Guido Di Sciascio

The Use of Antidepressant Drugs and the Lifetime Prevalence of Major Depressive Disorders in Italy

Background: The increased use of antidepressant drugs (ADs) improved the response to the needs of care although some community surveys have shown that subjects without lifetime psychiatric diagnosis (anxiety/depression) used ADs. Objectives: To evaluate the appropriateness and amount of prescription of psychotropic drugs in people with lifetime diagnosis of Major Depressive Disorder (MDD) by means of community survey with a semi-structured interview as a diagnostic instrument, administered by clinicians. Methods: Study design: community survey. Study population: samples randomly drawn, after stratification from the adult population of municipal records. Sample size: 4.999 people were drawn in 7 centres of 6 Italian regions. Tools: questionnaire on psychotropic drug consumption, prescription, health services utilization; Structured Clinical Interview for DSM-IV modified (ANTAS); Training: interviewers were trained psychologists or medical doctors. Results: 3.398 subjects were interviewed (68% of the recruited sample). The lifetime prevalence of DSM-IV MDD was 4.3% in males and 11.5% in females; antidepressant drugs were taken by 4.7% of subjects, 2.9% male and 5.9% female. 38% of males and 57% of females with lifetime diagnosis of MDD were taking ADs. Conclusions: Compared with studies using lay interviewers and structured tools the prevalence of the MDD was quite lower; ADs use was higher and tallied well with the data regarding antidepressant sales in Italy; the correspondence between lifetime diagnosis of MDD and ADs use was closer.

The lifetime prevalence of bipolar disorders and the use of antidepressant drugs in bipolar depression in Italy

BACKGROUND The prevalence of bipolar spectrum disorders in the community is under debate and the prescription of antidepressant drugs (ADs) in bipolar depression appears to be an underestimated problem. OBJECTIVES To evaluate the prevalence of bipolar disorders by means of a screening instrument in seven communities within six regions of Italy and evaluate the appropriateness and number of prescriptions for ADs in bipolar depression. METHODS STUDY DESIGN community survey. STUDY POPULATION samples randomly drawn, after stratification from the adult population of municipal records. SAMPLE SIZE 4999 people from seven communities within six regions of Italy. Tools: questionnaire on psychotropic drug consumption, prescription, health services utilization; Structured Clinical Interview NP for DSM-IV modified (ANTAS); Mood Disorder Questionnaire (MDQ). Training: interviewers were trained psychologists or medical doctors. STUDY LIMITATIONS the population studied did not represent a nationally representative multistage clustered area probability sample of households. RESULTS 3398 subjects were interviewed (68% of recruited sample). Positivity at MDQ (MDQ+) was higher in males (3.4% vs. 2.8%) but the difference was not significant (OR=1.2, P=0.37). The association between MDQ+ and Major Depressive Disorder (MDD) was statistically significant for both males (OR=14.9, P<0.0001) and females (OR=8.3, P<0.001); 30% of subjects with MDQ+ and MDD lifetime diagnosis were taking ADs. CONCLUSIONS These overall rates of being MDQ+ are similar to community surveys conducted within USA and the use of ADs in people with MDQ+ and MDD diagnoses are.

Sub-threshold depression and antidepressants use in a community sample: searching anxiety and finding bipolar disorder

BackgroundTo determine the use of antidepressants (ADs) in people with sub-threshold depression (SD); the lifetime prevalence of mania and hypomania in SD and the link between ADs use, bipolarity and anxiety disorders in SD.MethodsStudy design: community survey. Study population: samples randomly drawn, after stratification from the adult population of municipal records. Sample size: 4999 people from seven areas within six Italian regions. Tools: Questionnaire on psychotropic drug consumption, prescription; Structured Clinical Interview NP for DSM-IV modified (ANTAS); Hamilton Depression Rating Scale (HAM-D); Mood Disorder Questionnaire (MDQ); Short Form Health Survey (SF-12). SD definition: HAM-D > 10 without lifetime diagnosis of Depressive Episode (DE).ResultsSD point prevalence is 5.0%. The lifetime prevalence of mania and hypomania episodes in SD is 7.3%. Benzodiazepines (BDZ) consumption in SD is 24.1%, followed by ADs (19.7%). In SD, positive for MDQ and comorbidity with Panic Disorder (PD) or Generalized Anxiety Disorders (GAD) are associated with ADs use, whereas the association between a positive MDQ and ADs use, without a diagnosis of PD or GAD, is not significant. Only in people with DE the well-being (SF-12) is higher among those using first-line antidepressants compared to those not using any medication. In people with SD no significant differences were found in terms of SF-12 score according to drug use.ConclusionsThis study suggests caution in prescribing ADs to people with SD. In people with concomitant anxiety disorders and SD, it should be mandatory to perform a well-designed assessment and evaluate the presence of previous manic or hypomanic symptoms prior to prescribing ADs.

