Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and a periodic assessment of the patient are crucial to prevent misuse. A multidisciplinary group suggests strategies for all stakeholders involved in the management of pain and suggests the importance of the doctor-patient relationship

ALLEGRI, Massimo

Coluzzi, F

FANELLI, Guido

Gatti, R. C

GERRA, GILBERTO

Mammucari, M

Maremmani, I

Mugelli, A

Pinto, C

RAFFAELI, WILLIAM

Ripamonti, I. C

ROMUALDI, PATRIZIA

VIGANO', ROBERTO

English

Gerra, G

Allegri, M

Viganò, R

Romualdi, P

Raffaeli, W

COLUZZI, FLAMINIA

Fanelli, G.

Archivio della ricerca- Università di Roma La Sapienza

Abstract. – Opioids are drugs of referencefor the treatment of moderate to severe pain.Their proper use and a periodic assessment ofthe patient are crucial to prevent misuse. A mul-tidisciplinary group suggests strategies for allstakeholders involved in the management ofpain and suggests the importance of the doctor-patient relationship.Key Words:Chronic pain, Pain management, Opioid, Addic-tion, Doctor patient relationship.IntroductionAppropriate Pain ManagementThe diagnosis and treatment of pain is a clini-cal and ethical imperative, and access to con-trolled drugs for medical purposes, particularlypain medications, should be guaranteed to all pa-tients in need1,2. Current clinical practice recom-mendations indicate opioids as the gold standardfor treatment of moderate-to-severe acute andchronic pain, according to the WHO analgesicladder and other international guidelines3-7. To establish an appropriate and personalizedplan of care, a general assessment of the patientEuropean Review for Medical and Pharmacological SciencesThe prevention of analgesic opioids abuse:expert opinionI. MAREMMANI1, G. GERRA2, I.C. RIPAMONTI3, A. MUGELLI4,M. ALLEGRI5, R. VIGANÒ6, P. ROMUALDI7, C. PINTO8, W. RAFFAELI9,F. COLUZZI10, R.C. GATTI11, M. MAMMUCARI12, G. FANELLI51Vincent P. Dole Dual Diagnosis Unit, Department of Clinical and Experimental Medicine, "SantaChiara" University Hospital, University of Pisa, Pisa, Italy2Drug Prevention and Health Branch, United Nations Office On Drugs and Crime (UNODC), Vienna,Austria3Supportive Care in Cancer Unit, Department of Haematology and Pediatric Onco-Haematology,Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy4Department of Neurosciences, Drug Research and Child Health, University of Florence, Florence, Italy5Department of Surgical Science, University of Parma, Parma, Italy; Pain Therapy Service, Anesthesiaand Intensive Care, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, Italy6Azienda Ospedaliera Istituto Ortopedico Gaetano Pini, Milan, Italy7Department of Pharmacy and Biotechnology Alma Mater Studiorum, University of Bologna, Bologna8Medical Oncology IRCCS-Arcispedale S. Maria Nuova, Reggio Emilia, Italy9ISAL Foundation, Institute for Research on Pain, Rimini, Italy10Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anesthesiology,Intensive Care Medicine and Pain Therapy, Polo Pontino, Sapienza University of Rome, Latina, Italy11Department of Addiction, ASL di Milano, Milan, Italy12Primary Care, ASL RME, Rome, ItalyCorresponding Author: Massimo Mammucari, MD; e-mail: massimo.mammucari@libero.it 4203with pain is crucial, thus permitting an appropri-ate prescription of opioid medications. Accord-ingly, periodic re-assessment and accurate moni-toring are essential for the correct managementof pain pharmacotherapy (Table I).As reported in the World Drug Report8, at theinternational level availability of opioids formedical purposes does not correlate with abuse,misuse, or diversion2. Several countries withvery high per capita opioid-medication availabil-ity do not show high levels of abuse. In contrast,some countries with limited access to these med-ications for medical purposes present a high levelof abuse and misuse. Financial, cultural and leg-islative factors may interfere with the relation-ship beyond the role attributed to availability in asimplistic way.The effectiveness of opioid medications incontrolling pain and inducing analgesia may beassociated, in a minority of cases, with addic-tion, misuse and non-therapeutic use, particu-larly in vulnerable individuals. However, ad-diction is rare in patients with no previous his-tory of addiction9. Using