Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Aug 5;8(8):CD012535.
doi: 10.1002/14651858.CD012535.pub2.

Antidepressants for chronic non-cancer pain in children and adolescents

Tess E Cooper  1 , Lauren C Heathcote, Jacqui Clinch, Jeffrey I Gold, Richard Howard, Susan M Lord, Neil Schechter, Chantal Wood, Philip J Wiffen
Affiliations

Antidepressants for chronic non-cancer pain in children and adolescents

Tess E Cooper et al. Cochrane Database Syst Rev. .

Abstract

Background: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Antidepressants have been used in adults for pain relief and pain management since the 1970s. The clinical impression from extended use over many years is that antidepressants are useful for some neuropathic pain symptoms, and that effects on pain relief are divorced and different from effects on depression; for example, the effects of tricyclic antidepressants on pain may occur at different, and often lower, doses than those on depression. Amitriptyline is one of the most commonly used drugs for treating neuropathic pain in the UK.

Objectives: To assess the analgesic efficacy and adverse events of antidepressants used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.

Selection criteria: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any antidepressant with placebo or an active comparator.

Data collection and analysis: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed the evidence using GRADE and created three 'Summary of findings' tables.

Main results: We included four studies with a total of 272 participants (6 to 18 years of age) who had either chronic neuropathic pain, complex regional pain syndrome type 1, irritable bowel syndrome, functional abdominal pain, or functional dyspepsia. All of the studies were small. One study investigated amitriptyline versus gabapentin (34 participants), two studies investigated amitriptyline versus placebo (123 participants), and one study investigated citalopram versus placebo (115 participants). Due to a lack of available data we were unable to complete any quantitative analysis.Risk of bias for the four included studies varied, due to issues with randomisation and allocation concealment (low to unclear risk); blinding of participants, personnel, and outcome assessors (low to unclear risk); reporting of results (low to unclear risk); and size of the study populations (high risk). We judged the remaining domains, attrition and other potential sources of bias, as low risk of bias. Primary outcomesNo studies reported our primary outcomes of participant-reported pain relief of 30% or greater or 50% or greater (very low-quality evidence).No studies reported on Patient Global Impression of Change (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) as very low. We downgraded the quality of the evidence by three levels to very low because there was no evidence to support or refute. Secondary outcomesAll studies measured adverse events, with very few reported (11 out of 272 participants). All but one adverse event occurred in the active treatment groups (amitriptyline, citalopram, and gabapentin). Adverse events in all studies, across active treatment and comparator groups, were considered to be a mild reaction, such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort (very low-quality evidence).There were also very few withdrawals due to adverse events, again all but one from the active treatment groups (very low-quality evidence).No serious adverse events were reported across any of the studies (very low-quality evidence).There were few or no data for our remaining secondary outcomes (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) for these secondary outcomes as very low. We downgraded the quality of the evidence by three levels to very low due to too few data and the fact that the number of events was too small to be meaningful.

Authors' conclusions: We identified only a small number of studies with small numbers of participants and insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of antidepressants to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.There is evidence from adult randomised controlled trials that some antidepressants, such as amitriptyline, can provide some pain relief in certain chronic non-cancer pain conditions.There is no evidence from randomised controlled trials to support or refute the use of antidepressants to treat chronic non-cancer pain in children or adolescents.

PubMed Disclaimer

Conflict of interest statement

PW: none known.

TC: none known.

LH: none known.

JC: none known; JC is a specialist paediatric pain physician and treats patients with complex pain.

JG: none known; JG is a paediatric psychologist specialising in the assessment/evaluation and treatment of children and adolescents with chronic pain.

RH: none known; RH is a specialist paediatric pain clinician and treats patients with chronic pain.

SL: none known; SL is a specialist paediatric pain clinician and treats patients with chronic pain.

NS: none known; NS is a developmental paediatrician and treats children and adolescents with pain; NS directs the Chronic Pain Clinic at Boston Children’s Hospital and is on the faculty at Harvard Medical School.

