Anticonvulsant drugs in cocaine dependence: A systematic review and meta-analysis

A systematic review and meta-analysis according to the methodology developed by the Cochrane Collaboration and the Quality of Reporting of Meta-Analyses statement based on randomized controlled trials to evaluate the efficacy of anticonvulsants in subjects with cocaine dependence were performed. Fifteen randomized, double-blind, placebo-controlled clinical trials involving 1,236 patients were included. Two outcome measures were evaluated: retention in the anticonvulsant treatment (compared to the placebo treatment) and the subsequent cocaine use, measured by urinalysis results. The efficacy of the seven anticonvulsant drugs analyzed was not homogenous. On average, 50% of the enrolled participants were lost to follow-up. Treatments did not show an improvement in subject retention compared to placebo. Overall, the number of cocaine-positive urine samples was close to statistical significance (95% confidence interval = 0.85–1.06) compared to placebo. Available clinical trials indicate that there is insufficient evidence to justify the use of anticonvulsant drugs in treating cocaine dependence.     

Antipsychotic drugs for elderly patients with schizophrenia: A systematic review and meta-analysis

Elderly patients with schizophrenia are a particularly vulnerable group often excluded from clinical trials. Currently there is no evidence-synthesis about the efficacy and safety of antipsychotics in this subgroup.We reviewed all randomized-controlled-trials, about antipsychotics in elderly schizophrenics (last search Dec 12, 2017). Pairwise meta-analyses were conducted. The primary outcome was overall symptoms. Secondary outcomes included positive symptoms, negative symptoms, response, dropouts, quality of life, social functioning and side-effects.We included 29 references from 18 unique randomized-controlled-trials with 1225 participants published from 1958 to 2009. The definition of “elderly” was very heterogeneous across the studies (minimum age 46–65, mean age 57–73). There were evidence gaps for most drugs in many outcomes. In terms of efficacy paliperidone was associated with fewer dropouts due to inefficacy than placebo in the only placebo-controlled-trial. Olanzapine was superior to haloperidol in overall symptoms, negative symptoms and response, and it was associated with fewer dropouts than risperidone. Risperidone and haloperidol produced more prolactin increase than olanzapine, and olanzapine was associated with less use of antiparkinson medication than haloperidol.Although we found no marked differences of the effects of these drugs in the elderly, the evidence presented was based on very few usually small studies. To examine specifically whether there are differences in efficacy and side-effects in elderly, which differs in meaningful ways from the general population, studies in patients who are defined by critiera as truly geriatric, which incorporates older age together with multimorbidity and fraility dimensions, may be more informative.     

Efficacy of indirect dopamine agonists for psychostimulant dependence: a systematic review and meta-analysis of randomized controlled trials

Psychostimulant dependence is characterized by dopamine deficit, which could be reversed with indirect dopamine agonists (IDAs). A systematic review and meta-analysis of randomized, parallel-group, placebo-controlled clinical trials assessing the efficacy of IDAs in psychostimulant-dependent individuals were conducted. The study outcomes were psychostimulant abstinence, assessed by means of urinalysis, and retention in treatment. Risk of bias was determined using a Cochrane Collaboration instrument. Twenty-nine studies fulfilled the inclusion criteria, involving 2,467 participants. Compared with placebo, IDAs increased psychostimulant abstinence (standardized mean difference = 0.20; 95% confidence interval, 0.06-0.35; p = .005) but did not increase retention in treatment. Efficacy was larger in comorbid heroin-dependent individuals and was positively related with treatment length. No study was considered fully free of bias. IDAs appear to be efficacious for reducing psychostimulant use but did not improve retention. Efforts should be undertaken to reduce the risk of bias of clinical trials with psychostimulant-dependent individuals.     

Cocaine abuse versus cocaine dependence: Cocaine self-administration and pharmacodynamic response in the human laboratory

