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Andrea Cipriani

Publications and source records attributed to Andrea Cipriani.

At least 19 recordsLinked to original sources

Research agenda to advance anhedonia assessment, understanding and treatment: an ECNP-GALENOS expert meeting report.

Anhedonia, broadly defined as a reduced ability to experience interest or pleasure, represents an important transdiagnostic neuropsychiatric symptom dimension which may benefit from targeted diagnostics and treatments. Different lines of research have proposed that it comprises multiple facets, including deficits in anticipatory ('wanting') and consummatory ('liking') reward processing as well as reward learning and affects different aspects of life (eg, social, physical, cognitive). Certain facets-more specifically anticipation, motivation and reward learning-likely involve blunted phasic dopaminergic signalling. However, recent meta-analytical evidence of human depression studies indicates that prodopaminergic antidepressants produce relatively small improvements in anhedonia symptoms and suggest that mechanisms beyond dopamine likely contribute to anhedonia. This stimulated an expert meeting to review the literature and define priorities for future research in anhedonia. A central key priority is developing a translational biologically-informed nomenclature and consensus that solves the current mismatch between constructs, paradigms and measures, and mechanisms, which separates discrete reward-related processes such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure. Clinical research priorities are improved multimodal measurement tools, integrating neurobiological frameworks (eg, neuroimaging, electrophysiology and liquid biomarkers capturing dopaminergic, glutamatergic, opioid and immunometabolic pathways) and transdiagnostic studies across neuropsychiatric disorders and developmental stages. Innovative trial designs that explicitly target anhedonic phenotypes as a primary outcome and test mechanism-based interventions are also needed. Translational research recommendations include back-translation strategies that begin with patient-relevant phenotypes followed by the development of comparable human and animal tasks that target reward-related processes, such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure, improve cross-species behavioural paradigms and enhance methodological rigour and reproducibility. Collectively, these recommendations will help refine the conceptualisation of anhedonia and advance its role within precision psychiatry as a mechanistically grounded target across multiple disorders.

Humans↗

Improving access to antipsychotic medications for schizophrenia in Ethiopia, Nigeria, Rwanda, and South Africa: an evidence-based global consensus.

There are disparities in access to antipsychotics for schizophrenia across different country settings. Improving access to a wider and more equitable range of medications in low-income and middle-income countries is a priority. A multidisciplinary team of international experts, including individuals with lived experience, appraised the most relevant and recent information on antipsychotics in schizophrenia and contextualised it to four African countries (Ethiopia, Nigeria, Rwanda, and South Africa) using a validated consensus methodology. We recommended a list of drugs to prioritise to guide clinical implementation and research, and market shaping. We identified key evidence gaps: little of the existing evidence comes from the countries of interest, trials generally involve highly selected populations, and the complexity of real-world settings is not reflected. However, this methodology highlights a route forward to prioritise the best available evidence on pharmacological treatments for schizophrenia at a global scale, which could also be applied to treatments for other mental health conditions.

Humans↗

Seven criteria for improving effectiveness trials in psychiatry.

BACKGROUND: There are no published criteria for improving the quality of effectiveness of randomized controlled trials (RCTs) in psychiatry. METHOD: The authors review and systematize the relevant literature on effectiveness trials, with particular reference to psychiatry. RESULTS: In planning effectiveness RCTs in psychiatry, seven sets of issues need to be carefully considered: (i) study question (i.e. is the study question expressed in an answerable way?); (ii) reference population (i.e. what is the reference group or subgroup to which the trial results should be generalized?); (iii) patient sample (i.e. how far does the sample reflect the target population?); (iv) study settings (i.e. how representative are the study settings of routine clinical sites?); (v) study interventions (i.e. is the study intervention manualized, acceptable to patients and suitable for widespread use?); (vi) control condition (i.e. are the key characteristics of the control condition well described, and do they vary within and between sites?); and (vii) bias (e.g. attrition, blinding, concealment, consent and contamination). CONCLUSIONS: More effectiveness trials are needed which have sufficient statistical power to provide precise answers to assist clinicians in making treatment decisions. The development of effectiveness trials in psychiatry, both for studies of individual treatments and for service evaluations, may be enhanced by carefully considering and justifying decisions in relation to each of the seven key headings proposed here.