CW: none known; CW is a paediatrician and anaesthesiologist; CW specialises in pain and treats children and adults presenting chronic pain; CW also treats patients in palliative care.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Bahar 2008 {published data only}
    1. Bahar RJ, Collins BS, Steinmetz B, Ament ME. Double‐blind placebo‐controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents. Journal of Pediatrics 2008;152(5):685‐9. - PubMed
Brown 2016 {published data only}
    1. Brown SC, Johnston BC, Amaria K, Watkins J, Campbell F, Pehora C, et al. A randomized controlled trial of amitriptyline versus gabapentin for complex regional pain syndrome type I and neuropathic pain in children. Scandinavian Journal of Pain 2016;13:156‐63. - PubMed
Roohafza 2014 {published data only}
    1. Roohafza H, Pourmoghaddas Z, Saneian H, Gholamrezaei A. Citalopram for pediatric functional abdominal pain: a randomized, placebo‐controlled trial. Neurogastroenterology & Motility 2014;26(11):1642‐50. - PubMed
Saps 2009 {published data only}
    1. Chogle A, Saps M. Electrocardiograms changes in children with functional gastrointestinal disorders on low dose amitriptyline. World Journal of Gastroenterology 2014;20(32):11321‐5. - PMC - PubMed
    1. Saps M, Youssef NN, Miranda A, Nurko S, Hyman PE, Cocjin JT, et al. A multicenter randomized double blind placebo controlled study on the efficacy of amitriptyline in functional abdominal pain in children: effect of seasonal variation. Gastroenterology 2009;136(5 Suppl 1):A157.

References to studies excluded from this review

Agius 2013 {published data only}
    1. Agius AM, Jones NS, Muscat R. A randomized controlled trial comparing the efficacy of low‐dose amitriptyline, amitriptyline with pindolol and surrogate placebo in the treatment of chronic tension‐type facial pain. Rhinology 2013;51(2):143‐53. - PubMed
Alencar 2014 {published data only}
    1. Alencar FGP Jr, Viana PG, Zamperini C, Becker A. Patient education and self‐care for the management of jaw pain upon awakening: a randomized controlled clinical trial comparing the effectiveness of adding pharmacologic treatment with cyclobenzaprine or tizanidine. Journal of Oral & Facial Pain and Headache 2014;28(2):119‐27. - PubMed
Arnold 2015 {published data only}
    1. Arnold LM, Bateman L, Palmer RH, Lin Y. Preliminary experience using milnacipran in patients with juvenile fibromyalgia: lessons from a clinical trial program. Pediatric Rheumatology 2015;13(1):no pagination. - PMC - PubMed
Chappell 2009 {published data only}
    1. Chappell AS, Littlejohn G, Kajdasz DK, Scheinberg M, D'Souza DN, Moldofsky H. A 1‐year safety and efficacy study of duloxetine in patients with fibromyalgia. Clinical Journal of Pain 2009;25(5):365‐75. - PubMed
Guler 2005 {published data only}
    1. Guler N, Durmus E, Tuncer S. Long‐term follow‐up of patients with atypical facial pain treated with amitriptyline. New York State Dental Journal 2005;71(4):38‐42. - PubMed
Huber 2007 {published data only}
    1. Huber AM, Tomlinson GA, Koren G, Feldman BM. Amitriptyline to relieve pain in juvenile idiopathic arthritis: a pilot study using Bayesian metaanalysis of multiple N‐of‐1 clinical trials. Journal of Rheumatology 2007;31(5):1125‐32. - PubMed
Johnson 1997 {published data only}
    1. Johnson SP. Fluoxetine and amitriptyline in the treatment of fibromyalgia. Journal of Family Practice 1997;44(2):128‐30. - PubMed
Kalita 2014 {published data only}
    1. Kalita J, Kohat AK, Misra UK, Bhoi SK. An open labeled randomized controlled trial of pregabalin versus amitriptyline in chronic low backache. Journal of the Neurological Sciences 2014;342(1‐2):127‐32. - PubMed
Talaei 2009 {published data only}
    1. Talaei A, Siavash M, Majidi H, Chehrei A. Vitamin B12 may be more effective than nortriptyline in improving painful diabetic neuropathy. International Journal of Food Sciences and Nutrition 2009;60 Suppl 5:71‐6. - PubMed