a structured evidence-based review of 67 studies, Fishbain et al10. cal-culated the abuse/addiction rate to be 3.3%.When considering only patients with no history2015; 19: 4203-4206Assessment of physical, psychological, social/family existential suffering Assessment of background pain (and breakthrough pain in cancer patients)Assessment of the causes of pain with a proper diagnosis (for example assessing neuropathic, nociceptive or mixed pain)and evaluation of analgesic need Selection of drugs on the basis of the characteristics of pain Pharmacotherapy management (dose titration with immediate-release formulations to reach minimum effective doseand/or maximum tolerated, switching of route/opioid when needed, dose adjustments for tolerance, hyperalgesia, or ad-verse events) Periodic re-assessment of painCounseling and assessment of misuse risk (patient, family, caregiver)Multidisciplinary health care pathway for uncontrolled painTable I. Systematic, accurate, and personalized management of people suffering with pain.I. Maremmani, G. Gerra, I.C. Ripamonti, A. Mugelli, M. Allegri, R. Viganò, P. Romualdi, et al.dictive behavioural pattern characterized by thecompulsive cycle. Patients with unrelieved painmay in fact become focused on obtaining med-ications. For all these reasons, in patients withchronic pain a periodic review of the strategy anda detailed evaluation of behaviours are recom-mended (Table II).To better explain the uncommon risk of addic-tion in patients with pain, the conditions to in-duce addictive behaviour and opioid use disor-ders should be considered extensively. Addictionis not simply related to the exposure to opioidmedications, but to a complex series of socialand neurobiological factors inducing loss of con-trol over drug use. The addicted patient is char-acterized by compulsive use, craving, and contin-ued use despite harmful consequences. The ther-apeutic use of opioids in patients with pain isusually not associated with any risk factor whichunderlies the development of substance use dis-orders in the clinical history. Furthermore, neuro-biological data demonstrated that subjects suffer-of abuse/addiction, the percentage of abuse/ad-diction dropped to 0.2%10. Overall, these fig-ures suggest a low risk of opioid abuse/addic-tive behaviour in clinical practice. Existing evi-dence and clinical experience suggest that inappropriately-selected patients, opioids have alow addictive potential and, in addition to theirprimary analgesic action, they are able to re-duce suffering, enhance functional activity lev-el, and improve quality of life11. From a clinical perspective, the symptoms ofcompulsive/addictive behaviour in patients withpain should also be distinguished from those re-lated to “pseudoaddiction”. The term “pseudoad-diction” is used to describe a reversible conditionin patients with undertreated chronic pain show-ing erratic behaviour that resolves once pain be-comes adequately controlled12. To this end, prac-titioners working in the pain management areashould also differentiate the effects of tolerancein patients in need of higher dosage of opioidmedications to maintain analgesia from the ad-4204Appropriate use of opioidsImplement combination therapies with multiple drugs (aiming at opioid-sparing)Reserve the higher doses and long-acting formulations for patients with persistent pain after titrationPrefer safe packages (e.g. child-proof packaging)Prefer opioid with abuse-deterrent formulation or device should be preferredSchedule frequent monitoring visits Avoid under treatment of chronic pain Discourage multiple prescriptions (centralize the prescription to the specialist or the GP who is in charge of the patient)Avoid unecessary prescriptions Check drug adherence periodicallyShare the therapy strategy with the patient (including the benefit/risk ratio)Continuous counselingScreening patients at potential risk with validated tools (comorbidity drug abuse, non-drug abuse conditions, psychiatricconditions)Discuss patients’ management with other specialists (pain specialist, addiction specialist, GPs)Table II. Strategies to manage the opioid treatment.ing for neuropathic chronic pain undergo a seriesof neuro-plastic changes, which do not supportthe reinforcing, rewarding effects of opiates andpotential