Highlights
- •We conducted a randomized controlled trial of the effects of venlafaxine XR on spinal cord injury pain.
- •A total of 123 participants reported on 298 pain sites.
- •No effect was noted on neuropathic pain sites.
- •Some effects were noted for mixed pain sites.
- •Significant benefits in pain intensity and interference occurred for nociceptive pain.
Abstract
Objectives
To (1) determine the efficacy of venlafaxine XR for the treatment of pain (secondary
aim) in individuals with spinal cord injury (SCI) enrolled in a randomized controlled
trial (RCT) on the efficacy of venlafaxine XR for major depressive disorder (MDD)
(primary aim); and (2) test the hypothesis that venlafaxine XR would be effective
for both neuropathic and nociceptive pain.
Design
Multisite, double-blind, randomized (1:1) controlled trial with subjects block randomized
and stratified by site, lifetime history of substance abuse, and prior history of
MDD.
Setting
Six Departments of Physical Medicine and Rehabilitation in university-based medical
schools.
Participants
Individuals (N=123) with SCI and major depression between 18 and 64 years of age,
at least 1 month post-SCI who also reported pain.
Intervention
Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule.
Outcome Measures
A 0-to-10 numeric rating scale for pain, pain interference items of the Brief Pain
Inventory; 30% and 50% responders.
Results
The effect of venlafaxine XR on neuropathic pain was similar to that of placebo. However
venlafaxine XR resulted in statistically significant and clinically meaningful reductions
in nociceptive pain site intensity and interference even after controlling for anxiety,
depression, and multiple pain sites within the same individual. For those who achieved
a minimally effective dose of venlafaxine XR, some additional evidence of effectiveness
was noted for those with mixed (both neuropathic and nociceptive) pain sites.
Conclusions
Venlafaxine XR could complement current medications and procedures for treating pain
after SCI and MDD that has nociceptive features. Its usefulness for treating central
neuropathic pain is likely to be limited. Research is needed to replicate these findings
and determine whether the antinociceptive effect of venlafaxine XR generalizes to
persons with SCI pain without MDD.
Keywords
List of abbreviations:
GAD-7 (Generalized Anxiety Disorder-7 Scale), MDD (major depressive disorder), HAM-D (Hamilton Depression Rating Scale), SCI (spinal cord injury), SCIPI (Spinal Cord Injury Pain Instrument), SNRI (serotonin-norepinephrine reuptake inhibitor)To read this article in full you will need to make a payment
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References
- A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury.Pain. 2003; 103: 249-257
- Chronic pain problems in individuals with spinal cord injuries.Semin Clin Neuropsychiatry. 1999; 4: 186-194
- International Spinal Cord Injury Pain Classification: part I. Background and description.Spinal Cord. 2011; 50: 413-417
- International Spinal Cord Injury Pain (ISCIP) Classification: part 2. Initial validation using vignettes.Spinal Cord. 2012; 50: 404-412
- Pain following spinal cord injury: clinical features, prevalence, and taxonomy.IASP Newsletter. 2000; 3: 3-7
- Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial.Pain. 2002; 96: 365-373
- Anticonvulsant medication use for the management of pain following spinal cord injury: systematic review and effectiveness analysis.Spinal Cord. 2014; 52: 89-96
- Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury.Arch Phys Med Rehabil. 2007; 88: 1547-1560
- Trazodone hydrochloride in the treatment of dysesthetic pain in traumatic myelopathy: a randomized, double-blind, placebo-controlled study.Pain. 1987; 29: 151-161
- Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial.Pain. 2011; 152: 267-273
- A randomized controlled trial of venlafaxine XR for major depressive disorder after spinal cord injury: methods and lessons learned.J Spinal Cord Med. 2014; 37: 247-263
- Effectiveness of venlafaxine in patients hospitalized for major depression and melancholia.J Clin Psychiatry. 1995; 56: 450-458
- Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. The Venlafaxine XR 209 Study Group.J Clin Psychiatry. 1997; 58: 393-398
- Antidepressant efficacy of venlafaxine.Depress Anxiety. 2000; 12: 45-49
- Serotonin-norepinephrine reuptake inhibitors for the management of chemotherapy-induced peripheral neuropathy.Ann Pharmacother. 2014; 48: 626-632
