Corrado Barbui

University of Verona, Verona, Veneto, Italy

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Publications (339)1778.72 Total impact

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    ABSTRACT: Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.
    Full-text · Article · Feb 2016 · PLoS ONE

  • No preview · Article · Feb 2016 · The British Journal of Psychiatry

  • No preview · Article · Dec 2015 · The Lancet Psychiatry
  • G. Ostuzzi · C. Barbui
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    ABSTRACT: Although long-acting antipsychotics are widely used in individuals with psychotic disorders, it is unclear which long-acting preparation should be considered as first-line treatment in clinical practice. In this commentary, the main strengths and weaknesses of a recently published pragmatic randomised study comparing long-acting paliperidone palmitate v. long-acting haloperidol decanoate are briefly analysed.
    No preview · Article · Oct 2015 · Epidemiology and Psychiatric Sciences
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    ABSTRACT: Aims: In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach. Method: The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded. Results: During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation. Conclusions: The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that recommend avoiding the concurrent use of two or more antipsychotic drugs, and the confirmation of a link between citalopram and QTc prolongation supports the need for routine QTc monitoring. The relatively low proportion of patients with QTc prolongation not only suggests compliance with current safety warnings issued by regulatory authorities, but also casts some doubts on the clinical relevance of QTc prolongation related to some psychotropic drugs.
    No preview · Article · Oct 2015 · Epidemiology and Psychiatric Sciences
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    P Dazzan · C Barbui

