Transanal irrigation is a better choice for bowel dysfunction in adults with Spina bifida: A randomised controlled trial.

AIM: To compare transanal irrigation with conservative bowel management for the treatment of bowel dysfunction in Spina bifida (SB) patients. METHODS: Patients with SB and bowel dysfunction were randomly assigned to receive either transanal irrigation or conservative bowel management. The effectiveness of the treatment was defined as a decrease of 4 points in the neurogenic bowel dysfunction (NBD) score at week 10. Data on incontinence (Cleveland scores; Jorge-Wexner [JW]) and constipation (Knowles-Eccersley-Scott Symptom Constipation Score [KESS]) were recorded at 10 and 24 weeks after inclusion. Data were analysed on an intention-to-treat basis. RESULTS: A total of 34 patients were randomised: 16 patients to conservative bowel management and 18 patients to transanal irrigation. A total of 19/31 (61%) patients improved at week 10, 13 (76%) in the transanal irrigation group versus six (43%) in the conservative group (p = 0.056). In the irrigation group, the decrease in NBD score was -6.9 (-9.9 to -4.02) versus -1.9 (-6.5 to -2.8) in the conservative group (p = 0.049 in univariate and p = 0.004 in multivariate analysis). The NBD, Cleveland (JW and KESS) and Rosenberg scores were significantly lower in the transanal irrigation group than in the conservative bowel management group at week 10. CONCLUSIONS: This prospective, randomised, controlled, multicentre study in adult patients with SB suggests that transanal irrigation may be more effective than conservative bowel management.

Curcuma decreases serum hepcidin levels in healthy volunteers: a placebo-controlled, randomized, double-blind, cross-over study.

Hepcidin, secreted by hepatocytes, controls iron metabolism by limiting iron egress in plasma. Hepcidin is upregulated during inflammation through the activation of the signal transducer and activator of transcription 3 (STAT3) transduction pathway, which decreases iron bioavailability and may explain the anemia of chronic inflammatory disease. In vitro, it has been shown that curcumin can decrease hepcidin synthesis by decreasing STAT3 activity. We conducted a proof-of-concept study to assess the effect of curcuma on hepcidin synthesis in human. This was a placebo-controlled, randomized, double-blind, cross-over, two-period study performed in 18 healthy male volunteers. Subjects received a single oral dose of 6 g curcuma containing 2% of curcumin or placebo. Serum hepcidin and iron parameters were assessed repeatedly until 48 h after dosing. When compared with a placebo curcuma decreased hepcidin levels significantly at 6 h (-19%, P = 0.004), 8 h (-17%, P = 0.009), and 12 h (-17%, P = 0.007) and tended to decrease hepcidin at 24 h (-15%, P = 0.076). Curcuma also significantly increased serum ferritin levels at 6 and 8 h (+7% for both times, P = 0.018, 0.030, respectively) and had no effects on serum iron, transferrin, and transferrin saturation. This pilot study showed that curcuma decreases serum hepcidin levels in human and supports the idea that curcuma could be useful in treating hepcidin overproduction during inflammatory processes. Confirmatory studies in patients with chronic inflammation are now required to determine the optimal dose and therapeutic scheme of curcuma.

Specific and non-specific effects of psychotherapeutic interventions for depression: Results from a meta-analysis of 84 studies.

There is a long-standing and very active debate regarding which psychotherapeutic intervention should be used in depressive disorders. However, the effects of psychotherapies may result majorly from non-specific factors rather than from specific factors related to the type of psychotherapeutic intervention. We performed a systematic review and meta-analysis on aggregated data to understand how the effects of different psychotherapies are impacted by non-specific factors. We included randomized controlled trials that assessed the efficacy of psychotherapeutic interventions in the treatment of adult depressive disorders. The primary outcome was the change in depression score from baseline to the latest follow-up visit (i.e. response). A meta-regression was performed to predict response according to the type of intervention and non-specific factors (e.g. number of treatment sessions, length of follow-up, therapeutic allegiance of the investigator). The main analysis included 214 study arms from 84 trials. The effects of psychotherapies compared to the waiting list control condition failed to remain significant after adjusting for non-specific factors. Response increased with the number of treatment sessions (ß = 0.03, 95% CI [0.01; 0.04]) and the length of follow-up (ß = 0.01, 95% CI [0.00; 0.02]). Response also improved in case of presumed therapeutic allegiances among investigators (ß = 0.29, 95% CI [0.07; 0.52]). Response to psychotherapies seems to be closely related to non-specific effects. The development of a well-designed trial that controls for non-specific factors might help disentangle the effects of psychotherapies.

Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta-Analysis of Published and Unpublished Double-Blind Randomized Controlled Trials.

BACKGROUND: Nalmefene is a recent option in alcohol dependence treatment. Its approval was controversial. We conducted a systematic review and meta-analysis of the aggregated data (registered as PROSPERO 2014:CRD42014014853) to compare the harm/benefit of nalmefene versus placebo or active comparator in this indication. METHODS AND FINDINGS: Three reviewers searched for published and unpublished studies in Medline, the Cochrane Library, Embase, ClinicalTrials.gov, Current Controlled Trials, and bibliographies and by mailing pharmaceutical companies, the European Medicines Agency (EMA), and the US Food and Drug Administration. Double-blind randomized clinical trials evaluating nalmefene to treat adult alcohol dependence, irrespective of the comparator, were included if they reported (1) health outcomes (mortality, accidents/injuries, quality of life, somatic complications), (2) alcohol consumption outcomes, (3) biological outcomes, or (4) treatment safety outcomes, at 6 mo and/or 1 y. Three authors independently screened the titles and abstracts of the trials identified. Relevant trials were evaluated in full text. The reviewers independently assessed the included trials for methodological quality using the Cochrane Collaboration tool for assessing risk of bias. On the basis of the I2 index or the Cochrane's Q test, fixed or random effect models were used to estimate risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% CIs. In sensitivity analyses, outcomes for participants who were lost to follow-up were included using baseline observation carried forward (BOCF); for binary measures, patients lost to follow-up were considered equal to failures (i.e., non-assessed patients were recorded as not having responded in both groups). Five randomized controlled trials (RCTs) versus placebo, with a total of 2,567 randomized participants, were included in the main analysis. None of these studies was performed in the specific population defined by the EMA approval of nalmefene, i.e., adults with alcohol dependence who consume more than 60 g of alcohol per day (for men) or more than 40 g per day (for women). No RCT compared nalmefene with another medication. Mortality at 6 mo (RR = 0.39, 95% CI [0.08; 2.01]) and 1 y (RR = 0.98, 95% CI [0.04; 23.95]) and quality of life at 6 mo (SF-36 physical component summary score: MD = 0.85, 95% CI [-0.32; 2.01]; SF-36 mental component summary score: MD = 1.01, 95% CI [-1.33; 3.34]) were not different across groups. Other health outcomes were not reported. Differences were encountered for alcohol consumption outcomes such as monthly number of heavy drinking days at 6 mo (MD = -1.65, 95% CI [-2.41; -0.89]) and at 1 y (MD = -1.60, 95% CI [-2.85; -0.35]) and total alcohol consumption at 6 mo (SMD = -0.20, 95% CI [-0.30; -0.10]). An attrition bias could not be excluded, with more withdrawals for nalmefene than for placebo, including more withdrawals for safety reasons at both 6 mo (RR = 3.65, 95% CI [2.02; 6.63]) and 1 y (RR = 7.01, 95% CI [1.72; 28.63]). Sensitivity analyses showed no differences for alcohol consumption outcomes between nalmefene and placebo, but the weight of these results should not be overestimated, as the BOCF approach to managing withdrawals was used. CONCLUSIONS: The value of nalmefene for treatment of alcohol addiction is not established. At best, nalmefene has limited efficacy in reducing alcohol consumption.

Understanding the Antidepressant Debate in the Treatment of Major Depressive Disorder.