abuse13. Although the prescription-drugs abuse epi-demic in the United States14,15 has been interpret-ed in different ways, the real nature of the phe-nomenon remains unclear. A variety of factors,typical of the normative, cultural and social con-ditions in the US could have induced the over-whelming rate of abuse that seems to be uncom-mon16 and not expected in Europe and in Italy.This has led many experts in the US to proposestrategies to reduce the risk of diversion17,18. Toenhance the rate of appropriate use of opioidmedications in patients requiring analgesia amultimodal approach should be applied not onlyby physicians, but also by other stakeholders(Table III).For a long time analgesic opioids have beenused in small amounts and only for terminal can-cer patients with pain. With the recent approvalof the Italian law no. 38/2010, opioids have be-come more readily available to patients needinganalgesia. Although the access modalities to drugtherapies in Italy is different from those appliedin other countries and opioid abuse remains arare event in patients with chronic pain9,18,19, thestrategies to avoid drugs abuse should be careful-ly considered. Multimodal strategies should beimplemented and disseminated to reduce the po-tential risk of misuse and abuse: in particular thetraining of health professionals should providethe necessary skill for the mitigation of abuseand diversion. The use of opioids must be in fullcompliance with the approved indications toavoid misuse; however, the fear of abuse shouldnot discourage the appropriate use of these effec-tive drugs in the control of pain. Opioid treat-ment should not be denied in paediatric patients,according to the WHO indications. In fact mor-phine was recommended by WHO as second-linetreatment after paracetamol or ibuprofen for per-sisting moderate to severe pain in children20. Ap-propriate management of pain is also recom-mended, both during and/or after treatments anddiagnostic procedures21. In both these settingsabuse and diversion are unlikely.As a main element to avoid abuse and diver-sion, particular emphasis should be given to theconcept of “therapeutic alliance” between thehealthcare professional and the patient22. An in-dividualized approach, considering not only thepain, but the entire person affected and his/herown needs and expectations, would significantlyincrease not only the benefits of pain pharma-cotherapy and also decrease the risk of uncon-trolled and abusive use. General practitionersshould be fully involved in the multidisciplinarypathway of care in order to detect patients at riskearlier, centralize and monitor prescriptions, pe-riodically reassess the chronic pain situation andinvolve patient and family in the management ofopioid therapy. In this setting, a validation tool to4205The prevention of analgesic opioids abuse: expert opinion1. Health Authorities Mandatory training to physicians about the proper prescription of pain medications Public awareness campaigns on the proper use of pain medications Active surveillance of analgesic abuse2. Scientific SocietiesGuidelines to manage long-term opioid therapyValidation of tools to assess the risk of drugs abuse Multidisciplinary training program (for specialists and GPs) 3. PharmacistsSurveillance of suspected abuse of opioid painkillers (multiple prescriptions, incorrect dosage)Ensure the availability of all formulations of opioids (immediate, rapid or sustained-release)Counseling on the correct dosage and storage4. NursesSurvey and counselingParticipation to the multidisciplinary risk assessment plan5. Pharmaceutical companiesImplement child-proof packaging Implement abuse-deterrent formulationsPromote the approved indications and proper useActive monitoring and assessment of safety profile and risk/benefit ratioTable III. Multimodal strategies to manage the opioid risk.4206aid the early detection of patients at risk is alsocrucial. Lastly, appropriate modalities should beadopted to not deny the necessary opioid medica-tions to patients at risk of abuse affected by se-vere pain and addicted patients who are in needof analgesic interventions.–––––––––––––––––––AcknowledgementsEditorial assistance for the preparation of this manuscriptwas provided by Luca Giacomelli, PhD. The views ex-pressed herein are those of the authors and do not necessari-ly reflect the views of the United Nations.