Bias↗

Imputing missing standard deviations in meta-analyses can provide accurate results.

BACKGROUND AND OBJECTIVES: Many reports of randomized controlled trials (RCTs) fail to provide standard deviations (SDs) of their continuous outcome measures. Some meta-analysts substitute them by those reported in other studies, either from another meta-analysis or from other studies in the same meta-analysis. But the validity of such practices has never been empirically examined. METHODS: We compared the actual standardized mean difference (SMD) of individual RCTs and the meta-analytically pooled SMD of all RCTs against those based on the above-mentioned two imputation methods in two meta-analyses of antidepressants. RESULTS: Two meta-analyses included 39 RCTs of fluoxetine (n = 3,681) and 25 RCTs of amitriptyline (n = 1,832), which had actually reported means and SDs of the Hamilton Rating Scale for Depression. According to either of the two proposed imputation methods, the agreement between actual SMDs and imputed SMDs for individual RCTs was very good with ANOVA intraclass correlation coefficients between 0.61 and 0.97. The agreement between the actual pooled SMD and the imputed one was even better, with minimal differences in both their point estimates and 95% confidence intervals. CONCLUSION: For a systematic review where some of the identified trials do not report SDs, it appears safe to borrow SDs from other studies.

Amitriptyline↗

Efficacy of pharmacotherapy against core traits of borderline personality disorder: meta-analysis of randomized controlled trials.

We conducted a meta-analysis of published randomized, placebo-controlled clinical trials that evaluated the effect of pharmacotherapy in patients with borderline personality disorder. Comprehensive searches of the MEDLINE, EMBASE, PsychLIT and Cochrane Central Register of Controlled Trials databases were performed using web-based search engines. Twenty articles, reporting 22 placebo-controlled comparisons, were included in the meta-analysis: eight involved antipsychotics, seven antidepressants and seven mood stabilizers. Antidepressants (four studies, standardized mean difference -0.55, 95% confidence interval -0.92, -0.17) and mood stabilizers (six studies, standardized mean difference -1.74, 95% confidence interval -2.76, -0.73) were effective against affective instability and anger, but did not produce significant benefits against impulsivity and aggression, unstable relationships, suicidality and global functioning. Antipsychotics as a class had a positive effect in terms of impulsivity and aggression (three studies, standardized mean difference -0.31, 95% confidence interval -0.63, -0.003), interpersonal relationships (three studies, standardized mean difference -0.52, 95% confidence interval -0.87, -0.17) and global functioning (seven studies, standardized mean difference -0.56, 95% confidence interval -1.00, -0.11). No difference was observed between pharmacotherapy and placebo in terms of participants leaving the study early. Pharmacotherapy can exert a modest beneficial effect on some core traits of borderline personality disorder.

Adolescent↗

Validity of the impact factor of journals as a measure of randomized controlled trial quality.

OBJECTIVE: To assess whether the impact factor, a measure of the frequency with which journal articles are cited in the scientific literature, is a proxy measure of the quality of articles reporting the results of randomized controlled trials. METHOD: The quality of trials included in an ongoing Cochrane review concerned with the antidepressant fluoxetine was assessed using the Cochrane Collaboration Depression, Anxiety, and Neurosis quality assessment instrument, the Jadad scale, and the quality criterion of the Cochrane Collaboration Handbook. Journal impact factors were extracted from the Journal Citation Report. RESULTS: A total of 131 articles reported results from 132 clinical trials comparing fluoxetine with other antidepressants. The relationship between trial quality and the impact factor of journals where these studies were published, stratified by period of publication, revealed that journals with impact factors above 4 points published only trials with above-average overall quality ratings, while journals with impact factors below 4 points published both high- and low-quality trials. The Jadad scale revealed similar quality in trials published in journals with high, medium, and low impact factors (Pearson chi(2) = 0.298, p = .861), and the quality criterion of the Cochrane Collaboration Handbook showed unclear randomization in the majority of trials and in all 15 trials published in high-impact factor journals (Pearson chi(2) = 4.678, p = .096). CONCLUSION: The impact factor of journals is not a valid measure of randomized controlled trial quality.

