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THE RATIONAL USE OF ANTIDEPRESSANTS COMBINED WITH BENZODIAZEPINES

Rational use of drugs Research group. Master in Pharmaceutical Sciences UNIVERSITY OF SOROCABA, SOROCABA, SP, BRASIL. THE RATIONAL USE OF ANTIDEPRESSANTS COMBINED WITH BENZODIAZEPINES. Izabela Fulone Silvio Barberato Filho Luciane Cruz Lopes

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THE RATIONAL USE OF ANTIDEPRESSANTS COMBINED WITH BENZODIAZEPINES

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  1. Rational use of drugs Research group Master in PharmaceuticalSciences UNIVERSITY OF SOROCABA, SOROCABA, SP, BRASIL THE RATIONAL USE OF ANTIDEPRESSANTS COMBINED WITH BENZODIAZEPINES IzabelaFulone Silvio Barberato Filho Luciane Cruz Lopes THIRD INTERNACIONAL CONFERENCE FOR IMPROVING USE OF MEDICINES Antalya, Turkey

  2. BACKGROUND • Combining antidepressants and anxiolytics, mainly benzodiazepines (BDZ), is common practice in the treatment of major depression; • Meta-analysis shows that combined therapy presents a higher rate of response to depressive symptoms and lower dropout rate ONLY up to the fourth week. • From then on, the benefits recede.

  3. OBJECTIVES Evaluating the rational use of the antidepressants/benzodiazepines combination in major depression patients who were attended in the public health care system of Porto Feliz city, state São Paulo, Brazil.

  4. METHODS • Design: observacional, transversal, retrospective, analytical; • Setting: publichealthcare system in the city of Porto Feliz, São Paulo State, Brazil; • Inclusioncriteria: all patients under treatment with antidepressants, whether combined with benzodiazepines or not, who were attended by the public health care system; • Follow- up: january 2008 to december 2009; • Outcomes: • Primary: rational use of antidepressants combined with benzodiazepines or not (appropriate indication, adequate posology and recommended time of use); • Secundary: risk factors for Adverse Drug Reactions, severe drug interactions;

  5. METHODS • Termsdefinition • Monotherapy:therapywithonlyoneantidepressant; • Combinedtherapy: therapywithantidepressantplusbenzodiazepine; • Mixedtherapy: alternationbetweenmonotherapy, combinedtherapyandtherapywith more thanoneantidepressant; • Continuous use: continuosusing ≥ 1 month; • Rational use: appropriatedrug, adequateposologyandrecommendedduration;

  6. METHODS • Adequacy of the use of antidepressants • Appropriate drug: • indication according to clinical evidences; • absenceofcontraindications for use (absolutimpediment); • Adequate dosage: • dose by day considering age level; • Duration of the treatment: • at least three months for monotherapy (The Canadian Psychiatric Association, 2001; NICE, 2009; The Brazilian Medical Association, 2009); • up to 4 weeks for combined therapy (Cochrane Meta-analysis FURUKAWA et al., 2009);

  7. Methods • Source of data collection 1° step 2° step 3° step • Statistical analysis of the data: the frequencies were analyzed by means of proportions, Chi-square and Fisher exact;

  8. RESULTS

  9. 1601 ANTIDEPRESSANTS PRESCRIPTIONS Therapywith more thanoneantidepressant *p<0,05 Combinedtherapy Monotherapy 60 53,8 53,3 50 44,7 42,3 40 30 Proporção (%) 20 10 3,9 2,0 0 Other CID (n= 3212) • Major depression (n=1601) Treatment 23,7% (n=204) fluoxetina plusdiazepam 65,4% (p≤0,oo1) fluoxetine Figure 2: Types of therapies used for the treatment of major depression and other CID at SUS in Porto Feliz-SP, from January 2008 to December 2009.

