A Systematic Review of the Evidence for the Efficacy of Opioids for Chronic Non-

cancer Pain in Community-dwelling Older Adults

Michael David Cory O'Brien; Anne Pamela Frances Wand

DISCLOSURES 
Age Ageing. 2020;49(2):175-183

Abstract and Introduction

Abstract
Introduction: the ageing global population and concomitant increase in the use of opioid
analgesia have highlighted the need to evaluate the effectiveness of opioids for chronic pain
in older people.
Methods: a systematic review of the evidence for the efficacy of opioids for chronic non-
cancer pain in community-dwelling people aged 65 years or more was conducted using
PRISMA guidelines. The databases MEDLINE, EMBASE, Pubmed and PsychINFO were
searched. The quality of studies was assessed. Secondary aims were to assess correlates of
opioid use and the decision-making processes of prescribers.
Results: seven studies were identified of low to high quality. The majority of older people
experienced ongoing pain despite continuing opioid therapy. There were mixed results
regarding benefits of opioids in terms of activities of daily living and social engagement. In
nursing home residents, opioid use at baseline was associated with severe pain, severe
impairment in activities of daily living and a diagnosis of depression. Fear of causing harm to
older people was common amongst opioid prescribers, limiting prescription. Facilitators of
opioid prescription included educational interventions and access to an evidence base for
opioid use.
Conclusion: there is limited evidence supporting the use of long-term opioid use in older
people for chronic non-cancer pain and a lack of trials in this age group. Age-specific
guidelines are required addressing initial assessment, indications, monitoring and de-
prescribing.

Introduction
Chronic pain is common in older people occurring in 45–85%.[1] With an ageing population,
the management of chronic pain represents a major public health challenge. There is
considerable associated morbidity, as inadequate treatment may result in reduced quality of
life, social withdrawal, depression, sleep disturbance, cognitive impairment, disability and
malnutrition.[1]
Opioid therapy is widely used to treat long-term cancer pain, [2] although the evidence for
effectiveness for improving chronic pain and function is insufficient. [3] Despite this, the
prescription of opioids for chronic pain has dramatically risen. In the USA, the number of
opioid prescriptions supplied to older patients between 1996 and 2010 increased nine times.[4]
The adverse effects of opioid therapy are well known, including falls and fractures, cognitive
impairment and gastrointestinal problems.[5] Additionally, there has been an increase in the
prevalence of opioid overdose, abuse, addiction and diversion.[3] Other considerations in older
people include the significant changes in the pharmacokinetics and pharmacodynamics,
greater likelihood of polypharmacy—increasing the likelihood of drug interactions, and
medical comorbidities contributing to drug–disease interactions.[6] These potential harms
combined with the scale of use of opioids suggest the need for more targeted and evidence-
based treatment of chronic pain in older people, yet specific guidelines are lacking.[7]
The purpose of this review was to investigate the evidence for the efficacy of opioids for
chronic non-cancer pain in community-dwelling adults aged 65 years or more. Secondary
aims were to evaluate correlates of opioid use and decision-making processes for opioid use
by prescribers.

Methodology

Search Strategy
A literature search was conducted using MEDLINE, EMBASE, Pubmed and PsychINFO
databases until October 2018. Search terms used were [opioids OR narcotics] AND [(elderly
OR aged OR geriatric)] AND [(effectiveness OR efficacy OR benefit)] AND [non-cancer]
AND [pain] (See Appendix 1).

Inclusion Criteria
Studies were included if conducted in outpatient or community settings including primary
care, outpatient clinics, domiciliary settings and residential aged care facilities. Papers were
in English language and published between 2003 and October 2018. The focus was upon
adults aged 65+ with non-cancer pain that was chronic in duration (defined as >3 months).
[3]
 Only original research was included. The reference lists of included papers were hand-
checked to identify additional articles.

