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Pain management case studies
Pharmacy
ACC case studies no. 1 and 2 – November 2009
Produced by the Provider Engagement & Performance Unit,
Health Purchasing & Provider Relationships, ACC.
This case study has been recognised by the NZCP for continuing
education points for their pharmacist members.
The opinions expressed in this document are not necessarily the
official views of ACC.
Date of study: December 2008/January 2009
Date of report: November 2009
© ACC 2009
All rights reserved. No part of this document may be reproduced
in any form without written permission from ACC.
Contents
Case study 1 – Ankle Sprain
• Vignette
2
• Background
3
• Results and commentary
5
• Additional vignette information 1
13
• Additional vignette information 2
14
Case study 2 – Back Pain
22
• Vignette
22
• Background
23
• Results and commentary
25
Commentators
The commentary for these case studies is kindly provided by:
Cases 1, 2 Dr Linda Bryant
Clinical Advisory Pharmacist
Comprehensive Pharmaceutical Solutions
Dr Evan Begg
Professor of Clinical Pharmacology/Medicine
University of Otago, Christchurch
Acknowledgements:
ACC would like to acknowledge the assistance of:
The Members of the ACC Pharmaceutical Sector Liaison Group
The New Zealand College of Pharmacists
1
Case Study 1 – Ankle sprain
Vignette
Mrs Smith is a 75-year-old widow who hobbles in looking somewhat bruised and
battered and with plasters on her skinned hand, elbow and knee. Her ankle is slightly
swollen and tender, although it has reasonable movement. She says she tripped
about an hour ago when she misjudged the culvert outside her house and “made
a right mess” of herself. She is feeling a bit sore and her ankle is painful; however,
she has been to her general practice and been assured that it is just a sprain. As her
daughter is visiting this weekend (three days away) and wants to take her to the
garden show, she wants something to help her ankle and mobility.
You know Mrs Smith and have a record of her prescriptions. She takes:
Bendrofluazide
2.5mg mane
hypertension
Cilazapril
5mg mane
hypertension, heart failure
Frusemide
80mg mane
heart failure
Metoprolol CR
95mg mane
hypertension, post MI, heart failure
Aspirin
100mg mane
cardiovascular disease
Felodipine ER
10mg mane
hypertension
Simvastatin
40mg nocte
cardiovascular disease
Zopiclone
11.25mg nocte
sleep, especially since husband died 18 months ago
Amitriptyline
25mg nocte
unsure, but seems to help sleep
Omeprazole
10mg mane
GORD
Lactulose
10 – 20ml prn
constipation
Paracetamol
1g prn
osteoarthritis of the knee
Mrs Smith tells you her blood pressure is very good – just like a young person’s,
at about 120/70mmHg or less. She does get a little dizzy at times, so doesn’t want
anything that might make her “fuzzy”.
2
Background
Dr Linda Bryant
Mrs Smith is one of those people for whom medicines have accumulated over time.
Sometimes this occurs because there is a view that she is doing well and ‘don’t fix
what ain’t broke’. Sometimes this is exacerbated by a focus on risk factors such
as for cardiovascular events, and an attitude of ‘the lower the better’, which is not
necessarily the case for older people. People like Mrs Smith may present well, but
often will not readily mention some symptoms such as the dizziness and the falls
because perhaps she considers that this is a part of growing old. Unfortunately this
means that medicines may not be reviewed as they should and, as the person ages,
the dosages become excessive, and some medicines may not be necessary any more.
An outcome of this is the increased risk of falls.
While falls may result in non-fracture injuries such as head injuries and lacerations,
any internal injury, hip fractures in particular, can have a major detrimental impact
on the person’s mobility, independence, quality of life, general health status and
financial situation.1
Studies show that 17% of post-menopausal women are likely to suffer a hip fracture.
Of these there is a 10% early mortality, with 20% to 33% dying over the following 12
months.2, 3, 4 Morbidity is also high. Fifty per cent of women with a fractured hip are
unlikely to ever walk without assistance, and 25% will require long-term care.4, 5
Falls prevention is an issue that all pharmacists should be aware of. The ACC website
(www.acc.co.nz) has more information and resources regarding falls prevention, as
does the falls prevention strategy website.6
For Mrs Smith, the acute situation needs to be addressed – both the pain and her
concern about the time she is looking forward to spending with her daughter. Then
there is the rehabilitation time to be considered, and, in the longer term, prevention of
recurrence.
Dr Evan Begg
This is a not uncommon scenario of an elderly woman, presumably living alone, who
has tripped and fallen and has a ‘sprained ankle’. She has had another recent fall,
has been dizzy at times, and has a low recorded BP at present (for her age). Her past
history includes hypertension, CHF and an MI, for which she is on lots of medicines
(polypharmacy). Constipation and an apparent requirement for zopiclone and
amitriptyline complete a typical picture of prescribing for the elderly.
This case study illustrates both an acute management situation and opportunity for
future medicines rationalisation and falls prevention.
3
1.
Manage the acute problem:
•
make sure any wounds are clean and protected
•
re-examine the ankle to make sure the GP diagnosis of ‘sprain’ is fair, or
whether it needs further investigation (X-ray)
•
advise RICE, +/- physiotherapy or graded exercise plan (to stop stiffness
and to avoid DVT)
•
analgesia – paracetamol +/- codeine +/- low-dose NSAID
•
manage expectation of going to garden show in three days (or not!).
2. Some reasons for the acute problem:
•
postural hypotension – too much antihypertensive medication
•
background zopiclone and amitriptyline
•
probable variable compliance (everyone on this number of drugs is subject
to variable compliance).
3. Rationalise her current therapy and prevention of falls recurrence:
4
•
assess/avoid/handle postural hypotension
•
is her home dangerous for falls (e.g. two-storied)
•
reduce/rationalise drugs for hypertension – discuss with GP
•
reduce other drugs if possible (e.g. does she need simvastatin, zopiclone,
amitriptyline?)
•
attempt to withdraw zopiclone and amitriptyline in the long term –
discuss with client/GP
•
avoid constipating drugs (e.g. amitriptyline and felodipine). Codeine will
add to this problem
•
consider providing compliance aids – yellow card, pill organiser
•
provide medicine education – patient information leaflets/pharmacy
counselling.
Results and commentary
Total number of respondents n = 286
1
As there is no fracture, what non-pharmacological advice would you
give Mrs Smith?
response rate to question 1 – % of respondents
100%
Responded
No response
non-pharmacological advice – % of respondents
48%
49%
RICE
RICE plus other
3%
Other
Dr Linda Bryant
It is good to see virtually everyone advised RICE, and of the almost 50% who provided
further advice, there was a focus on Mrs Smith and her desire to attend the garden
show, and an indication of when to return to the general practitioner if there was no
improvement within 48 hours or a worsening of pain.
Some people added the ‘P’ to RICE, recommending Protection such as an ankle
support, which is also helpful.
With three days before the garden show, Mrs Smith had an opportunity to rest her
ankle and elevate it (ankle above her knee, above her hip). It would certainly have
been a good idea for her to use at least a walking stick for the garden show – or even a
wheelchair as was suggested, if it was a large garden show (three to four hours on her
feet).
For rehabilitation, Mrs Smith should also slowly improve her range of movement
with gentle pointing and flexing of her foot. Being 75, Mrs Smith can lose condition
(strength, balance, range of movement) very quickly, which increases her risk of
further falls and injury. She needs to have a balance between RICE for two to three
days and resuming gentle activity/muscle strengthening, as well as maintaining
cardiovascular health.
