Nimodipine in acute ischemic stroke: a double-blind controlled study

Nimodipine (BAY e 9736), a new dihydropyridine derivative, has been shown to reduce neurological deficits and mortality induced by acute cerebral ischemia in experimental studies. We investigated the effects of this calcium antagonist in patients with acute ischemic stroke through a randomized, double-blind, parallel-designed trial in which nimodipine was compared with placebo. Forty-one of 54 screened cases were found to fulfil the inclusion criteria (sudden occurrence of a focal neurological deficit secondary to an acute ischemic event in the carotid area diagnosed after a complete neurological work-up) and entered the study. Nineteen of them were treated with nimodipine (40 mg t.i.d. administered for 28 days) and the remaining 22 with placebo, given in identical tablets. In all patients the treatment started within 12 h after the onset of the symptoms. Course and intensity of the neurological deficit were evaluated by the Mathew Scale (slightly modified). Forty patients concluded the trial. Nimodipine was withdrawn in one case following the occurrence of a skin rash whose causative relation with the test drug could not be clarified. Altogether, however, nimodipine was well tolerated and no severe cardiovascular adverse reactions were observed. In terms of efficacy, the scores obtained by the Mathew Scale showed a higher rate of improvement on nimodipine than on placebo, thus indicating that patients receiving the latter drug did not fare as well as those receiving the test medication. Our data suggest that nimodipine may be beneficial in the treatment of acute stroke.     

Efficacy and safety of ginsenoside-Rd for acute ischaemic stroke: a randomized, double-blind, placebo-controlled, phase II multicenter trial

Background and purpose:  Ginsenoside-Rd is a selective competitive Ca²⁺ receptor antagonist. A phase II randomized, double-blind, placebo-controlled, multicenter study was conducted to examine the efficacy and safety of ginsenoside-Rd in patients with acute ischaemic stroke.
Methods:  A total of 199 patients were randomized equally to receive a 14-day infusion of placebo (group B), ginsenoside-Rd 10 mg (group A) or ginsenoside-Rd 20 mg (group C). Primary end-points were National Institutes of Health Stroke Scale (NIHSS) scores at 15 days. Secondary end-points were NIHSS scores and the Barthel Index at 8 days, the Barthel Index and the modified Rankin scale at 15 days and 90 days. The safety end-points included serious and non-serious adverse events, laboratory values and vital signs. Analysis was by intention to treat.
Results:  For the primary study outcome, there is significant difference amongst the three groups at 15 days in NIHSS scores ( P  = 0.0003). Comparing group A with B and group B with C, the difference in the mean for NIHSS was significant in statistics ( P  = 0.0004, P  = 0.0009 respectively). This is no significant difference between group A and C ( P  = 0.9640). For the secondary study outcome, ginsenoside-Rd did not improve neurological functioning. Incidence of serious and non-serious adverse events was similar amongst the three groups.
Conclusions:  Ginsenoside-Rd may be of some benefit in acute ischaemic stroke.     

Ginsenoside-Rd improves outcome of acute ischaemic stroke - a randomized, double-blind, placebo-controlled, multicenter trial

Background and purpose: Ginsenoside‐Rd is a receptor‐operated calcium channel antagonist and has shown promise as a neuroprotectant in our phase II study. As an extended work, we sought to confirm its efficacy and safety of Ginsenoside‐Rd in patients with acute ischaemic stroke. Methods: We conducted a randomized, double‐blind, placebo‐controlled trial involving 390 patients with acute ischaemic stroke in a 3:1 ratio to receive a 14‐day intravenous infusion of Ginsenoside‐Rd or placebo within 72 h after the onset of stroke. Our primary end‐point was the distribution of disability scores on the modified Rankin scale (mRs) at 90 days. Results: The efficacy analysis was based on 386 patients (Ginsenoside‐Rd group: 290; placebo group: 96). Ginsenoside‐Rd significantly improved the overall distribution of scores on the mRs, as compared with the placebo (P = 0.02; odds ratios [OR], 1.74; 95% confidence interval [CI], 1.08–2.78). There were significant differences between the two groups when we categorized the scores into 0–1 vs. 2–5 (P = 0.01; OR, 2.32; 95% CI, 1.23–4.38; 66.8% vs. 53.1%). It also improved the National Institutes of Health Stroke Scale (NIHSS) at 15 days [P < 0.01; least squares mean (LSM), ?0.77; 95% CI, ?1.31 to ?0.24]. Mortality and rates of adverse events were similar in the two groups. Conclusions: Ginsenoside‐Rd improved the primary outcome of acute ischaemic stroke and had an acceptable adverse‐event profile.     