Cocaine has high abuse liability but only a subset of individuals who experiment with it develop dependence. The DSM-IV (APA. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-R. American Psychiatric Association, Washington, DC, 2000) provides criteria for diagnosing cocaine abuse and cocaine dependence as distinct disorders- the latter characterized by additional symptoms related to loss of control over drug use. In this study, two groups of cocaine users (n = 8/group), matched on demographic factors and length of cocaine use history and meeting criteria for either cocaine abuse (CocAb) or cocaine dependence (CocDep), were compared on (1) measures related to impulsivity and sensation seeking, (2) response to experimenter-administered cocaine (0, 12.5, 25 and 50 mg/70 kg, i.v.), and (3) cocaine self-administration using a Relapse Choice and a Progressive Ratio Procedure (0, 12.5 and 25 mg/70 kg, i.v.). Groups did not differ on impulsivity or sensation seeking scores. After experimenter-administered cocaine, the CocAb group reported feeling more suspicious and observers rated them significantly higher on unpleasant effects (e.g., irritability, difficulty concentrating). In contrast, the CocDep group reported significantly greater desire for cocaine, which was sustained over the course of the study, and gave higher street value estimates for cocaine (p < 0.05). While cocaine self-administration was dose-related and generally comparable across the two procedures, the CocDep users chose to take significantly more cocaine than the CocAb users. These data suggest that, while regular long-term users of cocaine with cocaine abuse or dependence diagnoses cannot be distinguished by trait measures related to impulsivity, they do exhibit significant differences with regard to cocaine-directed behavior and response to cocaine administration.     

Systematic review of prospective studies investigating “remission” from amphetamine,cannabis, cocaine or opioid dependence

Aims

To review and summarize existing prospective studies reporting on remission from dependence upon amphetamines, cannabis, cocaine or opioids.

Methods

Systematic searches of the peer-reviewed literature were conducted to identify prospective studies reporting on remission from amphetamines, cannabis, cocaine or opioid dependence. Searches were limited to publication between 1990 and 2009. Reference lists of review articles and important studies were searched to identify additional studies. Remission was defined as no longer meeting diagnostic criteria for drug dependence or abstinence from drug use; follow-up periods of at least three years were investigated. The remission rate was estimated for each drug type, allowing pooling across studies with varying follow-up times.

Results

There were few studies examining the course of psychostimulant dependence that met inclusion criteria (one for amphetamines and four for cocaine). There were ten studies of opioid and three for cannabis dependence. Definitions of remission varied and most did not clearly assess remission from dependence. Amphetamine dependence had the highest remission rate (0.4477; 95%CI 0.3991, 0.4945), followed by opioid (0.2235; 95%CI 0.2091, 0.2408) and cocaine dependence (0.1366; 95%CI 0.1244, 0.1498). Conservative estimates of remission rates followed the same pattern with cannabis dependence (0.1734; 95%CI 0.1430, 0.2078) followed by amphetamine (0.1637; 95%CI 0.1475, 0.1797), opioid (0.0917; 95%CI 0.0842, 0.0979) and cocaine dependence (0.0532; 95%CI 0.0502, 0.0597).

Conclusions

The limited prospective evidence suggests that “remission” from dependence may occur relatively frequently but rates may differ across drugs. There is very little research on remission from drug dependence; definitions used are often imprecise and inconsistent across studies and there remains considerable uncertainty about the longitudinal course of dependence upon these most commonly used illicit drugs.     

The effect of prenatal cocaine exposure on neurobehavioral outcome: a meta-analysis

A meta-analysis was performed of the research published from 1985 to 1998 examining the effect of in utero exposure to cocaine on infant neuobehavioral outcome. The initial search for articles to include in the meta-analysis identified 18 studies with potentially meta-analytic variables. Of the studies originally retrieved, 13 failed to meet all of the inclusion criteria and were excluded from the meta-analysis. A total of 14 meta-analyses were performed comparing cocaine-exposed infants to nonexposed infants on NBAS cluster scales at birth and at 3–4 weeks of age. While the meta-analytic combination of studies produced a large enough sample size to drive statistical significance in a small majority of the tests of difference between the cocaine-exposed and nonexposed infants both at birth and soon after, the magnitude of all effects was small. The largest reliable differences appeared for the motor performance and abnormal reflexes clusters. Both also demonstrated a slight trend for increasing standard differences from birth to measures obtained at 3–4 weeks. The orientation and autonomic regulation clusters produced small, significant effects at both time periods, but the trend was for reduced effect sizes over time. All other effects appear truly negligible.     

