Lessons from the Literature

Volume 23, Number 7: July 2022

IAHPC Research Advisor Dr. Tania Pastrana selects one article from recently published medical literature and describes why it is worthwhile.

Under My Microscope

Dr. Tania Pastrana. Used with permission.

By Dr. Tania Pastrana
IAHPC Research Advisor

Pharmacovigilance in Hospice/Palliative Care: Net Effect of Amitriptyline or Nortriptyline on Neuropathic Pain: UTS/IMPACCT Rapid programme international consecutive cohort

Hussein A, Digges M, Chang S, Hunt J, Doogue M, Rowett D, Agar M, Sinnarajah A, Kain D, Allan S, Boland JW, Currow DC. Palliat Med 2022: 36(6); 938-944. DOI: 10.1177/02692163221085855

Neuropathic pain affects a majority of patients receiving palliative care. It causes distress and is associated with worsened treatment responses, which make treatment challenging. Because it is cost-effective, amitriptyline is listed as an essential medicine for pain and palliative care and belongs on the analgesic ladder at any stage.

This Australian study, led by Akram Hussein, quantified effectiveness and predictive factors for benefit and harm from amitriptyline or nortriptyline for neuropathic pain in palliative care with an international, prospective, consecutive cohort. The team recruited 150 patients with neuropathic pain diagnosed by clinicians at 21 sites in six countries: 110 were treated with amitriptyline and 40 were treated with nortriptyline.

The authors found that 43% of patients using amitriptyline and 19% of those using nortriptyline reported reduced pain within two weeks, while both medications showed similar rates of harms (dizziness, dry mouth, constipation, urinary retention). They concluded that amitriptyline was more effective than nortriptyline in the short-term reduction of neuropathic pain.

Their low cost make amitriptyline and nortriptyline good medications in low- and middle-income countries for this tricky symptom. Novel alternatives, such as much more expensive epidermal growth factor receptor (EGFR) inhibitors, have been proposed to treat patients with neuropathic pain.1 If you have treated neuropathic pain, I would love to hear about your experience.

  1. Cameron MG, Kersten C. Prospective Case Series of Neuropathic Cancer Pain in Patients Treated with an EGFR-inhibitor. Palliat Med 2002 (online). DOI: 10.1177/02692163221102003

Link to article

Background: Real-world effectiveness of interventions in palliative care need to be systematically quantified to inform patient/clinical decisions. Neuropathic pain is prevalent and difficult to palliate. Tricyclic antidepressants have an established role for some neuropathic pain aetiologies, but this is less clear in palliative care.

Aim: To describe the real-world use and outcomes from amitriptyline or nortriptyline for neuropathic pain in palliative care.

Design: An international, prospective, consecutive cohort post-marketing/phase IV/pharmacovigilance/quality improvement study of palliative care patients with neuropathic pain where the treating clinician had already made the decision to use a tricyclic antidepressant. Data were entered at set times: baseline, and days 7 and 14. Likert scales graded benefits and harms.

Setting/participants: Twenty-one sites (inpatient, outpatient, community) participated in six countries between June 2016 and March 2019. Patients had clinician-diagnosed neuropathic pain.

Results:One hundred and fifty patients were prescribed amitriptyline (110) or nortriptyline (40) of whom: 85% had cancer; mean age 73.2 years (SD 12.3); mean 0-4 scores for neuropathic pain at baseline were 1.8 (SD 1.0). By day 14, doses of amitriptyline were 57 mg (SD 21) and nortriptyline (48 mg (SD 21). Fifty-two (34.7%) patients had pain improvement by day 14 (amitriptyline (45/110 (43.3%); nortriptyline (7/40 (18.9%)). Thirty-nine (27.7%) had new harms; (amitriptyline 29/104 (27.9%); nortriptyline 10/37 (27.0%); dizziness (n = 23), dry mouth (n = 20), constipation (n = 14), urinary retention (n = 10)). Benefits without harms occurred (amitriptyline (26/104 (25.0%); nortriptyline (4/37 (10.8%)).

Conclusions: Benefits favoured amitriptyline while harms were similar for both medications.

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Encouraging Research Results

Trends analysis of specialized palliative care services in 51 countries of the WHO European region in the last 14 years. Palliat Med 2022; 34(8): 1044-56. DOI: 10.1177/0269216320931341

Forty-two countries (82%) increased the number of specialized services between 2005 and 2019 with changes for home care teams (104% increase-rate), inpatient services (82%), and hospital support teams (48%). High-income countries showed significant increase in all types of services (p < 0.001), while low-to-middle-income countries showed significant increase only for inpatient services. Central–Eastern European countries showed significant improvement in home care teams and inpatient services, while Western countries showed significant improvement in hospital support and home care teams. Home care was the most prominent service in Western Europe.

Advancing Global Palliative Care Over Two Decades: Health System Integration, Access to Essential Medicines, and Pediatrics. J Pain Symptom Manage 2022; 64(1): 58-69. DOI: 10.1016/j.jpainsymman.2022.03.001

Major progress has been made in the integration of palliative care into public health systems, access to controlled medicines, and pediatric palliative care. Whereas in 2000, integration of palliative care into public health care systems was on the agenda in just a few pioneering countries, by 2020 a global consensus had emerged that palliative care should be integral to all health systems including in universal health coverage and countries were increasingly taking steps to integrate it into national health systems. While limited availability of these medicines was barely recognized as a public health or drug control issue in 2000, it had become an important priority in global drug policy debates by 2020 and numerous countries had taken steps to improve access to these medicines. Pediatric palliative care, available mostly in a small number of wealthy countries in the 1990s, has seen rapid growth, especially in low- and middle-income countries, and now has a solid foothold in all world regions.

Face and Content Validity, Acceptability, Feasibility, and Implementability of a Novel Outcome Measure for Children with Life-Limiting or Life-Threatening Illness in Three Sub-Saharan African Countries. Palliat Med 2022: published online June 2. DOI: 10.1177/02692163221099583

The Children's Palliative Care Outcome Scale (C-POS) is the first measure developed for children with life-limiting and -threatening illness. C-POS items capture the core symptoms and concerns that matter to children and their families; it is feasible, comprehensible, and acceptable for use in clinical settings. Areas for further development and improvement are identified.

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