Crossover, double-blind clinical trial comparing almotriptan and ergotamine plus caffeine for acute migraine therapy

In this randomized, double-blind, crossover clinical trial, adult patients treated two migraine attacks: one with almotriptan 12.5 mg and the other with ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated with a significantly greater proportion of patients achieving 2-h pain free (20.9% vs. 13.7%; P  < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P  < 0.01) compared with ergotamine plus caffeine therapy; significant differences were not seen at 1 h. Rates for sustained pain free and sustained pain free plus no adverse events (AEs) also were significantly greater after almotriptan treatment than after the use of ergotamine plus caffeine ( P  < 0.05). Almotriptan was associated with a significantly lower rate of photophobia at 90 min ( P  < 0.05), phonophobia at 60, 90, and 120 min ( P  < 0.05 to <0.01), and nausea and vomiting at 90 and 120 min ( P  < 0.01) compared with ergotamine plus caffeine. A significantly greater proportion of patients were more satisfied with almotriptan than with ergotamine plus caffeine ( P  < 0.05). Sixteen patients reported adverse events during almotriptan treatment and 27 patients reported AEs during the ergotamine plus caffeine therapy. Most AEs were mild-to-moderate and did not result in treatment-related discontinuations. In conclusion, almotriptan was associated with significantly greater efficacy for treating migraine compared with ergotamine plus caffeine, was generally well tolerated and was associated with greater rate of treatment satisfaction.     

Neuroprotective treatment with Cerebrolysin in patients with acute stroke: a randomised controlled trial

Summary. Background and purpose. Cerebrolysin is a compound with neurotrophic and neuroprotective activity. It is produced by enzymatic breakdown of purified brain proteins and consists of low molecular weight peptides and amino acids. Cellular and animal models of cerebral ischaemia have shown that it is a potent neuroprotective agent. We explored the safety and preliminary outcome of Cerebrolysin treatment in patients with acute stroke. Methods. Randomised, placebo-controlled, parallel group trial. Patients with acute stroke were randomised within 24h of stroke onset to IV therapy with placebo or Cerebrolysin 50mL/day for 21 days. Both groups received concomitant treatment with ASA 250mg/day PO and pentoxifylline 300mg/day IV. Clinical examinations were performed on days 1, 3, 7, 21 and 90 post baseline. Outcome measures were the Canadian Neurological Scale, the Barthel Index, the Clinical Global Impressions, the Mini-Mental State Examination, and the Syndrome Short Test. Treatment emergent adverse events, lab tests, and vital signs were recorded to assess the safety of Cerebrolysin. Results. 146 patients were enrolled in two groups: 78 Cerebrolysin and 68 placebo. At baseline, no significant group differences were observed. Patients in the Cerebrolysin group had no significant improvement in the CNS score, the Barthel Index and the Clinical Global Impressions when compared to the placebo group. A significant improvement of cognitive function of the patients on Cerebrolysin was observed in the Syndrome Short Test when compared to the placebo group. Cerebrolysin was well tolerated and safe. Adverse events occurred with a similar frequency in both groups. Conclusion. The results demonstrate that neurotrophic treatment with Cerebrolysin is safe and well tolerated by patients with acute stroke. The findings, despite the small sample size, also indicate a potential treatment effect of Cerebrolysin in acute stroke. Larger studies, however, are needed to confirm and extend these findings.     

A randomized, double-blind, placebo-controlled study of the efficacy and safety of tolperisone in spasticity following cerebral stroke

To study the efficacy and safety of tolperisone - a centrally acting muscle relaxant with membrane stabilizing activity - in the treatment of stroke-related spasticity. This was a randomized, double-blind, placebo-controlled, multicenter study with parallel groups. Treatment lasted 12 weeks and was started with a titration period of variable length (dose range 300-900 mg tolperisone daily). The degree of spasticity determined on the Ashworth Scale in the most severely affected joint area was defined as primary target parameter. Hundred and twenty patients (43 females, 77 males) in a mean age of 63.3 +/- 10.6 years were recruited and received treatment. In the majority of patients both limbs of each side (right: n = 59; left: n = 56) were affected by the spasticity which on average had been present for 3.3 +/- 4.4 years. A 62% of the patients were treated with a daily dose >/=600 mg tolperisone. Tolperisone reduced the mean Ashworth Score by a mean of 1.03 +/- 0.71 compared with a mean reduction of 0.47 +/- 0.54 in the placebo group (P < 0.0001). A 78.3% of the patients on tolperisone versus 45% of the placebo patients experienced a reduction by at least 1 point on the Ashworth Scale (P < 0.0001). Functional and overall assessments of efficacy confirmed superior efficacy of tolperisone. Adverse events occurred less often on active treatment (n = 19) than on placebo (n = 26) and were mostly of mild-to-moderate intensity. No withdrawals caused by adverse events were reported in the tolperisone group. The findings of the present study demonstrate the efficacy and excellent tolerance of tolperisone in the treatment of spastic hypertonia following cerebral stroke. Study data further suggest that an individual dose titration which may exceed the recommended maximum dose of 450 mg daily results in optimized therapeutic benefit.     