Cost-Effectiveness of Asenapine in the Treatment of Patients with Bipolar I Disorder with Mixed Episodes in an Italian Context

IntroductionBipolar disorder is a chronic disease characterized by periods of mania or hypomania, depression, or a combination of both (mixed state). Because bipolar disorder is one of the leading causes of disability, it represents an important economic burden on society. Asenapine (ASE) is a new second-generation antipsychotic developed and approved for the treatment of manic or mixed episodes associated with bipolar disorder. The objective of the present study was to assess the cost-effectiveness of ASE compared to olanzapine (OLA) in the treatment of patients experiencing mixed episodes associated with bipolar I disorder in the context of the Italian National Health Service (NHS).MethodsA pharmacoeconomic model was developed to simulate the management of Italian bipolar I patients with mixed episodes over a 5-year time horizon by combining clinical parameters with resource utilization. An expert panel of Italian psychiatrists and health economists was responsible for adapting a UK model to the Italian context. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio, where effectiveness is measured in terms of quality adjusted life-years gained. Scenario analyses, sensitivity analyses, and a probabilistic sensitivity analysis were performed to test the robustness of the model.ResultsThis pharmacoeconomic model showed that ASE resulted to be dominant over OLA; in fact, ASE was associated with lower direct costs (derived largely by the savings from hospitalizations avoided) and also generated a better quality of life. Results were robust to changes in key parameters; both scenario analyses and sensitivity analyses demonstrated model reliability.ConclusionsResults from this study suggest that the management of bipolar I patients with mixed episodes using ASE as alternative to OLA can lead to cost saving for the Italian NHS and improve patients quality of life.

Eating disorders as a public health issue: Prevalence and attributable impairment of quality of life in an Italian community sample

Abstract The prevalence of eating disorders (ED) in the community is still under debate, as well as the measure of their impact on the well-being of individuals. It was decided to evaluate the prevalence of eating disorders in an Italian community sample as well as to measure the burden of the quality of life of people and to compare it to those attributable to other chronic illnesses. A community survey of 4,999 people using a questionnaire on health services utilization, the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), a semi-structured clinical interview derived from the non-patient version of the DSM-IV (SCID/NP) and Short Form Health Survey (SF-12) was conducted. A total of 3,398 individuals were interviewed (68% of those recruited). Lifetime prevalence for overall ED was 1.7%; for anorexia 0.7%; for bulimia 0.6% and for binge eating disorder 0.5%. ED was more frequent in women than in men. No cases of anorexia in men were identified. ED showed an attributable burden in impairing quality of life with no statistically significant differences with those due to major depressive disorder, bipolar spectrum disorders and Wilsons disease. Of the pathological conditions considered, only multiple sclerosis showed a worsening attributable burden. ED thus has a non-negligible frequency in Italy, with severe impact on quality of life comparable to that produced by severe chronic psychiatric and general medical conditions. These elements emphasize that ED is a serious public health issue.

Effects of treatment with etizolam 0.5 mg BID on cognitive performance: a 3-week, multicenter, randomized, double-blind, placebo-controlled, two-treatment, three-period, noninferiority crossover study in patients with anxiety disorder.

