How to switch from morphine or oxycodone to methadone in cancer patients? a randomised clinical phase II trial.

AIM: Opioid switching is a treatment strategy in cancer patients with unacceptable pain and/or adverse effects (AEs). We investigated whether patients switched to methadone by the stop and go (SAG) strategy have lower pain intensity (PI) than the patients switched over three days (3DS), and whether the SAG strategy is as safe as the 3DS strategy. METHODS: In this prospective, open, parallel-group, multicentre study, 42 cancer patients on morphine or oxycodone were randomised to the SAG or 3DS switching-strategy to methadone. The methadone dose was calculated using a dose-dependent ratio. PI, AEs and serious adverse events (SAEs) were recorded daily for 14 days. Primary outcome was average PI day 3. Secondary outcomes were PI now and AEs day 3 and 14 and number of SAEs. RESULTS: Twenty one patients were randomised to each group, 16 (SAG) and 19 (3DS) patients received methadone. The mean preswitch morphine doses were 900 mg/day in SAG and 1330 mg/day in 3DS. No differences between groups were found in mean average PI day 3 (mean difference 0.5 (CI -1.2-2.2); SAG 4.1 (CI 2.3-5.9) and 3DS 3.6 (CI 2.9-4.3) or in PI now. The SAG group had more dropouts and three SAEs (two deaths and one severe sedation). No SAEs were observed in the 3DS group. CONCLUSION: The SAG patients reported a trend of more pain, had significantly more dropouts and three SAEs, which indicate that the SAG strategy should not replace the 3DS when switching from high doses of morphine or oxycodone to methadone.

Clinical pharmacology of methadone for pain.

BACKGROUND: This topical review addresses methadone's pharmacology, its application in malignant and non-malignant pain conditions, practical issues related to methadone for the treatment of pain and its influence on QTc time. METHODS: Relevant papers were identified in PubMed and EMBASE. RESULTS: Methadone is advocated by experts as a second line opioid when first line opioids fail to provide a satisfactory balance between pain control and side effects (opioid switching). Although randomized-controlled studies are lacking, current evidence suggests that switching to methadone in this situation reduces pain intensity. However, interindividual variability in its pharmacokinetics make its application challenging and metabolism by CYP 3A4 and 2B6 implies a substantial risk of drug-drug interactions. Several ways of switching to methadone have been presented, with a gradual switch during 3 days or 'stop and go' as the dominating strategies. Episodes of torsade de pointes arrhythmia during methadone treatment have been reported in patients with other risk factors for arrhythmia, while small prospective studies have reported a small, lasting and stable increase in QTc time. The extensive use of methadone for opioid replacement in addicts has added additional patient barriers to its use for pain control. CONCLUSION: In spite of challenges related to the variable pharmacokinetics and concerns regarding increase in QTc time, current evidence indicates that opioid switching to methadone improves pain control in a substantial proportion of patients who are candidates for opioid switching. Measures must be instituted to secure that patients receiving methadone for pain are not considered opioid addicts.

[Geriatric psychiatry--a specialty gaining recognition]. / Alderspsykiatri--et fagfelt som finner sin plass.

Services for elderly, mentally ill people have developed in response to changing needs in society. In 1990 most of the 650 beds allocated to elderly patients in psychiatric hospitals were occupied by long-term care patients. Outpatient programmes hardly existed. In 1995 about 400 beds were allocated to geriatric psychiatry. They were served by 40 physicians and 20 psychologists. Out-patients' clinics were established. Most of the in-patients were short-term admissions. Nowadays, departments of geriatric psychiatry define themselves as diagnostic and short-term units. About a third of the in-patients suffer from dementia, a third from depression, and a third from various other psychiatric disorders. The authors recommend that a special unit for geriatric psychiatry should be established in every county in Norway. Funds should be allocated for professorships at all universities.

[Geriatric psychiatry--a specialty within psychiatry]. / Alderspsykiatri--en spesialisert form for psykiatri.

