Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol

<p>Abstract</p> <p>Background</p> <p>After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment.</p> <p>The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode.</p> <p>Methods</p> <p>SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents a continuation phase to Steps I and II and aims to establish longer-term effectiveness and acceptability of the above-examined treatment strategies up to week 25. The trial is supported by the Grant-in-Aid by the Ministry of Health, Labour and Welfare, Japan.</p> <p>Discussion</p> <p>SUN(^_^)D promises to be a pragmatic large trial to answer important clinical questions that every clinician treating patients with major depression faces in his/her daily practices concerning its first- and second-line treatments.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01109693">NCT01109693</a></p

Potential Impact of Benzodiazepine Use on the Rate of Hip Fractures in Five Large European Countries and the United States

Benzodiazepine use increases the risk of falls and has been associated with an increased risk of hip fractures. Our aim was to estimate the possible population impact of the use of benzodiazepines on the rate of hip fracture in France, Germany, Italy, Spain, the United Kingdom, and the United States. We conducted a literature review to estimate the pooled relative risk (RR) for hip fractures and use of benzodiazepines. Prevalence rates of benzodiazepine use in 2009 were calculated for each country using the IMS MIDAS database and three public databases in Denmark, the Netherlands, and Norway. Both the RR and prevalence rates were used for calculation of population attributable risks (PARs) of hip fractures associated with benzodiazepine use. The literature review showed an increased risk of hip fractures in benzodiazepine users (RR = 1.4, 95 % CI 1.2–1.6). Rate of benzodiazepine use showed considerable differences between countries, ranging from 4.7 % to 22.3 % of population ever in a 1-year period. These are reflected in results for the PARs; estimated attributions of benzodiazepines to the rate of hip fractures were 1.8 %, 95 % CI 1.1–2.6 (Germany); 2.0 %, 95 % CI 1.2–2.8 (United Kingdom); 5.2 %, 95 % CI 3.2–7.3 (Italy); 7.4 %, 95 % CI 4.5–10.0 (France); 8.0 %, 95 % CI 4.9–11.0 (United States); and 8.2 %, 95 % CI 5.1–12.0 (Spain). PAR estimates suggest that the potential attribution of benzodiazepine use on the population rate of hip fractures in the five specified European countries and the United States varies between 1.8 % and 8.2 %. During the next phase of the IMI-PROTECT study, a comparison with individual patient data will show whether this approach is valid

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

Are we going to increase the use of antidepressants up to that of benzodiazepines?

OBJECTIVE: The present study compared recent trends in benzodiazepine and antidepressant consumption in Italy and projected their global sales in the future. We investigated whether the increasing use of antidepressants is associated with a progressive reduction in benzodiazepine use. METHODS: Data concerning actual quantities of benzodiazepines and antidepressants dispensed in Italy from 1995 to June 2003 were obtained from IMS Health. For each agent, the number of defined daily doses (DDDs) per 1000 inhabitants per day and the annual expenditure in Euros was calculated. RESULTS: During the 9-year period, benzodiazepine consumption remained substantially stable, accounting for 50 DDDs/1000 per day in 2003. In the same period, antidepressant consumption dramatically rose, from 9 DDDs/1000 per day in 1995 to 26 DDDs/1000 per day in 2003, an increase of nearly three times. While the use of tricyclic antidepressants declined by one-third and that of other older agents remained substantially stable, the use of selective serotonin-reuptake inhibitors and newer agents (venlafaxine, mirtazapine, reboxetine) increased by 623%. Global consumption of antidepressants was projected to increase still further, and, in 2007, the total sales of antidepressants were projected to be similar to the total sales of benzodiazepines. The value of benzodiazepine sales increased from 322 million to 565 million Euros, an increase of 43%; similarly, the value of antidepressant sales increased from 186 million to 569 million Euros, an increase of 67%. CONCLUSIONS: In Italy, the consumption of benzodiazepines was not affected by the increased prescribing of selective serotonin-reuptake inhibitors and newer antidepressant

Automated valuation methods in atypical real estate markets using the mono-parametric approach

The appraisal objectivity depends on the possibility to quickly and easily access to reliable real estate data in order to apply appropriate appraisal approaches. In order to ensure the objectivity of the real estate appraisals, in recent years Automated Valuation Methods (AVM) have been developed, integrating computerized real estate databases and programming languages. The Automated Valuation Methods proposed at international level usually recur to regression models, aimed to return appraisal equations based on reliable real estate databases. This approach is not applicable in some markets where lack of data does not allow the implementation of regression models. This paper proposes to implement a valuation automatic method in order to appraise properties located in atypical markets, structuring a procedural algorithm based on the mono-parametric approach and able to return punctual values related to the subject’s specifics and to the market peculiarities in a very limited area. The paper proposes also the application of similarity degree coefficients in order to take into account the differences between the amounts of the real estate features, leading to the possibility to use the mono-parametric approach also when lack of data would not recommend it

Evaluation and comparison of deoxyribonucleic acid typing methods on human tissue fixed with different fixatives

Abstract. Commonly employed fixing fluids result in very satisfactory histomorphologic analysis; however, they don&apos;t allow deoxyribonucleic acid (DNA) typing methods to provide good results. This study investigated the effect of eight fixatives on DNA extracted from placenta samples. Fresh tissue (placenta) specimens were fixed by immersion in different fixing fluids for different periods (from 24 h to 60 days). Different DNA extraction methods were assayed. Gene Amp 2400 and 9700 Thermal Cyclers coupled to AmpFLSTR Identifier kit (Applied Biosystems), that allows the simultaneous amplification of 15 STRs loci, was used for quantification. Amplified products were analyzed by capillary electrophoresis on ABI PRISM 310 and 3100 Genetic Analyzers (Applied Biosystems).

Off-label and non-classical prescriptions of antipsychotic agents in ordinary inpatient practice

OBJECTIVE:To estimate the proportion of off-label prescriptions of antipsychotics (APs) in ordinary in-patient practice.METHOD:From the South-Verona Psychiatric Case Register all admissions to the in-patient unit during 2001-02 were extracted. Prescriptions of APs were defined off-label when dispensed outside the licensed indications. In addition, the proportion of "non-classical prescriptions" was calculated.RESULTS:During the 2 years surveyed AP agents were prescribed in 311 cases. Nearly 50% of second-generation AP prescriptions were for an off-label indication. In contrast, &lt;15% of first-generation AP prescriptions were for an off-label indication. About 30% of first- and second-generation agents were prescribed for a non-classical indication.CONCLUSION:Approved labels for second-generation AP agents cover a much narrower range of indications than any of the first-generation agents, and this explains the higher proportion of off-label prescriptions. In contrast, the everyday use of first- and second-generation APs cover a similar range of clinical indications

The changing pattern of inpatient antipsychotic drug use in Italy

[no abstract available