Guidelines based neuropathic pain management in the elderly. Published at Nova Southeastern University, 2014

1. Muneer Nagi1, Adam Fox1, Melissa Selinger1, Matt Penano1
1PharmD Candidates - Nova Southeastern University College of Pharmacy
CONCLUSION
 Considerations in the selection of pharmacological treatment of neuropathic pain in
the elderly include:
 Drug efficacy for the types of neuropathic pain
 Increased frequency of polypharmacy
 Side effect profile and tolerability specific to this population.
 Effective management of pre-existing comorbidities and risk reduction of developing
additional comorbidities before initiation or during pharmacological treatment
 Gabapentin and pregabalin: minimal side effects, favorable for polypharmacy
implications
 Tricyclic antidepressants: effective but SE problematic in elderly
 Topical lidocaine 5%: effective for some types of pain with negligible side effects
 SNRIs: effective and relatively well tolerated
 Opioids: long term safety unknown, but useful in combination therapy
 Tramadol: decreased seizure threshold, renal and hepatic dosing
 Carbamazepine, Lamotrigine: efficacy data inconsistent; used for trigeminal neuralgia
 Topical capsaicin: long-term safety unknown in high concentration patch
 Combination therapy: limited clinical data and must be individualized, but often seen
in practice
PHARMACIST ROLES
• In the elderly:
Knowledge of NP
Effectively assist to manage comorbidities
Prevent drug-disease interactions
Educate patient/caregiver
Monitor adherence, compliance, medication effectiveness, etc.
Effectively manage polypharmacy
LIMITATIONS
This paper did not consider in-depth details of superiority/noninferiority of medications,
cost analyses, and QOL implications. There are a limited amount of head-to-head
comparative studies, therefore they were not included. The samples included in the meta-
analyses did not consider nor analyze patients with pre-existing conditions and/or
polypharmacy.
REFERENCES1.Vinik A. The approach to the management of the patient with neuropathic pain. The Journal of clinical endocrinology and metabolism. Nov 2010;95(11):4802-4811.
2. Ahmad M, Goucke C. Management Strategies for the Treatment of Neuropathic Pain in the Elderly. Drugs Aging. 2002/12/01 2002;19(12):929-945.
3. Reisner L. Pharmacological Management of Persistent Pain in Older Persons. The Journal of Pain. 3// 2011;12(3, Supplement):S21-S29.
4. Schmader KEMD, Baron RDRMED, Haanpää MLMDPHD, et al. Treatment Considerations for Elderly and Frail Patients With Neuropathic Pain. Mayo Clinic Proceedings. Mar 2010 2010;85(3):S26-S32.
5. McCarberg BMD, Barkin RLP, Zaleon CP. The Management of Neuropathic Pain With a Focus Upon Older Adults. [Review]. American Journal of Therapeutics May 2012;19(3):211-227; 2012.
6. McCarberg B, Barkin RL, Zaleon C. The management of neuropathic pain with a focus upon older adults. American journal of therapeutics. May 2012;19(3):211-227.
7. O'Connor AB. Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy. PharmacoEconomics. 2009;27(2):95-112.
8. Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Current pain and headache reports. Jun 2012;16(3):191-198.
9. Stacey BR. Management of Peripheral Neuropathic Pain. American Journal of Physical Medicine & Rehabilitation. 2005;84(3):S4-S16.
10. Dworkin RH, O'Connor AB, Audette J, et al. Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update. Mayo Clinic Proceedings. 3// 2010;85(3, Supplement):S3-S14.
11. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. The Lancet Neurology. Aug 2010. 2013-02-24 2010;9(8):807-819.
12. Jensen MP, Chodroff MJ, Dworkin RH. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology. Apr 10 2007;68(15):1178-1182.
13. Chen H, Lamer TJ, Rho RH, et al. Contemporary Management of Neuropathic Pain for the Primary Care Physician. Mayo Clinic proceedings. Mayo Clinic. 2004;79(12):1533-1545.
14. Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain: Diagnosis, mechanisms, and treatment recommendations. Archives of Neurology. 2003;60(11):1524-1534.
15. Haanpää M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. PAIN. 1// 2011;152(1):14-27.
16. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: An evidence based proposal. Pain. 12/5/ 2005;118(3):289-305.
17. Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: Evidence-based recommendations. PAIN. 12/5/ 2007;132(3):237-251.
18. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. PAIN. 9// 2010;150(3):573-581.
19. Nobili A, Garattini S, Mannucci PM. Multiple diseases and polypharmacy in the elderly: challenges for the internist of the third millennium. Journal of Comorbidity. 2011;1(1):28–44.
20. Sinnige J, Braspenning J, Schellevis F, Stirbu-Wagner I, Westert G, Korevaar J. The Prevalence of Disease Clusters in Older Adults with Multiple Chronic Diseases - A Systematic Literature Review. PLoS One. Nov 2013. 2013-11-18 2013;8(11).
21. Patel KV, Guralnik JM, Dansie EJ, Turk DC. Prevalence and impact of pain among older adults in the United States: Findings from the 2011 National Health and Aging Trends Study. PAIN®. 12// 2013;154(12):2649-2657.
22. Fine PG. Chronic Pain Management in Older Adults: Special Considerations. Journal of Pain and Symptom Management. 8// 2009;38(2, Supplement):S4-S14.
23. Haanpää ML, Gourlay GK, Kent JL, et al. Treatment Considerations for Patients With Neuropathic Pain and Other Medical Comorbidities. Mayo Clinic Proceedings. 3// 2010;85(3, Supplement):S15-S25.
24. Guay DRP. Adjunctive pharmacological management of persistent, nonmalignant pain in older individuals. Aging Health. Feb 2006 2012-06-29 2006;2(1):135-144.
25. Sultan A, Gaskell H, Derry S, Moore A. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials. BMC Neurol. 2008/08/01 2008;8(1):1-9.
26. Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, Gabapentin, or Their Combination for Neuropathic Pain. New England Journal of Medicine. 2005;352(13):1324-1334.
27. Gordon DB, Love G. Pharmacologic management of neuropathic pain. Pain Management Nursing. 12// 2004;5, Supplement(0):19-33.
28. McGeeney BE. Pharmacological Management of Neuropathic Pain in Older Adults: An Update on Peripherally and Centrally Acting Agents. Journal of Pain and Symptom Management. 8// 2009;38(2, Supplement):S15-S27.
29. O'Connor AB, Dworkin RH. Treatment of Neuropathic Pain: An Overview of Recent Guidelines. The American Journal of Medicine. 10// 2009;122(10, Supplement):S22-S32.
30. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. General Hospital Psychiatry. 5// 2009;31(3):206-219.
31. Haslam C, Nurmikko T. Pharmacological treatment of neuropathic pain in older persons. Clinical interventions in aging. 2008;3(1):111-120.
32. Mou J, Paillard F, Turnbull B, Trudeau J, Stoker M, Katz NP. Efficacy of Qutenza® (capsaicin) 8% patch for neuropathic pain: A meta-analysis of the Qutenza Clinical Trials Database. PAIN. 9// 2013;154(9):1632-1639.
33. Vorobeychik Y, Gordin V, Mao J, Chen L. Combination Therapy for Neuropathic Pain. CNS Drugs. Dec 2011. 2012-01-12 2011;25(12):1023-1034.
BACKGROUND
• The elderly/geriatric population:
by 2030, will be about 70 million in the US4,5.
is anyone whom is 65 years or older2
has the highest prevalence of age-related comorbidities and chronic diseases,
including pains4
• Neuropathic pain (NP) :
 is one of the most common types of chronic pains in the elderly3
 arises from a lesion or a disease affecting the somatosensory system17
clinical manifestation is symptomatic experience of both parasthesias and
dysesthesia11
• Current pharmacological management include:
 TCA’s, SNRIs, calcium channel alpha 2 delta ligands, topical lidocaine 5%,
mu agonists, antiepileptics, and topical capsaicin (all strengths)17,18
 considerations for polypharmacy, multimorbidity, and age related changes in
pharmacokinetics4
• In 2002, insurance data showed that cost per patient with NP was $17 355 US vs.
