Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain

Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient’s self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient’s medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1–110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75–100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain

Transdermal opioids for cancer pain

Patients with moderate to severe malignancy-related pain frequently require the use of opioid pharmacotherapy. Unfortunately, many cancer patients continue to be prescribed subtherapeutic doses of pain medications resulting in undo suffering and diminished quality of life. The choice of analgesic pharmacotherapy should be individualized and based on the intensity and etiology of pain reported by the patient. Health care providers must be able to readily quantify the relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal fentanyl is effective and well tolerated pharmacotherapy for the cancer pain patients. However, clinicians need to be cognizant that the U.S./U.K. manufacturer's recommendations for equilalagesic dosing of transdermal fentanyl may result in initial doses that produce subtherapeutic levels and unrelieved pain in some patients. A more aggressive dosing algorithm for transdermal fentanyl using a 2:1 (mg/day of oral morphine: mcg/hr of transdermal fentanyl) conversion ratio that considers both a review of the literature and clinical experience should help clinicians individualize cancer pain pharmacotherapy. Transdermal buprenorphine is now being prescribed in Europe and Australia for chronic and cancer pain management. Buprenorphine's mixed agonist/antagonist activity, dosage ceiling, and high affinity to the opiate receptor limits its use to those patients who do not already require large daily doses of opioids. Thus, buprenorphine may not be an appropriate medication for some patients with advanced unremitting cancer pain

Economic Implications of Sleep Disorders

Sleep disorders such as insomnia, obstructive sleep apnoea (OSA), excessive daytime sleepiness (EDS) and fatigue, sleep deprivation and restless legs syndrome (RLS) are increasingly seen in clinical practice. Sleep is considered vital for preserving daytime cognitive function and physiological well-being. Sleep insufficiency may have deleterious effects on work-life balance, overall health and safety. The consequential economic burden at both the individual and societal levels is significant. Moreover, sleep disorders are commonly associated with other major medical problems such as chronic pain, cardiovascular disease, mental illness, dementias, gastrointestinal disorders and diabetes mellitus. Thus, in order to properly care for patients presenting with sleep-related morbidity, and to reduce the consequential economic burden, accurate screening efforts and efficacious/cost-effective treatments need to be developed and employed.Cost-of-illness, Dyssomnias, assessment, Fatigue, assessment, Intrinsic-sleep-disorders, assessment, Parasomnias, assessment, Restless-legs-syndrome, assessment, Sleep-apnoea-syndrome, assessment, Sleep-disorders, assessment.

The Need for an Iterative Process for Assessing Economic Outcomes Associated with SSRIs

Pharmacotherapeutic advances in the treatment of depression have included the development of the selective serotonin reuptake inhibitors (SSRIs), thereby providing alternatives to tricyclic antidepressants. Concurrent with these events have been significant structural (e.g. pharmaceutical formularies) and regulatory (e.g. required pharmacoeconomic evaluations) changes in the delivery, financing, and oversight of healthcare programmes throughout the world. International cost-containment initiatives are increasingly mandating a demonstration of value for money, defined in terms of a measurable health and/or financial outcome, and, in the case of medicines, attributable to a given expenditure, for a given pharmacotherapeutic option. We examine the inherent strengths and weaknesses of 5 study designs used to discern and contrast financial outcomes stemming from the use of antidepressant pharmacotherapy for the treatment of depressive illness [randomised controlled trials (RCTs); meta-analyses; decision-analytical models (DAMs); retrospective database investigations; randomised naturalistic inquiry]. We argue that the economic appraisal of pharmacotherapy requires an iterative process extending from the developmental (RCTs; meta-analyses; DAMs) through to the postmarketing phase (database reviews; naturalistic inquiry), thereby resulting in a porfolio of evidence as to the safety, efficacy and effectiveness of a given pharmacotherapeutic category (e.g. SSRIs) and/or a specific medication. Database reviews, while nonrandomised, and prospective naturalistic inquiry afford greater insight into the patterns of use and financial merits of prescribing specific pharmacotherapeutic options for the treatment of depression within the context of clinical practice as compared with RCTs, meta-analyses and DAMs. The portfolio of evidence to date indicates that the first-line use of SSRIs in the treatment of depression is clinically warranted, and represents value for money.Antidepressants, Clinical trial design, Cost analysis, Pharmacoeconomics, Serotonin uptake inhibitors

Hospital Length of Stay for Schizophrenia: Is Primary Payer an Influencing Factor?