Additional references

AMA 2013
    1. American Medical Association. Pediatric pain management. https://www.ama‐assn.org/ (accessed 25 January 2016).
AUREF 2012
    1. Cochrane Pain, Palliative and Supportive Care Group. PaPaS author and referee guidance. papas.cochrane.org/papas‐documents (accessed 16 July 2016).
Caes 2016
    1. Caes L, Boemer KE, Chambers CT, Campbell‐Yeo M, Stinson J, Birnie KA, et al. A comprehensive categorical and bibliometric analysis of published research articles on pediatric pain from 1975 to 2010. Pain 2016;157(2):302‐13. [DOI: 10.1097/j.pain.0000000000000403] - DOI - PubMed
Cooper 2017a
    1. Cooper TE, Fisher E, Gray A, Krane E, Sethna NF, Tilburg M, et al. Opioids for chronic non‐cancer pain in children and adolescents. Cochrane Database of Systematic Reviews 2017, Issue 7. [DOI: 10.1002/14651858.CD012538.pub2] - DOI - PMC - PubMed
Cooper 2017b
    1. Cooper TE, Heathcote L, Clinch J, Howard R, Krane E, Wiffen PJ. Antiepileptic drugs for chronic non‐cancer pain in children and adolescents. Cochrane Database of Systematic Reviews 2017, Issue 8. [DOI: 10.1002/14651858.CD012536.pub2] - DOI - PMC - PubMed
Cooper 2017c
    1. Cooper TE, Heathcote L, Anderson B, Gregoire MC, Ljungman G, Eccleston C. Non‐steroidal anti‐inflammatory drugs (NSAIDs) for cancer‐related pain in children and adolescents. Cochrane Database of Systematic Reviews 2017, Issue 7. [DOI: 10.1002/14651858.CD012563.pub2] - DOI - PMC - PubMed
Cooper 2017d
    1. Cooper TE, Fisher E, Anderson B, Wilkinson N, Williams G, Eccleston C. Paracetamol (acetaminophen) for chronic non‐cancer pain in children and adolescents. Cochrane Database of Systematic Reviews 2017, Issue 8. [DOI: 10.1002/14651858.CD012539.pub2] - DOI - PMC - PubMed
Dechartres 2013
    1. Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta‐epidemiological study. BMJ 2013;346:f2304. [DOI: 10.1136/bmj.f2304] - DOI - PMC - PubMed
Dechartres 2014
    1. Dechartres A, Altman DG, Trinquart L, Boutron I, Ravaud P. Association between analytic strategy and estimates of treatment outcomes in meta‐analyses. JAMA 2014;312:623‐30. [DOI: 10.1001/jama.2014.8166] - DOI - PubMed
Dharmshaktu 2012
    1. Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: a review. Journal of Clinical Pharmacology 2012;52(1):6‐17. - PubMed
Dickenson 2007
    1. Dickenson AH, Ghandehari J. Anti‐convulsants and anti‐depressants. Handbook of Experimental Pharmacology 2007;177:145‐77. - PubMed
Dworkin 2008
    1. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. Journal of Pain 2008;9(2):105‐21. [DOI: 10.1016/j.jpain.2007.09.005] - DOI - PubMed
Eccleston 2003
    1. Eccleston C, Malleson PM. Management of chronic pain in children and adolescents (Editorial). BMJ 2003;326:1408‐9. - PMC - PubMed
Eccleston 2017
    1. Eccleston C, Cooper TE, Fisher E, Anderson B, Wilkinson N. Non‐steroidal anti‐inflammatory drugs (NSAIDs) for chronic non‐cancer pain in children and adolescents. Cochrane Database of Systematic Reviews 2017, Issue 8. [DOI: 10.1002/14651858.CD012537.pub2] - DOI - PMC - PubMed
Finnerup 2015
    1. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta‐analysis. Lancet Neurology 2015;14(2):162‐73. - PMC - PubMed
Guyatt 2008