Bibliometrics↗

Are all antidepressants really the same? The case of fluoxetine: a systematic review.

OBJECTIVE: To systematically review the efficacy and tolerability of fluoxetine, the most widely studied of newer antidepressants, in comparison with all other antidepressants in the acute treatment of depression in patients aged more than 18 years. DATA SOURCES: Studies were identified through electronic searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2004. The terms FLUOXETIN* OR adofen or docutrix or erocap or fluctin or fluctine or fluoxeren or fontex or ladose or lorien or lovan or mutan or prozac or prozyn or reneuron or sanzur or saurat or zactin were used. MEDLINE (1966-2004) and EMBASE (1974-2004) were searched using fluoxetine and randomized controlled trial or random allocation or double-blind method. No language restrictions were applied. Reference lists of relevant papers and previous systematic reviews were hand-searched for published reports up to March 2004. STUDY SELECTION: Only randomized controlled trials (either blind or nonblind) were included. DATA SYNTHESIS: 131 randomized controlled trials were eligible. A p value less than .01 was chosen to test the null hypothesis, and a 99% confidence interval was calculated to detect statistically significant differences with a high degree of confidence. Fixed- and random-effects relative risks, odds ratios (ORs), and Peto ORs were routinely calculated for each outcome measure. In terms of efficacy, we found a statistically significant difference favoring sertraline and venlafaxine over fluoxetine. In terms of tolerability, patients allocated to fluoxetine were less likely to leave the study early only in comparison with those allocated to amitriptyline and pramipexole. CONCLUSIONS: This systematic review highlighted that there are differences between fluoxetine and specific comparator antidepressants. Several of the differences met a prespecified criterion for clinical significance. The statistical approach adopted in this systematic review could represent a useful tool for putting clinical trial data into practice.

Adult↗

Impact of regulatory changes on first- and second-generation antipsychotic drug consumption and expenditure in Italy.

BACKGROUND: In 1994 a change in drug reimbursement status was implemented in Italy according to cost-effectiveness criteria. The aim of this study was to examine the impact of these changes on the use of antipsychotic (AP) drugs. METHODS: Data concerning actual quantities of antipsychotic agents dispensed in Italy from 1995 to June 2003 were obtained from the Italian Ministry of Health. For each antipsychotic agent, the number of defined daily doses (DDDs) per 1,000 inhabitants per day was calculated, as well as the annual expenditure in Euros. RESULTS: From 1995 to June 2003 prescriptions for first-generation antipsychotic agents (FGAs) progressively decreased from 2.54 to 2.0 DDD/1,000/day; in contrast, prescriptions for second-generation antipsychotic agents (SGAs) progressively rose up to 1.75 DDD/1,000/day in 2003. Overall, from 1995 to 2003 antipsychotic prescriptions rose from 2.54 to 3.75 DDD/1,000/day. In 2003 the antipsychotic drug most frequently used was haloperidol, followed by olanzapine and risperidone. In 2003 the use of SGAs accounted for nearly 50% of overall DDD/1,000/day of AP agents. The cost of these new drugs, however, accounted for more than 80% of the total AP expenditure. CONCLUSIONS: In Italy, the progressive increase in the utilisation of SGAs has been accompanied by a moderate decrease in the utilisation of phenothiazines and by an almost constant use of butyrophenones. The policy of reimbursing the use of SGAs only in subjects who could not tolerate FGAs eventually failed to significantly affect the pattern of antipsychotic consumption and expenditure; moreover, when this policy was eliminated at the beginning of 2001, the pattern of consumption and expenditure did not change.

Antipsychotic Agents↗

Imputing response rates from means and standard deviations in meta-analyses.