    Preview · Article · Oct 2015 · Epidemiology and Psychiatric Sciences

  • No preview · Article · Aug 2015 · The British journal of psychiatry: the journal of mental science
  • M Nosè · G Turrini · C Barbui
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    ABSTRACT: In the populations of refugees and asylum seekers hosted in high-income countries, access to mental health care and psychotropic drugs, is a major challenge. A recent Swedish cross-sectional register study has explored this phenomenon in a national cohort of 43 403 young refugees and their families from Iraq, Iran, Eritrea, Ethiopia, Somalia and Afghanistan. This register study found lower rates of dispensed psychotropic drugs among recently settled refugees, as compared with Swedish-born residents, with an increase in the use with duration of residence. In this commentary, the results of this survey are discussed in view of their global policy implications for high-income countries hosting populations of refugees and asylum seekers.
    No preview · Article · Jul 2015 · Epidemiology and Psychiatric Sciences
  • Giovanni Ostuzzi · Laura Benda · Enrico Costa · Corrado Barbui
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    ABSTRACT: Patients with cancer are particularly vulnerable to depressive experiences, ranging from severe emotional reactions to proper depressive syndromes, including major depression. These experiences may deeply affect the course and outcome of the disease. The aim of this study was to assess the efficacy acceptability of antidepressants on the continuum of depressive experiences in patients suffering from cancer. MEDLINE, EMBASE, PsycINFO, CENTRAL, as well as websites of regulatory agencies, clinical trial repositories and pharmaceutical companies, were systematically searched for published and unpublished randomised trials assessing the efficacy of antidepressants versus placebo in patients with cancer. Efficacy of antidepressants at the end of the study was the primary outcome. The review protocol was registered with PROSPERO (CRD42014013440). A total of 19 studies contributed to the analysis. Antidepressants (particularly the selective serotonin-reuptake inhibitors and mianserin) were more effective than placebo in relieving depressive experiences in both patients with major depression or depressive symptoms (standardised mean difference -0.596, 95% confidence interval -1.041 to -0.150), as well as in patients with other cancer-related distressing symptoms (standardised mean difference -0.229, 95% confidence interval -0.419 to -0.039). We found evidence that efficacy was positively associated with length of treatment. No differences between antidepressants and placebo were found in terms of overall acceptability. Antidepressants should be considered as one treatment option for relieving the burden of depressive experiences in patients with cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Jun 2015 · Cancer Treatment Reviews
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    ABSTRACT: Background: Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have been shown to have a negative impact in terms of quality of life, compliance with anti-cancer treatment, suicide risk and likely even the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy and tolerability of antidepressants in this population group are few and often report conflicting results. Objectives: To assess the effects and acceptability of antidepressants for treating depressive symptoms in adults (18 years or older) with cancer (any site and stage). Search methods: We searched the following electronic bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 3), MEDLINE Ovid (1946 to April week 3, 2014), EMBASE Ovid (1980 to 2014 week 17) and PsycINFO Ovid (1987 to April week 4, 2014). We additionally handsearched the trial databases of the most relevant national, international and pharmaceutical company trial registers and drug-approving agencies for published, unpublished and ongoing controlled trials. Selection criteria: We included RCTs allocating adults (18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis) comparing antidepressants versus placebo, or antidepressants versus other antidepressants. Data collection and analysis: Two review authors independently checked eligibility and extracted data using a form specifically designed for the aims of this review. The two authors compared the data extracted and then entered data into RevMan 5 with a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by The Cochrane Collaboration. Main results: We retrieved a total of nine studies (861 participants), with seven studies contributing to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants and one-three armed study compared two antidepressants and a placebo arm. For the acute phase treatment response (6 to 12 weeks), we found very low quality evidence for the effect of antidepressants as a class on symptoms of depression compared with placebo when measured as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants) or as a proportion of people who had depression (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants). No trials reported data on the follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, providing very low quality evidence for the difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants). No clear evidence of an effect of antidepressants versus either placebo or other antidepressants emerged from the analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low quality evidence). We found very low quality evidence for the effect of antidepressants as a class in terms of dropouts due to any cause compared with placebo (RR 0.87, 95% CI 0.49 to 1.53, six RCTs, 455 participants), as well as between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the quality of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity. Authors' conclusions: Despite the impact of depression on people with cancer, available studies were very few and of low quality. This review found very low quality evidence for the effects of these drugs compared with placebo. On the basis of these results clear implications for practice cannot be made. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent should be prescribed may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. Large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer with depressive symptoms, with or without a formal diagnosis of a depressive disorder, are urgently needed to better inform clinical practice.
    No preview · Article · Jun 2015 · Cochrane database of systematic reviews (Online)
  • Corrado Barbui · Benedetto Saraceno
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    ABSTRACT: On 30 May 2014 the Italian Parliament approved a new law regarding forensic psychiatric hospitals. Forensic psychiatric hospitals are facilities that admit individuals who have committed a criminal offence but lack criminal responsibility because of a mental disorder and are deemed as dangerous to public safety. Here we report the key aspects of the new legislation together with some critical considerations. © The Royal College of Psychiatrists 2015.
    No preview · Article · Jun 2015 · The British journal of psychiatry: the journal of mental science