It is also important to remember that fear of falling is a risk factor for falling – and
Mrs Smith may have felt somewhat shocked and lost confidence. This is something
to check on in terms of Mrs Smith’s progress. A mild sprain requires about two to six
weeks before a return to full activity and a moderate sprain may take two to three
months. Mrs Smith’s activity level should be monitored.
The Pharmaceutical Society of New Zealand Self Care fact cards on Pain Relief and
Arthritis are very useful and provide good information, particularly as, in the acute
period when Mrs Smith may be a little ‘shaky’, she may not remember all your advice.
5
Table 1 and Chart 1 summarise the additional advice provided by respondents who
also recommended RICE.
table 1
RICE plus other 49.3%
Physical support
Pain mitigation strategies
16.4%
Use walking stick/crutches/hire wheelchair/postpone
garden visit
15.4%
Wear ankle support/ankle brace/support stockings
8.0%
Gentle massage/gentle movements involving ankle
7.3%
Rub Voltaren Emulgel/Antiflamme/Arnica on ankle for
swelling/bruising
2.8%
Regular paracetamol/increase paracetamol for pain relief
4.2%
Local treatment/(moist) heat/vibration treatment/
physiotherapy/ drink plenty of fluids
5.6%
Falls prevention measures/self-care card on sprains and
strains/sensible shoes
7.3%
Review after couple of days of RICE – if worse go to doctor/
physiotherapist
7.3%
Avoid Heat, Alcohol, Running, Massage (H.A.R.M.)
4.2%
Attend to skinned hand, elbow and knee/prevent infection
of grazes/abrasions
3.8%
Suggest vision/glasses check by optometrist/BP check/
medications review/mention dizziness to GP Informational advice
Other
chart 1: rice and other responses
40%
% of respondents
30%
15.4%
4.2%
20%
2.8%
3.8%
7.3%
10%
7.3%
4.2%
5.6%
7.3%
16.4%
8.0%
0%
Physical support
Pain mitigation
strategies
Note: Graph includes multiple answers.
6
Informational
advice
Other
Dr Evan Begg
Nearly everyone got the correct response – RICE, with very useful and varied
supportive suggestions. Good point about a wheelchair for the garden show, as
clearly her predisposition to falling will not have been alleviated by then. It would
be wise to counsel her that if she does not feel well enough, she may not be able to
attend the show. A slow and deliberate mobilisation strategy would also be helpful.
2
Would you recommend any pharmacological treatment to Mrs Smith?
response rate to question 2 – % of respondents
100%
Responded
No response
Recommend pharmacolgical treatment – % of respondents
92%
Yes
8%
No
Dr Linda Bryant
Yes, the option of having pharmacological treatment available is important, as almost
every respondent indicated. Some people are particularly stoic but it is important
to assure Mrs Smith that pain relief is important, both acutely and when she is
‘rehabilitating’. There is no benefit in being stoic and suffering unnecessary pain. It is
usually negotiating the choice of pain relief that is the issue.
Dr Evan Begg
It was no surprise to see that nearly 100% of pharmacists wanted her to have some
analgesia. This is appropriate.
7
3
If so, what pharmacological treatment would you recommend to
Mrs Smith?
response rate to question 3 – % of respondents
92%
8%
Responded
No response
chart2: recommended pharmacological treatment
100%
1% Possibly Panadeine®/codeine but with catution/no Panadeine®/codeine
6% Take paracetamol/possibly codeine but with caution
% of respondents
80%
60%
40% Continue/increase/
maximise paracetamol usage/
take her paracetamol
40%
20%
41% Take paracetamol/
recommend paracetamol
39%
22%
0%
Oral meds
Topical
products
(including
NSAIDs)
3%
Oral NSAIDs
Vitamin
(avoid/take with supplement
caution)
6%
Additional
information
sought
Dr Linda Bryant
Over one-third of pharmacists opted for paracetamol alone, which is a very safe,
cost-effective medicine, and it is likely that Mrs Smith will have some at home (given
her medication list). Getting Mrs Smith to take the paracetamol regularly for two
to three days will need to be negotiated. Suggesting that it will help her get to the
garden show, and she will be less ‘worn down’ by pain and broken sleep, will probably
convince her to try this. She should be assured that she only needs this intensity
of treatment for a few days (at least until after the garden show) and then she can
reduce the number of tablets according to her pain level.
Some recommended paracetamol plus codeine. The amount of codeine in the OTC
products is generally suboptimal, and can contribute to constipation, a condition that
Mrs Smith already seems to be prone to. The potential adverse effects outweigh any
extra benefit from the codeine.
8
About one in five pharmacists suggested using an oral NSAID, with some stipulating
with caution. Some specified to avoid completely. With the risk of exacerbating heart
failure and the ‘triple whammy’ (an ACE inhibitor + a diuretic + an NSAID)7 increasing
the risk of renal dysfunction, an NSAID should be avoided completely unless pain is
severe, in which case a general practitioner would be best to manage the potential
adverse effects by undertaking close monitoring of renal function and heart failure.
There is some debate about the use of NSAIDs in muscle injuries and little good
quality evidence of any benefit above regular paracetamol use, particularly for mild
to moderate sprains. There is also continuing debate about the use of NSAIDs
immediately after an acute injury, such as a sprain, inhibiting the role prostaglandins
have in helping healing.8 For Mrs Smith the risks would outweigh any potential extra
benefit over paracetamol.
Topical NSAIDs can be effective and safe as pain relief for sprains, but there is a
financial cost associated with this. Regular paracetamol dosing will provide similar
analgesia.
There were some recommendations for vitamin supplements. Vitamin D
(colecalciferol) is the important vitamin for reducing fracture risk in the older person
because as skin ages it is unable to absorb/convert sunlight to Vitamin D3 as
efficiently as young skin. The Auckland Bone Clinic recommends that people over 70
years receive Vitamin D. It is important to note that the dosage required is around
50,000iu (1.25mg) monthly, which requires a prescription.
The following venn diagram shows the overlap of pharmacological treatment
recommended by respondents.
venn diagram 1: recommended pharmacological treatments
Oral meds
119
(45.6%)
60
(23.0%)
35
16
(13.4%)
(6.1%)
Topical products
23
(8.8%)
Oral NSAIDs
4
4
(1.5%)
(1.5%)
9
Dr Evan Begg
Most respondents wanted to optimise paracetamol use. Recent FDA arguments9
have been to reduce paracetamol dosing in the elderly, rather than follow the usual
4gm per day for everyone. Her paracetamol clearance may be about half that of a 30
year old, so doses may need to reflect this (e.g. 500mg q6h). The New South Wales
Therapeutic Group Inc. has developed paracetamol use guidelines for in-hospital use.
These may be relevant to the community setting when determining dosing.10
Only a few (<6%) wanted to prescribe codeine in addition, and if so, with caution. It
would be useful to avoid codeine, considering her constipation, which might be worse
with immobility over the next few days.
It was interesting also that most respondents wanted to avoid NSAIDS. This is
rational on the surface (aggravation of BP and CHF, and the problems when given
with ACE inhibitor + two diuretics) but probably unnecessarily cautious, since she
is currently being overdiuresed, overtreated for hypertension, and having seriously
symptomatic postural hypotension. A few days of a low-dose NSAID (e.g. diclofenac
25mg bd or ibuprofen 200mg tds) in this situation is likely to assist the paracetamol
and avoid the need for codeine, and may even improve the postural hypotension.
The background omeprazole should cover GI worries also. It all depends on the
seriousness of the pain. If serious, then an NSAID might need to be considered (and
she should not contemplate attending the garden show).
The recommendations of a few regarding vitamin supplements are probably useful to
consider for the long term.