Assessment of cocaine and other drug dependence in the general population: "gated" versus "ungated" approaches

BACKGROUND: There is a need for large-scale epidemiological surveys to be (a) faithful to diagnostic specifications and (b) constrain time and participant burden associated with each section of a possibly lengthy interview. OBJECTIVE: To examine whether one "gating" approach devised for recent large-scale international psychiatric surveys results in a reduced number of identified cases of drug dependence and/or biases in estimated associations with background characteristics. DESIGN AND SETTING: Data from a recently released cross-sectional, nationally representative household survey, the United States National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analysed. PARTICIPANTS: Forty-three thousand ninety-three English speaking adults aged 18 years and over. MAIN OUTCOME MEASURES: Dependence upon cocaine and other illegal drug dependence, defined in two ways: "ungated" and "gated". "Ungated" dependence included all persons meeting criteria for DSM-IV dependence, without regard for DSM-IV drug abuse clinical features. "Gated" dependence required at least one feature of DSM-IV drug abuse. RESULTS: There was no statistically robust decrement in the estimated prevalence of cocaine or other drug dependence using a "gated" assessment. Patterns of association of cocaine dependence with background characteristics were not appreciably different when the gated and ungated approaches were applied. CONCLUSIONS: In panoramic mental health surveys, the inefficiency of an ungated approach must be balanced against the anticipated number of cases of dependence without associated social role impairments or harm. In this study, the reduction in the number of identified cocaine dependence cases appeared to be so small that even in a sample of over 40,000 participants, attenuation in population prevalence would prove difficult to detect.     

A systematic review of evidence on the association between cocaine use and seizures

Background

Institutional monographs/medical textbooks mention seizures as a neurological complication of cocaine, but no systematic reviews (SRs) have been published on this issue. We aimed to conduct a SR of the literature on the relationship between cocaine use and seizures and to summarize the biological plausibility of that relationship.

Methods

The pathophysiological mechanisms that may underlie an association between cocaine and seizures were summarized; a SR was then performed using three databases (EMBASE, Medline, PsycINFO) and the Cochrane-library to search for published papers (1980–2012) aimed at quantifying the associations between cocaine use and seizures. The inclusion criteria for selection were: articles based on clinical trials, cohort, case-control (CC) or cross-sectional (CS) studies, participants ≥14 years old and not pregnant, and use of cocaine in the last 72 h. Information was extracted, evaluated and cross-checked independently by two researchers.

Results

Of the 1243 potentially relevant articles initially identified; one CC and 22 CS studies were finally selected. The CC study did not find cocaine use to be a risk-factor for seizures. In addition to the limitations of the CS design, these studies had important methodological weaknesses and biases.

Conclusions

Despite its biological plausibility, no rigorous scientific evidence supports a causal relationship between cocaine use and seizures. The misinterpretation of the role of cocaine may have important implications in medical services. Well-conducted studies are urgently needed.     

Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis

Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research. Many studies have contrasted blood 5-HT levels in autistic patients and controls, but different measurement protocols, technologies, and biomaterials have been used through the years. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and between-study heterogeneity, while verifying whether and to what extent different methodological approaches influence the strength of this association. Our literature search strategy identified 551 papers, from which 22 studies providing patient and control blood 5-HT values were selected for meta-analysis. Significantly higher 5-HT levels in autistic patients compared to controls were recorded both in whole blood (WB) [O.R.=4.6; (3.1–5.2); P=1.0×10^−12], and in platelet-rich plasma (PRP) [O.R.=2.6 (1.8–3.9); P=2.7×10⁻⁷]. Predictably, studies measuring 5-HT levels in platelet-poor plasma (PPP) yielded no significant group difference [O.R.=0.54 (0.2–2–0); P=0.36]. Altogether, elevated 5-HT blood levels were recorded in 28.3% in WB and 22.5% in PRP samples of autistic individuals, as reported in 15 and 4 studies, respectively. Studies employing HPLC vs fluorometric assays yield similar cumulative effect sizes, but the former display much lower variability. In summary, despite some limitations mainly due to small study sample sizes, our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD, providing practical indications potentially useful for its inclusion in multi-marker diagnostic panels for clinical use.     

Associations between behavioral disinhibition and cocaine use history in individuals with cocaine dependence

Background

Behavioral disinhibition has been suggested as both a cause and consequence of substance use disorders. Many studies examining associations between behavioral disinhibition and substance use history have focused on individuals with alcohol dependence or non-dependent college students. In the present study, the relationship between behavioral disinhibition and cocaine use history in individuals with cocaine dependence is examined.

Methods

Forty-six non-treatment-seeking cocaine-dependent men and women completed impulsivity (Barratt Impulsiveness Scale; BIS) and novelty seeking (Temperament and Character Inventory; TCI) questionnaires at the baseline visit of an ongoing study. Unadjusted, and adjusted for gender and age, Pearson correlations were calculated between BIS, TCI, and cocaine use variables from the Structured Clinical Interview for DSM-IV and Timeline Follow-back (age of onset, quantity/frequency of past 30 day cocaine use).