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    ABSTRACT: PurposePneumonia is one of the major leading causes of morbidity and mortality among persons aged 65 years or older. Recently, several studies suggested an association between antipsychotic (AP) use and risk of pneumonia in elderly patients. The aim of the present systematic review and meta-analysis of observational studies was to investigate if first-generation and second-generation AP drugs increase the risk of pneumonia in the elderly and also in the younger population, and to ascertain the risk associated with exposure to individual drugs.Methods All observational cohort or case–control studies that reported data on pneumonia outcomes in individuals exposed to AP drugs as compared with individuals unexposed or with past exposure to AP drugs were included in the systematic review and meta-analysis. Study participants were of either sex and of any age with no restrictions in terms of diagnostic categories.ResultsThe risk of pneumonia was significantly increased by exposure to first-generation AP drugs (odds ratio (OR) 1.68, 95% confidence interval (95%CI) 1.39–2.04, I2 = 47%) and exposure to second-generation AP drugs (OR 1.98, 95%CI 1.67–2.35, I2 = 36.7%). The risk was similar among different diagnostic categories and age groups, in elderly and young-adult populations; the finding on age was corroborated by a meta-regression analysis, which did not detect any relationship between age and risk of pneumonia. Only few studies provided data on individual drugs.Conclusion Systematic review of current observational evidence suggests that exposure to first-generation and second-generation AP drugs is associated with an increased risk of pneumonia. The present systematic review expands previous knowledge by showing that the increased risk not only applies to elderly individuals but also to younger patients. The information about the risk of pneumonia for individual compounds is still very limited. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · May 2015 · Pharmacoepidemiology and Drug Safety
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    ABSTRACT: Only three observational studies investigated whether exposure to antipsychotics is associated with an increased risk of pulmonary embolism, with conflicting results. This study was therefore carried out to establish the risk of pulmonary embolism associated with antipsychotic drugs, and to ascertain the risk associated with first- and second-generation antipsychotic drugs, and with exposure to individual drugs. We identified 84,253 adult individuals who began antipsychotic treatment in a large Italian health care system. Cases were all cohort members who were hospitalized for non-fatal or fatal pulmonary embolism during follow-up. Up to 20 controls for each case were extracted from the study cohort using incidence density sampling and matched by age at cohort entry and gender. Each individual was classified as current, recent or past antipsychotic user. The occurrence non-fatal or fatal pulmonary embolism was the outcome of interest. Compared to past use, current antipsychotic use more than double the risk of pulmonary embolism (odds ratio 2.31, 95% confidence interval 1.16 to 4.59), while recent use did not increase the risk. Both conventional and atypical antipsychotic exposure was associated with an increase in risk, and the concomitant use of both classes increased the risk of four times (odds ratio 4.21, 95% confidence interval 1.53 to 11.59). Adding the results of this case-control study to a recent meta-analysis of three observational studies substantially changed the overall estimate, which now indicates that antipsychotic exposure significantly increases the risk of pulmonary embolism.
    Full-text · Article · Apr 2015 · BMC Psychiatry
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    ABSTRACT: Background An increasing number of studies have investigated the pharmacological prevention of post-traumatic stress disorder (PTSD) and acute stress disorder (ASD). This is the first systematic review to examine the effects of pharmacotherapies (eg, β blockers, hydrocortisone, and selective serotonin re-uptake inhibitors) given within the first month after a traumatic or aversive event to prevent PTSD or ASD compared with no pharmacotherapy or placebo control. Methods A systematic literature search in PubMed, PsycINFO, Embase, and the Cochrane database of randomised trials was done. Studies included randomised controlled trials, controlled clinical trials, and cohort studies; their overall quality was low to moderate. We computed the pooled incidence risk ratio (IRR): the risk of incidence of PTSD or ASD in the pharmacotherapy groups relative to the incidence of PTSD or ASD in the control groups. Additionally, we computed Hedges' g effect sizes for PTSD or ASD continuous outcomes. Findings 15 studies met inclusion criteria (1765 individuals). Pharmacotherapy was more effective in preventing PTSD or ASD than placebo or no intervention (14 studies, 1705 individuals, IRR 0·65, 95% CI 0·55–0·78; number needed to treat 11·36), although no effect was found when only randomised controlled trials were included (ten studies, 300 individuals, IRR 0·69, 95% CI 0·40–1·21). Hydrocortisone showed a large effect in reducing the risk of PTSD (five studies, 164 individuals, IRR 0·38, 95% CI 0·16–0·92). Interpretation No firm evidence was found for the efficacy of all early pharmacotherapies in the prevention of PTSD or ASD, but hydrocortisone reduced the risk of developing PTSD. The small number of studies and their limited methodological quality cast uncertainty about the effects. Funding None.
    Full-text · Article · Apr 2015 · The Lancet Psychiatry
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    ABSTRACT: Dose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the present study is to examine dose equivalence of antidepressants by a less arbitrary and more systematic method. We used data from all randomized, double-blind, flexible-dose trials comparing fluoxetine or paroxetine as standard drugs with any other active antidepressants as monotherapy in the acute phase treatment of unipolar depression. We calculated the ratio of the mean doses for each study and weighted it by the total sample size to find the weighted mean ratio for each drug, which was then used to define the drug׳s dosage equivalent to fluoxetine 40mg/d. We included 83 studies (14 131 participants). In the primary analysis, fluoxetine 40mg/day was equivalent to paroxetine dosage of 34.0mg/day, agomelatine 53.2mg/day, amitriptyline, 122.3mg/day, bupropion 348.5mg/day, clomipramine 116.1mg/day, desipramine 196.3mg/day, dothiepin 154.8mg/day, doxepin 140.1mg/day, escitalopram 18.0mg/day, fluvoxamine 143.3mg/day, imipramine 137.2mg/day, lofepramine 250.2mg/day, maprotiline 118.0mg/day, mianserin, 101.1mg/day, mirtazapine 50.9mg/day, moclobemide 575.2mg/day, nefazodone 535.2mg/day, nortriptyline 100.9mg/day, reboxetine 11.5mg/day, sertraline 98.5mg/day, trazodone 401.4mg/day, and venlafaxine 149.4mg/day. Sensitivity analyses corroborated the results except for doxepin. The number of studies for some drugs was small. The current method assumes dose response relationship of antidepressants. Our findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    Full-text · Article · Mar 2015 · Journal of Affective Disorders
  • C Barbui
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    ABSTRACT: Improving access and rational use of essential medicines at all levels of care is a global challenge. Key issues related to the provision and rational use of psychotropic medicines have recently been analysed by Padmanathan et al. who conducted a survey of the psychotropic medicines management cycle in Bihar, the third most populous state of India with approximately 104 million people, of whom 88.7% live in rural areas. It was found that availability, distance and cost were the main barriers to access and utilisation. Travelling was reported to be particularly problematic because it is expensive and may also be unfeasible for service users who are acutely ill. In this commentary, the results of this survey are discussed in view of their global policy implications for low-resource settings.
    No preview · Article · Mar 2015 · Epidemiology and Psychiatric Sciences
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    Valentino Conti · Mauro Venegoni · Ugo Moretti · Corrado Barbui

