Search

Camilla Gesi,1 Silvia Paletta,2 Maria Carlotta Palazzo,1 Bernardo Dell’Osso,1,3 Claudio Mencacci,1 Giancarlo Cerveri2 1Department of Mental Health and Addiction, ASST FBF Sacco, Milan, Italy; 2Department of Mental Health and Addiction, ASST Lodi, Lodi, Italy; 3School of Medicine University of Milan, Milan, ItalyCorrespondence: Silvia Paletta Email silvia.paletta@asst-Lodi.itAbstract: Cariprazine is an antipsychotic medication which received approval from the US Food and Drug Administration for the treatment of schizophrenia in September 2015. Cariprazine is a dopamine D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Furthermore, although to a more limited extent, cariprazine also exhibits partial agonism at the level of 5-HT1A receptors, thus exerting an antidepressant effect in addition to the antipsychotic effect. The most commonly encountered adverse events are extrapyramidal symptoms and akathisia. Short-term weight gain appears infrequently. Cariprazine is not associated with any clinically meaningful alterations in metabolic variables, prolactin, or ECG QT interval. Cariprazine is also approved for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Clinical trials of cariprazine are ongoing in patients with acute bipolar I depression and as adjunctive treatment to antidepressant therapy in patients with major depressive disorder. In this article, we present some significant clinical cases regarding the use of cariprazine, with the hope that our experience can provide insight or suggestions to be used in clinical practice.Keywords: cariprazine, schizophrenia, bipolar disorder, effectiveness, tolerability

Valentina Perrone,1 Diego Sangiorgi,1 Margherita Andretta,2 Giuseppe Ducci,3 Bruno Forti,4 Pier Cesare Francesa Morel,5 Marco Gambera,6 Giuseppe Maina,7 Claudio Mencacci,8 Francesco Saverio Mennini,9,10 Enrico Zanalda,11 Luca Degli Esposti1 1CliCon S.r.l., Health, Economics & Outcomes Research, Bologna, Italy; 2UOC Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, Vicenza, Italy; 3Mental Health Department, ASL Roma 1, Rome, Italy; 4Mental Health Department - Azienda ULSS n 1 “Dolomiti”, Veneto Region, Italy; 5Janssen-Cilag SpA, Milano, Italy; 6“OSPEDALE P. PEDERZOLI” Casa di Cura Privata S.p.A., Peschiera del Garda, Verona, Italy; 7Department of Neuroscience “Rita Levi Montalcini”, University of Turin, University Hospital San Luigi Gonzaga, Turin, Italy; 8Department of Neuroscience, ASST Fatebenefratelli Sacco, Milan, Italy; 9EEHTA - CEIS (Centre for Economic and International Studies), Faculty of Economics, University of Rome “Tor Vergata”, Rome, Italy; 10Institute for Leadership and Management in Health Care, Kingston University, London, UK; 11Department of Mental Health ASL TO3 & AOU San Luigi Gonzaga, Collegno, TO, ItalyCorrespondence: Valentina PerroneCliCon S.r.l. Health, Economics & Outcomes Research, via Murri, 9, Bologna, 40137, ItalyTel +39 0544 38393Fax +39 0544 212699Email valentina.perrone@clicon.itPurpose: To analyse the healthcare resource consumption and related costs for the Italian National Health System of patients estimated to be affected by treatment-resistant depression (TRD) in Italy.Patients and Methods: This was an observational retrospective study based on administrative databases, including those related to residential/semiresidential structures, of Veneto Region and the Local Health Unit of Bergamo in Italy (for a total of around 6 million health-assisted subjects). Between July 2011 and December 2017, all adult patients with a third antidepressant (AD) after ≥ 2 AD (each one with at least ≥ 4 weeks duration, ≥ 1 prescription at maximum dosage reported in datasheets, a grace period ≤ 30 days when switching AD and treatment maintained ≥ 9 months) were included. Overall and psychiatry-related healthcare resources consumption and related costs were estimated on a 12-months based analysis. Data were re-proportioned to the Italian population.Results: We have previously estimated a total of 101,455 patients with TRD in Italy (130,049 considering the mean maximum dosage of AD). Of them, 44.2% had at least a psychiatric hospitalization/visit or accessed a residential/semiresidential structure, and 31% added another AD or a mood stabilizer/antipsychotic drug. Patients with at least one psychiatry-related hospitalization increased over the number of antidepressant lines from 12.0% during first line up to 24.5% during fourth line. Direct healthcare costs increased from € 4,405 for first line to € 9,251 from fifth line onwards. Psychiatry-related costs went from € 1,817 (first line) to € 4,606 (fifth line onwards) and were mainly driven by residential/semiresidential structures and hospitalizations.Conclusion: An upward trend with number of AD lines was observed for all healthcare resource utilization and consequently for all direct costs, thus indicating an increasing burden for patients as they move forward AD lines.Keywords: depression, healthcare costs, real-world, TRD