10
4
Why would you recommend this treatment?
response rate to question 4 – % of respondents
92%
8%
Responded
No response
The following venn diagrams show the overlap of why the pharmacological treatment
was recommended.
venn diagram 2: Why oral meds were recommended
Effective treatment
61
(26.5%)
12
45
(19.6%)
37
(5.2%)
(16.1%)
Safe treatment
34
(14.8%)
37
To prevent
adverse events
4
(16.4%)
(1.7%)
venn diagram 3: Why topical products were recommended
Effective treatment
32
(31.1%)
35
(34.0%)
2
14
(1.9%)
(13.6%)
Safe treatment
9
(8.7%)
10
To prevent
adverse events
1
(9.7%)
(1.0%)
11
venn diagram 4: Why Oral NSAIDs were recommended
Effective treatment
21
(35.6%)
6
(10.2%)
5
10
(8.5%)
(16.9%)
Safe treatment
9
(15.3%)
6
To prevent
adverse events
2
(10.2%)
(3.4%)
Dr Linda Bryant
The rationale for selecting a particular medicine, noted by the majority of
respondents, included good consideration of the safety of the medicine, and
avoidance of adverse effects. These are suitable considerations when balancing the
risk-benefit of a treatment.
Being 75 years old and on multiple medicines, Mrs Smith is at a high risk of adverse
effects and medicine interactions. Her cardiovascular condition, particularly her heart
failure, is at increased risk of exacerbation with NSAIDs. She also appears to be prone
to constipation (lactulose) and her zopiclone and amitriptyline may make her more
prone to the CNS effects of codeine.
There is also a need to consider the financial situation of a 75-year-old woman and,
along with safety and effectiveness, cost-effectiveness of treatment needs to be
considered.
Dr Evan Begg
This is a typical cost-benefit situation, as most respondents have noted. Overall it is
likely that optimising paracetamol, in the setting of RICE, will probably be adequate
for pain relief. If more analgesia is required, then a couple of days of a low dose of a
low-toxicity NSAID (ibuprofen or diclofenac) would be better tolerated than codeine.
12
Additional vignette information 1
During the course of your conversation Mrs Smith tells you that she also had quite
a nasty fall a few months ago. Again, she did not fracture anything as a result of
this incident, but did end up with a number of bruises.
What non-pharmacological advice would you now give Mrs Smith given
that this is not the first time she has had a fall?
(Hint: look at ACC website for information on falls prevention and referral into the Tai
Chi programmes on www.acc.co.nz)
response rate to question 5 – % of respondents
99.7%
Responded
No response 0.3%
chart 3: response themes
100%
91.6%
80%
63.5%
% of respondents
5
60%
49.1%
40%
33.3%
20%
4.9%
1.4%
0%
Exercise
Preventive care
Health
management
Home safety
Nutrition
Self-monitoring
Dr Linda Bryant
For older people, poor nutrition, lack of mobility and social isolation appear to herald
the start of a relatively rapid deterioration. The advice to promote activities such as
Tai Chi is excellent, as it provides not only good learning to help prevent falls, but also
an opportunity for socialisation. (People at home alone for more than 16 hours per day
and who lack a social network have an increased risk of falling.)
13
Checking the environment is important (ACC pamphlets are available at www.
acc.co.nz), as well as checking for possible visual and hearing loss issues. It is also
important to recognise that the fear of falling is a high risk factor for a fall (20% to 40%
of older people who haven’t fallen have a fear of falling; 40% to 70% of older people
who have fallen have a fear of falling).11, 12
Dr Evan Begg
Falls are probably the key problem for Mrs Smith, and can be disastrous in this age
group. Her polypharmacy in this context is therefore of some concern, and there may
be opportunity to review her current medicines use.
This question was generally handled well, in terms of fall prevention, environmental
awareness, and exercise. Perhaps more elaboration as to the why and what sort
of exercise would have been helpful (i.e. all gentle, with slow strengthening, and
assisted (physio) in the early phases). However, any advice re exercise and exercise
programmes needs to be tempered by an assessment as to the likely adherence. Mrs
Smith has had 75 years establishing her behaviour pattern, and she is unlikely to
adopt any radical change, so any change will need to be introduced slowly and be well
supported.
Simplifying her medication to avoid postural hypotension would also be a priority at
this stage.
Additional vignette information 2
Mrs Smith says she sometimes has trouble remembering to take her medicines and
is interested in your medicine use (compliance) review service. She understands
that you will send a report of her review to her general practitioner and agrees for
you to undertake a medicine use review for her.
14
What are some questions you would want to ask with respect to
adherence to this medication regimen?
response rate to question 6 – % of respondents
99.3%
Responded
No response 0.7%
chart 4: adherence themes
100%
78.5%
80%
58.8%
60%
28.9%
29.9%
29.2%
Other
40%
Compliance aids
% of respondents
20%
10.6%
Vision
Dose form suitability
Dosage times/suitability
(time to take)
0%
Medicines knowledge
(extra/excess medicines is a subset)
12.3%
Effectiveness/AE
6
Dr Linda Bryant
Respondents covered this well and the questions asked, particularly around potential
adverse effects (drowsiness, dizziness) and the perceived effectiveness or necessity
(zopiclone, frusemide), indicated concerns about some of the medicines potentially
increasing the risk of falls. There was also concern about the need to take, and
accuracy of taking, so many medicines.
With blood pressure being relatively low (query heart rate), and concerns about
dizziness, the considerations about the need for all the blood pressure lowering
15
medicines were raised. With heart failure requiring the ACE inhibitor and -blocker,
the felodipine could be reduced/stopped, and perhaps the cilazapril and thiazide
combined in one tablet (Inhibace Plus®) to reduce the number of medicines and
reduce the risk of medicine being taken incorrectly. Similarly, when pursuing the
taking of medicines, the continued need for frusemide at 80mg should also be
considered.
The other area of questioning regarding knowledge or effectiveness of medicines
concerned zopiclone and amitriptyline, with concern that sedatives (especially when
combined) increase the risk of falls. Amitriptyline can cause postural hypotension and
possible blurred vision, which are also contributing factors. It can also contribute to
constipation.
The 78.5% of respondents who provided dosage times/suitability (time to take) as a
response also provided responses as outlined in Table 2.
table 2
Dosage times/suitability (time to take)
%
Effectiveness/AE
23.2
Medicines knowledge (extra/excess medicines is a subset)
45.1
Dose form suitability
9.2
Vision
7.8
Compliance aids
20.8
Other
20.8
Note: Table contains multiple answers.
Dr Evan Begg
Discussion of dosing times, while very useful, seemed to be considered more
important by respondents than reducing the number of medications (although this
may have been assumed within medicine rationalisation). It would be useful to assess
her ideas about why she was falling so often, and whether she thought she needed all
the medication. There is a lot of pressure (e.g. in some guidelines for antihypertensive
and statin use) to prescribe medicines for small reductions in absolute risk, which
become somewhat meaningless if the patient suffers adverse consequences from
complications of a fall (e.g. DVT). It would be useful to enquire about whether she has
had or been offered compliance aids such as yellow cards, pill organisers, and patient
information leaflets. These should be discussed.
The problem of zopiclone ‘addiction’ and amitriptyline use might have been raised,
along with acknowledging the difficulty in removing these. In terms of dosing times,
compliance is best with once daily dosing, and nearly as good with twice daily dosing.
Dosing more frequently is associated with a marked fall-off in compliance. In the
elderly, the half-life of most drugs is prolonged, which often allows dosing that is tds
or qid in younger patients to be changed to bd or od.