BACKGROUND Etizolam is an anxiolytic drug with a pharmacologic profile similar to that of the classic benzodiazepines. Neurochemical research suggests that etizolam may have selectivity for the subpopulation of Y-aminobutyric acid type A receptors associated with anxiety (ie, alpha1, beta2, gamma2). This property, plus its characterization as a ligand with fewer of the adverse events typical of full agonists (impaired cognitive function, tolerance, and dependence), led to its selection for this study. OBJECTIVES The primary aim of this study was to test for the noninferiority of etizolam 0.5 mg BID versus placebo in affecting cognitive function in patients with mild to moderate anxiety disorder of recent onset (<1 month). Anxiety measures and tolerability were also assessed. METHODS Patients between the ages of 18 and 65 years were eligible for enrollment. This double-blind, placebo-controlled study was performed in 5 centers in Italy using a 2-treatment, 3-period crossover design. Patients were randomized to 3-week sequences of either etizolam-placebo-placebo or placebo-etizolam-etizolam. They were evaluated at 4 scheduled visits (screening and days 7, 14, and 21). Cognitive function was assessed using scores from the Wechsler Adult Intelligence Scale (WAIS) Digit Span test (total forward and backward scores and the time required to perform the test). Anxiety was measured using the Hamilton Anxiety Rating Scale (HAM-A) and the State-Trait Anxiety Inventory (STAI) for screening and to monitor adequacy of therapy. Blood pressure, heart rate, weight, and adverse events were also recorded. RESULTS A total of 77 white patients were enrolled (mean age, 33.3 years [range, 22-60 years]; 62.3% female; mean weight, 65.2 kg). With a power of 0.80, the difference between the effects of etizolam and placebo on WAIS Digit Span performance was not significant for total score (0.102 [90% CI, -0.130 to 0.335]) or time required for completion (0.029 second [90% CI, -0.574 to 0.632]). Anxiety, as measured using the HAM-A and STAI instruments, did not differ significantly between groups. No significant differences were found between etizolam 0.5 mg BID and placebo for cardiovascular events, weight changes, or adverse events. Mild or moderate somnolence was reported by 7 of 77 patients (9.1% [3 patients while receiving etizolam and 4 patients while receiving etizolam and placebo]). CONCLUSIONS No significant differences between etizolam 0.5 mg BID and placebo were found for cognitive function or anxiety measures in these patients with anxiety. Etizolam was well tolerated.

The attributable burden of panic disorder in the impairment of quality of life in a national survey in Italy

Introduction/Objective: The aim was to measure the lifetime prevalence of panic disorder (PD) in an Italian community sample, and to estimate the burden attributable to PD in compromising the quality of life (QoL) of people diagnosed with it. Methods: Community survey was conducted on a sample of 4,999 randomly selected adult subjects. Instruments used were semi-structured clinical interview Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), administered by clinicians and allowing diagnosis according to Diagnostic and Statistical Manual of Mental Disorder (4th ed.; DSM-IV); Short Form Health Survey (SF-12). Results: The lifetime prevalence of PD was 3.6% (4.4% in females, 2.5% in males; p = .002). People with PD had a lower SF-12 score than the standardized community sample (35.5 ± 6.5 vs. 38.4 ± 5.9; p < .0001) with a mean difference (attributable burden) of 2.9 ± 0.7, that is, lower than PD with agoraphobia (AP; 4.2 ± 2.4). Wilson Disease (WD), Multiple Sclerosis, Major Depressive Disorder and Eating Disorders (ED) show a higher attributable burden in impaired QoL than PD, while the attributable burden of PD with AP is not lower than in ED and WD. Conclusions: The burden attributable to the impairment of QoL following a lifetime diagnosis of PD was found to be not so great compared to the impairment caused by Major Depressive Disorder (MDD) or neurological conditions. The comorbidity of PD with AP worsens QoL significantly.

Switching antipsychotic medication to aripiprazole: position paper by a panel of Italian psychiatrists.

Introduction: Patients with schizophrenia or bipolar disorder treated with antipsychotic medication can frequently experience lack of efficacy and persistent side-effects, so much so that switching from one antipsychotic to another with a different side-effect profile has become a recommended strategy for improving the tolerability and safety of long-term antipsychotic treatment. Aripiprazole is an atypical antipsychotic with proven efficacy in schizophrenia and bipolar I disorder, with a pharmacological profile distinct from other available antipsychotics and a side-effect profile that is different from other agents in the class; these characteristics make it a possible alternative in patients requiring a change in antipsychotic treatment due to lack of efficacy or persistent side-effects. Areas covered: A panel of Italian experts in psychiatry met to discuss the appropriateness of current strategies for the switch to aripiprazole in patients with schizophrenia or bipolar disorder once a clinician has decided to adopt this choice and also to propose alternate strategies where required. The strategies for the switch to aripiprazole presented in this position paper consider various scenarios encountered in clinical practice, highlight the importance of tapering the prior antipsychotic based on its pharmacological characteristics and provide detailed guidance throughout the entire switching process. Literature searches were conducted using the PubMed database and the search strategy (aripiprazole and switching); additional references were added from the reference lists of the papers obtained and also from the authors’ knowledge of the topic. Expert opinion: Few studies have addressed the indications for antipsychotic switching and the best practical strategies to achieve the desired goal in the clinical practice setting. Studies on antipsychotic switching should clarify why, when and how a switch should be done. The results should standardize the reasons for switching an antipsychotic, assess the optimal time to switch and evaluate the best ways to switch. Both clinical and pharmacological factors should be considered when a patient needs to switch antipsychotics, and specific guidelines for antipsychotic switching that address all these factors are needed.