Exclusion Criteria
Studies conducted in inpatient hospital or hospice settings, reviews, discussion papers, letters
and single case reports were excluded. The grey literature was excluded. Alternative
indications for opioids such as acute pain or secondary to malignancy were excluded.
Prevalence studies and research only investigating harms of opioids were not the focus of this
review, and therefore excluded. Studies which combined data from older and younger adults
but did not perform a separate subgroup analysis for older people were excluded.

Assessment of Quality
The validated Standard Quality Assessment criteria guidelines were used to evaluate the
quantitative papers.[8] Fourteen items are scored depending on the degree to which the
specific criteria are met (yes = 2, partial = 1, no = 0). Items not applicable to a certain study
were marked 'n/a' and were excluded from the calculation of the total. The total is expressed
as an overall percentage. Qualitative articles were evaluated using the Quality appraisal
checklist devised by Attree and Milton.[9] This checklist addresses methodological rigour
under various subheadings including study design, sampling, data collection, analysis and
findings, reflexivity, value and ethics. A quality scoring system ranging from A (no or few
flaws), B (some flaws), C (considerable flaws, but the study still had some value) to D
(significant flaws that threaten the validity of the whole study) was assigned for each
subheading. An overall quality score (A–D) is then assigned to the article.

Data Extraction and Synthesis

All abstracts identified in the initial database search were screened against the inclusion
criteria by the first author. The full text of included papers were independently reviewed by
both authors who assessed eligibility for inclusion. Disagreement was resolved through
discussion until consensus reached.
A systematic review was then conducted using the PRISMA approach.[10] A standardised data
extraction form was used by both authors to gather the following information from included
studies: (i) study characteristics; (ii) reported outcomes; (iii) methodological strengths and
limitations and (iv) overall assessment of methodological quality.

Results

Details of the search process are displayed in a PRISMA flowchart (Figure 1). However, 943
studies were identified through database searches and 13 additional papers from alternative
sources. Seven papers met inclusion criteria.
Characteristics and Methodology of the Selected Studies
A summary of the included studies, key findings and quality assessment are displayed
in Table 1. The full detailed Table comparing the studies is available via the online
supplement. Two studies were set in residential aged care facilities, [11,12] and the remaining
five in community settings.[13–17] Four studies were cross-sectional in design, [13–16] two were
prospective[11,12] and one was a retrospective chart review. [17] There was one qualitative study
employing focus group interviews[16] and one mixed methods study with a minor qualitative
component.[13] Sample size ranged from 10 to 10,372. All of the quantitative papers measured
pain using individual-validated scoring tools and all were self-report. [11–15,17] Three studies
examined the correlates of opioid use.[12,14,16] One study examined the decision-making
processes for opioid prescribers.[16] Additional outcomes such as quality of life and function
were assessed in three studies.[12,13,15] Cognition and depression were assessed in two studies.
[12,15]

Primary Aim: Efficacy of Opioids

Community Dwellers. Pain Relief: A small cross-sectional community study of 21 people
showed that 73% of participants reported pain relief after taking opioids. [13] However, opioid
use was not associated with pain intensity, and on average, the majority of people still
experienced moderate levels of pain, despite taking regular opioids.[13] Half of the participants
self-discontinued opioid therapy when they felt pain was well controlled. Two subjects
reported overusing prescribed opioids in an attempt to manage persistent pain. Amongst 652
community-dwelling individuals suffering chronic osteoarthritis of the knee/hip, people with
severe osteoarthritis were more likely to be taking opioids, and despite this, reported ongoing
severe pain.[14] One chart review of 10 retrospective cases attending a tertiary-care pain
program showed a reduction in the average Numeric Pain Scale rating from 6.35 to 2.95 in
carefully selected patients (people without contraindications and who were cognitively and
physically able to take opioids or supervised).[17] A cross-sectional study investigating 115
older adults with dementia found that people with significant cognitive impairment and older
age were more likely to experience untreated pain. [15] Few patients were using weak opioids
and none were using strong opioids. Of those, three (15%) had ongoing pain, despite regular
use of opioids.[15] All studies concluded that analgesia was underutilized and sub-therapeutic
according to local recommendations.
Physical Functioning: In chronic osteoarthritis pain, adherence with opioid medication was
significantly related to pain interference with sleep, but not other daily activities or pain
intensity.[13] Opioid use did not improve general activity, mood, walking ability or
relationships.