Giancarlo Cerveri,1 Camilla Gesi,2 Claudio Mencacci21Mental Health Department, ASST Lodi, Lodi, Italy; 2Mental Health Department, ASST Fatebenefratelli-Sacco, Milan, ItalyAbstract: The clinical presentation of schizophrenia encompasses symptoms divided into three dimensions: positive, negative, and cognitive. Negative symptoms (NS), in particular, have a major impact on the quality of life of the affected subject, and, differing from positive symptoms, are often associated with a limited response to pharmacotherapy. To date, studies specifically investigating NS in schizophrenia are scant; therefore, proper selection of therapy for NS remains a major unmet medical need. Given the heterogeneity of the clinical presentation of schizophrenia, the treatment of NS, as well as therapy for other associated symptoms, should be largely individualized according to a patient’s specific characteristics. In this paper, we review current knowledge on NS and construct a clinical algorithm for the treatment of schizophrenic conditions with pronounced NS. Overall, data from the literature suggest that second-generation antipsychotics, such as cariprazine and amisulpride, should be preferred over first-generation antipsychotics (FGAs), as they are associated with better functional outcomes and lower cognitive impairment. The combination of antipsychotics and antidepressants may also improve NS while addressing some affective disorders associated with schizophrenia; however, no clear information is available on the effects of this combination on primary NS or on the mechanism of action of the combination. In the proposed clinical algorithm, we suggest that cariprazine should be used as first-line treatment for patients with predominant NS, and that amisulpride should be considered as an alternative in cases of cariprazine failure. Further treatment lines may include the use of olanzapine and quetiapine, and add-on therapy with antidepressants.Keywords: cariprazine, mental disorders, symptoms

Claudio Mencacci,1 Eugenio Aguglia,2 Giovanni Biggio,3 Lodovico Cappellari,4 Guido Di Sciascio,5 Andrea Fagiolini,6 Giuseppe Maina,7 Alfonso Tortorella,8 Pablo Katz,9 Claudio Ripellino9 1Department of Mental Health, Fatebenefratelli Hospital, Milan, 2Department of Clinical and Molecular Biomedicine, University of Catania, Catania, 3Department of Experimental Biology and Center of Excellence for the Neurobiology of Drug Dependence, University of Cagliari, Calgiari, 4Department of Mental Health, Camposampiero Hospital, Padova, 5Department of Psychiatry, Policlinico Hospital, Bari, 6Department of Molecular Medicine, University of Siena and Department of Mental Health, University of Siena Medical Center, Siena, 7Department of Neurosciences, University of Torino, Torino, 8Department of Mental Health, University of Naples SUN, Naples, 9CSD Medical Research Srl, Milan, Italy Background: Major depression is a commonly occurring, seriously impairing, and often recurrent mental disorder. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the treatments most commonly used for major depressive disorder. The objective of this study was to assess the cost-effectiveness of SSRIs and SNRIs in the treatment of major depressive disorder in two Italian regional settings, ie, Veneto and Sardinia. Methods: A decision analytic model was adapted from the Swedish Dental and Pharmaceutical Benefits Agency to reflect current clinical practice in the treatment of major depressive disorder in the most significant Italian regions. This adaptation was possible as a result of collaboration with an expert panel of Italian psychiatrists and health economists. The population comprised patients with a first diagnosis of major depressive disorder and initiating one SSRI or SNRI drug for the first time. The time frame used was 12 months. Efficacy and utility data for the model were retrieved from the literature and validated by the expert panel. Local data were used for resource utilization and for treatment costs based on the perspective of each regional health service. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the model. Results: Base case analysis showed that escitalopram is associated with the largest health gain (in quality-adjusted life years) and a lower total cost at one year for Sardinia (except for sertraline, against which it was cost-effective) and for Veneto, and therefore dominates the other treatment strategies, given that more quality-adjusted life years are achieved at a lower total cost. Scenario analyses and probabilistic sensitivity analyses support the robustness of the model. Conclusion: The results indicate that escitalopram is the most cost-effective pharmacologic treatment strategy for both regional health services compared with all SSRIs and all SNRIs used in the first-line treatment of major depressive disorder. Keywords: antidepressants, major depressive disorder, cost-effectiveness quality of life, Italy