The principle of intention-to-treat analysis must be strictly applied to both individual randomized controlled trial and meta-analysis but, in doing so, would involve imputation of some missing data. There is little literature on how to perform this in the case of meta-analysis. For dichotomous outcome measures, one possible strategy is to carry out a sensitivity analysis based on the so-called best case/worst case analyses. For continuous outcomes, it may be possible to achieve this if we can dichotomise the continuous outcomes. Here, we empirically examined the appropriateness of converting continuous outcomes (expressed as mean+/-SD) into dichotomous outcomes (expressed as response rates) in four completed meta-analyses of depression and anxiety, assuming normal distribution of the continuous outcome measures. The agreement between the actually observed versus the imputed raw numbers of responders was indicated by an intraclass correlation coefficient of 0.97 (95% confidence interval 0.95-0.98). The pooled relative risks of the four meta-analyses based on the imputed values were virtually identical to those based on the actually observed values. When individual trials report the means+/-SDs of their outcome measures but fail to report response rates, it may therefore be possible to impute the response rates based on the means+/-SDs, and then submit the meta-analysis to worst case/best case analyses. This would allow a more robust and clinically interpretable estimation of the true, underlying treatment effect to be made.

Data Interpretation, Statistical↗

Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials.

OBJECTIVE: Observational studies suggest that long-term lithium treatment has a strong antisuicidal effect in mood disorders, but it is uncertain whether this association is a genuine therapeutic effect or is due to confounding factors in nonrandomized studies. The authors conducted a systematic review and meta-analysis of randomized trials to investigate the effect of lithium, compared to placebo and other active treatments, on the risk of suicide, deliberate self-harm, and all-cause mortality in patients with mood disorder. METHOD: The data source was the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE (1966-June 2002), EMBASE (1980-June 2002), CINAHL (1982-March 2001), PsycLIT (1974-June 2002), PSYNDEX (1977-October 1999), and LILACS (1982-March 2001). The Cochrane Central Register of Controlled Trials (CENTRAL) was searched with the term "lithium" for new records entered into the database from 1999 to 2003. Studies selected included randomized, controlled trials comparing lithium with placebo or all other compounds used in long-term treatment for mood disorders (unipolar depression, bipolar disorder, schizoaffective disorder, dysthymia, and rapid cycling, diagnosed according to DSM or ICD criteria). Of 727 references identified in the search, 52 articles were marked as possibly relevant on the basis of the abstract, and 32 randomized, controlled trials were eligible for inclusion in the review. Two independent reviewers extracted the data, and disagreements were resolved by consensus with a third reviewer. Methodological quality was assessed according to the criteria of the Cochrane Collaboration. When the outcomes of interest were not reported, an attempt was made to obtain the required data from the original authors. RESULTS: In 32 trials, 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds. Patients who received lithium were less likely to die by suicide (data from seven trials; two versus 11 suicides; odds ratio=0.26; 95% confidence interval [CI]=0.09-0.77). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio=0.21; 95% CI=0.08-0.50). There were fewer deaths overall in patients who received lithium (data from 11 trials; nine versus 22 deaths; odds ratio=0.42, 95% CI=0.21-0.87). CONCLUSIONS: Lithium is effective in the prevention of suicide, deliberate self-harm, and death from all causes in patients with mood disorders.

Cause of Death↗

International dosage differences in fluoxetine clinical trials.

OBJECTIVE: International differences are thought to exist in dosages used by clinicians treating mood disorders. This study examined international dosage differences in antidepressant clinical trials, using a database formed and maintained as a component of a Cochrane review of comparative clinical trials of fluoxetine. METHODS: This systematic review included 132 studies. A detailed set of methodological features and results were abstracted from the original publications and entered into an electronic database. Mean and maximum fluoxetine dosages were compared across countries. To evaluate the dosages of comparison medications, a defined daily dosage (DDD) ratio was calculated as the trial mean dosage divided by the DDD for that drug. RESULTS: Both the maximum and mean dosages for fluoxetine and comparison medications were higher in trials conducted in the US (fluoxetine weighted mean dosage 49.18 mg; 95% CI, 41.30 to 57.05), compared with trials conducted in Europe (fluoxetine weighted mean dosage 29.98 mg; 95% CI, 25.28 to 34.68). Since most clinical trials were conducted in Europe or the US, we could not determine whether different dosages tended to be used in other regions. CONCLUSIONS: International differences in prescriber behaviour may influence, and in turn be influenced by, the conduct of clinical trials. It is difficult to reconcile such differences with the principles of evidence-based medicine.

Drug Administration Schedule↗