Behavior Disorder Patients Research Articles

Reduced P300 amplitude during a visuospatial attention task in idiopathic rapid eye movement sleep behavior disorder

ObjectivesIdiopathic rapid eye movement sleep behavior disorder (IRBD) patients are prone to cognitive deficits, which include attention, executive, and visuospatial dysfunctions. Even patients with normal cognition may exhibit subclinical electrophysiological dysfunction. This study aimed to evaluate visuospatial attention processing in IRBD patients with normal cognition and to compare their findings with those of age- and sex-matched healthy controls. MethodsWe recorded event-related potentials (ERPs) and performance measures during a variant of the Posner task in 14 IRBD patients and 14 control subjects. Behavioral data and the mean P300 amplitude were compared between groups. ResultsNo group difference was found for reaction time or accuracy, but a significant group effect was observed for the P300 amplitude. IRBD patients had reduced P300 amplitude (μV) than controls in both valid (IRBD: 0.53 ± 1.05 vs Controls: 1.61 ± 0.95; p = 0.008) and invalid (IRBD: 0.74 ± 0.99 vs Controls: 1.73 ± 0.86; p = 0.009) conditions. The P300 amplitude was correlated with Montreal cognitive assessment (MOCA) scores (r = 0.424, p = 0.024). ConclusionReduced P300 amplitude during the Posner task provides electrophysiological evidence for subclinical visuospatial attention deficits in cognitively normal IRBD patients. The results of this study imply that cortical dysfunction is already present in patients with IRBD in their early disease stage.

Is there a common motor dysregulation in sleepwalking and REM sleep behaviour disorder?

This study sought to determine if there is any overlap between the two major non-rapid eye movement and rapid eye movement parasomnias, i.e. sleepwalking/sleep terrors and rapid eye movement sleep behaviour disorder. We assessed adult patients with sleepwalking/sleep terrors using rapid eye movement sleep behaviour disorder screening questionnaires and determined if they had enhanced muscle tone during rapid eye movement sleep. Conversely, we assessed rapid eye movement sleep behaviour disorder patients using the Paris Arousal Disorders Severity Scale and determined if they had more N3 awakenings. The 251 participants included 64 patients with rapid eye movement sleep behaviour disorder (29 with idiopathic rapid eye movement sleep behaviour disorder and 35 with rapid eye movement sleep behaviour disorder associated with Parkinson's disease), 62 patients with sleepwalking/sleep terrors, 66 old healthy controls (age-matched with the rapid eye movement sleep behaviour disorder group) and 59 young healthy controls (age-matched with the sleepwalking/sleep terrors group). They completed the rapid eye movement sleep behaviour disorder screening questionnaire, rapid eye movement sleep behaviour disorder single question and Paris Arousal Disorders Severity Scale. In addition, all the participants underwent a video-polysomnography. The sleepwalking/sleep terrors patients scored positive on rapid eye movement sleep behaviour disorder scales and had a higher percentage of 'any' phasic rapid eye movement sleep without atonia when compared with controls; however, these patients did not have higher tonic rapid eye movement sleep without atonia or complex behaviours during rapid eye movement sleep. Patients with rapid eye movement sleep behaviour disorder had moderately elevated scores on the Paris Arousal Disorders Severity Scale but did not exhibit more N3 arousals (suggestive of non-rapid eye movement parasomnia) than the control group. These results indicate that dream-enacting behaviours (assessed by rapid eye movement sleep behaviour disorder screening questionnaires) are commonly reported by sleepwalking/sleep terrors patients, thus decreasing the questionnaire's specificity. Furthermore, sleepwalking/sleep terrors patients have excessive twitching during rapid eye movement sleep, which may result either from a higher dreaming activity in rapid eye movement sleep or from a more generalised non-rapid eye movement/rapid eye movement motor dyscontrol during sleep.

REM Sleep EEG Instability in REM Sleep Behavior Disorder and Clonazepam Effects.