Residential Care
An observational cohort study assessed analgesia use and prevalence of pain across a 6-
month period in 350 nursing home residents.[11] Despite the use of regular analgesia,
including non-opioid formulations, there was no change in pain symptoms from baseline to 6
months follow-up.[11] A longitudinal observational study of 10,372 nursing home residents
over the age of 65 years did report pain symptoms, but reported significant improvement in
activities of daily living (ADL) and social engagement in those taking long-acting opioids
compared to short acting.[12] Although the sample size was large, the total number of opioid
prescriptions was low (short acting 18.9%, long acting 3.3%) and results were confounded by
concurrent non-opioid analgesics.[12]

Secondary Aims
Correlates of Opioid use. Opioid use was more likely in people with severe osteoarthritis
pain, a history of coronary artery disease or cancer; however, in post hoc analysis, the
majority of people with severe osteoarthritis pain did not have a history of cancer.
  Amongst nursing home residents, opioid use at baseline was associated with daily pain,
[14]

severe pain, severe ADL impairment and a diagnosis of depression.[12]

Decision-making Processes of Opioid Prescribers. A methodologically robust qualitative
study utilised a number of focus groups assessing clinicians' opinions on opioid prescription.
Forty-two percent of participants suggested that opioids were effective when used in the
'right' older person; i.e. those who can understand the regimen and can anticipate the side
effects.[16] Fear of causing harm was the main barrier to opioid prescribing (secondary to
anecdotal accounts of adverse outcomes), along with inability to establish the aetiology of
pain. Facilitators for opioid prescription included patient and caregiver educational
interventions and having access to well-conducted studies demonstrates evidence for opioid
use, including validated tools for calculating initial opioid doses.

Assessment of Quality
The quality of the quantitative studies ranged between 41 and 86% with a mean score of
58.3% (Table 1). The single qualitative paper received the highest quality rating of A.[9]
Discussion

The literature evaluating the efficacy for opioid therapy for chronic non-cancer pain in
community-dwelling older people was reviewed. Seven studies were identified. Three studies
demonstrated partial pain relief with opioid use,[11,13,17] albeit two in very small samples,
[13,17]
 one of which was significantly methodologically flawed, [17] whilst four studies showed
that pain persisted despite use of regular opioids.[11,13–15] In all studies, analgesia dosing was
assessed as inadequate according to local guidelines. Only one study evaluated opioid use and
quality of life, and few considered related measures such as mood and enjoyment.