Single-blind, placebo-controlled multicenter trial of vigabatrin in the treatment of epilepsy

A single-blind, placebo-controlled multicenter trial of vigabatrin was carried out in 101 epileptic patients (mostly with partial seizures) refractory to conventional therapy. The study design included four consecutive periods: (i) an observation phase (run-in), (ii) a placebo period, (iii) fixed-dosage add-on vigabatrin (2 g/day) and (iv) dose titration (up to a maximum of 4 g/day) to optimize clinical response. Each period lasted 8 weeks, except for the titration phase, which could be extended to 16 weeks. 90 patients completed the trial. Eleven dropped out, one patient developing absence status and 4 cases showing an increased seizure frequency. In the patients completing the trial, the median number of seizures/month decreased from 16 (inter-quartile range 8–34) during placebo to 5 (2–10) during the last 8 weeks on vigabatrin (p<0.0001). Both partial and generalized tonic clonic (mostly secondary) seizures were significantly reduced. A greater than 50% reduction in seizure frequency (compared to placebo) was observed in 60 patients. Sedation and weight gain were the most frequently reported adverse events.

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Sommario Centouno pazienti affetti da epilessia farmaco-resistente (nella maggior parte dei casi con crisi parziali) sono stati inclusi in uno studio policentrico con vigabatrin somministrato in aggiunta alla terapia preesistente secondo un disegno sperimentale controllato in singolo cieco. Il protocollo prevedeva 4 fasi consecutive (osservazione basale, placebo, vigabatrin 2 g/die, vigabatrin a dose individualizzata in base alla risposta clinica, sino ad un massimo di 4 g/die), ciascuna della durata di 8 settimane ad eccezione della fase di ottimizzazione della posologia che poteva essere prolungata a 16 settimane. Novanta pazienti hanno completato lo studio, mentre 11 (tra cui 1 che ha presentato stato di piccolo male e 4 che hanno riferito un aumento della frequenza delle crisi) hanno interrotto il trattamento precocemente. Nei pazienti che hanno completato lo studio, la frequenza mensile delle crisi è diminuita da un valore mediano di 16 (range interquartile 8–34) durante placebo a 5 (2–10) durante l'ultima fase di trattamento con vigabatrin (p<0.0001). Sia le crisi parziali che le crisi generalizzate tonico-cloniche (per lo più secondariamente generalizzate) sono diminuite significativamente. Una riduzione delle crisi di oltre il 50% è stata osservata in 60 pazienti. Gli effetti collatterali più frequentemente osservati sono stati sedazione ed aumento ponderale.

     

A multinational, double-blind trial with a new antidepressant maprotiline (Ludiomil) and amitriptyline

An account is given of a multinational double-blind trial, in which the tetracyclic antidepressant maprotiline (Ludiomil®) was compared with amitriptyline. Two hundred and eleven patients participated; of these 191 completed the trial. In 68% of the cases, endogenous depression was diagnosed; the remaining cases were diagnosed as reactive or other depressions. Hamilton's Rating Scale for Depression was used, and unwanted effects were registered on standardized scales. No statistically significant difference in antidepressive effect assessed by Total Hamilton Score (THS) and global evaluation was found between maprotiline and amitriptyline. However, a significant difference in favour of maprotiline was shown in the global evaluation of unwanted effects and as regards the individual symptoms “blurred vision” and “sweating”. The laboratory tests disclosed no positive difference between the two preparations. Advantages and disadvantages of multicentre trials are discussed and the value of standardized scales is pointed out. Factor analysis carried out on the same material is mentioned.     

Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial

The aim of the study was to assess the safety and feasibility of a clinical trial on the effect of vinpocetine, a synthetic ethyl ester of apovincamine, in acute ischaemic stroke. Thirty consecutive patients with computed tomography verified diagnosis of acute ischaemic stroke, who could receive drug treatment within 72 h of stroke onset, were enrolled. The patients were randomly allocated to receive either low-molecular weight dextran alone or in combination with vinpocetine. Poor outcome was defined as being dead or having a Barthel index of < 70 or a Rankin score of 3--5. Intention-to-treat analysis was applied. One-tenth of all hospitalized patients with acute ischaemic stroke were eligible for the trial. Thirty eligible patients were treated with either low-molecular weight dextran alone (mean age 57.9 +/- 11.6 years, n = 15) or in combination with vinpocetine (mean age 60.8 +/- 6.6 years, n = 15). The two treatment groups were comparable with respect to major prognostic variables. A relative risk (RR) reduction of poor outcome at 3 months follow-up was 30% (RR = 0.7; 95% confidence interval [CI] 0.1--3.4), as defined by the modified Barthel Index, and 60% as defined by the modified Ranking score (RR = 0.4, 95% CI: 0.1--1.7). The National Institute of Health (NIH--NINDS) Stroke Scale score was marginally significantly better in the vinpocetine treated group at 3 months of follow-up (P = 0.05, ANOVA). No significant adverse effects were seen. This pilot study shows that a full-scale randomized double-blind, placebo-controlled trial of vinpocetine treatment in acute ischaemic stroke is feasible and warranted.     

A randomized,controlled trial of aerobic exercise in combination with paroxetine in the treatment of panic disorder

Abstract

Objectives. Regular aerobic exercise (running) has been shown to be superior to a pill placebo in the treatment of panic disorder. Combined drug and exercise treatment has not been investigated in randomized controlled studies to date. Methods. This is a randomized, 10-week, controlled, parallel group, pilot study. A total of 75 outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10) received either (1) exercise plus paroxetine 40 mg/day (n=21), (2) relaxation plus paroxetine (n=17), (3) exercise plus pill placebo (n=20), or (4) relaxation plus pill placebo (n=17). Changes in the Panic and Agoraphobia Scale (P&A), and the Clinical Global Impression Scale (CGI) underwent repeated measure analysis. Results. Effects sizes were large for all groups (d=1.53–3.87), however not significantly different. Paroxetine-treated patients were significantly more improved than placebo-treated patients. On the CGI, patients in the exercise groups (plus paroxetine or placebo) had a trend toward better improvement compared to relaxation (P=0.06). Response and remission rates were higher in the paroxetine compared to pill placebo groups. Conclusions. While paroxetine was superior to placebo, aerobic exercise did not differ from relaxation training in most efficacy measures.     

Buprenorphine augmentation improved symptoms of OCD,compared to placebo - Results from a randomized,double-blind and placebo-controlled clinical trial

BackgroundIn the search for new psychopharmacologic options in the treatment of obsessive-compulsive disorders (OCD), some findings suggested that augmentation with buprenorphine, a partial-opioid agonist used to treat opioid addiction, moderate acute pain and moderate chronic pain, is worthy of consideration. Accordingly, to explore this possibility further, a double-blinded, placebo-controlled clinical trial was performed.MethodA total of 43 patients (mean age: 34.41 years; SD = 6.58; 53.5% males) with refractory OCD and treated with SSRIs or clomipramine at therapeutic dosages were randomly assigned either to an adjuvant buprenorphine or to an adjuvant placebo condition. Patients completed the Yale-Brown-Obsessive-Compulsive Scale (Y-BOCS) at baseline, weeks 3, 9 and 12 (study completion). Buprenorphine (2–4 mg; sublingual) and placebo (tablets with identical shape, color, consistency, and scent) were given daily.ResultsSymptoms of obsessive-compulsive disorders decreased over time, but more so in the buprenorphine than in the placebo condition. Substantial improvements were observed up to week 3 and then 9. Response and partial response were observed in the buprenorphine at week 9 more than in the placebo condition. The advantage had disappeared by week 12.ConclusionsThe pattern of results suggests that adjuvant buprenorphine augmentation can reduce symptoms of obsessive-compulsive disorders after only three weeks, compared to a placebo. Adjuvant buprenorphine seems to accelerate symptom improvement.     