16
What outcomes would you expect to achieve by improving her
adherence?
response rate to question 7 – % of respondents
99.3%
Responded
No response 0.7%
chart 5: Responses by theme
100%
80%
71.5%
68.3%
% of respondents
60%
40%
32.0%
31.7%
20%
8.8%
8.5%
Other
Compliance aid
Improved medicines knowledge
Falls prevention
Meds rationalisation
0%
QOL improvement
3.9%
Chornic condition improvement
7
Dr Linda Bryant
The ultimate goal is an improvement in health-related quality of life for people,
although this is difficult to measure routinely. Improvement in adherence,
as respondents indicated, should improve the control of chronic conditions
(cardiovascular disease/heart failure, osteoarthritis), and reduce falls, which can have
a high negative impact on quality of life. These outcomes would be achieved through
the rationalisation of medicines and improved knowledge of medicines and how to
use them appropriately.
17
venn diagram 5: Overlap of two main themes by respondents
Chronic condition
improvement
68
(25.1%)
126
(46.5%)
Meds
rationalisation
77
(28.4%)
Dr Evan Begg
Her medications could probably be reduced (not too abruptly) by about half, with
obvious improvements in compliance and well-being. She should feel improvement
in terms of decreased postural hypotension from stopping felodipine, as blood
pressure effects from this relate almost immediately to blood concentrations.
Similarly, removing one of the diuretics would decrease the postural hypotension.
This would probably be best achieved by removing the thiazide, and halving the dose
of frusemide. It would probably be too much for her to have the amitriptyline stopped
at this stage since she will be cherishing sleep. It would be very useful to have
discussions with the GP on the various options for simplifying her therapy, particularly
with regard to postural hypotension.
18
8
How would you measure whether those outcomes were achieved?
response rate to question 8 – % of respondents
99%
Responded
No response 1%
Table 3
#
%
68
25.1
Chronic condition improvement
49
72.1
QOL improvement
24
35.3
Meds rationalisation
29
42.6
Falls prevention
29
57.4
Dispensing patterns
17
25.0
Improved medicines knowledge
1
1.5
Compliance aid
3
4.4
Other
8
11.8
77
28.4
Chronic condition improvement
35
45.5
QOL improvement
27
35.1
Meds rationalisation
42
54.5
Falls prevention
23
29.9
Dispensing patterns
20
26.0
Improved medicines knowledge
5
6.5
Compliance aid
4
5.2
Other
5
6.5
126
46.5
Chronic condition improvement
95
75.4
QOL improvement
58
46.0
Meds rationalisation
59
46.8
Falls prevention
51
40.5
Dispensing patterns
37
29.4
Improved medicines knowledge
7
5.6
Compliance aid
5
4.0
Other
13
10.3
Q7: Chronic condition improvement theme
Q8 Theme
Q7: Meds rationalisation
Q8 Theme
Q7: Chronic condition improvement theme and meds rationalisation
Q8 Theme
Note: Table includes multiple answers.
Note: The Q7 headings link back to venn diagram 5.
19
Dr Linda Bryant
When considering a service, the question after “What outcomes do we expect to
achieve?” is “So, how do we know we have achieved the expected outcomes?”.
Evaluation of a service is important for sustainability.
Measuring the quality of life for an individual (as opposed to a study population)
is difficult and time consuming. While disease-specific instruments (heart failure,
asthma, etc) may be more amenable to measuring change, they are too specific for
multiple co-morbidity use. For Mrs Smith, quality of life would be more specific to her
own goals, such as attending the garden show.
To monitor the impact of our intervention we would expect that Mrs Smith would be
comfortable with any changes made to her medicines (i.e. reduced pain, reasonable
sleep, less dizziness), would have improved adherence (monitor collection) and
would have fewer falls (an objective measure). There is no mention of previous
hospitalisations, but there would be an expectation that improvement in her
medicines (choice and use) would help prevent hospitalisations, though this is
difficult to compare without a randomised controlled study. Clinical indicators (e.g.
blood pressure, HbA1c, lipid profile, etc) should be in the optimal ranges for this client.
Dr Evan Begg
Respondents recognised that there is much that can be done to improve her overall
well-being, and in particular to decrease the likelihood of recurrence of her falls. A
controlled plan for her rehabilitation, and her medicine rationalisation, will need a
multidisciplinary approach. This will involve the GP (medicine and dose adjustments),
practice nurse (BP monitoring, and compliance aids and counselling), physiotherapist
(immediate management and future proofing), pharmacist (compliance aids and
counselling, attendance to dexterity related to pill bottles) and occupational therapist
(home visit and fall avoidance procedures). Involvement of a family member/friend
could also be very fruitful. Effectiveness will be ‘measured’ as usual in follow-up visits.
She is likely to report greater well-being, less postural hypotension and fewer falls.
20
Bibliography
ACC Falls Prevention Strategy 2005 - 2015.
http://www.acc.co.nz/preventing-injuries/injury-prevention-strategies/PI00132
Best Practice Advocacy Centre (BPAC) Polypharmacy POEM. May 2006.
http://www.bpac.org.nz/resources/campaign/polypharmacy/polypharm_poem.asp
Prevention of Hip Fracture Amongst People Aged 65 Years and Over. June 2003.
New Zealand Guidelines Group.
http://www.nzgg.org.nz/guidelines/dsp_guideline_popup.cfm?&guidelineID=6
References
1.
Norton R, Butler M, Robinson E, Lee-Joe T, Campbell AJ. Declines in physical
functioning attributable to hip fracture among older people: a follow up study
of case-control participants. Disability and Rehabilitation 2000; 22:345-351.
2. Norton D, Measday J, Grenfell R, Mackay C, Teed A, Macdonald C. GPpharmacist liaison: a rural case study. Australian Family Physician 2003;
32(3):191-192.
3. Keene G, Parker M, Pryor G. Mortality and morbidity after hip fracture. BMJ
1993; 307:1248-1250.
4. Riggs B, Melton L. The worldwide problem of osteoporosis: insights afforded
by epidemiology. Bone 1995; 307(Suppl):505-511s.
5. Ryan P, Blake G, Fogelman I. Postmenopausal screening for osteopenia. British
Journal of Rheumatology 1992; 31:823-828.
6. http://www.acc.co.nz/preventing-injuries/injury-prevention-strategies/
PI00132
7. Savage, R. A dangerous trio. Prescriber Update June 2002.
http://www.medsafe.govt.nz/profs/PUarticles/DangTrio.htm
8. Braund R, Abbott JH. Analgesic choice when treating musculoskeletal sprains
and strains. New Zealand Journal of Physiotherapy 2007; 35: 54-60.
http://www.physiotherapy.org.nz/index02/Publications/.../35(2)p54-60.pdf
9. 30 June 2009 – www.time.com/time/health/article/0,8599,1908042,00.html
10. December 2008 http://www.ciap.health.nsw.gov.au/nswtag/publications/
posstats/Paracetamol231208.pdf
11. Boyd R, Stevens JA. Falls and fear of falling: burden, beliefs and behaviours.
Age and Ageing 2009; 38:423-438.
12. Scheffer AC, Schuurmans MJ, van Dijk N, van der Hooft T, de Rooij SE. Fear
of falling: measurement strategy, prevalence, risk factors and consequences
among older persons. Age and Ageing 2008; 37:19-24.
21
Case Study 2 – Back pain
Vignette
Mrs Jones is a relatively new patient to your pharmacy. She is a 35-year-old laboratory
technologist, but having had chronic back pain for nine months now has meant that
she is unable to work more than three to four hours a day. Mrs Jones has been to the
chronic pain clinic at the hospital. Her current medicines are:
Amitriptyline
10mg daily
neuropathic pain
Paroxetine
30mg mane
depression
Tramadol
Up to 100mg three times daily prn
neuropathic pain
Paradex®
2 tablets prn
neuropathic pain
Sumatriptan
50mg as required
migraine
Paramax®
2 prn
migraine
Mrs Jones generally takes two tablets (50mg) of tramadol when she gets up every
morning. About twice a week she also takes two tablets in the late afternoon –
though she tries to avoid these as she has heard that they are narcotics. She also
takes two tablets of Paradex® most nights. Sumatriptan is taken about once every
two weeks as required for migraines, and Paramax® about twice a week if she thinks
she’s getting a migraine, and they often work.