    Full-text · Article · Feb 2015 · International Journal of Ophthalmology
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    ABSTRACT: Background Pharmacological treatment is widely used for post-traumatic stress disorder (PTSD) despite questions over its efficacy. Aims To determine the efficacy of all types of pharmacotherapy, as monotherapy, in reducing symptoms of PTSD, and to assess acceptability. Method A systematic review and meta-analysis of randomised controlled trials was undertaken; 51 studies were included. Results Selective serotonin reuptake inhibitors were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.23, 95% CI -0.33 to -0.12). For individual pharmacological agents compared with placebo in two or more trials, we found small statistically significant evidence of efficacy for fluoxetine, paroxetine and venlafaxine. Conclusions Some drugs have a small positive impact on PTSD symptoms and are acceptable. Fluoxetine, paroxetine and venlafaxine may be considered as potential treatments for the disorder. For most drugs there is inadequate evidence regarding efficacy for PTSD, pointing to the need for more research in this area. Royal College of Psychiatrists.
    Full-text · Article · Feb 2015 · The British journal of psychiatry: the journal of mental science
  • Corrado Barbui

    No preview · Article · Jan 2015 · Addiction
  • C Barbui · V Conti
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    ABSTRACT: One of the major challenges with antidepressant (AD) use is poor adherence and early treatment discontinuation. In addition to socio-demographic and clinical variables, treatment discontinuation may also be related to the capacity of the health system to assure and maintain continuity and intensity of care. Among health system factors that may interfere with adherence to pharmacological treatment, use of generic drugs may play a key role. It has been argued that, although the lower cost of generics may favour persistence on treatment, a widespread a priori scepticism about their effectiveness and safety by doctors and patients may have an opposite effect. This compelling research question has recently been addressed by an observational cohort study that involved 16 778 Medicare fee-for-service beneficiaries who received a new depression diagnosis and initiated generic v. brand AD therapy. The study found that generic initiation was associated with improved adherence. The benefits resulted from the lower out-of-pocket cost associated with generic ADs. In this commentary, we discuss the main findings of this study in view of its methodological strengths and limitations, and we suggest implications for policy.
    No preview · Article · Dec 2014 · Epidemiology and Psychiatric Sciences

Publication Stats

7k Citations
1,778.72 Total Impact Points


  • 2002-2015
    • University of Verona
      • Department of Medicine
      Verona, Veneto, Italy
  • 1993-2004
    • Mario Negri Institute for Pharmacological Research
      • • Laboratory of Epidemiology and Social Psychiatry
      • • Department of Biomedical Engineering
      Milano, Lombardy, Italy