There is a long-standing polemic concerning the usefulness of antidepressants in the treatment of major depressive disorder. In this paper, we propose to highlight some aspects of this controversy by exploring the mutual influence of psychopharmacology and trial methodologies. Indeed, antidepressant efficacy, if not proved, was accepted before antidepressant randomised controlled trials (RCTs) were run. While RCTs became a gold standard to meet the requirements of the regulatory bodies, methodological tools were required to measure outcomes and to test whether antidepressants provide statistically significant benefits as compared with a placebo. All these methodological options have nonetheless introduced fuzziness in our interpretation of study results, in terms of clinical meaningfulness and in terms of transposability to a real life settings. Additionally, selective publication raises concerns about the published literature, and results in many paradoxes. Instead of providing easy answers, the application of the RCT paradigm in MDD raises numerous questions. This is probably in the nature of all scientific studies, but it can be in contradiction with clinicians' expectations, who want to be sure that the treatment will (or will not) work for their individual patients.

Limbic versus cognitive target for deep brain stimulation in treatment-resistant depression: accumbens more promising than caudate.

High-frequency deep brain stimulation (DBS) represents a major stake for treatment for treatment-resistant depression (TRD). We describe a preliminary trial of DBS of two potential brain targets in chronic TRD: the nucleus accumbens (Acb) and, in the event of failure, the caudate nucleus. Patients were followed for 6 months before surgery (M0). From M1 to M5, they underwent stimulation of the Acb target. PET scans allowed us to track metabolic modifications resulting from this stimulation. The caudate target of nonresponders was stimulated between M5 and M9. Patients then entered an extension phase, in which it was possible to adapt stimulation parameters and treatments. Six patients were included and four were operated on. At M5, none of the patients were either responders or remitters, but we did observe a decrease in Hamilton Depression Rating Scale (HDRS) scores. Three patients were switched to caudate stimulation, but no improvement was observed. During the extension phase, the Acb target was stimulated for all patients, three of whom exhibited a significant response. A decrease in glucose metabolism was observed after Acb stimulation, in the posterior cingulate gyrus, left frontal lobe, superior and medial gyrus, and bilateral cerebellum. An increase in metabolism was observed in the bilateral frontal lobe (superior gyrus), left frontal lobe (medial gyrus), and right limbic lobe (anterior cingulate gyrus). The results of this trial suggest that Acb is a more promising target than the caudate. NCT01569711.

Cranberry versus placebo in the prevention of urinary infections in multiple sclerosis: a multicenter, randomized, placebo-controlled, double-blind trial.

OBJECTIVE: Our aim was to assess the usefulness of cranberry extract in multiple sclerosis (MS) patients suffering from urinary disorders. METHODS: In total, 171 adult MS outpatients with urinary disorders presenting at eight centers were randomized (stratification according to center and use of clean intermittent self-catheterization) to cranberry versus placebo in a 1-year, prospective, double-blind study that was analyzed using a sequential method on an intent-to-treat basis. An independent monitoring board analyzed the results of the analyses each time 40 patients were assessed on the main endpoint. Cranberry extract (36 mg proanthocyanidins per day) or a matching placebo was taken by participants twice daily for 1 year. The primary endpoint was the time to first symptomatic urinary tract infection (UTI), subject to validation by a validation committee. RESULTS: The second sequential analyses allowed us to accept the null hypothesis (no difference between cranberry and placebo). There was no difference in time to first symptomatic UTI distribution across 1 year, with an estimated hazard ratio of 0.99, 95% CI [0.61, 1.60] (p = 0.97). Secondary endpoints and tolerance did not differ between groups. CONCLUSION: Taking cranberry extract versus placebo twice a day did not prevent UTI occurrence in MS patients with urinary disorders. Trial Registration NCT00280592.

Which placebo to cure depression? A thought-provoking network meta-analysis.