Mrs Jones says that she thinks she is doing fairly well and wants to extend her work
hours. Her GP told her that there is another drug she could use for pain (gabapentin)
and she wishes to know more about it. Her general health is fine in terms of blood
pressure, etc.
22
Background
Dr Linda Bryant
Chronic pain is a very difficult condition to treat, and there is a lot of
misunderstanding about this condition, with some public perception that this
is ‘malingering’.13 Yet it is a very real and devastating condition. Because of the
complexity of the condition it is often treated through a chronic pain clinic, which
is a specialised clinic with a strong interdisciplinary focus. As well as the medical
pain specialist, the team usually includes specialist nurses, clinical psychologists,
physiotherapists, and good connections with social services. The treatment is very
much individualised (pharmacological and non-pharmacological), and sometimes the
combination of medicines is very complex.
The impact of chronic pain on a person’s lifestyle and functioning is often dramatic
and extensive. There is a need for clear communication among the healthcare
providers and identification of the lead provider for care relating to the chronic pain,
to avoid mixed messages occurring.
It appears that Mrs Jones is doing well, as she says herself, but that she is eager to
“do even better”, perhaps pushing herself. Having progressed this well, and looking
to change something, it is probably timely for the team that individualised her
treatment to review it, because, as the respondents to the case study indicated, this
combination of conditions and medicines will need as much care and monitoring to
change as it probably took to reach.
Dr Evan Begg
This is a problem of a relatively young working (professional) woman (aged 35) with
chronic back pain, migraines and background depression. She has (appropriately)
been referred to the chronic pain clinic, and is now on multiple medications affecting
the CNS. Paradoxically, she is enquiring about a possible additional drug for
neuropathic pain, yet feels she is currently doing well.
Overall this is far more a diagnostic problem than a simple medicines rationalisation.
It is most likely that one of her three neuropsychiatric problems is dominant, and
the others of varying importance. Once this is clarified, simplifying the medications
should be the aim.
1.
The fundamental problems:
•
chronic back pain: Information is needed on timing of onset, aggravating
and alleviating features, diagnosis and how firm this is, investigations,
and response or otherwise to the different medicines
23
•
migraine: There is little information about her migraine history. This is
likely to have been a much more chronic problem than the back pain, and
the current frequency of attacks is worrying
•
depression: Again there is little information. Is this the fundamental
problem? Maybe her psychiatrist should be more involved?
•
psychosocial setting: Is there a reason for a general inability to cope?
•
work setting: Is this aggravating all of the above?
2. Polypharmacy:
24
•
her medications have an effect on most central neurotransmitters,
making predictability of effect very difficult
•
her multiple interactions make it very difficult for this to be simply
embraced, in the setting of much that is unknown about the primary
problems
•
she is interested in the new drug (gabapentin) mentioned by her GP.
Results and commentary
Total number of respondents n = 280
What are the key areas you would question Mrs Jones about, to
determine the advice you would give her?
response rate to question 1 – % of respondents
99.3%
Responded
No response 0.7%
chart 6: Thematic responses
100%
81.3%
80%
% of respondents
60%
54.0%
42.1%
40%
25.9%
19.1%
20%
19.1%
21.2%
Allergies
Migraine oriented
Comorbidity
Exercise/lifestyle
Alternative advice/
support sought
Meds oriented
queries
0%
Activities that impact
on back pain
5.8%
Back pain severity,
location, regularity
1
Dr Linda Bryant
As the majority of pharmacists suggested, there is a necessity to determine the type
of pain, how much it has improved, over what sort of time period, and any changes
in activity types or pain levels, particularly as Mrs Jones indicates that she considers
that she is doing so well that she could extend her work hours. Noting changes to
25
medicines use, such as a reduction in her use of prn analgesia, would help establish
any variability in pain levels. A check on any changes in frequency or intensity of her
migraines and whether her response to her migraine medication remained stable
would also be helpful.
Although it seems that Mrs Jones is doing well (wanting to increase her work
hours) I would be interested in any comments she makes about symptoms that
could indicate possible serotonin toxicity (muscle weakness, hyperreflexia, lack of
coordination, shivering, fever, chills, sweats, irritability, raised body temperature,
nausea, abdominal cramps, tachycardia, headache, hypo- or hypertension and CNS
symptoms).
From the improvement Mrs Jones has indicated she is experiencing, exploring
her knowledge of the dosing of the medicines, and her views on her medicines’
effectiveness and potential adverse effects, would be useful to try and understand
why, beyond her mentioning it, she is interested in gabapentin, particularly when
she appears to be ready to extend her work hours. It may be that she is comfortable
with her current treatment and is trying to balance the option of changing medicines
against staying with a treatment that is working for her.
I would be interested in what other medicines had been tried, including
complementary medicines. This is because I note that Mrs Jones had been to the
chronic pain team, and I am aware that these teams are usually fairly conservative
and do not initiate ‘complex’ regimes without having first tried the more
straightforward regimes. I would also ask about non-pharmacological methods of
pain control, and check whether/when Mrs Jones had her next appointment with the
chronic pain team.
Mrs Jones has indicated that she is primarily using regular amitriptyline (10mg nocte),
Paradex® (2 nocte) and tramadol (100mg mane) for pain, with an occasional extra two
tramadol in the late afternoon about twice a week.
Dr Evan Begg
As correctly noted by nearly all respondents, multiple themes emerge. The order of
batting in this regard was medicine queries (81%), back pain (54%), exercise/lifestyle
(42%), and others (around 20% to 25%). To me the fundamental nature of the three
underlying complaints needs to be resolved, and more attention needs to be paid to
the migraines and depression. Certainly the migraines seem to be a larger current
problem than the back pain, and the depression may be in a quiescent phase (as she
is keen to increase her working hours). The setting of this case, however, biases us
towards the back pain.
Having elucidated more about the problems, a full medicines history (extending far
earlier than nine months) would be useful to try to identify drugs she likes/dislikes,
and whether she generally likes to rely on medicines or not. This raises further
questions about other lifestyle cures and alternative medicines. We need to know a
lot more about where she is coming from.
26
2
Are there any potential (medicines) interactions in Mrs Jones’ current
therapy?
response rate to question 2 – % of respondents
100%
Responded
No response
potential (medicines) interactions – % of respondents
99.6%
Yes
No 0.4%
Dr Linda Bryant
There are a number of potential medicine interactions in the current therapy for Mrs
Jones, as all but one respondent identified. There are potential pharmacodynamic
and pharmacokinetic interactions. The issue becomes whether they are clinically
important or not for the individual.
Dr Evan Begg
All respondents except one correctly answered ‘yes’.
27
3
If yes, what are they?
chart 7: potential (medicines) interactions identified
200%
180%
13.6% Other combinations
160%
16.1% Paradex® plus
Paroxetine
% of respondents
140%
120%
66.7% Paroxetine plus
Tramadol
1.8% Paramax® plus
Tramadol
28.0% Amitriptyline
plus Paradex®
12.5% Paradex® plus
Tramadol
100%
60.2% Paraoxetine plus
Sumatriptan
80%
60%
58.8% Amitriptyline plus
Paroxetine
40%
49.8% Amitriptyline
plus Tramadol
20%
24.4% Serotonin enhancers
0%
Serotonin
toxicity
12.2%
9.0% Multiple CNS
depressants
CNS toxicity
59.5%
Paracetamol
toxicity
Other
Note: Graph includes multiple answers.