Claudio Mencacci,1 Guido Di Sciascio,2 Pablo Katz,3 Claudio Ripellino31Ospedale Fatebenefratelli, Milan, Italy; 2Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy; 3CSD Medical Research Srl, Milan, ItalyBackground: 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, one-way 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.Keywords: CEA, depression, escitalopram, Lombardy, ICER, SSRI

Michele Fornaro1, Icro Maremmani2,3, Pier Luigi Canonico4, Paolo Carbonatto5, Claudio Mencacci6, Giovanni Muscettola7, Luca Pani8, Riccardo Torta9, Claudio Vampini10, Fabio Parazzini11, Arina Dumitriu12, Giulio Perugi2,31Department of Neurosciences, Section of Psychiatry, University of Genova, Genoa, Italy; 2Dipartimento di Psichiatria Università di Pisa, Pisa, Italy; 3Institute of Behavioural Sciences "G. De Lisio", Pisa, Italy; 4Università di Novara, Novara, Italy; 5Societa' Italiana di Medicina Generale (SIMG) Turin, Italy; 6Ospedale Fatebenefratelli, Milan, Italy; 7Università di Napoli, Naples, Italy; 8Istituto di Neurogenetica e Neurofarmacologia, CNR, Cagliari, Italy; 9Ospedale Molinette, Turin, Italy; 10Ospedale Maggiore, Verona, Italy; 11GPA net, Milan, Italy; 12Boehringer Ingelheim S.p.A., Milan, ItalyObjective: To assess the prevalence and distribution of medically unexplained painful somatic symptoms (PSSs) versus nonpainful somatic symptoms (NPSSs) in patients diagnosed with major depressive episode (MDE).Method: A total of 571 outpatients diagnosed with MDE according to DSM-IV-TR criteria were consecutively enrolled into a cross-sectional, multicentric, observational study over a period of 7 months. Subjects were evaluated by means of the ad hoc validated 30-item Somatic Symptoms Checklist (SSCL-30) and Zung's questionnaires for depression and anxiety. The 32-item Hypomania Checklist (HCL-32) was also administered in order to explore any eventual association of PSSs or NPSSs with sub-threshold (DSM-IV-TR [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision] not recognized) bipolar disorder (BD).Results: In our sample, just 183 patients (32%) did not report painful somatic symptoms (NPSSs). Of these, 90 patients (15.76%) had no somatic symptoms at all. The remaining 388 (68%) had at least one PSS being subdivided as follows: 248 (43%) had one or two PSSs, while 140 (25%) experienced two or more. Patients with at least one PSS also reported a greater number of nonpainful somatic symptoms than NPSS. Bipolar patients (associated with higher HCL-32 scores) were less represented across PSS cases than NPSS subjects. Conversely, females were more prone to having a higher number of total somatic symptoms (and bipolar features).Conclusion: PSSs are common in patients with MDE, especially among those patients reporting fewer somatic symptoms in general as opposed to those patients who exhibit more somatic symptoms (both PSSs and NPSSs) with lower relative number of PSSs. A major therapeutic implication is that antidepressant monotherapy could be used with more confidence in unexplained PSS patients than in NPSS patients because of the latter group's lower frequency of (sub)-threshold bipolar features.Keywords: major depressive episode, MDE, bipolar disorder, BD

Purpose: Cognitive impairment is a core feature of major depressive disorder (MDD), and dysfunctions in this area strongly contribute to MDD-associated disability. Whether cognitive impairment has an independent clinical course and a unique impact on HRQOL is still debated. We sought to characterize the relationship between depression severity and HRQOL, evaluating the burden of concentration difficulties on HRQOL.Methods: Six hundred ninety-two patients with unipolar depressive disorders recruited in 19 Italian centers answered a self-administered survey (SF-12 questionnaire, socio-demographic information). A psychiatrist completed a standardized data collection form encompassing a depression severity scale (MADRS) and clinical information.Results: There was a strong graded association between the severity of depressive symptoms and both the physical (ω 2 = 0.13; p < 0.01) and mental (ω 2 = 0.34; p < 0.01) SF-12 domains. Additionally, we observed a strong association between concentration difficulties and all HRQOL outcomes independent of other symptoms of depression and robust to adjustment for possible confounders.Conclusions: Our data corroborate previous findings suggesting that cognitive impairment is a feature of unipolar depressive disorders partially independent of the severity of other symptoms, and may represent a specific target of therapy with a strong impact on patients' functioning and quality of life. [ABSTRACT FROM AUTHOR]