We aimed to analyze quantitatively rapid eye movement (REM) sleep electroencephalogram (EEG) in controls, drug-naïve idiopathic REM sleep behavior disorder patients (iRBD), and iRBD patients treated with clonazepam. Twenty-nine drug-naïve iRBD patients (mean age 68.2 years), 14 iRBD patients under chronic clonazepam therapy (mean age 66.3 years), and 21 controls (mean age 66.8 years) were recruited. Power spectra were obtained from sleep EEG (central derivation), using a 2-second sliding window, with 1-second steps. The power values of each REM sleep EEG spectral band (one every second) were normalized with respect to the average power value obtained during sleep stage 2 in the same individual. In drug-naïve patients, the normalized power values showed a less pronounced REM-related decrease of power in all bands with frequency <15 Hz than controls and an increase in the beta band, negatively correlated with muscle atonia; in patients treated with clonazepam there was a partial return of all bands <15 Hz toward the control values. The standard deviation values of the normalized power were higher for untreated patients in all EEG bands and were almost completely normalized in patients treated with clonazepam. The REM sleep EEG structure changes found in this study disclose subtle but significant alterations in the cortical electrophysiology of RBD that might represent the early expression of the supposed neurodegenerative processes already taking place at this stage of the disease and might be the target of better and effective future therapeutic strategies for this condition.

Association of pediatric allergic rhinitis with the ratings of attention-deficit/hyperactivity disorder.

Allergic rhinitis (AR) is currently the most prevalent allergic disease in children and adolescents. Surveys conducted by population-based studies of East Asia revealed an increased prevalence of behavioral disorders in patients with AR. Thus, in this study, we explored the prevalence of attention-deficit/hyperactivity disorder (ADHD) in pediatric patients with AR. A total of 333 children (6-12 years of age) with AR and a total of 322 age-matched controls were included in this study. An otorhinolaryngologist diagnosed all AR cases and evaluated the severity of the disease. Skin-prick test results for 18 major allergens, Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), Child Behavior Checklist (CBCL), and Swanson, Nolan, and Pelham version IV (SNAP-IV) scores were recorded. In total, 320 age-matched controls and 323 children with AR completed the study. With respect to the Total Nasal Symptom Score and the PRQLQ, the condition of the experimental group was more serious than that of the controls. The scores on the hyperactivity/impulsivity and inattention subscales, which evaluate ADHD symptoms, and those on the CBCL subscales were significantly higher in patients with AR than in the controls (all p values were <0.01). From the results of the Pearson correlation, we deduced that there were significant positive correlations between the AR-related data and each subscale of the CBCL and SNAP-IV in the AR group. Moreover, two basic characteristics (males and environmental exposure to tobacco smoke) present significant positive and age showed a significant negative correlations affect ADHD symptom in both the AR group and the control group. Also, in the "pure AR" group, hierarchical regression analyses were performed to determine the subtests of the PRQLQ, which are significant predictors of SNAP-IV and CBCL. Apart from AR per se, the possible comorbidities of impulsivity and inattention are important when managing children with AR. It is essential to evaluate the symptoms of ADHD in children and adolescents with AR.

Patent highlights December 2016-January 2017.

Patent highlights December 2016-January 2017.

Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder.