Efficacy of Opioids
A small well-designed study demonstrated some benefits from opioids for chronic back,
spinal or arthritis pain.[13] However, patients self-regulated use by stopping opioid therapy
when pain was well controlled, or took opioid doses larger than prescribed due to persistent
pain. This may support opioid use for acute nociceptive pain and emphasise the need for de-
escalation and cessation. However, the sample size was 21 and there was no screening for
prior opioid misuse and/or consideration of comorbidities, which may impact efficacy.
Another small case series showed a reduction in average Numeric Pain Scale rating after low
dose oral morphine.[17] The majority (80%) of subjects suffered neuropathic pain and were co-
administered a gabapentanoid agent. Further, patients were 'carefully selected' retrospectively
in this study of low methodological quality, with limited generalisability. Efficacy amongst
community-dwelling older people with cognitive impairment was limited, with most subjects
reporting ongoing pain despite opioid use.[15] Similarly, in those suffering chronic
osteoarthritis, persistent pain was present notwithstanding long-term opioid use. [14] These
findings were consistent across studies with quality limited by exclusive reliance upon self-
reporting pain tools and cross-sectional design. A validated scale such as the Brief Pain
Inventory may be more comprehensive in measuring the impacts of chronic pain. [18] Efficacy
of opioids in nursing home residents was limited with the majority of analgesic users at
baseline still reporting persistent pain, despite regular opioids. [11] The generalisability of
results was limited as people with serious cognitive impairment, speech and language
problems and severe physical illness were excluded.
The effect of pain on physical and psychological functioning may be most relevant to
patients[19] and yet was rarely evaluated. Improvement in function in terms of activities of
daily living and social engagement with long-term opioid use in nursing home residents was
demonstrated.[12] This study did not include residents taking pro re nata (PRN) opioids, opioid
doses or consider the possibility of patients having switched opioids previously due to
intolerability. Similarly, the opioid groups were small in number and confounded by
including non-opioid analgesics. These reported functional benefits[12] contrast with evidence
suggesting inadequate efficacy for opioids for chronic non-cancer pain in adults.[20]
There was limited evidence that opioid use significantly improved sleep quality in relation to
pain.[13] This possibly alludes to the sedating effect of opioid medications, and must be
considered together with data regarding nocturnal falls. [3] Despite improvement in
interference with sleep, there was no benefit with respect to quality of life in terms of mood,
social engagement, other daily activities or pain intensity. [13] This contrasted with another
study reporting long-term opioid use improved the quality of life and social engagement
amongst nursing home residents.[12] This aligns with younger adults, where the evidence for
improved physical, emotional or cognitive function with long-term opioid therapy is
inconclusive.[21]

Correlates of Opioid use

There were a number of associations with opioid use identified in this review. Opioid use was
more common in older people with severe osteoarthritis and a history of coronary artery
disease,[14] perhaps due to avoidance of non-steroidal therapy associated with cardiac side
effects.[14] This was a high-quality study (86%), controlling for many co-variants such as
physical activity, body mass index and exercise. [14] Opioid usage in nursing home residents
was seen in those with frequent and severe pain, limited function and depression.[12] This was
also reflected in a previous analysis of the same data set, showing the risk of depression and
use of concurrent antidepressants and benzodiazepines was increased in those experiencing
daily pain.[23] This is a concerning combination, with the harms of polypharmacy well
documented.[24]

Decision-making Processes in Opioid Prescribers

Caution with opioid prescription in older people was seen amongst experienced clinicians.
[16]
 Fear of adverse effects, supported by anecdotal accounts remained a key determinant for
opioid use. This concern is well founded, as a recent review found that opioids for chronic
pain are associated with increased risk of overdose, opioid abuse, fractures, myocardial
infarction and sexual dysfunction.[3] Factors facilitating the use of opioid prescription
included education amongst patients and caregiver as well as peer reviewed evidence to
support indications and advise safe dosing regimens.[16] However, most educational resources
do not focus on older people,[7] with clear implications for prescriber decision-making.