–––––––––––––––––-–––Conflict of InterestThe Authors declare that there are no conflicts of interest.References1) INTERNATIONAL PAIN SUMMIT OF THE INTERNATIONAL ASSO-CIATION FOR THE STUDY OF PAIN. Declaration of Mon-tréal: declaration that access to pain manage-ment is a fundamental human right. J Pain PalliatCare Pharmacother 2011; 25: 29-31.2) Access to controlled drugs for medical purposeavailable at http://www.unodc.org/unodc/en/drug-prevention-and-treatment/access-to-controlled-drugs-for-medical-purposes.html. Last access the10th May, 2015.3) WORLD HEALTH ORGANIZATION. Cancer pain relief.Geneva: World Health Organization, 1986.4) SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK CON-TROL OF PAIN IN ADULTS WITH CANCER. A national clini-cal guideline. SIGN – Scottish IntercollegiateGuidelines Network, November 2008.5) CARACENI A, HANKS G, KAASA S BENNETT MI, BRUNELLIC, CHERNY N, DALE O, DE CONNO F, FALLON M, HAN-NA M, HAUGEN DF, JUHL G, KING S, KLEPSTAD P,LAUGSAND EA, MALTONI M, MERCADANTE S, NABAL M,PIGNI A, RADBRUCH L, REID C, SJOGREN P, STONE PC,TASSINARI D, ZEPPETELLA G; EUROPEAN PALLIATIVE CARERESEARCH COLLABORATIVE (EPCRC); EUROPEAN ASSOCIA-TION FOR PALLIATIVE CARE (EAPC). Use of opioid anal-gesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. LancetOncol 2012; 13: 58-68.6) RIPAMONTI CI, SANTINI D, MARANZANO E, BERTI M,ROILA F; ESMO GUIDELINES WORKING GROUP. Man-agement of cancer pain: ESMO Clinical PracticeGuidelines. Ann Oncol 2012; 23: vii139-154.7) CHEUNG CW, QIU Q, CHOI SW, MOORE B, GOUCKE R,IRWIN M. Chronic opioid therapy for chronic non-cancer pain: a review and comparison of treat-ment guidelines. Pain Physician 2014; 17: 401-414. 8) http://www.unodc.org/documents/wdr2014/World_Drug_Report_2014_web.pdf9) PORTER J, JICK H. Addiction rare in patients treatedwith narcotics. N Engl J Med 1980; 302: 123.10) FISHBAIN DA, COLE B, LEWIS J, ROSOMOFF HL, ROSO-MOFF RS. What percentage of chronic nonmalig-nant pain patients exposed to chronic opioidanalgesic therapy develop abuse/addictionand/or aberrant drug-related behaviors? Astructured evidence-based review. Pain Med2008; 9: 444-459.11) TRESCOT AM, HELM S, HANSEN H, BENYAMIN R, GLASERSE, ADLAKA R, PATEL S, MANCHIKANTI L. Opioids in themanagement of chronic non-cancer pain. PainPhysician 2008; 11: S5-S62.12) WEISSMAN DE, HADDOX JD. Opioid pseudoaddic-tion--an iatrogenic syndrome. Pain 1989; 36: 363-366.13) NIIKURA K, NARITA M, BUTELMAN ER, KREEK MJ ANDSUZUKI T. Neurophatic and chronic pain stimulidownregulate central mu-opioid and dopaminer-gic transmission. Trends Pharmacol Sci 2010; 31:299-305.14) FRANKLIN GM, AMERICAN ACADEMY OF NEUROLOGY.Opioids for chronic noncancer pain: a position pa-per of the American Academy of Neurology. Neu-rology 2014; 83: 1277-1284.15) MOORMAN-LI R, MOTYCKA CA, INGE LD, CONGDON JM,HOBSON S, POKROPSKI B. A review of abuse-deter-rent opioids for chronic non-malignant pain. P T2012; 37: 412-418.16) MANCHIKANTI L, BENYAMIN R, DATTA S, VALLEJO R,SMITH H. Opioids in chronic noncancer pain. Ex-pert Rev Neurother 2010; 10: 775-789. 17) ALEXANDER L, MANNION RO, WEINGARTEN B, FANELLIRJ, STILES GL. Development and impact of pre-scription opioid abuse deterrent formulation tech-nologies. Drug Alcohol Depend 2014; 138: 1-6.18) CICERO TJ, ELLIS MS. Abuse-Deterrent Formulationsand the Prescription Opioid Abuse Epidemic inthe United States Lessons Learned From Oxy-Contin. JAMA Psychiatry 2015; 72: 424-430.19) HOJSTED J, SJOGREN P, HOJSTED J, SJOGREN P. Addic-tion to opioids in chronic pain patients: A litera-ture review. Eur J Pain 2007; 11: 490-518.20) WORLD HEALTH ORGANIZATION. WHO guidelines onthe pharmacological treatment of persisting painin children with medical illnesses, 2012.21) RIPAMONTI CI, BOSSI P, SANTINI D, FALLON M. Pain re-lated to cancer treatments and diagnostic proce-dures: a no man’s land? Ann Oncol 2014; 25:1097-1106.22) MAMMUCARI M, LAZZARI M, MAGGIORI E, GAFFORIO P,TUFARO G, BAFFINI S, MAGGIORI S, PALOMBO E, DE MEOB, SABATO AF. Role of the informed consent, frommesotherapy to opioid therapy. Eur Rev MedPharmacol Sci 2014; 18: 566-574.I. Maremmani, G. Gerra, I.C. Ripamonti, A. Mugelli, M. Allegri, R. Viganò, P. Romualdi, et al.