During healthy rapid eye movement sleep, skeletal muscles are actively forced into a state of motor paralysis. However, in rapid eye movement sleep behavior disorder-a relatively common neurological disorder-this natural process is lost. A lack of motor paralysis (atonia) in rapid eye movement sleep behavior disorder allows individuals to actively move, which at times can be excessive and violent. At first glance this may sound harmless, but it is not because rapid eye movement sleep behavior disorder patients frequently injure themselves or the person they sleep with. It is hypothesized that the degeneration or dysfunction of the brain stem circuits that control rapid eye movement sleep paralysis is an underlying cause of rapid eye movement sleep behavior disorder. The link between brain stem degeneration and rapid eye movement sleep behavior disorder stems from the fact that rapid eye movement sleep behavior disorder precedes, in the majority (∼80%) of cases, the development of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, which are known to initially cause degeneration in the caudal brain stem structures where rapid eye movement sleep circuits are located. Furthermore, basic science and clinical evidence demonstrate that lesions within the rapid eye movement sleep circuits can induce rapid eye movement sleep-specific motor deficits that are virtually identical to those observed in rapid eye movement sleep behavior disorder. This review examines the evidence that rapid eye movement sleep behavior disorder is caused by synucleinopathic neurodegeneration of the core brain stem circuits that control healthy rapid eye movement sleep and concludes that rapid eye movement sleep behavior disorder is not a separate clinical entity from synucleinopathies but, rather, it is the earliest symptom of these disorders. © 2017 International Parkinson and Movement Disorder Society.

Diagnostic Value of Isolated Mentalis Versus Mentalis Plus Upper Limb Electromyography in Idiopathic REM Sleep Behavior Disorder Patients Eventually Developing a Neurodegenerative Syndrome.

To compare two electromyographic (EMG) montages, isolated mentalis muscle versus mentalis in combination with upper limb muscles in the baseline diagnostic video-polysomnography (V-PSG) of patients with idiopathic REM sleep behaviors disorder (IRBD) who eventually were diagnosed with a clinically defined neurodegenerative syndrome. Forty-nine patients were included. At baseline, diagnosis of RBD was based on a typical history of dream enactment behaviors plus V-PSG showing REM sleep with qualitative increased EMG activity and/or abnormal behaviors. Quantification of EMG activity (tonic, phasic and "any") in the mentalis and upper limb muscles (biceps brachii-BB, n = 36 or flexor digitorum superficialis-FDS, n = 13) was performed manually and compared with published cut-offs. Nine (18.4%) patients had either tonic or phasic EMG below the cut-offs for the isolated mentalis and four of them (11.1 %) also had values below the cut-off for the mentalis combined with BB. All 13 patients recorded with the FDS were above the mentalis combined with FDS cut-off. For the diagnosis of IRBD, sensitivity of isolated mentalis was 81.6% and of the combination of mentalis plus upper limb muscles was 91.8% (p = .03). Audiovisual analysis showed abnormal REM sleep behaviors in all nine patients with values below the cut-offs. Quantification of EMG activity in the upper limbs combined with the mentalis increases the ability to diagnose IRBD when compared with the isolated measurement of the mentalis. Detection of typical abnormal behaviors during REM sleep with audiovisual analysis is essential for the diagnosis of IRBD in patients with EMG values below the published cut-offs.

Is increased spinal nociception another hallmark for Parkinson's disease?

Augmented spinal nociception during the "off" phase has been observed early in Parkinson's disease further increasing with disease duration. To find out whether increased spinal nociception represents a premotor feature, experimental pain sensitivity was assessed in idiopathic REM-sleep behavior disorder (IRBD) patients with or without signs of a neurodegenerative disorder compared to early Parkinson's disease (ePD) patients and healthy controls (HC). Spinal nociception as measured by the nociceptive flexion reflex (NFR) and experimental pain sensitivity as measured by heat and electrical pain thresholds were determined in 14 IRBD, 15 ePD patients in the medication-defined "off" state and 27 HC in an explorative cohort study. No significant differences between IRBD and HC were found with regard to spinal nociception (NFR) and experimental pain sensitivity. However, IRBD patient with anosmia and/or abnormal DaTSCAN tended to increased experimental pain sensitivity. In contrast, early PD patients exhibited increased NFR responses compared to HC, and a tendency for increased spinal nociception compared to IRBD patients. Increased spinal nociception may represent an early but not a premotor, non-motor feature of PD. Whether increased pain sensitivity already presents a premotor feature should be assessed in further studies.