Implications for Research

The evidence for long-term opioid use for managing chronic pain at any age is limited. [25] In
contrast to the limited literature in older adults, a systematic review of opioids for chronic
pain in the general adult population identified 40 publications.[3] Opioids were not effective
and concerningly, no studies evaluated long-term (>1 year) outcomes related to pain, quality
of life, opioid abuse or addiction.[3] Although there are numerous guidelines for the
pharmacological management of chronic pain in younger adults, [20] there are few guidelines
for older people.[7,26] By contrast, the risk of harm with opioids are well reported in older
people.[27,28] Importantly, opioid prescribers' decision-making is influenced by the available
evidence and access to education.[16] To meet this gap, randomised controlled clinical trials
(RCTs) of older people are needed to directly investigate the effectiveness of opioids for pain
reduction, physical functioning, psychosocial well-being and quality of life. To assess these
aspects of effectiveness, opioids could be compared to simple analgesia in an RCT design for
a particular chronic pain condition e.g. osteoarthritis. A step-wise approach to de-prescribing
opioids could be evaluated using a methodology modelled upon studies examining de-
prescribing of antipsychotics in residential care residents, see for example. [29] Essential to
such studies is training facility staff on how to manage pain with individualised non-
pharmacological strategies and assessing participants before and at various time points after
incremental opioid de-prescribing. Such research could provide a paradigm shift in chronic
pain management, similar to what occurred in antipsychotic prescribing for behavioural and
psychological symptoms of dementia (BPSD).[29]
The natural history of opioid use remains unclear, including monitoring of opioid use and de-
prescribing practices. Clinicians may be reluctant to shift ingrained patterns of prescribing.
[16]
 Similar fears about de-prescribing were noted, but not realised, in landmark studies of the
management of BPSD in older adults.[30] Thus, longitudinal research directly evaluating the
outcomes of opioid de-prescribing in older people could have major implications for clinician
decision-making and patient safety. Additional qualitative research could further illuminate
why and when opioid therapy is commenced and in which settings, as well as prescriber
attitudes, knowledge and determinants of follow-up.
This review revealed that people with severe cognitive impairment are under-represented in
studies of opioid efficacy. This is important as there is emerging evidence for the use of
opioids in managing BPSD.[30] This indication for opioid use is interesting given the
intersection of BPSD, pain and agitation. One recent study demonstrated a reduction in
antipsychotic and benzodiazepine requirements in those prescribed opioids for pain,
[30]
 suggesting benefit and requiring replication.
The medico-legal ramifications of opioid prescribing have been understudied. The role of
prescription medications in unintentional deaths has been raised[28,31] and cases described
where prescribers were referred to a professional standards body.[32] Awareness of the
complex behaviours of opioid users and acknowledging self-awareness around clinician
fatigue and time pressures were highlighted. [32] Strategies to enhance prescribing for chronic
non-cancer pain include knowing your legal obligations, prescribing according to practice
guidelines, setting patient expectations early with clear boundaries, utilising patient education
and self-management tools, employing tools for pain assessment and reviewing treatment
plans regularly.[32] Therefore, the absence of clear guidelines for opioid prescription for
chronic non-cancer pain in older adults may render prescribers medicolegally vulnerable.
A novel (ageless) online management approach has been developed in response to the opioid
epidemic and could be adapted for older adults. For example, the American Medical
Association has online digital tools, addressing both education and treatment with opioids,
which engage audiences across multiple social media platforms whilst providing templates
and links for people to navigate and share their experiences with opioids. [33] This is an
innovative way to raise awareness and highlight concerns about opioid use.

Limitations
Despite an extensive search, there were few eligible papers. Another recent review of opioid
use in older adults identified additional studies.[34] However, many of these studies which
included older people combined their data with younger subjects (<65 years) without sub-
group analysis of their results according to age, and thus did not meet our inclusion criteria. It
has been emphasised that management recommendations cannot simply be extrapolated from
studies in younger cohorts.[6,26] The validity of the initial database screening process would
have been enhanced had both authors performed independent searches. Studies were limited
to those published in English, potentially missing other relevant studies and limiting
generalisability. This may be especially relevant as the pharmacokinetics and
pharmacodynamics of opioids varies in different cultural groups, with implications for
determining effective dosing regimens. The grey literature was excluded, which may have
resulted in publication bias.

Conclusion

There is limited evidence supporting the use of long-term opioid use in older people for
chronic non-cancer pain. The lack of robust trials in this population is problematic, especially
in light of the prevalence of use and significant associated harms. Research is urgently
needed to inform age-specific guidelines, which address considerations for initial assessments
of chronic pain, evidence-based indications for opioid use (i.e. which medical conditions),
and assessment of broader outcomes than just pain relief, such as function, mood, and quality
of life, adverse effects, procedures for monitoring and review of efficacy and procedures for
weaning and ceasing opioids safely.

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