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck‐Ytter Y, Alonso‐Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924‐6. [DOI: 10.1136/bmj.39489.470347.AD] - DOI - PMC - PubMed
Guyatt 2011
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction ‐ GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64:383‐94. [DOI: 10.1016/j.jclinepi.2010.04.026] - DOI - PubMed
Guyatt 2013a
    1. Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso‐Coelle P, et al. Making an overall rating of the confidence in effect estimates for a single outcome and for all outcomes. Journal of Clinical Epidemiology 2013;66(2):151‐7. [DOI: 10.1016/j.jclinepi.2012.01.006] - DOI - PubMed
Guyatt 2013b
    1. Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables ‐ binary outcomes. Journal of Clinical Epidemiology 2013;66(2):158‐72. [DOI: 10.1016/j.jclinepi.2012.01.012] - DOI - PubMed
Hall 2013
    1. Hall GC, Morant SV, Carroll D, Gabriel ZL, McQuay HJ. An observational descriptive study of the epidemiology and treatment of neuropathic pain in a UK general population. BMC Family Practice 2013;14:28. [DOI: 10.1186/1471-2296-14-28] - DOI - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Hoffman 2010
    1. Hoffman DL, Sadosky A, Dukes EM, Alvir J. How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy?. Pain 2010;149(2):194‐201. [DOI: 10.1016/j.pain.2009.09.017] - DOI - PubMed
L'Abbé 1987
    1. L'Abbé KA, Detsky AS, O'Rourke K. Meta‐analysis in clinical research. Annals of Internal Medicine 1987;107:224‐33. - PubMed
McQuay 1998
    1. McQuay H, Moore R. An Evidence‐based Resource for Pain Relief. Oxford (UK): Oxford University Press, 1998.
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, the PRISMA Group. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Medicine 2009;6(7):e1000097. - PMC - PubMed
Moore 2008
    1. Moore RA, Barden J, Derry S, McQuay HJ. Managing potential publication bias. In: McQuay HJ, Kalso E, Moore RA editor(s). Systematic Reviews in Pain Research: Methodology Refined. Seattle (WA): IASP Press, 2008:15‐24. [ISBN: 978‐0‐931092‐69‐5]
Moore 2009
    1. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD007076.pub2] - DOI - PMC - PubMed
Moore 2010a
    1. Moore RA, Eccleston C, Derry S, Wiffen P, Bell RF, Straube S, et al. "Evidence" in chronic pain ‐ establishing best practice in the reporting of systematic reviews. Pain 2010;150(3):386‐9. [DOI: 10.1016/j.pain.2010.05.011] - DOI - PubMed
Moore 2010b
    1. Moore RA, Straube S, Paine J, Phillips CJ, Derry S, McQuay HJ. Fibromyalgia: moderate and substantial pain intensity reduction predicts improvement in other outcomes and substantial quality of life gain. Pain 2010;149(2):360‐4. - PubMed
Moore 2010c
    1. Moore RA, Moore OA, Derry S, Peloso PM, Gammaitoni AR, Wang H. Responder analysis for pain relief and numbers needed to treat in a meta‐analysis of etoricoxib osteoarthritis trials: bridging a gap between clinical trials and clinical practice. Annals of the Rheumatic Diseases 2010;69(2):374‐9. [DOI: 10.1136/ard.2009.107805] - DOI - PMC - PubMed
Moore 2010d
    1. Moore RA, Smugar SS, Wang H, Peloso PM, Gammaitoni A. Numbers‐needed‐to‐treat analyses ‐ do timing, dropouts, and outcome matter? Pooled analysis of two randomized, placebo‐controlled chronic low back pain trials. Pain 2010;151(3):592‐7. [DOI: 10.1016/j.pain.2010.07.2013] - DOI - PubMed