The prevention of analgesic opioids abuse. Expert opinion

Mugelli, Alessandro

Vigan&#242

Romualdi, Patrizia

Fanelli, Giovanni

Florence Research

The prevention of analgesic opioids abuse: expert opinion

Ripamonti, Ic

Viganò, R

Gatti, Rc

PINTO, CHRISTIAN

Archivio istituzionale della ricerca - Alma Mater Studiorum Università di Bologna

Archivio istituzionale della Ricerca -  Università degli Studi di Parma

13 October 2022University of Parma Research RepositoryThe prevention of analgesic opioids abuse: expert opinion / Maremmani, I; Gerra, G; Ripamonti, I C;Mugelli, A; Allegri, M; Viganò, R; Romualdi, P; Pinto, C; Raffaeli, W; Coluzzi, F; Gatti, R C; Mammucari, M;Fanelli, G. - In: EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES. - ISSN 2284-0729. -19:21(2015), p. 4203-6.OriginalThe prevention of analgesic opioids abuse: expert opinionPublisher:PublishedDOI:Terms of use:openAccessPublisher copyright(Article begins on next page)Anyone can freely access the full text of works made available as "Open Access". Works made availableAvailability:This version is available at: 11381/2798536 since: 2015-12-14T15:43:56ZThis is the peer reviewd version of the followng article:Abstract. – Opioids are drugs of referencefor the treatment of moderate to severe pain.Their proper use and a periodic assessment ofthe patient are crucial to prevent misuse. A mul-tidisciplinary group suggests strategies for allstakeholders involved in the management ofpain and suggests the importance of the doctor-patient relationship.Key Words:Chronic pain, Pain management, Opioid, Addic-tion, Doctor patient relationship.IntroductionAppropriate Pain ManagementThe diagnosis and treatment of pain is a clini-cal and ethical imperative, and access to con-trolled drugs for medical purposes, particularlypain medications, should be guaranteed to all pa-tients in need1,2. Current clinical practice recom-mendations indicate opioids as the gold standardfor treatment of moderate-to-severe acute andchronic pain, according to the WHO analgesicladder and other international guidelines3-7. To establish an appropriate and personalizedplan of care, a general assessment of the patientEuropean Review for Medical and Pharmacological SciencesThe prevention of analgesic opioids abuse:expert opinionI. MAREMMANI1, G. GERRA2, I.C. RIPAMONTI3, A. MUGELLI4,M. ALLEGRI5, R. VIGANÒ6, P. ROMUALDI7, C. PINTO8, W. RAFFAELI9,F. COLUZZI10, R.C. GATTI11, M. MAMMUCARI12, G. FANELLI51Vincent P. Dole Dual Diagnosis Unit, Department of Clinical and Experimental Medicine, "SantaChiara" University Hospital, University of Pisa, Pisa, Italy2Drug Prevention and Health Branch, United Nations Office On Drugs and Crime (UNODC), Vienna,Austria3Supportive Care in Cancer Unit, Department of Haematology and Pediatric Onco-Haematology,Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy4Department of Neurosciences, Drug Research and Child Health, University of Florence, Florence, Italy5Department of Surgical Science, University of Parma, Parma, Italy; Pain Therapy Service, Anesthesiaand Intensive Care, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, Italy6Azienda Ospedaliera Istituto Ortopedico Gaetano Pini, Milan, Italy7Department of Pharmacy and Biotechnology Alma Mater Studiorum, University of Bologna, Bologna8Medical Oncology IRCCS-Arcispedale S. Maria Nuova, Reggio Emilia, Italy9ISAL Foundation, Institute for Research on Pain, Rimini, Italy10Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anesthesiology,Intensive Care Medicine and Pain Therapy, Polo Pontino, Sapienza University of Rome, Latina, Italy11Department of Addiction, ASL di Milano, Milan, Italy12Primary Care, ASL RME, Rome, ItalyCorresponding Author: Massimo Mammucari, MD; e-mail: massimo.mammucari@libero.it 4203with pain