Table 4
Serotonin toxicity
28
%
Amitriptyline, Tramadol, Paroxetine, Sumatriptan all Serotonin Enhancers / Multiple
Serotonin Enhancers increase risk of Serotonin toxicity (synergistic effects)
24.4
Amitriptyline + Paroxetine = increased risk of Serotonin toxicity / increased
drowsiness / increased Serum Amitriptyline / Paroxetine decreases metabolism of
Amitriptyline / increased risk of TCA toxicity / increased CNS toxicity
58.8
Paroxetine + Tramadol = increased risk of Serotonin toxicity / decreased analgesic
effect of Tramadol / increased CNS toxicity / increased risk of seizure / inhibits
Tramadol metabolism
66.7
Paradex® + Paroxetine = increased risk of Serotonin toxicity / increase in Paroxetine
levels
16.1
Sumatriptan + Amitriptyline = risk of Serotonin toxicity
4.7
Tramadol + Sumatriptan = Serotonin syndrome/CNS toxicity
5.0
Metoclopramide (Paramax®) + Paroxetine = Serotonin syndrome/Extrapyramidal side
effects
3.9
Table 4 continued
CNS toxicty
Multiple CNS depressants increase risk of CNS toxicity / drowsiness/sedation/
impaired concentration / more risk of accidents
9.0
Amitriptyline + Tramadol = increased risk of CNS toxicity / lower seizures threshold /
increased risk of seizures / drowsiness / respiratory depression / cholinergic effects /
decreased analgesic effect of Tramadol / increased toxicity of Tramadol / cons
49.8
Paroxetine + Sumatriptan = increased blood pressure / increased risk of CNS toxicity /
serotonin toxicity / exacerbate migraines / dyskinesia
60.2
Paradex® + Tramadol = Opioid duplication / antagonise gastrointestinal effects of
Metoclopramide / increased drowsiness / constipation / risk of respiratory depression
12.5
Amitriptyline + Paradex® = Opioid duplication / increased Amitriptyline / increased
drowsiness
28.0
Metoclopramide (Paramax®) + Tramadol both CNS depressants / Tramadol inhibits
1.8
effect of Metoclopramide in Paramax® / CNS/respiratory depressant effects
Paracetamol toxicity
Paramax® + Paradex® = risk of Paracetamol “double-up” / paracetamol toxicity / liver
toxicity
59.5
Other
%
Drug interaction(s) not clinically significant / may be beneficial
4.7
Dextropropoxyphene (Paradex®) may antagonise effects of Metoclopramide
1.8
(Paramax®) on G.I. system
Other drug interactions/effects
5.4
Monotherapy preferable to combination of drugs for this treatment
0.4
Note: Table includes multiple answers.
Dr Linda Bryant
Paroxetine is an inhibitor of cytochrome P450 2D6 (CYP2D6), and is a selective
serotonin reuptake inhibitor. This leads to potential interactions with:
•
Amitriptyline
Metabolised by CYP2D6 and therefore inhibition of the CYP2D6 by paroxetine
can increase the serum concentrations of amitriptyline. This may result in up
to a 400% increase of the Area Under the Curve (AUC). There is wide variation
in the activity of CYP2D6 among individuals, even without taking into account
the poor metabolisers (7% to 10% of the Caucasian population) and extensive
metabolisers. This combination should be used with caution and the person
advised of the symptoms of tricyclic antidepressant toxicity (e.g. sedation,
dry mouth, blurred vision, constipation, urinary retention) and/or excessive
serotonergic activity (e.g. CNS irritability, altered consciousness, confusion,
myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary
dilation, diaphoresis, hypertension and tachycardia).
29
•
Tramadol
The mechanism of action of tramadol is through binding to the μ-opioid
receptors, and through inhibition of noradrenalin and serotonin reuptake. It is
metabolised to the active analgesic metabolite M1, through CYP2D6 and to a
lesser extent CYP3A4. M1 appears to be metabolised by CYP3A4. Inhibition of
CYP2D6 can inhibit this metabolism and reduce the amount of M1 and cause
accumulation of the parent compound, tramadol.
This leads to the potential reduction in analgesia (less metabolite), and has
an additive effect on the serotonin and noradrenaline receptors, leading to
possible serotonin toxicity. While there are reports of this interaction causing
serotonin toxicity, it is not inevitable.
With tramadol and antidepressants both reducing the seizure threshold, there
is the possibility that this combination can promote a seizure, particularly for
people with a low seizure threshold.
•
Sumatriptan
Paroxetine inhibits the reuptake of serotonin. Sumitriptan (and other 5-HT1D
agonists or triptans) can also increase serotonin concentrations and so there
is a risk of precipitating serotonin syndrome. This is normally not of clinical
importance but mild to severe serotonin toxicity may occur in up to 10% of
people, as can (rarely) dyskinesia. The triptans may have low affinity for
5-HT1A (the sub-receptors affected by SSRIs) and do not penetrate the bloodbrain barrier well.
It may be difficult for Mrs Jones to differentiate between serotonin syndrome
and sumitriptan-induced cardiac adverse effects (chest tightness) and other
possible adverse effects such as nausea, tingling, dizziness. The symptoms
of the serotonin toxicity - nausea, abdominal cramps, tachycardia, headache,
fever, chills, sweats, hypo- or hypertension and CNS symptoms - may also
appear similar to the symptoms of migraine.
•
Paradex® (dextropropoxyphene)
Dextropropoxyphene is a ‘dirty’ drug which is metabolised primarily by
CYP3A4 and also appears to be a weak inhibitor of CYP2D6. This may
potentially lead to increased CNS effects with the antidepressants and
tramadol.
The combination of these medicines has the potential to contribute to serotonin
toxicity/CNS adverse effects. The pharmacokinetic and pharmacodynamic actions
need to be considered and quantified for Mrs Jones as an individual, particularly when
there are any changes to her medicines.
Paracetamol
As was indicated, there is a risk of paracetamol overdose, due to her taking two
medicines containing paracetamol on a prn basis, though her current usage is well
within the recommended maximum daily dosage.
30
Dr Evan Begg
It was pleasing that nearly all picked serotonin toxicity/syndrome as the main
problem, followed by CNS toxicity. Paracetamol toxicity also featured in around
60% of answers; however, it should be noted that the aggregate doses of this were
quite low, and there are no clear interactions involving paracetamol (apart from
administration of two separate drugs containing it).
When addressing drug interactions, it is useful to think in terms of pharmacodynamic
interactions (altered action), and pharmacokinetic interactions (altered
concentrations). Pharmacodynamic interactions dominate in this case, although
substantial pharmacokinetic interactions are also present and aggravate the
pharmacodynamic effects.
The main pharmacodynamic interactions are serotonin enhancement (amitriptyline,
paroxetine, tramadol and sumatriptan), which will cause a whole variety of CNS
and gut stimulatory effects, mu narcotic CNS agonist effects (tramadol and
dextropropoxyphene), which will largely manifest as CNS depression, and gut effects
(amitriptyline, paroxetine, tramadol, dextropropoxyphene and metoclopramide) via
anticholinergic, serotonin, and mu opioid effects.
The net gut effects are difficult to predict since there are both stimulatory serotonin
effects (involving most drugs) and prokinetic dopamine effects (metoclopramide)
competing with mu opioid inhibitory effects (tramadol, dextropropoxyphene), and
anticholinergic effects (amitriptyline).