BACKGROUND: Antidepressants are often considered to be mere placebos despite the fact that meta-analyses are able to rank them. It follows that it should also be possible to rank different placebos, which are all made of sucrose. To explore this issue, which is rather more epistemological than clinical, we designed an unusual meta-analysis to investigate whether the effects of placebo in one situation are different from the effects of placebo in another situation. METHODS: Published and unpublished studies were searched for by three reviewers on Medline, the Cochrane Library, Embase, clinicaltrials.gov, Current Controlled Trial, in bibliographies, and by mailing key organizations. The following studies in first-line treatment for major depressive disorder were considered to construct an "evidence network": 1) randomized controlled trials (RCTs) versus placebo on fluoxetine, venlafaxine and 2) fluoxetine versus venlafaxine head-to-head RCTs.Two network meta-analyses were run to indirectly compare response and remission rates among three different placebos: 1) fluoxetine placebo, 2) venlafaxine placebo, and 3) venlafaxine/fluoxetine placebo (that is, placebo compared to both venlafaxine and fluoxetine). Publication biases were assessed using funnel plots and statistically tested. RESULTS: The three placebos were not significantly different in terms of response or remission. The antidepressant agents were significantly more efficacious than the placebos, and venlafaxine was more efficacious than fluoxetine. The funnel plots, however, showed a major publication bias. CONCLUSION: The presence of significant levels of publication bias indicates that we cannot even be certain of the conclusion that sucrose equals sucrose in trials of major depressive disorder. This result should remind clinicians to step back to take a more objective view when interpreting a scientific result. It is of crucial importance for their practice, far more so than ranking antidepressant efficacy.

Improving study design for antidepressant effectiveness assessment.

Antidepressants effectiveness in major depressive disorder (MDD) is still questioned because the extrapolation of randomized controlled trial (RCT) results to "real life" settings is problematic. The application of the RCT paradigm in a disorder of this type, where global care plays a central role, raises questions regarding the internal and external validity of this type of study. Outcome measurement, attrition rates, the ability of the double-blind design to control for expectations, placebo response, the representativeness of trial participants and publication bias are major methodological pitfalls. This review discusses these issues. It is illustrated using original data and proposes some alternatives for assessing antidepressant effectiveness via different approaches. Some are easy to implement, such as ecological measures, qualitative approaches, improvement of analytical strategy and improvement of blinding procedures. Some are sophisticated, involving temporary deception to deal with the confounding effect of expectations, and they raise ethical issues. Others resort to external validity, this being the case in observational studies. But all are necessary to explore antidepressant effectiveness.

Subthalamic nucleus modulates social and anxogenic-like behaviors.

In Parkinson's disease, global social maladjustment and anxiety are frequent after subthalamic nucleus (STN) stimulation and are generally considered to be linked with sociofamilial alterations induced by the motor effects of stimulation. We hypothesized that the STN is per se involved in these changes and aimed to explore the role of STN in social and anxogenic-like behaviors using an animal model. Nineteen male Wistar rats with bilateral lesions of the STN were compared with 26 sham-lesioned rats by synchronizing an ethological approach based upon direct observation of social behaviors and a standardized approach, the elevated plus maze (EPM). Comparisons between groups were performed by a Mann-Whitney-Wilcoxon test. Lesioned rats showed impairments in their social (P=0.05) and aggressive behaviors with a diminution of attacking (P=0.04) and chasing (P=0.06). In the EPM, concerning the open arms, the percentage of distance, time, inactive time, and entry were significantly decreased in lesioned rats (P=0.02, P=0.01, P=0.04, and P=0.05). The time spent in non-protected head dips was also diminished in the lesioned rats (P=0.01). These results strongly implicate the STN in social behavior and anxogenic-like behavior. In human, as DBS induces changes in the underlying dynamics of the stimulated brain networks, it could create an abnormal brain state in which anxiety and social behavior are altered. These results highlight another level of complexity of the behavioral changes after stimulation.

Obsessive compulsive disorder networks: positron emission tomography and neuropsychology provide new insights.

BACKGROUND: Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. METHODS AND FINDINGS: This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state (18)FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. CONCLUSION: As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes.