is crucial, thus permitting an appropri-ate prescription of opioid medications. Accord-ingly, periodic re-assessment and accurate moni-toring are essential for the correct managementof pain pharmacotherapy (Table I).As reported in the World Drug Report8, at theinternational level availability of opioids formedical purposes does not correlate with abuse,misuse, or diversion2. Several countries withvery high per capita opioid-medication availabil-ity do not show high levels of abuse. In contrast,some countries with limited access to these med-ications for medical purposes present a high levelof abuse and misuse. Financial, cultural and leg-islative factors may interfere with the relation-ship beyond the role attributed to availability in asimplistic way.The effectiveness of opioid medications incontrolling pain and inducing analgesia may beassociated, in a minority of cases, with addic-tion, misuse and non-therapeutic use, particu-larly in vulnerable individuals. However, ad-diction is rare in patients with no previous his-tory of addiction9. Using a structured evidence-based review of 67 studies, Fishbain et al10. cal-culated the abuse/addiction rate to be 3.3%.When considering only patients with no history2015; 19: 4203-4206Assessment of physical, psychological, social/family existential suffering Assessment of background pain (and breakthrough pain in cancer patients)Assessment of the causes of pain with a proper diagnosis (for example assessing neuropathic, nociceptive or mixed pain)and evaluation of analgesic need Selection of drugs on the basis of the characteristics of pain Pharmacotherapy management (dose titration with immediate-release formulations to reach minimum effective doseand/or maximum tolerated, switching of route/opioid when needed, dose adjustments for tolerance, hyperalgesia, or ad-verse events) Periodic re-assessment of painCounseling and assessment of misuse risk (patient, family, caregiver)Multidisciplinary health care pathway for uncontrolled painTable I. Systematic, accurate, and personalized management of people suffering with pain.I. Maremmani, G. Gerra, I.C. Ripamonti, A. Mugelli, M. Allegri, R. Viganò, P. Romualdi, et al.dictive behavioural pattern characterized by thecompulsive cycle. Patients with unrelieved painmay in fact become focused on obtaining med-ications. For all these reasons, in patients withchronic pain a periodic review of the strategy anda detailed evaluation of behaviours are recom-mended (Table II).To better explain the uncommon risk of addic-tion in patients with pain, the conditions to in-duce addictive behaviour and opioid use disor-ders should be considered extensively. Addictionis not simply related to the exposure to opioidmedications, but to a complex series of socialand neurobiological factors inducing loss of con-trol over drug use. The addicted patient is char-acterized by compulsive use, craving, and contin-ued use despite harmful consequences. The ther-apeutic use of opioids in patients with pain isusually not associated with any risk factor whichunderlies the development of substance use dis-orders in the clinical history. Furthermore, neuro-biological data demonstrated that subjects suffer-of abuse/addiction, the percentage of abuse/ad-diction dropped to 0.2%10. Overall, these fig-ures suggest a low risk of opioid abuse/addic-tive behaviour in clinical practice. Existing evi-dence and clinical experience suggest that inappropriately-selected patients, opioids have alow addictive potential and, in addition to theirprimary analgesic action, they are able to re-duce suffering, enhance functional activity lev-el, and improve quality of life11. From a clinical perspective, the symptoms ofcompulsive/addictive behaviour in patients withpain should also be distinguished