Results

As expected, elevated motor impulsivity and novelty seeking were each associated with younger age of dependence onset. Also, individuals with lower levels of persistence on the TCI reported more days of cocaine use over the previous month. Unexpectedly, increased novelty seeking and attentional impulsivity were associated with fewer days of cocaine use and less money spent on cocaine, respectively. Controlling for age and gender did not substantially change the pattern of observed associations.

Conclusions

The present study provides preliminary evidence for associations between behavioral disinhibition and cocaine use history in cocaine-dependent individuals. Given our relatively small sample size and the correlational nature of our findings, further research is needed to replicate and extend our results.     

Pharmacist services provided in general practice clinics: A systematic review and meta-analysis

BackgroundIntegration of pharmacists into primary care general practice clinics has the potential to improve interdisciplinary teamwork and patient care; however this practice is not widespread.ObjectiveThe aim of this study was to review the effectiveness of clinical pharmacist services delivered in primary care general practice clinics.MethodsA systematic review of English language randomized controlled trials cited in the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and International Pharmaceutical Abstracts was conducted. Studies were included if pharmacists had a regular and ongoing relationship with the clinic; delivered an intervention aimed at optimizing prescribing for, and/or medication use by, clinic patients; and were physically present within the clinic for all or part of the intervention, or for communication with staff. The search generated 1484 articles. After removal of duplicates and screening of titles and abstracts against inclusion criteria, 131 articles remained. A total of 38 studies were included in the review and assessed for quality. Seventeen studies had common endpoints (blood pressure, glycosylated hemoglobin, cholesterol and/or Framingham risk score) and were included in meta-analyses.ResultsTwenty-nine of the 38 studies recruited patients with specific medical conditions, most commonly cardiovascular disease (15 studies) and/or diabetes (9 studies). The remaining 9 studies recruited patients at general risk of medication misadventure. Pharmacist interventions usually involved medication review (86.8%), with or without other activities delivered collaboratively with the general practitioner (family physician). Positive effects on primary outcomes related to medication use or clinical outcomes were reported in 19 studies, mixed effects in six studies, and no effect in 13 studies. The results of meta-analyses favored the pharmacist intervention, with significant improvements in blood pressure, glycosylated hemoglobin, cholesterol and Framingham risk score in intervention patients compared to control patients.ConclusionsPharmacists co-located in general practice clinics delivered a range of interventions, with favorable results in various areas of chronic disease management and quality use of medicines.     

Valproate in the treatment of PTSD: systematic review and meta analysis

ABSTRACT

Objective: Anticonvulsants are used in clinical practice for the treatment of PTSD. However, a systematic investigation of their effects in the treatment of PTSD is currently lacking from the literature. Our aim is to review and appraise the evidence for the use of the anticonvulsant valproate for the treatment of PTSD.

Methods: We performed a systematic review and meta-analysis of the literature where valproate was used for the treatment of PTSD. Studies of treatment of PTSD with valproate were located using a search protocol which was applied to the electronic databases CINAHL, EMBASE, MEDLINE and PSYCHINFO. A search of the National PTSD Centre Pilots Database and of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) were also conducted.

Findings: We only found one single-blinded study, four open-label studies and three case reports. These data do not allow for robust conclusions because of the design of the studies which are of limited patient number and open to bias. However, the studies reported that valproate was generally effective for the treatment of symptoms of PTSD by reducing hyperarousal, improving irritability and anger outbursts and improving mood.

Conclusions: The limited evidence base suggests that valproate can be effective as a monotherapy for the treatment of both PTSD and mood symptoms. A double blind controlled study should be the next step to robustly study the efficacy of valproate on the treatment of PTSD.     