Glycine antagonist (GV150526) in acute stroke: a multicentre, double-blind placebo-controlled phase II trial

GV150526 is a novel glycine antagonist at the NMDA receptor complex. It is a potent neuroprotective agent in animal models of acute stroke including permanent middle cerebral artery occlusion in the rat. GV150526 was very well tolerated in early human studies. The purpose of this randomised, double-blind, multicentre, placebo-controlled trial was to assess the safety and population pharmacokinetics of GV150526 in patients with a clinical diagnosis of acute stroke. Exploratory assessment of efficacy, quality of life and resource utilisation was also undertaken. Upon clinical diagnosis of acute stroke within 12 h of onset of symptoms, patients were treated with a loading dose of 800 mg GV150526 (or placebo), followed by 5 maintenance doses of 400 mg GV150526 (or placebo) given every 12 h over 3 days. Following observation of asymptomatic hyperbilirubinaemia, the maintenance dose was reduced mid-study to 200 mg. CT/MRI scanning was not mandatory prior to treatment. The study treated 128 patients (38 with GV 800 mg/400 mg, 48 with GV 800 mg/200 mg and 42 with placebo). Fewer patients with mild stroke (NIH scores < or =5) were enrolled in the GV150526-treated groups than in the placebo group (placebo 38%, GV 800 mg/400 mg 18%, GV 800 mg/200 mg 15%). There was also an imbalance in the proportion of patients with haemorrhagic strokes (placebo 5%, GV 800 mg/400 mg 3%, GV 800 mg/200 mg 15%). Mortality at 1 month was unbalanced between treatment groups, being 10, 18 and 17% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively (no significant difference). Similarly, adverse events, though consistent with an acute stroke population, appeared more often in the GV 800 mg/200 mg group. Functional outcomes at 1 month also showed imbalances, the percentage of patients with a Barthel Index score of > or =95 at 1 month being 52, 39 and 27% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively. These results probably reflect a prognostically significant baseline difference between the groups rather than the effect of GV150526. GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified.     

Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.

The objective of this study is to conduct a dose-finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5-HT(1A) agonist properties and additional high affinity for D(3) and D(4) receptors. An open label study documented improvements in PD patients with levodopa-induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo-controlled, double-blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary-based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention-to-treat population. No significant changes occurred on sarizotan compared to placebo on any diary-based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan- and placebo-treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome.     

Propranolol (Inderal) and clonidine (Catapressan) in the prophylactic treatment of migraine

Twenty-one patients continued a double-blind crossover study to compare the prophylactic effect on migraine of propranolol and clonidine. The daily dosage of propranolol and clonidine was 160 mg and 100 μg, respectively.
Statistical analysis did not show any significant difference between the two drugs in respect to headache or nausea. The number of sickleave days and the use of symptomatic drugs were both less on propranolol treatment than on clonidine, but there was no statistically conclusive difference.     

A double-blind, placebo-controlled trial of fish oil concentrate (MaxEpa) in stroke patients

The feeding of large amounts of fish or fish oils to healthy volunteers has been shown to reduce plasma triglycerides and platelet aggregation, and prolong the skin bleeding time. To determine whether a commercially available marine oil (MaxEpa) would have similar effect in stroke patients, we performed a double-blind, placebo-controlled study in 11 patients (7 men, 4 women) with completed stroke (7) or transient ischemic attacks (TIA's) (4). Ten 1 ml opaque capsules containing either MaxEpa or olive oil were given daily for 6 weeks, and then the patients were crossed-over. Aspirin was avoided during the trial. The data were analyzed by paired-sample t-tests. A significant reduction was found in serum triglycerides, but total serum cholesterol and HDL cholesterol were unaffected. The bleeding time was modestly prolonged after 3 weeks of treatment, but the differences between MaxEpa and olive oil treatments were not significant at 6 weeks. Aside from an increase in collagen-stimulated malondialdehyde formation no other statistically significant changes in hemostatic factors were observed. We conclude that the ingestion of up to 10 MaxEpa capsules daily for 6 weeks has little influence on such established risk factors as cholesterol concentration and platelet function in patients with stroke or TIA's.     

Pilot efficacy and tolerability: a randomized, placebo-controlled trial of levetiracetam for essential tremor.

The purpose of this pilot single-site study was to assess efficacy and safety of levetiracetam for essential tremor, using a placebo-controlled, double-blind, randomized crossover design with an interim analysis planned after completion of the first 10 to 15 subjects. The study was designed to detect a mean 30% reduction in composite tremor score, comparable to that of primidone or propranolol, which can be demonstrated with 30 or fewer subjects. Each treatment arm included baseline tremor assessments, a 4-week medication titration, 2 weeks of stable dose, and treatment tremor assessments. Levetiracetam was titrated to 3,000 mg/day or to a lower maximal tolerated dose. The median age was 72 years, with 28 years median tremor duration. There was no statistically significant difference in response between placebo and levetiracetam on any tremor rating scale or accelerometry measure. The 95% confidence interval for the true mean difference between placebo and levetiracetam treatments was +18.5 to -22.5%, which excludes the minimum 30% drop required to consider levetiracetam clinically effective to a degree comparable to primidone or propranolol. Whether levetiracetam has lesser-degree antitremor efficacy was not addressed in this pilot study.     