from those re-lated to “pseudoaddiction”. The term “pseudoad-diction” is used to describe a reversible conditionin patients with undertreated chronic pain show-ing erratic behaviour that resolves once pain be-comes adequately controlled12. To this end, prac-titioners working in the pain management areashould also differentiate the effects of tolerancein patients in need of higher dosage of opioidmedications to maintain analgesia from the ad-4204Appropriate use of opioidsImplement combination therapies with multiple drugs (aiming at opioid-sparing)Reserve the higher doses and long-acting formulations for patients with persistent pain after titrationPrefer safe packages (e.g. child-proof packaging)Prefer opioid with abuse-deterrent formulation or device should be preferredSchedule frequent monitoring visits Avoid under treatment of chronic pain Discourage multiple prescriptions (centralize the prescription to the specialist or the GP who is in charge of the patient)Avoid unecessary prescriptions Check drug adherence periodicallyShare the therapy strategy with the patient (including the benefit/risk ratio)Continuous counselingScreening patients at potential risk with validated tools (comorbidity drug abuse, non-drug abuse conditions, psychiatricconditions)Discuss patients’ management with other specialists (pain specialist, addiction specialist, GPs)Table II. Strategies to manage the opioid treatment.ing for neuropathic chronic pain undergo a seriesof neuro-plastic changes, which do not supportthe reinforcing, rewarding effects of opiates andpotential abuse13. Although the prescription-drugs abuse epi-demic in the United States14,15 has been interpret-ed in different ways, the real nature of the phe-nomenon remains unclear. A variety of factors,typical of the normative, cultural and social con-ditions in the US could have induced the over-whelming rate of abuse that seems to be uncom-mon16 and not expected in Europe and in Italy.This has led many experts in the US to proposestrategies to reduce the risk of diversion17,18. Toenhance the rate of appropriate use of opioidmedications in patients requiring analgesia amultimodal approach should be applied not onlyby physicians, but also by other stakeholders(Table III).For a long time analgesic opioids have beenused in small amounts and only for terminal can-cer patients with pain. With the recent approvalof the Italian law no. 38/2010, opioids have be-come more readily available to patients needinganalgesia. Although the access modalities to drugtherapies in Italy is different from those appliedin other countries and opioid abuse remains arare event in patients with chronic pain9,18,19, thestrategies to avoid drugs abuse should be careful-ly considered. Multimodal strategies should beimplemented and disseminated to reduce the po-tential risk of misuse and abuse: in particular thetraining of health professionals should providethe necessary skill for the mitigation of abuseand diversion. The use of opioids must be in fullcompliance with the approved indications toavoid misuse; however, the fear of abuse shouldnot discourage the appropriate use of these effec-tive drugs in the control of pain. Opioid treat-ment should not be denied in paediatric patients,according to the WHO indications. In fact mor-phine was recommended by WHO as second-linetreatment after paracetamol or ibuprofen for per-sisting moderate to severe pain in children20. Ap-propriate management of pain is also recom-mended, both during and/or after treatments anddiagnostic procedures21. In both these settingsabuse and diversion are unlikely.As a main element to avoid abuse and diver-sion, particular emphasis should be given to theconcept of “therapeutic alliance” between thehealthcare professional and the patient22. An