Objective: The purpose of this study was 3-fold: (i) to determine the distribution of US patients diagnosed with schizophrenia and requiring a hospitalisation in the calendar year 1988 or 1992, by primary payer type (Medicare; Medicaid; or private insurance); (ii) to discern the mean inpatient length of stay and charge per day in 1988 or 1992, by payer type; and (iii) to test for time trends between 1988 and 1992, for inpatient hospital length of stay and charge per day. Design and setting: A retrospective study using the Healthcare Cost and Utilisation Project (HCUP-3) Nationwide Inpatient Sample (NIS), Release 1, as the database. Patients and participants: The study population was selected from all 1988 and 1992 discharges of patients that were >=10 years of age; had an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic code of 295.00 to 295.95, indicating schizophrenia as the primary diagnosis; were hospitalised between 1 and 40 days; and had Medicare, Medicaid, or private insurance, inclusive of fee-for-service or managed care, identified as the primary source of insurance coverage. The final sample used for this analysis consisted of 22 479 discharges from 1988, and 33 969 discharges from 1992. Main outcome measures and results: After adjusting for potentially confounding factors, the mean hospital length of stay for schizophrenia decreased by over 1 day (from 10.1 to 9.0; pPharmacoeconomics, Schizophrenia, Cost-analysis, Hospitalisation, Reimbursement

Trends in the Rate of Self-Report and Diagnosis of Erectile Dysfunction in the United States 1990-1998: Was the Introduction of Sildenafil an Influencing Factor?

Objective: To present the pattern of self-report and diagnosis of erectile dysfunction in the US over the time period 1990 through 1998 and examine whether the introduction of sildenafil in March 1998 influenced these findings. Study design and methods: Retrospective database analysis. Data from the National Ambulatory Medical Care Survey (NAMCS) for the years 1990 through 1998 were used. Data from office-based physician-patient encounters for which either a complaint of erectile dysfunction as one of the reasons for requesting an encounter [National Center for Health Statistics (NCHS) code 1160.3] or a diagnosis of erectile dysfunction [International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 302.72 or 607.84] was documented were extracted for men aged >=40 years. National estimates per year were derived for: 1. the number of office-based physician-patient encounters for which a complaint of erectile dysfunction was documented as a reason for requesting an encounter and the number of office-based physician-patient encounters for which a diagnosis of erectile dysfunction was documented; 2. the rate per 1000 office-based physician-patient encounters for which a complaint of erectile dysfunction as a reason for requesting the encounter was documented and the rate per 1000 office-based physician-patient encounters for which a diagnosis of erectile dysfunction was documented; and 3. the rate per 1000 US male population aged >=40 years with a complaint of erectile dysfunction as a reason for requesting an encounter and the rate per 1000 US male population aged >=40 years with a diagnosis of erectile dysfunction. Results: The number of office-based physician-patient encounters for which a complaint of erectile dysfunction was documented increased from 764 682 in 1990 to 1 273 730 in 1998. The number of office-based physician-patient encounters with a recorded diagnosis of erectile dysfunction more than doubled over the time period examined, from 647 418 in 1990 to 1 495 793 in 1998. Office-based encounters for which a complaint of erectile dysfunction was documented as a reason for requesting an appointment increased from 5.7 per 1000 in 1990 to 7.0 per 1000 in 1998; the rate of diagnosis of erectile dysfunction increased from 4.8 per 1000 in 1990 to 8.2 per 1000 in 1998. The population-adjusted rate of complaint of erectile dysfunction increased from 17.5 per 1000 in 1990 to 24.2 per 1000 in 1998; the rate of diagnosis increased from 14.9 per 1000 in 1990 to 28.4 per 1000 in 1998. In 1998, 2 142 776 office-based physician-patient encounters documented the prescribing of sildenafil; of these, 41% were for patients with a recorded diagnosis of erectile dysfunction. Conclusions: The introduction of sildenafil was found not to have influenced the established upward trend in the documented rate of self-report of erectile dysfunction or the diagnosis of erectile dysfunction. However, the prescribing of sildenafil appears to offer greater insight into the actual magnitude of the problem erectile dysfunction represents in the US. Findings suggest there is a reluctance on the part of patients to discuss concerns about erectile dysfunction with their physician and a reluctance on the part of physicians to document patients' expressed concerns regarding erectile dysfunction and/or to record a diagnosis of erectile dysfunction.Erectile dysfunction, Erectile dysfunction, Pharmacoeconomics, Sildenafil