Association of maternal arsenic exposure with birth size: A systematic review and meta-analysis

ObjectivesChronic exposure to arsenic during pregnancy or early life continues to be a major global health problem worldwide, affecting hundreds of millions of people. However, its effects on birth size are uncertain. The aim of this study is to summarized the association between maternal arsenic exposure and birth size.MethodsA comprehensive literature search was conducted on the maternal arsenic exposure and birth size (birth weight, birth length, head circumference and chest circumference) through databases (PubMed, Qvid Medline, Web of Science, Cochrane and EMBASE), the last search was in March 2019. Heterogeneity was testes by using the Q statistic and stratifying for epidemiological factors. The possibility of publication bias was assessed through Begg’s test.ResultsA total of 12 studies provided sufficient data were included. Meta-analysis revealed that maternal arsenic exposure was associated with the decrease of birth weight (β = −25.0 g; 95% CI: −41.0, −9.0) and head circumference (β = −0.12 cm; 95% CI: −0.24, −0.01) in random-effect model, birth length (β = −0.12 cm; 95% CI: −0.17, −0.07) in fixed-effect model, no significant reduction was suggested in chest circumference (β = −0.74 cm; 95% CI: −1.78, 0.3). In addition, we found that the birth weight decreased stronger in women living in the Americas, or appling the exposure marker of urine.ConclusionsMaternal arsenic exposure is associated with the decrease of the birth weight, length and head circumference. Millions of people are still exposured to high-level arsenic, therefore, high quality epidemiologic studies that involve large samples are necessary to determine the precise relationships between maternal arsenic exposure with birth size. And that effective mitigation measures are also need to prevent arsenic exposure in women of reproductive age.     

Effects of glyphosate exposure on sperm concentration in rodents: A systematic review and meta-analysis

BackgroundCorrelation between exposure to glyphosate and sperm concentrations is important in reproductive toxicity risk assessment for male reproductive functions. Many studies have focused on reproductive toxicity on glyphosate, however, results are still controversial. We conducted a systematic review of epidemiological studies on the association between glyphosate exposure and sperm concentrations of rodents. The aim of this study is to explore the potential adverse effects of glyphosate on reproductive function of male rodents.MethodsSystematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Embase, WANFANG and CNKI databases with different combinations of glyphosate exposure and sperm concentration. 8 studies were eventually identified and random-effect model was conducted. Heterogeneity among study results was calculated via chi-square tests. Ten independent experimental datasets from these eight studies were acquired to synthesize the random-effect model.ResultsA decrease in sperm concentrations was found with mean difference of sperm concentrations(MDsperm) = −2.774 × 10⁶/sperm/g/testis(95%CI = −0.969 to −4.579) in random-effect model after glyphosate exposure. There was also a significant decrease after fitting the random-effect model: MDsperm = −1.632 × 10⁶/sperm/g/testis (95%CI = −0.662 to −2.601).ConclusionsThe results of meta-analysis support the hypothesis that glyphosate exposure decreased sperm concentration in rodents. Therefore, we conclude that glyphosate is toxic to male rodent’s reproductive system.     

Factors in sustained recovery from cocaine dependence

The goal was to identify factors that predicted sustained cocaine abstinence and transitions from cocaine use to abstinence over 24 months. Data from baseline assessments and multiple follow-ups were obtained from three studies of continuing care for patients in intensive outpatient programs (IOPs). In the combined sample, remaining cocaine abstinent and transitioning into abstinence at the next follow-up were predicted by older age, less education, and less cocaine and alcohol use at baseline, and by higher self-efficacy, commitment to abstinence, better social support, lower depression, and lower scores on other problem severity measures assessed during the follow-up. In addition, higher self-help participation, self-help beliefs, readiness to change, and coping assessed during the follow-up predicted transitions from cocaine use to abstinence. These results were stable over 24 months. Commitment to abstinence, self-help behaviors and beliefs, and self-efficacy contributed independently to the prediction of cocaine use transitions. Implications for treatment are discussed.     

Efficacy,tolerability, and safety of low-dose and high-dose baclofen in the treatment of alcohol dependence: A systematic review and meta-analysis

A systematic review of the current literature on the efficacy of baclofen, particularly the effect of dosing, for the treatment of alcohol dependence (AD) is missing. We therefore conducted a systematic review and meta-analysis of currently available randomized placebo-controlled trials (RCTs). A systematic literature search for RCTs in AD patients comparing baclofen to placebo was performed in September 2017. The effect of baclofen treatment, and the moderating effects of baclofen dosing (low-dose (LDB) 30–60?mg versus high-dose (HDB) targeted as >60?mg/day), and the amount of alcohol consumption before inclusion were studied. Three treatment outcomes were assessed: time to lapse (TTL), percentage days abstinent (PDA), and percentage of patients abstinent at end point (PAE). 13 RCTs from 39 records were included. Baclofen was superior to placebo with significant increases in TTL (8 RCTs, 852 patients; SMD=0.42; 95% CI 0.19–0.64) and PAE (8 RCTs, 1244 patients; OR=1.93; 95% CI 1.17–3.17), and a non-significant increase in PDA (7 RCTs, 457 patients; SMD=0.21; 95% CI ?0.24 to 0.66). Overall, studies with LDB showed better efficacy than studies with HDB. Furthermore, tolerability of HDB was low, but serious adverse events were rare. Meta-regression analysis showed that the effects of baclofen were stronger when daily alcohol consumption before inclusion was higher. Baclofen seems to be effective in the treatment of AD, especially among heavy drinkers. HDB is not necessarily more effective than LDB with low tolerability of HDB being an import limitation.     

