普拉克索治疗抑郁症并发不安腿综合征疗效观察

目的探讨普拉克索治疗抑郁症并发不安腿综合征的疗效。方法对30例抑郁症并发不安腿综合征患者应用普拉克索治疗,观察治疗全程。于治疗前后采用不安腿综合征病情严重程度评定量表、抑郁自评量表评定临床疗效。结果本组患者治疗后不安腿综合征病情严重程度评定量表、抑郁自评量表评分均较治疗前显著降低（P〈0．01）。结论普拉克索治疗抑郁症并发不安腿综合征疗效显著,能显著改善患者的抑郁情绪和不安腿症状。     

Pramipexole: new use for an old drug – the potential use of pramipexole in the treatment of restless legs syndrome

Restless legs syndrome (RLS) is characterized by paraesthesias–dysesthesias and motor restlessness worsening at rest–in the evening, with at least temporary relief by activity. Its etiology is unknown, though it could be secondary to various conditions. It is well known, however, that dopamine plays a crucial role in the pathophysiology of RLS, as dopaminergic agonists achieve marked improvement. Pramipexole is a nonergoline compound with selectivity for D3 dopamine receptors. This drug is very effective in the treatment of idiopathic and secondary RLS and in treatment-resistant patients, as shown by double-blind, placebo-controlled studies in adults. In children, studies are much more limited, and RLS is often misdiagnosed as “growing pain” or attention deficit hyperactivity disorder. Pramipexole has been successful in open studies, eliminating clinical symptoms. This medication has the advantage of being free of the frequently encountered problems seen with ergot derivatives. The side-effects are limited, particularly at the dosages usually prescribed for RLS treatment: They are much lower than in Parkinson’s disease, and inappropriate sleepiness and sleep attacks, particularly while driving, or compulsive behavior have not been seen. Compared with the adverse reactions of levodopa, including tolerance, rebound, and augmentation phenomena in RLS, which led to usage of dopamine agonists as first line of treatment for RLS, pramipexole has had one of the best profiles. Augmentation can still be noted with the drug, but after longer usage time compared with many other dopamine agonists. Although excessive daytime sleepiness has been noted, sleep attacks have not been encountered in RLS patients treated with pramipexole.     

Long-term treatment with pramipexole in restless legs syndrome

The aim of the present study was to look at the long-term efficacy and side effects profiles of pramipexole in a large cohort of drug naïve patients with regard to dopaminergic medications. In all, 195 consecutive restless legs syndrome (RLS) patients who were prescribed pramipexole more than 1 year previously, agreed to undergo a telephone interview to assess both the efficacy and side effects of pramipexole. Forty-three patients had discontinued pramipexole: 20 because of side effects, six because of a lack of efficacy, six for both and 11 for other reasons. Patients who continued pramipexole for more than 1 year ( n  = 152) reported a mean decrease in RLS symptoms severity of 80.9% (SD = 19.6%). At the onset of treatment, the most common side effects were nausea (30%), tiredness (9%), dizziness (8%), headache (4%), insomnia (3%), dry mouth (2%), difficulty to concentrate (1.3%) and sleepiness (0.7%), At 30 months, most patients ( n  = 124/152; 81.6%) reported an absence of side effects of pramipexole. None of the adverse effects occurred in more than 5% of patients at follow-up. The present study confirms, in a large cohort of unselected patients, that pramipexole is effective and safe in the long-term treatment of RLS.     

Meta-analysis of the efficacy and safety of long-acting non-ergot dopamine agonists in Parkinson’s disease

A meta-analysis of randomized controlled trials (RCT) was performed to evaluate the efficacy and safety of long-acting non-ergot dopamine agonists (NEDA) versus placebo in Parkinson’s disease (PD). A comprehensive literature search up to February 2013 was performed, and the weighted mean differences (WMD) and relative risks (RR) with 95% confidence intervals (CI) were calculated. Nine RCT (n = 2857) which assessed the rotigotine transdermal patch, extended-release pramipexole, and ropinirole prolonged-release, were included. Compared with placebo, long-acting NEDA achieved greater improvements in Unified Parkinson’s Disease Rating Scale activities of daily living (ADL) score (WMD −1.77, 95% CI −2.13 to −1.41), motor score (WMD −4.18, 95% CI −4.94 to −3.43) and the ADL and motor subtotal score (WMD −5.12, 95% CI −6.16 to −4.07), as well as a reduction in “off” time (WMD −1.29, 95% CI −1.64 to −0.93) and an increase in “on” time without troublesome dyskinesia (WMD 1.55, 95% CI 1.06 to 2.04). Compared with placebo, long-acting NEDA were associated with a higher risk of nausea, but no difference was found in headache incidence. Higher risks of dizziness, somnolence, constipation, vomiting, and insomnia were only found in early PD while higher risks of dyskinesia and hallucination were only found in advanced PD. The results of our meta-analysis showed that the use of long-acting NEDA can reduce the symptoms of PD patients. However, long-acting NEDA were also associated with a higher incidence of adverse events, especially in early PD patients, compared with placebo.     