The main pharmacokinetic interaction involves CYP2D6 inhibition by paroxetine,
which effectively phenocopies the patient to appear to be like a genetically slow
metaboliser. Therefore all other drugs metabolised by CYP2D6 are potentially
affected. Specifically here, these include amitriptyline and its active metabolite
nortriptyline, and tramadol and its active metabolite nortramadol (M1).
Given that paroxetine is being given (with assumed compliance) at a full dose (30mg
per day), a full enzyme-inhibiting effect on the other drugs can be assumed. Thus
the amitriptyline dose, aimed at neuropathic pain rather than depression, could
in fact be approaching antidepressant concentrations. In terms of tramadol, the
pharmacokinetic effect of CYP2D6 inhibition is rather complex since both parent
tramadol and one of the major metabolites (nortramadol (M1)) are both active, but
not in identical ways. Overall, since nortramadol is more potent, and is largely mu
opioid in effect, we could expect enhanced serotonin activity from increased parent
drug, and decreased mu opioid activity from decreased nortramadol, thus decreasing
the analgesic effect of tramadol.
31
4
Do you think these are clinically important interactions for Mrs Jones?
response rate to question 4 – % of respondents
98.6%
Responded
No response 1.4%
Are these clinically important interactions?
7.1%
91.4%
No
Yes
No response 1.4%
Dr Linda Bryant
When we look at a list of medicines as ‘purists’, Mrs Jones’ list immediately screams
out an alert – and we tend to want to ‘fix it up’. In order to rationalise our ‘gut
instincts’, because there are potentially clinically important interactions possible in
this list of medicines, it is important to question Mrs Jones, particularly about any
possible adverse effects she is experiencing. Mrs Jones may not recognise some drugrelated problems as adverse effects, such as insomnia due to serotonin toxicity, some
cognitive slowing, increased heart rate, etc, so we have to be aware of the specific
adverse effects that are likely, and ask specific questions to determine the relevance
to the particular person.
Dr Evan Begg
Most people correctly indicated ‘yes’. Serotonin toxicity was again stressed (71%),
followed by CNS toxicity (38%) and paracetamol toxicity (32%) (see Chart 8). While the
serotonin axis was expected, I wonder if some people have underestimated the CNS
toxicity, and overestimated the possibility of paracetamol toxicity.
32
If yes, why?
response rate to question 5 – % of respondents
91.4%
Responded
8.6%
No response
chart 8: Why these are clinically important interactions
80%
70.7%
60%
37.9%
40%
31.6%
18.0%
12.9%
11.3%
Potentially life
threatening
Review meds
Migraine linkage
Paracetamol toxicity
CNS toxicity
0%
Serotonin toxicity
9.0%
8.6%
Other
20%
Not clinically
important
% of respondents
5
Note: Graph contains multiple answers.
Dr Linda Bryant
In this case Mrs Jones is feeling well enough that she is considering extending her
work activity – an indication that the combination must be working adequately and
she is probably not experiencing obvious adverse effects. Her list of medicines may
not look pretty – but they appear to be working for her. Any changes risk interfering
with a stable interaction, noting that her medicines use, even of prn medicines, is
reasonably consistent.
The prescribed dose of amitriptyline is low, although the serum concentration may
be higher than we would expect if Mrs Jones was not on paroxetine. This will need to
be remembered if the paroxetine is stopped, remembering that antidepressants are
continued for at least six to nine months after a response – therefore the fact that
Mrs Jones appears to be ‘doing fairly well now’ is not necessarily a reason to stop the
paroxetine.
33
The tramadol dose is also relatively low, and so there is a need to ensure that she
does not start increasing the dose without medical input. Similarly, the use of
Paradex® is low (two at night) and Paramax® use is intermittent.
The potential interactions above do occur and can be dramatic, but they are not
clinically important in every person. Chronic back pain is a complex problem and
management is usually a fine balance between providing ideal treatments and
obtaining suitable analgesia. Mrs Jones’s list begs for some intervention and it is
difficult to resist the temptation to interfere with her medication profile, but we
simply have inadequate historic information at this stage.
Dr Evan Begg
The serotonin and CNS effects possible are described above in question 3. There is not
enough information available to know if she has suffered from these effects or not,
and clearly appropriate questions need to be asked.
Regarding paracetamol, the purported doses seem to be 1g daily for five of seven days,
and 2g for the other two days. This does not seem particularly concerning, especially
since she is relatively young and there are no clear pharmacokinetic interactions
(paracetamol is largely glucuronidated, with some sulfation, and none of the other
drugs inhibit these processes). CNS toxicity may result from the summation of
amitriptyline plus nortriptyline, tramadol plus nortramadol, and dextropropoxyphene.
Of these, consideration should be given to discontinuing dextropropoxyphene (an
awful narcotic drug, very lethal in overdose), and somehow rationalising the complex
CYP2D6 pharmacology. The key drug in this regard is paroxetine, as it is influencing
amitriptyline and tramadol (and respective metabolite) concentrations. It would be
great if paroxetine could be discontinued, but this should only take place under the
direction of someone with detailed knowledge of her depression and its timing.
34
What information would you discuss with Mrs Jones regarding the use
of gabapentin?
response rate to question 6 – % of respondents
99.6%
Responded
No response 0.4%
chart 9: gabapentin information
100%
90.7%
80%
% of respondents
60%
55.6%
38.0%
40%
31.2%
29.7%
21.9%
20%
1.4%
Other
3.9%
Health check
3.9%
Treatment type
Compliance
information
Interactions
Contraindication
Indication for use
Funding
0%
Dosage regime
4.3%
Treatment length
9.7%
Adverse effects
6
Note: Graph contains multiple answers.
Dr Linda Bryant
From the first question I would have explored Mrs Jones’ reasons for asking about
the gabapentin. Some people like to know what else is available ‘just in case’, the
general practitioner may have tweaked her interest, or Mrs Jones may think that the
gabapentin will be the panacea that will get her back to work faster (perhaps she
perceives that her current treatment is ‘second rate’ because she is not on the latest
‘new’ medicine).
I would assure Mrs Jones that gabapentin was an effective medicine, by comparing
it with tricyclic antidepressant efficacy. There is not a lot of difference in numbersneeded-to-treat (NNT) and so selection is really based on the individual. The NNT for
neuropathic pain (number to reduce pain by 50%) is approximately four (note that this
is not complete resolution of pain).
35
Although the adverse effects are usually minor and tolerance can develop, the
potential for unwanted effects include:
table 5
Number needed to harm
Somnolence
∼ 11%
NNH 9
Fatigue
∼ 6%
NNH 17
Dizziness
∼ 12%
NNH 8
Ataxia
∼ 5%
NNH 20
Possible weight gain
1.7%
Diplopia
4%
tremor, muscle
weakness/pain, difficulty
concentrating
It is particularly important that Mrs Jones knows that she could not drive or
operate machinery until she has established whether these adverse effects affect
her (preferably one to two weeks). There is also little information for use during
pregnancy and so if Mrs Jones wishes to become pregnant, she should enter a group
discussion with her general practitioner, pain team ± gynaecologist.
Dr Evan Begg
Given that Mrs Jones reported to be generally fairly happy with the status quo, it
would seem that her question re gabapentin was probably largely exploratory, and
in response to the GP mentioning it. In other words, perhaps she was only asking
for general information as a step care possibility for the future. In this case most
discussion should focus on the relative value of gabapentin compared with current
neuropathic drugs, especially related to efficacy. It would of course be useful, as
noted, to discuss the downsides of adding gabapentin, and in particular CNS toxicity
(in the context of pharmacodynamic interactions). The idea could be raised of
replacing a current drug, e.g. amitriptyline, with gabapentin, thereby avoiding some
pharmacokinetic interactions (gabapentin is eliminated largely renally unchanged,
and therefore is not subject to CYP2D6 inhibition).