Social cognitive function in neurodegenerative diseases

The ability to perceive, analyze people's mental states, intentions, thoughts and feelings is an important cognitive function for normal social behavior and interaction. Over the past decade, more attention has been paid to studying how behavioral disorders in patients with neurodegenerative diseases may be explained by theory of mind deficit and whether it can be useful for differential diagnosis. The authors consider the issues of neuroanatomy, neurophysiology of a special kind of cognitive functions provided normal social interaction and interpersonal relationship, problems of its determining in neurodegenerative diseases.

Quality of life in patients with an idiopathic rapid eye movement sleep behaviour disorder in Korea.

There have been few quality of life studies in patients with idiopathic rapid eye movement sleep behaviour disorder. We compared the quality of life in idiopathic rapid eye movement sleep behaviour disorder patients to healthy controls, patients with hypertension, type 2 diabetes mellitus without complication and idiopathic restless legs syndrome. Sixty patients with idiopathic rapid eye movement sleep behaviour disorder (24 female; mean age: 61.43±8.99) were enrolled retrospectively. The diagnosis was established based on sleep history, overnight polysomnography, neurological examination and Mini-Mental State Examination to exclude secondary rapid eye movement sleep behavior disorder. All subjects completed questionnaires, including the Short Form 36-item Health Survey for quality of life. The total quality of life score in idiopathic rapid eye movement sleep behaviour disorder (70.63±20.83) was lower than in the healthy control group (83.38±7.96) but higher than in the hypertension (60.55±24.82), diabetes mellitus (62.42±19.37) and restless legs syndrome (61.77±19.25) groups. The total score of idiopathic rapid eye movement sleep behaviour disorder patients had a negative correlation with the Pittsburg Sleep Quality Index (r=-0.498, P<0.001), Insomnia Severity Index (r=-0.645, P<0.001) and the Beck Depression Inventory-2 (r=-0.694, P<0.001). Multiple regression showed a negative correlation between the Short Form 36-item Health Survey score and the Insomnia Severity Index (β=-1.100, P=0.001) and Beck Depression Inventory-2 (β=-1.038, P<0.001). idiopathic rapid eye movement sleep behaviour disorder had a significant negative impact on quality of life, although this effect was less than that of other chronic disorders. This negative effect might be related to a depressive mood associated with the disease.

Neuropsychological and behavioral disorders and their correlations with the severity of the traumatic brain injury

The goal of this study was to evaluate the different neuropsychological and behavioral disorders of patients with traumatic brain injury (TBI) and to study their correlations with the epidemiological and neurotraumatic characteristics. It was a cross-sectional study including 30 patients with TBI conducted in the physical medicine and rehabilitation department. The analysis of memory impairment was performed by the (MMS) and the (GOAT) tests. The psychological profile was evaluated by the HAD scale. Behavioral disorders were tested by the agitated behavior scale. Otherwise, the executive functions were evaluated by the DEX scale. The global social-functional evolution was measured by the GOS scale. The mean age was 32.19 ± 12.37 years with a sex-ratio of 3,5. The mean follow-up period was 3,9 ± 2.24 years. Fifteen patients (55.6%) had severe TBI. Memory disorders were observed in 9 patients (36%) when evaluated by the MMS scale and in 5 patients (18.5%) by the GOAT scale. Depressive symptoms were found in 17 patients (70.4%); Moreover, anxiety was noted in 15 patients (55.6%). Behavioral troubles, such as aggressiveness and agitation were noted respectively in 17 (63%) and 6 patients (22.2%). Severe agitation level was found in one patient (3.7%). Abnormal executive functions were noted in 17 patients (76.7%) with an average. Dex score of 23.68 ± 22.8. The most affected dimensions were intentionality and negative affect. Dex score of 23.68 ± 22.8. The most affected dimensions were intentionality and negative affect. We have found correlations between cognitive impairment and the education level ( P < 0.01), between aggression and male sex ( P < 0.01) and between abnormal executive functions and the initial GSC score ( P = 0.04, r = –0.43). The lack of overall improvement (GOS scale) was correlated to the degree of abnormal executive function ( P = 0.02). The executive function disorders, depressed mood and the memory disorders seemed to be the most frequent among neuropsychological disorders in TBI. We noted that it is so important to evaluate neuropsychological disorders in TBI because they were underestimated. We have started this experience despite the lack of means in our department. The evaluation of the executive function in addition to the classic neurospsychological assessment is essential to propose efficient means of rehabilitation.

