyramidal dysfunction, as did 46.3% (n = 169/365) of previously exposed patients. Hypokinetic Parkinsonism was the most prevalent disorder. The severity of movement disorders and negative symptoms were correlated; however, the effect sizes were small. Logistic regression analysis indicated that the salient risk factors for all patients were: previous antipsychotic exposure [odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.6-3.6] and poor premorbid functioning (OR = 1.8; 95% CI 1.2-2.6). For the non-exposed group (n = 167), the significant risk factors were: having severe mental illness in the family (OR = 2.9; 95% CI 1.2-7.2) and poor premorbid functioning (OR = 2.3; 95% CI 1.0-5.3). For the previously exposed group (n = 368), the significant variables were: poor premorbid functioning (OR = 1.8; 95%CI 1.2-2.8) and shorter duration of untreated psychosis (OR = 0.78; 95% CI 0.64-0.94). Although antipsychotic exposure was associated with extrapyramidal signs, the results indicate that many first-episode patients with no exposure to antipsychotics also had extrapyramidal dysfunction. In this group, family history and poor premorbid functioning appear to be associated with increased risk for movement disorders.     

盐酸氨溴索不同用药途径辅助治疗小儿肺炎的疗效分析

目的分析盐酸氨溴索不同用药途径辅助治疗小儿肺炎的临床疗效。方法将105例小儿肺炎患者用随机数字表法分为3组雾化组、静脉组和口服组各35例。3组均按常规方法给予抗感染、对症支持治疗。观察3组症状、体征消失时间和有效率及药物不良反应。结果雾化组、口服组和静脉组总有效率分别为91．43％（32／35）、88．57％（31／35）和88．57％（31／35）,差异无统计学意义（P〉0．05）,但雾化组显效率（34．29％,12／35）高于口服组（11．43％,4／35）和静脉组（17．14％,6／35）,差异有统计学意义（P〈0．05）。雾化组在咳嗽、肺部湿啰音消失及平均住院时间上较口服组和静脉组短,差异有统计学意义（P〈0．05）。3组均未出现严重药物不良反应。结论盐酸氨溴索雾化吸入治疗小儿肺炎疗效较好,且较为安全。     

西肽普兰与喹硫平联用相关排尿困难和尿潴留

1例69岁女性患者因胸痛入院。入院第2天夜间睡眠差,给予曲唑酮50mg,1次/d睡前服,用药4d症状未改善。停用曲唑酮,改用西酞普兰10mg,每晚睡前口服,但症状仍未见明显改善。诊断为抑郁症,给予西酞普兰20mg,联合喹硫平50mg,每晚睡前口服。服用后出现排尿踌躇、费力,尿量减少。第6天出现排尿困难、尿潴留。停用西酞普兰及喹硫平,行尿道插管。5d后症状缓解,自行排尿。     

Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial

Rational

It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia.

Objective

This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial.

Methods

Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45?years. All patients were inpatients and were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion: 20 to risperidone (6?mg/day) plus sildenafil (75?mg/day) and 20 to risperidone (6?mg/day) plus placebo. The principal measure of outcome was Positive and Negative Syndrome Scale (PANSS).

Results

Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F?=?4.77, df?=?1; P?=?0.03; F?=?5.91, df?=?1, P?=?0.02 respectively).

Conclusion

Therapy with 75?mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11).     

Effect of adjunctive paroxetine on serum levels and side-effects of tricyclic antidepressants in depressive inpatients

Rationale: Previous studies showed that adjunctive paroxetine increases tricyclic antidepressant (TCA) serum levels by inhibiting cytochrome P4502D6. This effect has, however, been examined only in experimental studies using low doses of TCAs in healthy volunteers. Objective: The present study investigated TCA serum level changes and side-effects after the addition of paroxetine in depressed patients treated with doses customarily used for inpatients. Method: 14 patients who had a moderate or severe depressive episode according to ICD-10 and who had not sufficiently responded (≤25% reduction of the Hamilton depression scale) to 3-week monotherapy with amitriptyline (n=9) or imipramine (n=5) with daily doses between 125 and 200 mg/day, received 20 mg/day paroxetine additionally under steady state conditions. Results: After 2 weeks the serum levels of the metabolites nortriptyline (from 88±49 ng/ml to 176±57 ng/ml) and desipramine (from 152±78 ng/ml to 338±104 ng/ml) had risen to a significantly greater extent than those of the parent compounds amitriptyline (123±50 ng/ml to 195±128 ng/ml) and imipramine (from 75±36 ng/ml to 98±51 ng/ml). It is noteworthy that, with the exception of one case of incipient delirium, the combination therapy was well tolerated despite high TCA serum level rises. Conclusion: The higher increase of the metabolites as compared with the parent compounds can be explained by a paroxetine-induced inhibition of the liver enzyme cytochrome P4502D6, which catalyses the second step of the TCA metabolism, i.e. the hydroxylation of the metabolites. Blood levels should be meticulously monitored, if TCAs are combined with paroxetine. Received: 8 March 1999 / Final version: 23 July 1999     

Effects of adjunctive antidepressant therapy with quetiapine on clinical outcome, quality of sleep and daytime motor activity in patients with treatment-resistant depression

OBJECTIVE: To investigate the effects of antidepressant therapy plus quetiapine on major depression, motor activity, daytime sleepiness and quality of sleep. METHODS: Patients (N = 27) with major depressive disorder received a standard antidepressant treatment (Venlafaxine, Escitalopram) plus flexible dose of quetiapine. Patients' depression was monitored with HAM-D-21, motor activity was continuously measured with actigraphy and sleep parameters with the Pittsburgh Sleep Quality Index (PSQI) over 4 weeks. RESULTS: Whereas depression, quality of sleep and daytime sleepiness showed a significant improvement over 4 weeks, change of daytime motor activity was significant only between the wash out period and the last 2 days of the study. Repeated measures of variance indicate an independent influence of quetiapine on improved depression, motor activity and sleep. While we found only a mild decrease of daytime sleepiness during the first week of treatment, the further decline of daytime sleepiness got significant after 2 weeks of treatment with quetiapine, even at high mean daily doses and despite the sedative effects of quetiapine. CONCLUSIONS: Antidepressant treatment plus quetiapine is possibly a suitable treatment strategy to improve clinical depression, quality of sleep and motor activity. Future research is needed to understand the pharmacological interactions between antidepressants and quetiapine in major depression.     