in-dividualized approach, considering not only thepain, but the entire person affected and his/herown needs and expectations, would significantlyincrease not only the benefits of pain pharma-cotherapy and also decrease the risk of uncon-trolled and abusive use. General practitionersshould be fully involved in the multidisciplinarypathway of care in order to detect patients at riskearlier, centralize and monitor prescriptions, pe-riodically reassess the chronic pain situation andinvolve patient and family in the management ofopioid therapy. In this setting, a validation tool to4205The prevention of analgesic opioids abuse: expert opinion1. Health Authorities Mandatory training to physicians about the proper prescription of pain medications Public awareness campaigns on the proper use of pain medications Active surveillance of analgesic abuse2. Scientific SocietiesGuidelines to manage long-term opioid therapyValidation of tools to assess the risk of drugs abuse Multidisciplinary training program (for specialists and GPs) 3. PharmacistsSurveillance of suspected abuse of opioid painkillers (multiple prescriptions, incorrect dosage)Ensure the availability of all formulations of opioids (immediate, rapid or sustained-release)Counseling on the correct dosage and storage4. NursesSurvey and counselingParticipation to the multidisciplinary risk assessment plan5. Pharmaceutical companiesImplement child-proof packaging Implement abuse-deterrent formulationsPromote the approved indications and proper useActive monitoring and assessment of safety profile and risk/benefit ratioTable III. Multimodal strategies to manage the opioid risk.4206aid the early detection of patients at risk is alsocrucial. Lastly, appropriate modalities should beadopted to not deny the necessary opioid medica-tions to patients at risk of abuse affected by se-vere pain and addicted patients who are in needof analgesic interventions.–––––––––––––––––––AcknowledgementsEditorial assistance for the preparation of this manuscriptwas provided by Luca Giacomelli, PhD. The views ex-pressed herein are those of the authors and do not necessari-ly reflect the views of the United Nations.–––––––––––––––––-–––Conflict of InterestThe Authors declare that there are no conflicts of interest.References1) INTERNATIONAL PAIN SUMMIT OF THE INTERNATIONAL ASSO-CIATION FOR THE STUDY OF PAIN. Declaration of Mon-tréal: declaration that access to pain manage-ment is a fundamental human right. J Pain PalliatCare Pharmacother 2011; 25: 29-31.2) Access to controlled drugs for medical purposeavailable at http://www.unodc.org/unodc/en/drug-prevention-and-treatment/access-to-controlled-drugs-for-medical-purposes.html. Last access the10th May, 2015.3) WORLD HEALTH ORGANIZATION. Cancer pain relief.Geneva: World Health Organization, 1986.4) SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK CON-TROL OF PAIN IN ADULTS WITH CANCER. A national clini-cal guideline. SIGN – Scottish IntercollegiateGuidelines Network, November 2008.5) CARACENI A, HANKS G, KAASA S BENNETT MI, BRUNELLIC, CHERNY N, DALE O, DE CONNO F, FALLON M, HAN-NA M, HAUGEN DF, JUHL G, KING S, KLEPSTAD P,LAUGSAND EA, MALTONI M, MERCADANTE S, NABAL M,PIGNI A, RADBRUCH L, REID C, SJOGREN P, STONE PC,TASSINARI D, ZEPPETELLA G; EUROPEAN PALLIATIVE CARERESEARCH COLLABORATIVE (EPCRC); EUROPEAN ASSOCIA-TION FOR PALLIATIVE CARE (EAPC). Use of opioid anal-gesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. LancetOncol 2012; 13: 58-68.6) RIPAMONTI CI, SANTINI D, MARANZANO E, BERTI M,ROILA F; ESMO GUIDELINES WORKING GROUP. Man-agement of cancer pain: ESMO Clinical PracticeGuidelines. 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The prevention of analgesic opioids abuse: expert opinion

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