Time perception in patients with dementia with Lewy bodies.

Disturbances of time perception could explain some behavioral disorders in patients with dementia with Lewy bodies (DLB), and the aim of this preliminary study was to evaluate time perception in these patients. 7 patients with DLB (mean age = 82±6,8 years) were compared to 7 cognitively normal subjects (m = 81.2±6,8 years) for spatiotemporal orientation, verbal estimation, semantic knowledge, rhythm perception and verbal time estimation. The scores on the semantic scale of temporality were statistically different between the two groups, and patients made more rhythm errors than the control sample. Moreover, a significant improvement between the first and second assessment on verbal time estimation was found in the control subjetcs but not in the patients. Time perception seems to be disturbed in patients with DLB, but more studies are required to understand this result with the behavioural disorders.

Screening tools for clinical characteristics of probable REM sleep behavior disorder in patients with Parkinson's disease.

IntroductionThe REM sleep behavior disorder (RBD) screening questionnaire (RBDSQ) has been used as a screening tool for RBD. We investigated the clinical characteristics of probable RBD (pRBD) using the RBDSQ in patients with Parkinson's disease (PD).MethodsSeventy patients with PD (age: 69.2 ± 8.9 years old, 31 males and 49 females, length of PD morbidity: 7.4 ± 6.4 years, Hoehn and Yahr: 2.7 ± 0.8) underwent examination including the RBDSQ and Mini-Mental State Examination (MMSE) in both 2011 and 2013. We assessed the changes and characteristics of pRBD associated with PD during the two year interval.ResultsNineteen patients (27.1%) in 2011 and 27 patients (38.6%) in 2013 were diagnosed as having pRBD because they scored 6 or higher on the RBDSQ. During the 2 year interval, twelve patients showed persistent pRBD, 15 developed pRBD, and 7 showed improved pRBD. In 2013, PD patients with pRBD took higher amounts of levodopa equivalents and scored lower on the MMSE than those without pRBD. Also, more PD patients with pRBD had dementia than those without pRBD. Similarly, more patients with persistent and developed pRBD had dementia than those without.ConclusionWe found that RBD symptoms might fluctuate during the clinical course of PD, and RBD symptoms might temporarily affect cognitive impairment.

The role of the melanoma gene MC1R in Parkinson disease and REM sleep behavior disorder

The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep behavior disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R variants were identified, including 7 common variants with frequency > 0.01. None of the common variants was associated with PD or RBD in the different regression models. In a meta-analysis with fixed-effect model, the p.R160W variant was associated with an increased risk for PD (odds ratio = 1.22, 95% confidence interval = 1.02–1.47, p = 0.03) but with significant heterogeneity (p = 0.048). Removing one study that introduced the heterogeneity resulted in nonsignificant association (odds ratio = 1.11, 95% confidence interval, 0.92–1.35, p = 0.27, heterogeneity p = 0.57). Rare variants had similar frequencies in patients and controls (10.54% and 10.15%, respectively, p = 0.75), and no cumulative effect of carrying more than one MC1R variant was found. The present study does not support a role for the MC1R p.R160W and other variants in susceptibility for PD or RBD.