$5 715 US without NP7
OBJECTIVES
 Discuss current pharmacological management.
 Identify adverse events associated with pharmacological treatment(s).
 Present potential comorbid conditions.
METHODS
Literature
Search
• Databases used: Science Direct, Proquest Central, Nation Institute of Health PubMed Central
• Key Words: neuropathic pain, management, epidemiology, elder, combination therapy, multimorbidity
• Applied Boolean Search Operator using “AND” to narrow our results
Search
Period
• 2000 to present
Inclusion
Criteria
• Full text only, English language, peer-reviewed, scholarly articles, relevance to objectives
Exclusion
Criteria
• Animal studies, non–English text, and expert review/opinions.
Results
• 5 primary references selected; 27secondary references selected
Pharmacological Stepwise Management
First Line
 TCAs
 SNRIs
 Calcium
channel α2-δ
ligands
 Lidocaine
Second Line
 Opiates
 Tramadol
Third Line
 Antiepileptic
 Topical Capsaicin
 Combination
therapy
RESULTS
References Study/Article types Objectives/Endpoints Comments
“Algorithm for Neuropathic Pain
Treatment: An evidenced based
proposal” by Finnerup et. al [2005]
 Meta-analyses of
randomized double-blind
placebo-controlled RCTs
 Up-to-date calculations of NNT and
NNH are used as the basis for
evidence-based treatment
algorithm.
 Lowest NNTs are: TCA’s, then
opioids, gabapentin, and
pregabalin in peripheral
neuropathic pain
 Limited data on central NP
“Pharmacologic management of
neuropathic pain: Evidence-based
recommendations” by Dworkin et. al
[2007]
 Meta-analyses of RCTs and
systematic reviews
 Review and
recommendations
 EBM Clinical Guidelines
 Review results of RCTs
 Present evidenced-based
guidelines for pharmacological
management
 Provide specific recommendations
based on statistically significant
efficacy data of the medications
and reduction of chronic NP.
 Endorsed by the American Pain
Society
 Only oral or topical
pharmacotherapy in adults are
presented in these guidelines
 Did not consider combination
therapy due to lack of data during
that period.
“The evidence for pharmacological
treatment of neuropathic pain” by
Finnerup et al. [2010]
 Updated meta-analyses of
double-blind placebo
controlled RCTs
 Up-to-date calculations of NNT and
NNH values in neuropathic pain
 Discussion of these measures for
treatment strategies
 Carbamazepine no longer
considered as a treatment option
 Combination therapy considered,
but discussion is limited due to
inadequate published studies
“Treatment Considerations for Elderly
and Frail Patients With Neuropathic
Pain” by Schmader et al. [2010]
 Supplemental article
 Primary and secondary
literature used
 Review how aging and frailty affect
the treatment of older adults with
neuropathic pain
 Discusses general considerations
for geriatric pharmacotherapy
“Combination Therapy for
Neuropathic Pain: A Review of
Current Evidence” by Vorobeychik et
al. [2011]
 Review article
 Primary and secondary
literature used ?????