A major downside of gabapentin, and all the other CNS acting drugs, is potential
effects on driving and operating machinery. Alcohol history is also relevant in this
regard.
36
What information would you discuss with Mrs Jones’ general
practitioner regarding the introduction of gabapentin into her medicine
regime?
response rate to question 7 – % of respondents
99.3%
Responded
No response 0.7%
chart 10: informational themes
70%
62.2%
60%
50%
% of respondents
42.8%
40%
30%
27.7%
27.3%
29.9%
20%
7.9%
Other
5.4%
Interactions
Health check
Adverse effects
AE/monitoring
Try another med
first
Change meds
regime
Funding
0%
6.8%
Pregnancy advice
12.6%
10.8%
10%
Dose regime
7
Dr Linda Bryant
Mrs Jones is currently on a complex regime that has been established by the chronic
pain clinic. Although there are unlikely to be pharmacokinetic interactions, there
are potential pharmacodynamic interactions and therefore the pain team should be
consulted (directly or through the general practitioner) prior to the introduction of
gabapentin.
Because of the complexity of chronic back pain, there would need to be a good reason
for changing treatment. Mrs Jones does not appear to be suffering any adverse
effects, and she seems to be having an improvement in pain relief. While I can see
some potential changes to her medicines, this would require close supervision of
Mrs Jones and ensuring she had an understanding of the potential adverse effects.
For example, the amitriptyline appears to be effective and even though there may be
higher serum concentrations than expected from a 10mg dosage, it could be increased
to 20mg. If there were no unacceptable adverse effects, then the prn medicines,
Paradex® initially, then tramadol, could be reduced.
37
With respect to gabapentin, I would reiterate the comparative efficacy of gabapentin
in terms of NNT compared with amitriptyline (i.e. little difference), and mention
the adverse effects to be expected, plus the requirement for slow dose titration. I
would also include a comment about the reduced bioavailability of gabapentin with
increasing doses (i.e. doubling the dose does not double the serum concentration or
AUC).
Dr Evan Begg
More information is required about the history and diagnoses, as without correct
diagnoses any treatment is inappropriate. The major points of interest were the
dosing regimen, and the possible addition of gabapentin. A large number (43%)
also discussed the possibility of changing medications (mainly in the direction of
simplifying the regimen). The possibility of gabapentin introduction allowing the
removal of perhaps amitriptyline and Paradex® was raised. It would be useful also
to review the depression angle, as paroxetine is the major drug causing interactions.
Perhaps there could have been a higher priority on psychosocial aspects of all of the
problems, and potential lifestyle adjustments. There is some tension between who is
primarily managing the patient – the GP, the chronic pain team, or the psychiatrist.
38
What advice would you have given Mrs Jones if she had presented nine
months ago with acute lower back pain?
(Hint: Look at the ACC New Zealand Acute Lower Back Pain Guide)
response rate to question 8 – % of respondents
99.3%
Responded
No response 0.7%
chart 11: advice provided by themes
100%
88.5%
80.2%
80%
60%
50.7%
47.5%
40%
23.4%
23.4%
19.1%
20%
17.6%
15.1%
7.2%
7.9%
Assess work
environment
Meds
recommended
Clinical
aseessmnet
No heavy lifting
Work rotation
Exercise
See other health
professional
See GP if no
improvement
Continue working
Stay active
Assess clinical
history
0%
Assess pain
history
5.0%
ACC ALBP for
self-management
12.6%
9.7%
Other
% of respondents
8
Note: Graph includes multiple answers.
39
table 6: informational themes
%
Assess pain history
9.7
Assess clinical history
23.4
Stay active
88.5
Continue working
47.5
See GP if no improvement
23.4
See other health professional
50.7
Exercise
19.1
Work rotation
17.6
No heavy lifting
12.6
Clinical assessment
Meds recommended
5.0
80.2
ACC ALBP for self-management
7.2
Assess work environment
7.9
Other
15.1
Note: Table includes multiple answers.
Dr Linda Bryant
Yes, ‘backs like (safe) movement’ and so staying active is important advice. This is
contrary to the advice of some years ago when people would be told to rest in bed,
leading to weakened muscles and more problems. The advice to stay active, continue
working and do exercise (but no heavy lifting) was very appropriate. Referral for safe
exercises and activity may be appropriate.
In order to maintain safe mobility, clear information needs to be provided on back
care (see the New Zealand Acute Low Back Pain Guide14) and good analgesia. Regular
(with emphasis on regular) paracetamol is still a good basal analgesia. Mrs Jones
is young with no apparent risk factors, and so supplementation with an NSAID prn
could be helpful.
If you had concerns about Red Flags, or Mrs Jones didn’t find any improvement in two
to three days, then referral to a medical practitioner would be required. It may also be
appropriate to give Mrs Jones an indication of the timeframe for improvement (usually
resolves in four to six weeks, but expect significant improvement within one to two
weeks).
Red Flags
Red Flags help identify potentially serious conditions. They include:
40
•
urinary or faecal incontinence, abnormal gait, lower limb weakness
•
severe worsening pain, especially at night or when lying down
•
significant trauma
•
weight loss, history of cancer, fever
•
use of intravenous drugs or steroids
•
patient over 50 years old.
Yellow Flags
Yellow Flags indicate psychosocial barriers to recovery. They include:
•
belief that pain and activity are harmful
•
‘sickness behaviours’ (like extended rest)
•
low or negative moods, social withdrawal
•
treatment that does not fit best practice
•
problems with claims and compensation
•
history of back pain, time-off, other claims
•
problems at work, poor job satisfaction
•
heavy work, unsociable hours
•
overprotective family or lack of support.
Dr Evan Begg
The main themes highlighted were that she should stay active, and that medications
would be recommended. To me a detailed assessment and accurate diagnosis would
be the main priority. The diagnosis will dictate the therapeutic direction.
Page six of the New Zealand Acute Low Back Pain Guide outlines the steps you need
to take to assess the presentation of acute low back pain to exclude Red Flags.
This assessment is critical as it will determine whether you are able to recommend
treatment or have to refer the client to a doctor.
Page 10 of the Guide outlines the management options for acute low back pain. Page
23 outlines Yellow Flag assessments and management options if your client returns to
you after trying treatment to manage the pain.
41
Bibliography
Baxter K (ed). Stockley’s Drug Interactions. 8th ed. RPS Publishing, 2007.
Flockhart D. Cytochrome P450 drug interaction table.
http://medicine.iupui.edu/clinpharm/DDIs/
Management of non-specific back pain and lumber radicular pain. BPAC Journal June
2009. http://www.bpac.org.nz/magazine/2009/june/nsbackpain.asp
Neurontin Product Data Sheet.
http://www.medsafe.govt.nz/profs/Datasheet/n/Neurontincap.htm
New Zealand Acute Low Back Pain Guide.
http://www.nzgg.org.nz/guidelines/0072/acc1038_col.pdf
Saarto T, Wiffen PJ. Antidepressants for neuropathic pain.
http://www.cochrane.org/reviews/en/ab005454.html
Wiffen PJ, McQuay HJ, Rees J, Moore RA. Gabapentin for acute and chronic pain.
http://www.cochrane.org/reviews/en/ab005452.html
References
13. ‘Malingering’ is defined as: Exaggerating or feigning illness in order to escape duty
or work.
14. http://www.acc.co.nz/about-acc/research-sponsorship-and-projects/researchand-development/evidence-based-healthcare-reports/index.htm#Clinical_
Guidelines
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ACC5327 Printed November 2009 ISBN: 978–0–478–31468–7