  10. 1355 usersofantidepressants EXCLUDED users 1,4% (n=7) deadpatients 21,1% (n=102) incompleteforms 77,5% (n= 376) patientswhose medical recordswerenotfound 64,3% (n=870) usersofantidepressantswith medical recordsdulycompleted 30,5% (n= 265) major depression PATIENTS 69,5% (n=605) patientswithothers CID (InternationalClassificationofDiseases) 41,5% (n=110) in combinedtherapy 44,5% (n=118) in monotherapy 13,9% (n=37) in mixedtherapy 62,7% (n=69) in continuous use 60,1% (n=71) in continuous use 1601 antidepressants PRESCRIPTIONS 94,3% (n=67)withappropriatedrug 94,3% (n=67) withappropriatedrug 94,3% (n= 67) adequateposology 94,3% (n=67)adequateposology 1,4% (n=1) in recommendedduration 64,8% (n=46) in recommendedduration Figure. 1: Characterizationofthe use ofantidepressants RATIONAL USE

  11. SEVERE DRUG INTERATIONS 265 PATIENTS with major depression 1601 antidepressants PRESCRIPTIONS 9% (n=169) SEVERE DRUG INTERACTIONS 13,6% (n=36) with SEVERE DRUG INTERATIONS 40,2% (n=68) fluoxetineplusamytriptilyne Cardiotoxicity Toxicitywithtricyclicantidepressants Figure 2: Characterizationoftheseveredruginterations

  12. RISK FACTORS FOR ADVERSE DRUG REACTIONS POLIPHARMACY 84,5% (n=224) - AgentsactionontheRenin-angiotensin system (14,8%) - Psycholeptics (14,5%) Diuretics (9,7%) COMORBITIES 57,7% (n=153) -Arterial hypertension 35,3% -Diabetes mellitus 10,8% ADVANCED AGE 27% (n=72) elderly

  13. CONCLUSIONS/ IMPLICATIONS • KEY LESSONS • High consumption of fluoxetine and diazepam; • More use of combined therapy, especially the combinations of serotonin reuptake inhibitor plus BDZ; • Prolonged use of combined therapy: over 50% of patients have used it for more than one year; Overuse of BDZ exposes patients to dependence, tolerance and fractures; • Monotherapy favors the rational use of the medicine better than combined therapy;

  14. CONCLUSIONS/ IMPLICATIONS • KEY LESSONS • The most common severe drug interaction was selective serotonin reuptake inhibitors more tricyclicsantidepressants (possible risk of cardiotoxicity or toxicity with tricyclic); • Polimedicated patients with no pharmacotherapeutic follow-up, which indicates that the patient is not well assisted;

  15. CONCLUSIONS/ IMPLICATIONS • Policyimplications • Elaboration of pattern policies for the treatment of major depression in Brazil; • Education of patients on the risk of dependence to BDZ; • Continued education of prescribers, mainly on adverse effects of prolonged use of BDZ, mainly by elderly people; • Future research • Assessment of the effectiveness of the antidepressant therapy applied; • Analysis of suspected Adverse Drug Reactions; • Cost analysis;

  16. REFERENCES • BARBUI, C. et al. Depression in adults (drug and other physical treatments). BMJ ClinicalEvidence, v. 06, n. 1003, 2007. • DEPRESSION: the treatment and management of depression in adults. Nice ClinicalGuideline 90, Inglaterra, oct. 2009. • FLECK, M. P. A. et al. Review of the guidelines of the Brazilian Medical Association for the treatment of depression. RevBrasPsiquiatr, v. 31, p. S7-17, 2009. • FURUKAWA T. A. et al. Antidepressants plus benzodiazepines for major depression. In: THE COCHRANE LIBRARY, Issue 10. Art. No. CD001026. DOI: 10.1002/14651858.CD001026.pub1. 2011. • KENNEDY, S. et al. Clinical Guidelines for the Treatment of Depressive Disorders. Medications and Other Biological Treatments. The Canadian Journal of Psychiatry, v. 46, supl. 1, june 2001.

  17. teşekkür ederim THANK YOU VERY MUCH!

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