 Summary of relevant information
on this topic
 Not intended to be an analytic
review
 Summarizes published RCTs
relevant to combination therapy
for non-cancer related NP and
cancer-related NP
DISCUSSION
Treatment Comorbid Considerations Comorbidity Precautions Polypharmacy Considerations Side Effects in Elderly Contraindicated
Co-morbidities
FirstLineTreatment
Calcium channel α2-δ
ligands5,10,16-18
 Gabapentin
 Pregabalin
Insomnia
Fibromyalgia (pregabalin)
Restless leg syndrome (pregabalin)
Partial onset seizures
Anxiety (pregabalin)
Mood (gabapentin)
ESRD (pregabalin)
Hepatic insufficiency (gabapentin)
Hepatic/renal insufficiency
Fall or fracture risk
Uncontrolled HTN
CHF
Known altered mental status
No clinically significant drug
interactions
Antacids reduce absorption
(gabapentin)
Drugs that are known to depress the
CNS
Peripheral edema
Cognitive impairment
Gait impairment
Blurred vision
 CHF class III/IV
SNRIs5,10,16-18
 Duloxetine
 Venlafaxine
Depression
Anxiety
Fibromyalgia (duloxetine)
Chronic arthritis pain (duloxetine)
Chronic lower back pain (duloxetine)
Hepatic/renal insufficiency
Seizure history
Uncontrolled HTN
(venlafaxine)
MAOIs
Serotonergics
NSAIDs
Warfarin
Blood pressure elevations
(minimal with duloxetine)
Hyponatremia
Constipation
Sedation
Arrhythmia
(venlafaxine)
Hepatic insufficiency
(duloxetine)
ESRD (duloxetine)
TCAs5,10,16-18
 Secondary
Nortripyline
Desipramine
 Tertriary
Amitrypyline
*use should be avoided
Insomnia
Depression
Overactive bladder
Alzheimer's patients treated
with ACh inhibitors
Known cognitive decline
Uncontrolled HTN
QTc prolonging drugs
MAOIs
Serotonergics
NSAIDs
Warfarin
Anticholinergic effects
Cognitive changes
Orthostasis (fall risk)
Hip fractures (nortriptyline)
Cardiotoxicity
Sedation
Weight gain
Blood pressure elevations
 Hepatic failure
 Heart block
 Recent MI
 Glaucoma
 Prostatic hypertrophy
 Urinary retention
 Chronic constipation
Lidocaine 5% patches5,10,16-
18
Localized pain History of adverse cardiac
events
Class I antiarrhythmics
(Minimal systemic absorption [<5%])
 Rash
 Erythema
 Broken skin
 Severe hepatic
impairment
SecondLineTreatment
Opioids5,10,16-18
 Morphine
 Oxycodone
 Methadone
 Levorphanol
 Tapentadol
 Oxymorphone
Breakthrough pain
Acute or chronic pain of other etiologies
History of adverse cardiac events
(tapentadol)
Severe renal insufficiency (CrCL
>30mL/min) (tapentadol)
Renal insufficiency
(morphine)
Hepatic impairment
History of substance abuse
COPD
Cardiac insufficiency
Known cognitive decline
QTc prolonging drugs (methadone)
Drugs that are known to depress the
CNS
MAOI
Anticoagulants
Drowsiness
Dizziness
Constipation
Gastroparesis
Impaired cognition
Pruritis
Respiratory Depression
Decrease in motor function (fall
risk)
Cardiovascular collapse
Hyperalgesia
 Ileus
 Arrhythmia
 Respiratory depression
Tramadol5,10,16-18 Breakthrough pain
Acute or chronic pain of other etiologies
Seizure history
Renal insufficiency
Hepatic impairment
Serotonergic
MAOIs
Antipsychotics
CYP450 2D6 inhibitors
CYP450 3A4 inhibitors
Medications that are known to
decrease seizure threshold
 Drowsiness
 Dizziness
 Constipation
 Seizure risk
 Orthostatic hypotension
ThirdLineTreatment
Anticonvulsants5,10,16-18
 Carbamazepine
 Lamotrigine
Epilepsy Renal insufficiency
Hepatic insufficiency
 Strong CYP inducers/inhibitors  Anticholinergic effects
 Drowsiness
 Dizziness
 Cognitive impairment
 Blurred vision
 Coordination difficulties
 AV block
Topical capsaicin5,10,16-18,32
 OTC and 8% (Rx)
Localized pain No known drug interactions  Erythema/local skin irritation Broken skin
Combination Therapy29, 33 Varies Varies  Varies Varies  Varies