Allan L, Hays H, Jensen NH, Le Polain de Waroux, B, Bolt M, Donald R, Kalso E. Br Med J 2001; 322:1-7

Prepared by: : Dr. Peter Lawlor

Received during: Journal Club on the Tertiary Palliative Care Unit, Grey Nuns Hospital

Abstract:

Objectives: to compare patients' preference for transdermal fentanyl or sustained release oral morphine, their level of pain control, and their quality of life after treatment.
Design: Randomised, multicentre, international, open label, crossover trial Setting: 35 centres in Belgium, Canada, Denmark, Finland, the United Kingdom, the Netherlands, and South Africa.
Participants: 256 patients (aged 26-82 years) with chronic non-cancer pain who had been treated with opioids.
Main outcome measures: Patients' preference for transdermal fentanyl or sustained release oral morphine, pain control, quality of life, and safety assessments.
Results: Of 212 patients, 138 (65%) preferred transdermal fentanyl, whereas 59 (28%) preferred sustained release oral morphine and 15 (7%) expressed no preference. Better pain relief was the main reason for preference for fentanyl given by 35% of patients. More patients considered pain control as being "good" or "very good" with fentanyl than with morphine (35% v 23%, P=0.002). These results were reflected in both patients' and investigators' opinions on the global efficacy of transdermal fentanyl. Patients receiving fentanyl had on average higher quality of life scores than those receiving morphine. The incidence of adverse events was similar in both treatment groups; however, more patients experienced constipation with morphine than with fentanyl (48% v 29%, P=0.001). Overall, 41% of patients experienced mild or moderate cutaneous problems associated with wearing the transdermal fentanyl patch, and more patients withdrew because of adverse events during treatment with fentanyl than with morphine (10% v 5%). However, within the subgroup of patients naïve to both fentanyl and morphine, similar numbers of patients withdrew owing to adverse effects (11% v 10%), respectively).
Conclusion: Transdermal fentanyl was preferred to sustained release oral morphine by patients with chronic non-cancer pain previously treated with opioids. The main reason for preference was better pain relief, achieved with less constipation and an enhanced quality of life.

Comments:

Strengths/uniqueness: This is a randomized, crossover study that also incorporated a measure of quality of life.

Weakness:Unfortunately, owing to some pragmatic reasons, this study did not incorporate blinding and a double-dummy feature. It is, therefore, possible that the placebo effect associated with applying the patch could have contributed substantially to the greater preference for this treatment. One wonders whether the preference would be as great for fentanyl if both opioids had achieved the same level of pain control. The patients were not asked directly why they preferred fentanyl over morphine, but the authors inferred that their preference was due to a better quality of life, as reflected in the quality of life assessment scores.

Relevance to Palliative Care: It must be emphasized that the patients in this study had chronic non-malignant pain. Despite this, the finding of less constipation in the fentanyl treated group is in keeping with findings from studies in cancer pain patients. It is clearly difficult to extrapolate findings from a non-cancer pain population to that of an end-of-life/palliative care population.

A cross-national study of the course of persistent pain in primary care.

Gureje O, Simon GE, Von Korff M. Pain 2001; 92:195-200.

Prepared by: : Dr. Robin Fainsinger

Received during: Journal Rounds on the Tertiary Palliative Care Unit, Grey Nuns Hospital

Abstract:

Data from the World Health Organization's study of psychological problems in general health care were used to examine the course of persistent pain syndromes among primary care patients. Across 15 sites in 14 countries, 3197 randomly selected primary care patients completed baseline and 12-month follow-up assessments of pain, other somatic symptoms, and anxiety and depressive disorders (the Composite International Diagnostic Interview), and an assessment of occupational role disability (the Social Disability Schedule). Of patients with a persistent pain condition at baseline, 49% had not recovered 12 months later. The probability of non-recovery varied significantly across study centers and was significantly associated with the number of pain sites at baseline. After adjustment for age, sex, and study centre, baseline anxiety or depressive disorder did not predict non-recovery of persistent pain. Among those without a persistent pain disorder at baseline, the rate of onset was 8.8% with a significant variability in risk across centres. The baseline characteristics predicting the onset of persistent pain disorder were psychological disorder, poor self-rated health, and occupational role disability. A persistent pain disorder at baseline predicted the onset of a psychological disorder to the same degree that a baseline psychological disorder predicted the subsequent onset of persistent pain. Persistent pain conditions are common among primary care patients, and the probability of resolution over 12 months is approximately 50%. We found a strong and symmetrical relationship between persistent pain and psychological disorder. Impairment of daily activities appears to be a central component of that relationship.

Comments:

Strengths/uniqueness: Multi-site, multi-cultural studies are time consuming and difficult to implement, making this 14 country pain study a commendable effort.