- Evidence-based guideline: treatment of painful diabetic neuropathy—report of the American Association of Neuromuscular and Electrodiagnostic Medicine, the American Academy of Neurology, and the American Academy of Physical Medicine & Rehabilitation.Muscle Nerve. 2011; 43: 910-917
- Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis.Pain Physician. 2013; 16: E705-E714
- Efficacy of antidepressants as analgesics: a review.J Clin Pharmacol. 2012; 52: 6-17
- Systematic review: the treatment of noncardiac chest pain with antidepressants.Aliment Pharmacol Ther. 2012; 35: 493-500
- The use of antidepressants for headache prophylaxis.CNS Neurosci Ther. 2011; 17: 462-469
- Efficacy of venlafaxine extended-release monotherapy for first-episode depression with painful physical symptoms.Neuroreport. 2013; 24: 364-369
- Management of depression in the presence of pain symptoms.Psychiatr Danub. 2010; 22: 4-13
- The PHQ-9: validity of a brief depression symptom severity measure.J Gen Intern Med. 2001; 16: 606-613
- Diagnosis and definition of treatment-resistant depression.Biol Psychiatry. 2003; 53: 649-659
- Screening for neuropathic pain after spinal cord injury with the Spinal Cord Injury Pain Instrument (SCIPI): a validation study.Spinal Cord. 2014; 52: 407-412
- Pain assessment: global use of the Brief Pain Inventory.Ann Acad Med Singapore. 1994; 23: 129-138
- Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations.J Pain. 2008; 9: 105-121
- A structured interview version of the Hamilton Depression Rating Scale: evidence of reliability and versatility of the administration.J Psychiatr Res. 1990; 24: 335-350
- A brief measure for assessing generalized anxiety disorder: the GAD-7.Arch Intern Med. 2006; 166: 1092-1097
- Practical clinical trials for translating research to practice: design and measurement recommendations.Med Care. 2005; 43: 551-557
- Chronic pain and spinal cord injury: review and comment.Clin J Pain. 1992; 8: 119-122
- The International Spinal Cord Injury Basic Pain Dataset.Spinal Cord. 2008; 46: 818-823
- A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury.Neurology. 2013; 80: 533-539
- Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial.Neurology. 2006; 67: 1792-1800
- Cut point determination in the measurement of pain, and its relationship to psychosocial, and functional measures after traumatic spinal cord injury: a retrospective spinal cord injury model system analysis.Arch Phys Med Rehabil. 2011; 92: 419-424
- Development of a metric for a day of manageable pain control: derivation of pain severity cut-points for low back pain and osteoarthritis.Pain. 2003; 106: 35-42
- Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial.Pain. 2009; 146: 253-260
- Efficacy of venlafaxine for symptomatic relief in young adult patients with functional chest pain: a randomized, double-blind, placebo-controlled, crossover trial.Am J Gastroenterol. 2010; 105: 1504-1512
- Venlafaxine extended release in the short-term treatment of depressed and anxious primary care patients with multisomatoform disorder.J Clin Psychiatry. 2006; 67: 72-80
- A randomized, double-blind, placebo-controlled study of venlafaxine XR in out-patients with tension-type headache.Cephalalgia. 2007; 27: 315-324
- Escitalopram and venlafaxine for the prophylaxis of migraine headache without mood disorders.Clin Neuropharmacol. 2009; 32: 254-258
- Duloxetine versus placebo in patients with chronic low back pain: a 12-week, fixed-dose, randomized, double-blind trial.J Pain. 2010; 11: 1282-1290
- Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury.Pain. 2009; 141: 52-59
- Long-term use of gabapentin for treatment of pain following traumatic spinal cord injury.Clin J Pain. 2002; 18: 116-121
- Antidepressants for neuropathic pain: a Cochrane review.J Neurol Neurosurg Psychiatry. 2010; 81: 1372-1373
Article info
Publication history
Published online: December 16, 2014
Footnotes
The contents of this article were developed under a grant from the Department of Education, National Institute on Disability and Rehabilitation Research (grant no. H133A060107). However, those contents do not necessarily represent the policy of the Department of Education, and you should not assume endorsement by the Federal Government.
Supported by Pfizer in the form of study drug (0600B1-4439).
Clinical Trial Registry No.: NCT00592384.
Disclosures: none.
Identification
Copyright
© 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