Cost-effectiveness evaluation of escitalopram in major depressive disorder in Italy

Background Depression has a lifetime prevalence of 10%–25% among women and 5%–12% among men. Selective serotonin reuptake inhibitors (SSRIs) are the most used and the most cost-effective treatment for long-term major depressive disorder. Since the introduction of generic SSRIs, the costs of branded drugs have been questioned. The objective of this study was to assess the cost-effectiveness (€ per quality-adjusted life year [QALY]) of escitalopram (which is still covered by a patent) compared with paroxetine, sertraline, and citalopram, the patents for which have expired. Methods A decision analytic model was adapted from the Swedish Dental and Pharmaceutical benefits agency model to reflect current clinical practice in the treatment of depression in Italy in collaboration with an expert panel of Italian psychiatrists and health economists. The population comprised patients with a first diagnosis of major depressive disorder and receiving for the first time one of the following SSRIs: escitalopram, sertraline, paroxetine, and citalopram. The time frame used was 12 months. Efficacy and utility data for the original model were validated by our expert panel. Local data were considered for resource utilization and for treatment costs based on the Lombardy region health service perspective. Several scenario simulations, oneway sensitivity analyses, and Monte Carlo simulations were performed to test the robustness of the model. Results The base case scenario showed that escitalopram had an incremental cost-effectiveness ratio (ICER) of €4395 and €1080 per QALY compared with sertraline and paroxetine, respectively. Escitalopram was dominant over citalopram, which was confirmed by most one-way sensitivity analyses. The escitalopram strategy gained 0.011 QALYs more than citalopram, 0.008 more than paroxetine, and around 0.007 more than sertraline. Monte Carlo simulations indicated that ICER values for escitalopram were centered around €1100 and €4400 per QALY compared with paroxetine and sertraline, respectively. Although there is no official cost-effectiveness threshold in Italy, the value of €25,000 per QALY could be acceptable. All ICER values retrieved in all analyses were lower than this threshold. Conclusion The findings from this cost-effectiveness analysis indicate that escitalopram could be accepted as a cost-effective strategy for the Lombardy region health service compared with the other SSRIs studied. The present assessment is based on ICER values resulting from this analysis, which are lower than the thresholds proposed by health care authorities in other European Union countries. These benefits are driven by the effectiveness of escitalopram, which result in an improved health-related quality of life, a higher probability of sustained remission, and better utilization of health care resources. The study results are robust and in line with other pharmacoeconomic analyses comparing escitalopram with other SSRIs.

EUDOR-A multi-centre research program: A naturalistic, European Multi-centre Clinical study of EDOR Test in adult patients with primary depression

BackgroundElectrodermal reactivity has been successfully used as indicator of interest, curiosity as well as depressive states. The measured reactivity depends on the quantity of sweat secreted by those eccrine sweat glands that are located in the hypodermis of palmar and plantar regions. Electrodermal hyporeactive individuals are those who show an unusual rapid habituation to identical non-significant stimuli. Previous findings suggested that electrodermal hyporeactivity has a high sensitivity and a high specificity for suicide. The aims of the present study are to test the effectiveness and the usefulness of the EDOR (ElectroDermal Orienting Reactivity) Test as a support in the suicide risk assessment of depressed patients and to assess the predictive value of electrodermal hyporeactivity, measured through the EDOR Test, for suicide and suicide attempt in adult patients with a primary diagnosis of depression.Methods and design1573 patients with a primary diagnosis of depression, whether currently depressed or in remission, have been recruited at 15 centres in 9 different European countries. Depressive symptomatology was evaluated through the Montgomery-Asberg Depression Scale. Previous suicide attempts were registered and the suicide intent of the worst attempt was rated according to the first eight items of the Beck Suicide Intent Scale. The suicide risk was also assessed according to rules and traditions at the centre. The EDOR Test was finally performed. During the EDOR Test, two fingers are put on gold electrodes and direct current of 0.5 V is passed through the epidermis of the fingers according to standards. A moderately strong tone is presented through headphones now and then during the test. The electrodermal responses to the stimuli represent an increase in the conductance due to the increased number of filled sweat ducts that act as conductors through the electrically highly resistant epidermis. Each patient is followed up for one year in order to assess the occurrence of intentional self-harm.DiscussionBased on previous studies, expected results would be that patients realizing a suicide attempt with a strong intent or committing suicide should be electrodermally hyporeactive in most cases and non-hyporeactive patients should show only few indications of death intent or suicides.Trial registrationThe German Clinical Trials Register, DRKS00010082. Registered May 31st, 2016. Retrospectively registered.