Lack of Association between Impulse Control Disorders and REM Sleep Behavior Disorder in Patients with Parkinson’s Disease

Purpose: Rapid eye movement sleep behavior disorder (RBD) and impulse control disorders (ICDs) are common in subjects with Parkinson’s disease. The association between these two conditions has been contradictory. The aim of this study is to analyze the association between these two non-motor symptoms. Methods: Consecutive subjects with Parkinson’s disease attending the Movement Disorders Outpatient Clinic were included. The presence of ICDs was assessed using the Questionnaire for Impulse Control Disorders Rating Scale. RBD was diagnosed by an overnight, single night polysomnography. Results: Fifty-five consecutive subjects with Parkinson’s disease were included. The prevalence of ICDs and related behaviors was 23.6% (ICD in 14.5% and related behaviors in 9.1%). RBD was diagnosed in 47.2% of the patients. No differences were found in the frequency of ICDs and related behaviors when comparing subjects with and without RBD (23% versus 24.1%, p = 0.926, respectively). Conclusion: No association between the presence of RBD and the frequency of ICDs in subjects with Parkinson’s disease was found.

Role of Antiepileptic Drugs in Cognitive and Behavioral Disorders in Patients with Autism Spectrum Disorders

Role of Antiepileptic Drugs in Cognitive and Behavioral Disorders in Patients with Autism Spectrum Disorders

Depressed REM Sleep Behavior Disorder Patients Are Less Likely to Recall Enacted Dreams than Non-Depressed Ones.

ObjectiveREM sleep behavior disorder (RBD) is associated with psychiatric symptoms, such as anxiety and alexithymia. However, only a few studies on the relationship between depression and RBD have been published. In this study, we investigated the occurrence of depression and associated factors in patients with RBD.MethodsIn total 94 patients (mean age: 61.9±12.7 years, male: 70.2%) diagnosed as RBD were examined using detailed clinical histories, the Beck Depression Inventory (BDI), the Epworth Sleepiness Scale (ESS), and nocturnal polysomnography (PSG).ResultsThe mean BDI score of all patients was 12.4±10.3 and 44.7% of RBD patients showed depressed mood (BDI >11 points). Depressed RBD patients were less able to recall enacted dreams than were non-depressed patients (61.9% vs. 86.5%, p=0.008). Logistic regression analysis showed that failure to recall enacted dreams was significantly associated with depression, after controlling for confounding variables including the respiratory disturbance index and a history of psychiatric disorders (odds ratio=0.323, p=0.041).ConclusionIn this study, 44.7% of RBD patients were found to suffer from depressed mood. And, depression was found to be associated with reduced ability to recall enacted dreams. We suggest that routine evaluation of depression be performed in RBD patients, particularly when failure to recall enacted dreams is evident. We speculate that such failure may be associated with emotional dysregulation or neurodegeneration.

Gastrointestinal symptom is a significant indicator of nigrostriatal dopaminergic degeneration in idiopathic REM sleep behavior disorder patients

Gastrointestinal symptom is a significant indicator of nigrostriatal dopaminergic degeneration in idiopathic REM sleep behavior disorder patients