The aim of this article is to describe the prevalence of mental disorders in the elderly and how the psychiatric services for these patients ought to be organized in Norway. Geriatric psychiatry is a special branch of psychiatry. Its areas of concern are the assessment and treatment of mental disorders which frequently occur in the elderly. The most prevalent psychiatric disorders are depression and dementia. Functional psychosis and anxiety disorders are less prevalent, but nevertheless disorders causing great concern. Psychiatric morbidity frequently coexists with physical illness. An elderly patient suffering from a mental disorder often has a combination of psychological, social and physical needs. The resources allocated to psychiatric services for old people are scarce. Efforts should be made to establish a special unit for geriatric psychiatry in every county in Norway. Each unit should serve approximately 150-200,000 inhabitants, and should consist of both an in-patients' and an out-patients' clinic. It is recommended that there should be 1 to 1.5 beds per 1000 elderly aged 65 years and over.

A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients.

A total of 115 elderly patients (60-85 years of age) with DSM III diagnosis of major depressive episode were randomly assigned to 6 weeks of treatment with either mirtazapine, 15-45 mg/day, or amitriptyline, 30-90 mg/day. Efficacy was assessed biweekly, using the Hamilton Rating Scale for Depression (HRSD) and Montgomery and Asberg Depression Rating Scale (MADRS) as primary outcome variables. The treatment with both drugs resulted in a similar reduction of total HRDS and MADRS scores, with no statistically significant differences between treatment groups at any assessment point or at endpoint. Statistically significant differences favouring amitriptyline were present according to CGI-Global Improvement Scale at endpoint, HRDS cognitive disturbance factor at weeks 2, 4 and 6 and endpoint and retardation factor at week 6. Adverse events were reported by a similar number of patients in both treatment groups. Additional research is needed to assess further the efficacy and tolerability of mirtazapine among elderly depressed patients.

[Psychiatry for the elderly--a specialty field in progress]. / Psykiatri for eldre--et fagfelt i utvikling.

Services concerned specially with elderly people who are mentally ill have developed in response to changing needs and expectations in society. In Norway, more than 600 beds in psychiatric hospitals are allocated to geriatric psychiatry (gerontopsychiatry), and are served by 20 senior registars and 19 psychiatric trainees. There are hardly any outreach programmes. Most of the beds in the hospitals are occupied by long-term psychiatric patients. There is little consensus as to what type of patients these beds should primarily serve. The authors recommend that a special unit to deal with geriatric psychiatry be organized in every county in Norway. Funds should also be allocated for professorships in this field.

Effect of selenium on sheep lymphocyte responses to mitogens.

The effect of selenium (Se) on sheep lymphocyte response to mitogens was studied. In an indoor experiment lambs were fed a basal diet containing 0.13 mg Se kg-1, and supplemented with, respectively, 0.1 or 0.5 mg Se kg-1, either as sodium selenite or as selenomethionine. Enhancement of the proliferative response of lymphocytes to phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A was found in lambs following selenium supplementation at the lower levels. The highest dietary selenium content, however, induced decreased mitogen response. Transient increases in lymphocyte response to PHA and PWM by ewes supplemented with selenium was demonstrated in one field study and a combined effect of selenium and vitamin E was seen in another. There was no stimulatory effect on the mitogen response of lymphocytes from sheep supplemented with dietary vitamin E alone.

Influence of selenium on antibody production in sheep.

Three experiments were carried out, using sheep fed a marginally low selenium diet, to study the effect of selenium supplementation on the antibody response to tetanus toxoid and on the serum IgG concentration. Six groups of three six-month-old lambs were fed a basal diet containing 0.13 mg Se kg-1 supplemented with either 0.1, 0.5 or 1.0 mg Se kg-1, as sodium selenite or as selenomethionine. These animals generally showed enhanced antibody response to tetanus toxoid, parainfluenza-3 virus and Corynebacterium pseudotuberculosis, and their total serum IgG concentrations were higher than in unsupplemented control animals although few responses were statistically significant. In two field studies significantly higher titres to tetanus toxoid were detected in ewes injected with 100 mg selenium as barium selenate, although no influence on serum IgG concentrations was detected. Lambs from selenium supplemented ewes had significantly higher titres to tetanus toxoid than lambs from ewes in the control group. Dietary vitamin E supplementation had a similar effect on the antibody response to tetanus toxoid in ewes, though no additive effect was seen when vitamin E was given together with selenium.