Comparison of pramipexole with and without domperidone co-administration on alertness, autonomic, and endocrine functions in healthy volunteers

AIMS: To investigate the effects of the D2-receptor agonist pramipexole with and without the co-administration of the peripherally acting D2-receptor antagonist domperidone on measures of alertness, autonomic and endocrine function. METHODS: Sixteen male volunteers participated in four weekly sessions of pramipexole 0.5 mg, domperidone 40 mg, their combination, and placebo administered according to a balanced, double-blind design. Alertness (visual analogue scales (VAS), critical flicker fusion frequency, pupillographic sleepiness test), autonomic (pupil diameter, light and darkness reflexes, blood pressure, heart rate, salivation, temperature) and endocrine (prolactin, thyroid-stimulating hormone (TSH), growth hormone (GH)) functions were assessed. Data were analyzed with anova with multiple comparisons. RESULTS: The pre-post treatment changes in VAS alertness were reduced by pramipexole with and without domperidone (mean difference from placebo (95% confidence interval), mm): pramipexole -15.75 (-23.38, -8.13), combination -11.84 (-20.77, -2.91). Treatment condition significantly affected pupil diameter measured in different ways (resting pupil diameter (F(3,45) = 8.39, P < 0.001), initial diameter of the light reflex response (F(3,42) = 3.78, P < 0.05), and light (F(3,45) = 5.21, P < 0.005) and dark (F(3,45) = 3.36, P < 0.05) diameters of the darkness reflex response). Pramipexole without domperidone consistently increased pupil diameter on all measures (P < 0.05), whereas with domperidone only the increase in resting and dark diameters reached significance. Pramipexole reduced light reflex amplitude and increased latency, whereas the combination affected latency only. Concentrations of prolactin and TSH were increased by domperidone. Pramipexole reduced prolactin and increased GH concentrations. CONCLUSIONS: The attenuation of the central pupillary effects of pramipexole by domperidone indicates that domperidone had access to some central D2-receptors.     

Pramipexole in treatment-resistant depression: a 16-week naturalistic study

Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB. Pramipexole in treatment‐resistant depression: a 16‐week naturalistic study. Bipolar Disord 2002: 4: 307–314. © Blackwell Munksgaard 2002 Objective: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D₂–D₃ dopamine agonist, in patients with drug‐resistant depression. Methods: The study sample consisted of in‐patients with major depressive episode, according to the DSM‐IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a >50% reduction of the Montgomery–Asberg Depressive Rating Scale (MADRS) total score and a score of 1 or 2 on the Clinical Global Impression scale (CGI‐I) at endpoint. Side‐effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). Results: Thirty‐seven patients were enrolled. Of these, 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses, 19 completed the 16‐week follow‐up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 ± 8.4 at baseline to 13.9 ± 11.5 at endpoint (p < 0.001) and the CGI‐S decreased from 4.6 ± 0.8 at baseline to 2.8 ± 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI‐I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. Conclusions: These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.     

Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.

BACKGROUND: The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants. Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder. The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression. METHODS: In a double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II disorder, depressive phase on therapeutic levels of lithium or valproate were randomly assigned to treatment with pramipexole (n = 10) or placebo (n = 11) for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale. RESULTS: All subjects except for one in each group completed the study. The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect. A therapeutic response (>50% decrease in Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo (p =.02). One subject on pramipexole and two on placebo developed hypomanic symptoms. CONCLUSIONS: The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression.     

普拉克索和罗匹尼罗对体外培养的多巴胺神经元的神经营养作用

目的 :探讨新型选择性多巴胺D3受体激动剂普拉克索和罗匹尼罗对多巴胺神经元的神经营养作用及其机制。方法 :在大鼠的腹侧中脑细胞和不同部位星形胶质细胞培养基中加入普拉克索和罗匹尼罗刺激 ,观察药物对多巴胺神经元存活的影响。结果 :药物直接作用或从黑质区星形胶质细胞培养基中提取的条件培养液均可使酪氨酸羟化酶 (TH )阳性神经元数量增加 ,同时培养液中脑源性神经营养因子 (BDNF)和胶质细胞源性神经营养因子(GDNF)含量增加。而其他脑区的星形胶质细胞不能产生类似作用。结论 :普拉克索和罗匹尼罗对多巴胺神经元具有神经营养作用 ,这可能是由于其使特定区域星形胶质细胞产生并分泌了神经营养因子。