Acute and chronic anxiogenic-like response to fluoxetine in rats in the elevated plus-maze: modulation by stressful handling.

While antidepressants are widely prescribed to humans for the treatment of anxiety, the results achieved with animal anxiety models are conflicting. The experimental procedure and the prior test history of the animals are critical parameters that are largely susceptible to influence the results and their interpretation. We compared the effect of 5mg fluoxetine administered to six groups of rats subjected to the psychopharmacological test of the elevated plus-maze, under experimental conditions designed to demonstrate the effect of handling and one daily injection on the response to fluoxetine. The results show that for animals with the same recent experience, fluoxetine, when administered once or over a period of 15 days, induces anxiogenic-like behaviour. On the other hand, our results also show that stressful handling has an anxiolytic-like effect modulating the anxiogenic-like effect of fluoxetine, without eliminating it altogether.

Subthalamic nucleus stimulation affects theory of mind network: a PET study in Parkinson's disease.

BACKGROUND: There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: To this end, we conducted (18)FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucose metabolism and impaired ToM in several cortical areas: the bilateral cingulate gyrus (BA 31), right middle frontal gyrus (BA 8, 9 and 10), left middle frontal gyrus (BA 6), temporal lobe (fusiform gyrus, BA 20), bilateral parietal lobe (right BA 3 and right and left BA 7) and bilateral occipital lobe (BA 19). There were also correlations between increased cerebral glucose metabolism and impaired ToM in the left superior temporal gyrus (BA 22), left inferior frontal gyrus (BA 13 and BA 47) and right inferior frontal gyrus (BA 47). All these structures overlap with the brain network that mediates ToM. CONCLUSION/SIGNIFICANCE: These results seem to confirm that STN DBS hinders the ability to infer the mental states of others and modulates a distributed network known to subtend ToM.

Behavioral effects of four antidepressants on an ischemic rat model of emotional disturbances.

The aim of this study was to examine the psychopharmacological effects of antidepressants on post-ischemic rats. Global transient cerebral ischemia was performing with the four-vessels occlusion method. Locomotor activity, neurological scores and activity during the 20 min forced swimming test (FST) session were comparatively evaluated in sham-operated and ischemic animals. Three doses of four antidepressants or saline were then intraperitoneally administered 23.5, 5 and 1h before the 5 min FST session, and 0.5h before the elevated plus-maze (EPM). Histological quantification of neuronal loss was performed at the end of the experiments. Results show that before treatment, ischemic animals present significantly greater spontaneous motor activity, a neurological score and an immobility time in the 20 min FST lower than sham-operated animals. After treatment, compared to the saline group, we show an antidepressant-like activity in the FST with all the molecules, except with the fluvoxamine, and an anxiolytic-like effect in the EPM, with at least one dose of each compounds. The observed effect is very similar according to whether or not the animals were ischemic, with a tendency to react more important for ischemic animals versus sham-operated. This difference is significant in the FST for the immobility time and in the EPM for the ratio of distance, of time, of number of entrances and non-protected head dips with the 45 mg dose of milnacipran. These results demonstrate that even though global transient cerebral ischemia induces important cerebral lesions, it modifies little the effects of the different antidepressants, whatever their primary pharmacological target, with a particular effectiveness with the dual serotonin and norepinephrine reuptake inhibitor milnacipran.

[Risperidone use in child and adolescent psychiatric patients]. / Prescription de la rispéridone chez l'enfant et l'adolescent.

In a plural and multidisciplinary process of care, it would be fruitful to ally complementary, pharmacologic and psychodynamic approaches. We have done a review of the literature on the effectiveness and the cautions for prescription of risperidone, a second generation antipsychotic drug. Risperidone has proved helpful in treating children and adolescents with autism spectrum, conduct and bipolar disorders, Tourette's syndrome, and schizophrenia. The principal side effects are sedation, weight gain, and metabolic disturbances. Extrapyramidal symptoms, QTc prolongation, and hyperprolactemia with clinical signs are infrequent and not clinically significant. The benefit/risk is clearly in favor of the prescription when it is accompanied with the precautions and with the adequate monitoring.