Moore 2010e
    1. Moore RA, Derry S, McQuay HJ, Straube S, Aldington D, Wiffen P, et al. ACTINPAIN writing group of the IASP Special Interest Group (SIG) on Systematic Reviews in Pain Relief. Clinical effectiveness: an approach to clinical trial design more relevant to clinical practice, acknowledging the importance of individual differences. Pain 2010;149:173‐6. [PUBMED: 19748185] - PubMed
Moore 2011a
    1. Moore RA, Straube S, Paine J, Derry S, McQuay HJ. Minimum efficacy criteria for comparisons between treatments using individual patient meta‐analysis of acute pain trials: examples of etoricoxib, paracetamol, ibuprofen, and ibuprofen/paracetamol combinations after third molar extraction. Pain 2011;152(5):982‐9. [DOI: 10.1016/j.pain.2010.11.030] - DOI - PubMed
Moore 2011b
    1. Moore RA, Mhuircheartaigh RJ, Derry S, McQuay HJ. Mean analgesic consumption is inappropriate for testing analgesic efficacy in post‐operative pain: analysis and alternative suggestion. European Journal of Anaesthesiology 2011;28(6):427‐32. [DOI: 10.1097/EJA.0b013e328343c569] - DOI - PubMed
Moore 2012
    1. Moore RA, Straube S, Eccleston C, Derry S, Aldington D, Wiffen P, et al. Estimate at your peril: imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses. Pain 2012;153(2):265‐8. [DOI: 10.1016/j.pain.2011.10.004] - DOI - PubMed
Moore 2013a
    1. Moore RA, Straube S, Aldington D. Pain measures and cut‐offs ‐ 'no worse than mild pain' as a simple, universal outcome. Anaesthesia 2013;68(4):400‐12. [DOI: 10.1111/anae.12148] - DOI - PubMed
Moore 2013b
    1. Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. BMJ 2013;346:f2690. [DOI: 10.1136/bmj.f2690] - DOI - PubMed
Moore 2014a
    1. Moore RA, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non‐cancer pain and chronic neuropathic pain. Pain Practice 2014;14(1):79‐94. - PubMed
Moore 2014b
    1. Moore RA, Cai N, Skljarevski V, Tölle TR. Duloxetine use in chronic painful conditions ‐ individual patient data responder analysis. European Journal of Pain 2014;18(1):67‐75. [DOI: 10.1002/j.1532-2149.2013.00341.x] - DOI - PMC - PubMed
Moore 2015
    1. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database of Systematic Reviews 2015, Issue 7. [DOI: 10.1002/14651858.CD008242.pub3] - DOI - PMC - PubMed
Moulin 2014
    1. Moulin D, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Research and Management 2014;19(6):328‐35. - PMC - PubMed
NICE 2013
    1. National Institute for Health and Care Excellence (NICE). Neuropathic pain ‐ pharmacological management: the pharmacological management of neuropathic pain in adults in non‐specialist settings. www.nice.org.uk/guidance/cg173 (accessed 17 October 2016).
Nüesch 2010
    1. Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, et al. Small study effects in meta‐analyses of osteoarthritis trials: meta‐epidemiological study. BMJ 2010;341:c3515. [DOI: 10.1136/bmj.c3515] - DOI - PMC - PubMed
O'Brien 2010
    1. O'Brien EM, Staud RM, Hassinger AD, McCulloch RC, Craggs JG, Atchinson JW, et al. Patient‐centered perspective on treatment outcomes in chronic pain. Pain Medicine 2010;11(1):6‐15. [DOI: 10.1111/j.1526-4637.2009.00685.x] - DOI - PubMed
PedIMMPACT 2008