Weakness:It would have been interesting to read comments on clinical implications of the connection between persistent pain, pain onset and psychological and disability disorders.

Relevance to Palliative Care:This study highlights the need to consider disability/psychological impact on pain problems, and ensure psychological and rehabilitation support are not forgotten in our enthusiasm to use pharmacological management.

Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Downloadable PDF file

Eisenberg E, Lurie Y, Braker C, Daoud D, Ishay A. Neurology 2001;57:505-9

Prepared by: Dr. Sharon Watanabe

Received during: Journal Club on the Tertiary Palliative Care Unit

Abstract:

Objective: To study the efficacy of lamotrigine in relieving the pain associated with diabetic neuropathy.
Methods: The authors randomly assigned 59 patients to receive either lamotrigine (titrated from 25 to 400 mg/day) or placebo over a 6-week period. Primary outcome measure was self-recording of pain intensity twice daily with a 0 to 10 numerical pain scale (NPS). Secondary efficacy measures included daily consumption of rescue analgesics, the McGill Pain Questionnaire (MPQ), the Beck Depression Inventory (BDI), the Pain Disability Index (PDI), and global assessment of efficacy and tolerability. Results: Twenty-four of 29 patients (83%) receiving lamotrigine and 22 of 30 (73%) patients receiving placebo completed the study. Daily NPS in the lamotrigine-treated group was reduced from 6.4 +/- 0.1 to 4.2 +/- 0.1 and in the control group from 6.5 +/- 0.1 to 5.3 +/- 0.1 (p < 0.001 for lamotrigine doses of 200, 300, and 400 mg). The results of the MPQ, PDI, and BDI remained unchanged in both groups. The global assessment of efficacy favored lamotrigine treatment over placebo, and the adverse events profile was similar in both groups.
Conclusions: Lamotrigine is effective and safe in relieving the pain associated with diabetic neuropathy.

Comments:

Strengths/uniqueness:
This investigation fulfils all the key criteria for a well-designed study: randomisation, concealment of allocation, intent-to-treat analysis, balanced treatment group characteristics, and completeness of follow-up.

Weaknesses:
The study was conducted at a single centre and the number of subjects was relatively small. However, the results are consistent with two other small randomized double-blind placebo-controlled trials of lamotrigine conducted in patients with painful HIV-associated neuropathy and central post-stroke pain. The trial was supported by the manufacturer of the drug.

Relevance to Palliative Care: This study was conducted in a population of patients with chronic non-cancer pain, which limits applicability of the results to the palliative setting. Lamotrigine appears to be well tolerated. However, the titration process takes weeks. Therefore, lamotrigine would only be useful for palliative patients who are relatively early in the trajectory of their illness.

A Case Series of Patients Using Medicinal Marihuana for Management of Chronic Pain under the Canadian marihuana Medical Access Regulations. Downloadable PDF file

Lynch ME, Young J, Clark AJ. J Pain & Symptom Manage 2006; 32(5):497-501.

Prepared by: Dr. Doreen Oneschuk

Received during: Journal Rounds on the Tertiary Palliative Care Unit, November 16, 2006

Abstract
The Canadian Marihuana Medical Access Regulations (MMAR) Program allows Health Canada to grant access to marihuana for medical use to those who are suffering from grave and debilitating illnesses. This is a report on a case series of 30 patients followed at a tertiary care pain management center in Nova Scotia who have used medicinal marihuana for 1-5 years under the MMAR program. Patients completed a follow-up questionnaire containing demographic and dosing information, a series of 11-point numerical symptom relief rating scales, a side effect checklist, and a subjective measure of improvement in function. Doses of marihuana ranged from less than 1 to 5 g per day via the smoked or oral route of administration. Ninety-three percent of patients reported moderate or greater pain relief. Side effects were reported by 76% of patients, the most common of which were increased appetite and a sense of well-being, weight gain, and slowed thoughts. Limitations of the study include self-selection bias, small size, and lack of a control group. The need for further study using controlled trials is discussed along with an overview of the MMAR program.

Comments

Strengths/uniqueness:
One of limited studies that examines this topic. Interesting to know the dosing of marihuana used by chronic pain patients. A concise summary of the Canadian Marihuana Medical Access Regulations.

Weaknesses:
A case series with lack of a control group. Authors also identify small sample size and self selection bias. Validity and reliability of the questionnaire used, particularly in regards to functional change, is questioned. Patients were followed in the clinic 'at least annually'. Questionnaires were completed during follow-up appointments or were sent by mail, but exact frequency of completion per patient is not identified.

Relevance to Palliative Care:
A similar survey of marihuana use in patients with advanced cancer would be of interest. Timing/frequency of the assessment tools used in such a study would need to be altered to accommodate limited life spans.