Chlorpromazine versus every other antipsychotic for schizophrenia: A systematic review and meta-analysis challenging the dogma of equal efficacy of antipsychotic drugs

It is one of the major psychiatric dogmas that the efficacy of all antipsychotic drugs is same. This statement originated from old, narrative reviews on first-generation antipsychotics, but this old literature has never been meta-analysed. We therefore conducted a meta-analysis of randomised controlled trials on the efficacy of chlorpromazine versus any other antipsychotic in the treatment of schizophrenia. If the benchmark drug chlorpromazine were significantly more or less effective than other antipsychotics, the notion of equal efficacy would have to be rejected. We searched the Cochrane Schizophrenia Group׳s specialized register, MEDLINE, EMBASE, PsychInfo and reference lists of relevant articles. The primary outcome was response to treatment. We also analyzed mean values of schizophrenia rating scales at endpoint and drop-out rates. 128, mostly small, RCTs with 10667 participants were included. Chlorpromazine was compared with 43 other antipsychotics and was more efficacious than four (butaperazine, mepazine, oxypertine and reserpine) and less efficacious than other four antipsychotics (clomacran, clozapine, olanzapine and zotepine) in the primary outcome. There were no statistically significant efficacy differences between chlorpromazine and the remaining 28 antipsychotics. The most important finding was that, due to low numbers of participants (median 50, range 8–692), most comparisons were underpowered. Thus we infer that the old antipsychotic drug literature was inconclusive and the claim for equal efficacy of antipsychotics was never evidence-based. Recent meta-analyses on second-generation antipsychotics were in a better position to address this question and small, but consistent differences between drugs were found.     

Guanfacine for attention deficit and hyperactivity disorder in pediatrics: A systematic review and meta-analysis

To review the evidence from randomized controlled trials (RCTs) on the safety and efficacy of guanfacine in pediatric attention deficit hyperactivity disorder (ADHD), a bibliographic search up to May 2014 was performed using the Cochrane Library׳s Central Register of Controlled Trials, the Embase, PsycINFO, and Medline databases, and clinical trials registers. The search terms used were: [“guanfacine”] and [“child” or “adolescent” or “pediatrics”] and [“randomized controlled trial”] and [“Attention Deficit Disorder with Hyperactivity” or “Attention Deficit Disorder” or “Attention Hyperactivity Disorder” or “Hyperactivity” or “ADHD”]. A meta-analysis was performed using response, defined as a score≤2 on the Clinical Global Impression Improvement score, as the outcome measure. In all, 7 out of 48 studies were included, for a total of 1752 participants. All studies compared guanfacine versus placebo, with a duration ranging from 6 to 16 weeks. In all, the Clinical Global Impression Improvement score was reported as a secondary measure. Overall, 694/1177 (59.0%) participants in the guanfacine group benefited from the treatment compared to 192/575 (33.3%) in the placebo group (pooled OR 3.2; 95%CI 2.4–4.1). The participants with at least one adverse event were 948 (82.4%) in the guanfacine and 376 (67.9%) in the placebo group (OR 2.6; 95%CI 1.6–4.4). Somnolence (OR 4.9), sedation (OR 2.8), and fatigue (OR 2.2), were the adverse events with the greatest risk of occurrence in the guanfacine versus the placebo group. On the basis of seven randomized, placebo controlled trials guanfacine resulted safe and effective in treating children and adolescents with ADHD     

Antipsychotic drugs and cerebrovascular events in elderly patients with dementia: a systematic review

Recently, Canadian, US and European health regulatory agencies issued warnings about an increased risk of stroke and death in elderly patients with dementia receiving atypical antipsychotics. Assessing both randomised and non-randomised evidence, this systematic review found conflicting findings, particularly for risperidone. More research is needed to better inform clinical practice.