    1. McGrath PJ, Walco GA, Turk DC, Dworking RH, Brown MT, Davidson K, et al. Core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials: PedIMMPACT. Journal of Pain 2008;9(9):771‐83. - PubMed
RevMan 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Ripamonti 2008
    1. Ripamonti C, Bandieri E. Pain therapy. Critical Reviews in Oncology/Hematology 2008;70:145‐59. [DOI: 10.1016/j.critrevonc.2008.12.005] - DOI - PubMed
Stinson 2006
    1. Stinson JN, Kavanagh T, Yamada J, Gill N, Stevens B. Systematic review of the psychometric properties, interpretability and feasibility of self‐report pain intensity measures for use in clinical trials in children and adolescents. Pain 2006;125(1‐2):143‐57. [DOI: 10.1016/j.pain.2006.05.006] - DOI - PubMed
Straube 2008
    1. Straube S, Derry S, McQuay HJ, Moore RA. Enriched enrolment: definition and effects of enrichment and dose in trials of pregabalin and gabapentin in neuropathic pain. A systematic review. British Journal of Clinical Pharmacology 2008;66(2):266‐75. [DOI: 10.1111/j.1365-2125.2008.03200.x] - DOI - PMC - PubMed
Straube 2010
    1. Straube S, Derry S, Moore RA, Paine J, McQuay HJ. Pregabalin in fibromyalgia ‐ responder analysis from individual patient data. BMC Musculoskeletal Disorders 2010;11:150. [DOI: 10.1186/1471-2474-11-150] - DOI - PMC - PubMed
Sultan 2008
    1. Sultan A, Gaskell H, Derry S, Moore RA. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials. BMC Neurology 2008;8:29. [DOI: 10.1186/1471-2377-8-29] - DOI - PMC - PubMed
Thorlund 2011
    1. Thorlund K, Imberger G, Walsh M, Chu R, Gluud C, Wetterslev J, et al. The number of patients and events required to limit the risk of overestimation of intervention effects in meta‐analysis ‐ a simulation study. PLoS ONE 2011;6(10):e25491. [DOI: 10.1371/journal.pone.0025491] - DOI - PMC - PubMed
United Nations 2015
    1. United Nations. World population prospects 2015 ‐ population indicators. esa.un.org/unpd/wpp/Download/Standard/Population/ (accessed 29 February 2016).
von Baeyer 2007
    1. Baeyer CL, Spagrud LJ. Systematic review of observational (behavioural) measures of pain for children and adolescents aged 3 to 18 years. Pain 2007;127(1‐2):140‐50. [DOI: 10.1016/j.pain.2006.08.014] - DOI - PubMed
Walsh 1983
    1. Walsh TD. Antidepressants in chronic pain. Clinical Neuropharmacology 1983;6(4):271‐95. - PubMed
Watson 1982
    1. Watson CP, Evans RJ, Reed K, Merskey H, Goldsmith L, Warsh J. Amitriptyline versus placebo in postherpetic neuralgia. Neurology 1982;32(6):671‐3. - PubMed
Watson 1998
    1. Watson CP, Vernich L, Chipman M, Reed K. Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial. Neurology 1998;51(4):1166‐71. - PubMed
WHO 2012
    1. World Health Organization. WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses. Geneva: WHO Press, World Health Organization, 2012. [ISBN 978 92 4 154812 0] - PubMed
Wiffen 2017a
    1. Wiffen P, Cooper T, Anderson AK, Gray A, Gregoire MC, Ljungman G, et al. Opioids for cancer‐related pain in children and adolescents. Cochrane Database of Systematic Reviews 2017, Issue 7. [DOI: 10.1002/14651858.CD012564.pub2] - DOI - PMC - PubMed
World Bank 2014
    1. World Bank. Data ‐ population ages 0‐14 (% of total). data.worldbank.org/indicator/SP.POP.0014.TO.ZS (accessed 29 February 2016).

Publication types

MeSH terms

LinkOut - more resources