IMPULSIVE-COMPULSIVE DISORDERS IN PARKINSON'S DISEASE. CLINICAL CASES

Objective – a description of clinical cases of impulsive­compulsive disorders in Parkinson , s disease. The first clinical case. Patient N. , 75 years old, suffering for 15 years from Parkinson , s disease, akinetic­rigid form of the disease, stage 4 by Hyun–Yar. Since 2009, he received levodopa/carbidopa 250/25 mg 5 times/day (daily dose of 1250 mg of levodopa); pramipexole 3.5 mg per day (daily dose 3.5 mg), amantadine sulfate 100 mg 5 times/day (daily dose 500 mg). While taking antiparkinsonian drugs the patient developed behavioral disorders such as dopamine disregulatory syndrome combined with punding, hypersexuality and compulsive shopping accompanied by visual hallucinations. The total equivalent dose of levodopa was 1600 mg per day. The second clinical case. Patient R. , 52 years old, suffers from Parkinson , s disease about 5 years, a mixed form. She complained of slowness of movement, tremor in her left hand, sleep disturbances, poor mood. The clinic was appointed piribedil 50 mg 3 times per day. Despite the fact that the patient took only one of dopaminergic drugs in a therapeutic daily dose, she developed impulsive­compulsive disorder as hyper­ sexuality, compulsive shopping and binge eating. Results. In the first clinical case for correction of behavioral disorders in patients with Parkinson , s disease levodopa/carbidopa dose was reduced to 750 mg per day (3/4 Tab. 4 times a day); added to levodopa/benserazide dispersible 100 mg morning and levodopa/benserazide 100 mg before sleep (total dose of levodopa of 950 mg per day). Amantadine sulfate and pramipexole were canceled. It was added to the therapy of atypical neuroleptic clozapine dose 6,25 mg overnight. After 3 months marked improvement, regressed visual hallucina­ tions, improved family relationships, background mood became more stable. The patient continue to sing karaoke, but this hobby has be­ come less intrusive. In the second clinical event correction impulsive­compulsive disorders piribedil was replaced with pramipexole 1.5 mg prolonged form one time a day. At the control examination after 3 months behavioral disorders completely regressed. Conclusion. This article describes two clinical cases of impulsive­compulsive disorders in patients with Parkinson s disease, methods of di­ agnosis and correction capabilities of these disorders.

Using venlafaxine to treat behavioral disorders in patients with autism spectrum disorder

To test the efficacy of venlafaxine at a dose of 18.75 mg/day on the reduction of behavioral problems such as irritability and hyperactivity/noncompliance in patients with intellectual disabilities and autism spectrum disorder (ASD). Our secondary hypothesis was that the usual doses of zuclopenthixol and/or clonazepam would decrease in the venlafaxine-treated group. In a randomized double-blind study, we compared six patients who received venlafaxine along with their usual treatment (zuclopenthixol and/or clonazepam) with seven patients who received placebo plus usual care. Irritability, hyperactivity/noncompliance, and overall clinical improvement were measured after 2 and 8 weeks, using validated clinical scales. Univariate analyses showed that the symptom of irritability improved in the entire sample (p = 0.023 after 2 weeks, p = 0.061 at study endpoint), although no difference was observed between the venlafaxine and placebo groups. No significant decrease in hyperactivity/noncompliance was observed during the study. At the end of the study, global improvement was observed in 33% of participants treated with venlafaxine and in 71% of participants in the placebo group (p = 0.29). The study found that decreased cumulative doses of clonazepam and zuclopenthixol were required for the venlafaxine group. Multivariate analyses (principal component analyses) with at least three combinations of variables showed that the two populations could be clearly separated (p b 0.05). Moreover, in all cases, the venlafaxine population had lower values for the Aberrant Behavior Checklist (ABC), Behavior Problems Inventory (BPI), and levels of urea with respect to the placebo group. In one case, a reduction in the dosage of clonazepam was also suggested. For an additional set of variables (ABC factor 2, BPI frequency of aggressive behaviors, hematic ammonia at Day 28, and zuclopenthixol and clonazepam intake), the separation between the two samples was statistically significant as was the Bartlett's test, but the Kaiser–Meyer–Olkin Measure of Sampling Adequacy was below the accepted threshold. This set of variables showed a reduction in the cumulative intake of both zuclopenthixol and clonazepam. Despite the small sample sizes, this study documented a statistically significant effect of venlafaxine. Moreover, we showed that lower doses of zuclopenthixol and clonazepam were needed in the venlafaxine group, although this difference was not statistically significant. This was confirmed by multivariate analyses, where this difference reached statistical significance when using a combination of variables involving zuclopenthixol. Larger-scale studies are recommended to better investigate the effectiveness of venlafaxine treatment in patients with intellectual disabilities and ASD.