Effects of acute fluoxetine, paroxetine and desipramine on rats tested on the elevated plus-maze.

Antidepressants are usually prescribed for the treatment of depression but more recently have also been recommended for the treatment of anxiety disorders. The purpose of this study was to investigate the anxiogenic- or anxiolytic-like effects of an acute administration of antidepressants (serotonergic and noradrenergic compounds) in male Wistar rats submitted to the elevated plus-maze. Fluoxetine (2.5, 5, 10, 15mg/kg), paroxetine (0.1, 0.5, 3, 12mg/kg) and desipramine (2.5, 5, 10mg/kg) or their vehicles were administered intraperitoneally 30min prior to testing. Diazepam (0.5, 1.5, 2.5mg/kg) was used as a positive comparator for anxiolytic effect. In comparison with control animals, the percentage of time the rats treated with fluoxetine (5 and 10mg/kg) and paroxetine (3 and 12mg/kg) spent in the open arms decreased. The percent of inactive time spent in the open arms also decreased in rats given fluoxetine (5 and 10mg/kg) and paroxetine (12mg/kg). Desipramine was inactive on all these parameters. In conclusion, acute treatment with fluoxetine and paroxetine, but not with desipramine, produced a pattern of anxiety behavior. Thus, the pharmacological mechanism appears to be due more to serotonergic than adrenergic neurotransmission. The elevated plus-maze exhibits good sensitivity for detecting anxiogenic effects of antidepressant drugs and the conventional parameters are sufficient and reliable for detecting such effects.

Does rat global transient cerebral ischemia serve as an appropriate model to study emotional disturbances?

We used two validated psychopharmacological methods, the forced swimming test (FST 20 min and 5 min) and the elevated plus-maze (EPM), to quantify depression-like and anxiety-like behavior induced by transient global cerebral ischemia in the rat. We also validated use of these methods for the study of antidepressant (imipramine) and anti-anxiety drugs (diazepam). Twelve days after surgery to provoke transient global ischemia, spontaneous motor activity was 40% higher in ischemic rats than in sham-operated controls. Duration of immobility during the FST 20 min and 5 min was 28 and 30% shorter, respectively, than in controls. Treatment with imipramine (3 x 30 mg/kg i.p.) induced a significantly shorter duration of immobility during the FST 5 min, but with no difference between ischemia and control rats. The EPM demonstrated that ischemia did not induce any change in the six behavior parameters measured. Diazepam (1.5 mg/kg i.p.) induced significant anxiolytic effects which were similar in ischemic and sham-operated animals. Both tests failed to demonstrate perturbed performance but conversely, these findings did disclose the sensitivity of ischemia-exposed rats to the action of imipramine and diazepam, demonstrating the usefulness of these tests as psychopharmocological tools for evaluating the effect of psychotropics in the ischemic rat.

Psychomotor and cognitive effects of piribedil, a dopamine agonist, in young healthy volunteers.

Piribedil is a dopamine agonist acting on D2 and D3 central nervous system dopamine receptors. This drug has been administered to 12 young healthy male volunteers (age 22 +/- 2 years) according to a single center randomized, double-blind, two ways cross-over, placebo controlled trial, including a washout period of one week. Placebo and piribedil were administered by a single intravenous infusion over 2 h (3 mg). Psychomotor performance and cognitive functions were assessed through a standardized and computerized psychometric tests battery and a continuous electroencephalogram (EEG) mapping. Piribedil improved simple reaction time (P=0.02), immediate (P=0.045 and 0.004), and delayed free recall (P=0.05), dual coding test (P=0.02) and increased theta and fast beta waves on the EEG (P < 0.05 and 0.001, respectively). No deleterious effect was observed on the tests exploring attention and concentration via the other procedures. It is concluded that a single intravenous perfusion of piribedil 3 mg improves alertness and the information processing speed within the central nervous system, in healthy volunteers.