喹硫平与唑吡坦联用致抗精神病药恶性综合征

1例55岁女性患者,因行为异常、躁动、失眠等症状给予喹硫平0.2g,1次/d口服;唑吡坦5mg,每晚睡前服。用药9d后出现吞咽困难、多汗,随后逐渐出现言语不利,偶处于谵妄状态,双手不自主抽动,四肢肌张力增高。T38℃,BP171/87mmHg。实验室检查：WBC24.2×109/L,CK22820U/L,CK-MB225U/L,肌红蛋白1790U/L,LDH2565U/L。停用喹硫平及唑吡坦,纠正电解质紊乱,行保肝、营养支持治疗,应用血液透析。第10天患者症状明显改善,共住院36d出院。     

利培酮联合小剂量帕罗西汀治疗精神分裂症阴性症状临床观察

目的探讨利培酮联合小剂量帕罗西汀治疗精神分裂症阴性症状的临床疗效和安全性。方法将60例精神分裂症患者随机分为治疗组（利培酮＋帕罗西汀）和对照组（利培酮）各30例,利培酮治疗剂量2—8mg／d,帕罗西汀10～40mg／d,疗程8周,治疗后采用阴性症状量表和副反应量表评定临床疗效与不良反应。结果两组治疗后阴性症状量表总分和因子分均显著下降,差异有统计学意义（P〈0．05）,治疗组阴性症状量表总分、情感平淡、思维贫乏、意志缺乏、兴趣缺乏等因子分较对照组下降明显,差异有统计学意义（P〈0.05）。不良反应两组无显著性差异（P〉0．05）。结论利培酮联合小剂量帕罗西汀治疗精神分裂症阴性症状疗效优于单用利培酮治疗。     

Efficacy of quetiapine for impulsivity and affective symptoms in borderline personality disorder

Data on the efficacy of quetiapine in borderline personality disorder (BPD) are still scarce. We aimed to investigate the efficacy of quetiapine for impulsivity and a broad range of affective symptoms in BPD. In this 12-week open-label study, we included individuals with BPD who presented to psychiatric in- and outpatient services. After a gradual titration of quetiapine, a flexible dose (range, 100-800 mg) was administered. The main outcome measures consisted of the scores on patient-rated questionnaires (Barratt Impulsiveness Scale, Buss-Durkee Hostility Inventory, Affective Lability Scale, Spielberger State and Trait Anxiety Inventory, Spielberger State and Trait Anger Inventory, and Beck Depression Inventory) and on neurocognitive tasks related to impulsivity (Stroop Color Word Task and IOWA Gambling Task). A mixed linear model, correcting for age, sex, antidepressant use, and weeks in psychotherapy, was applied. Forty-one patients (34 females and 7 males; mean [SD] age, 27.0 [9.0] years) were enrolled in the study, 32 of which completed the trial. Patients' scores decreased significantly (mean [SD] difference; P value) on the Barratt Impulsiveness Scale (19.7 [2.0]; P < 0.0001), Buss-Durkee Hostility Inventory (11.5 [1.4]; P < 0.0001), Affective Lability Scale (0.75 [0.08]; P < 0.0001), Beck Depression Inventory (25.0 [1.7]; P < 0.0001), Spielberger State and Trait Anxiety Inventory state (19.9 [1.9]; P < 0.0001) and trait (20.8 [1.7]; P < 0.0001) subscale, and Spielberger State and Trait Anger Inventory state (7.3 [1.1]; P < 0.0001) and trait (10.1 [1.0]; P < 0.0001) subscale. In addition, patients showed significantly less inference on the Stroop Color Word Task and had more 'good choices' on the IOWA Gambling Task. These results suggest that quetiapine may be efficacious in the treatment of impulsivity and affective symptoms in BPD.     

Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment

Abrupt interruption or cessation of selective serotonin reuptake inhibitor (SSRI) treatment may result in discontinuation or treatment interruption symptoms. Recent reports suggested these symptoms occur more frequently with shorter half-life SSRIs. Previous studies indicated a 5-8-day treatment interruption resulted in fewer discontinuation-emergent adverse events in fluoxetine-treated patients than in paroxetine-treated patients. This study examines the effects of shorter treatment interruption (3-5 days), as would occur if patients miss just a few doses of medication. Patients successfully treated for depression with fluoxetine or paroxetine underwent treatment interruption in a double-blind fashion. Treatment interruption-emergent symptoms were assessed using the Discontinuation-Emergent Signs and Symptoms checklist. Other assessments included the Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions-Severity scale and a social functioning questionnaire. Of 150 patients enrolled, 141 completed the study. Following treatment interruption, fluoxetine-treated patients experienced fewer treatment interruption-emergent events than did paroxetine-treated patients. The paroxetine treatment group also experienced significant increases in depressive symptoms, clinical global severity scores and difficulty in social functioning; the fluoxetine treatment group did not. These results are consistent with reports suggesting abrupt interruption of treatment with paroxetine is more often associated with somatic and psychological symptoms than is abrupt interruption of fluoxetine. Patients treated with fluoxetine appeared to be protected by its longer half-life.