A double blind randomized pilot trial of naloxone in the treatment of acute ischemic stroke

Attention has focused on naloxone, an opiate receptor antagonist, because of its potential benefit in reversing neurological damage after acute cerebral ischemia. To evaluate the safety and possible efficacy of high-dose naloxone in ischemic stroke patients we planned a double blind pilot study. Between January 1989 and May 1990 24 patients were randomly assigned to the naloxone or placebo group according to age and neurological deficit. Naloxone was given in a loading dose of 5 mg/kg over 10 minutes followed by a 24-hour infusion at the rate of 3.5mg/kg/h. 10 patients experienced minor side effects but none of them had to discontinue the treatment. 9 patients improved: 6 in the naloxone group and 3 in the placebo group, but no significant difference was found using the non parametric Mann-Whitney test. Our study suggests that naloxone is safe at the dose used, but the results do not support the planning of similar trials on a larger scale.

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Sommario è stata posta grande attenzione sul Naloxone, un antagonista dei recettori degli oppiacei, e sulla sua potenziale utilità nel far regredire il danno neurologico dopo un'ischemia cerebrale acuta. Per valuatare la sicurezza e la possibile efficacia di alte dosi di naloxone nei pazienti con ictus ischemico, abbiamo programmato uno studio pilota in doppio cieco. Dal gennaio 1989 al maggio 1990 ventiquattro pazienti sono stati assegnati casualmente al gruppo Naloxone o a quello Placebo secondo l'età e il deficit neurologico. Il naloxone venne somministrato in una dose di carico di 5 mg/kg in 10 minuti seguita da un 'infusione di 24 ore (3.5 mg/kg/h). Dieci pazienti ebbero effetti collaterali minori ma nessuno di essi dovette interrompere il trattamento. Nove pazienti migliorarono: sei nel gruppo Naloxone e tre nel gruppo placebo, ma non fu trovata alcuna differenza significativa usando il test non parametrico di Mann-Whitney. Il nostro studio suggerisce che il naloxone è sicuro alla dose usata, ma i risultati non giustificano la pianificazione di trials più grandi con le stesse caratteristiche.

     

Baclofen treatment in Tourette syndrome: a double-blind, placebo-controlled, crossover trial

OBJECTIVE: To investigate the effectiveness of baclofen for the treatment of tics in children with Tourette syndrome (TS). BACKGROUND: Baclofen, which contains both gamma-aminobutyric acid (GABA) and phenylethylamine moieties, was suggested in an open-label protocol to be an effective treatment for TS. This is a double-blind, placebo-controlled study to investigate this medication in children with TS. METHODS: Subjects received, in a randomized sequence, 4-week medication cycles of baclofen (20 mg three times daily) and placebo with a 2-week intervening washout period between the cycles. Outcome measures included the Clinical Global Impression (CGI) scale, and the Yale Global Tic Severity Scale (YGTSS), the latter including subscales for total tics and overall impairment. Measures were assessed at baseline and on days 28, 42, and 70 of the study. RESULTS: Ten children (seven boys and three girls, aged 8 to 14) with TS participated. Nine subjects completed the protocol; one dropped out for psychosocial reasons. No major side effects were reported. The mean change in CGI score (-0.9) after 4 weeks of baclofen treatment as compared with placebo treatment showed a significant improvement (95% CI, -1.7 to -0.1; p = 0.04). All subjects showed some amelioration in total YGTSS score during baclofen treatment. The mean change in total YGTSS score (-14.7) approached significance (95% CI, -30.3 to 0.9; p = 0.06). Examination of differences between baclofen and placebo treatment groups expressed as a percent change from baseline showed that baclofen had a statistically significant effect on both outcome measures. Subscales of the YGTSS showed that the reduction in total tic scores was primarily due to a reduction in the impairment score rather than a decrease in tics. CONCLUSIONS: Children with TS may benefit from treatment with baclofen, although improvements may be related to factors other than tics. Larger studies directly comparing baclofen against other tic-suppressing agents are recommended.