Amitriptyline for Pain


The effects of amitriptyline on knee pain management

Based on an article titled “Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double-blind, placebo-controlled trial” 

Originally written by: Wluka et al., 2021

By: Murielle Nsiela 

Amitriptyline is a drug available as a prescription drug used to treat migraines, back pains, and nerve pains at low doses.1 In addition, it can also be used as an antidepressant to treat depression and low mood. 

Amitriptyline as an antidepressant

As an antidepressant, the drug works by elevating a chemical in the brain known as serotonin, which improves mood. It further alters how the nerves receive pain signals, ultimately causing the pain to go away. The drug as an antidepressant takes effect within one to two weeks; however, reaching full efficacy can take between four to six weeks.2 

Amitriptyline as a painkiller

Amitriptyline as a painkiller also takes one to two weeks to take effect. However, it requires six weeks to take full effect as a painkiller. It is suggested to take the amitriptyline in the evening or before bed, as the drug can cause drowsiness. The drug is available in two different forms: a tablet and a liquid. Amitriptyline in both tablet and liquid forms has three different strengths: 10mg, 25mg, and 50mg. 

Furthermore, there is a selection of individuals that can and cannot take the drug. The drug is suitable for most adults over the age of 18 and children over the age of two. However, certain people cannot take the drug if they have had an allergic reaction to amitriptyline or other medication. In addition, if an individual has heart problems, the drug can exacerbate the situation. If they have a liver or kidney problem, epilepsy, and if they are pregnant or breastfeeding, they should consult their healthcare practitioner. This advice is also for individuals with type 1 or 2 diabetes, as the drug changes blood sugar levels, and for those who have taken antidepressants before, as other antidepressants can alter how amitriptyline works.1 

Side effects of amitriptyline

Like any other drug, amitriptyline does cause some side effects. However, as the doses administered are lower for pain management compared to antidepressant dosage, the side effects are milder and tend to disappear after a few days. Common side effects include constipation, drowsiness, dry mouth, dizziness, difficulty in urinating, and headaches. However, the more severe side effects include irregular heartbeat, muscle cramps, feeling weak, suicidal thoughts, yellow skin, and swelling or redness of the eyes.1 

Drug-drug interactions

Other prescribed drugs can interact with amitriptyline, such as Benadryl, fish oil, paracetamol, Nexium, Lexapro, Zoloft, vitamin C, vitamin B12, and vitamin D3. These drugs can, therefore, not be administered at the same time as amitriptyline, as it can cause serious side effects. Furthermore, there is an interaction of amitriptyline with alcohol, so individuals are advised to seek a doctor’s opinion before taking the drug if they are planning on drinking alcohol around the same time.3 

As amitriptyline is used to treat pain, a clinical study by Wluka et al., (2021), was carried out to determine whether using low dose amitriptyline decreases pain in individuals with knee osteoarthritis compared to benztropine used as an active placebo over three months. Knee osteoarthritis causes pain and disability, and is estimated to affect 654 million globally.4 Individuals with osteoarthritis generally live with extreme chronic pain.5 The disease affects and limits knee function, affects the quality of life of an individual, and further leads to joint replacements, which can be costly.6 Generally, osteoarthritis management aims to decrease pain, reduce disease progression, and improve function.12

The management guidelines focus on educating patients on the disease, managing weight, and exercise therapy; however, these interventions are not as effective.7, 8 The other intervention for knee pain includes using medicines; however, the effects of medicines are limited. Taking paracetamol as an example, this has been said to have few clinical benefits.9 In addition, the use of Non-steroidal anti-inflammatory drugs (NSAIDs) does provide small to moderate effects on pain reduction. However, these have serious side effects, especially amongst the elderly, therefore limiting their effectiveness.10 Therefore, there is an unmet need for pain control in individuals with knee osteoarthritis.11, 12 

The study has the potential of providing a new therapeutic approach to the treatment of knee osteoarthritis. It is repurposing the use of an old drug that most clinicians are aware of to treat a different issue. 160 individuals with knee osteoarthritis were recruited for the study. The participants were randomly divided into two groups and given low dose amitriptyline (25mg) or the placebo benztropine (1mg). The study looked at two outcomes in participants: whether knee pain was reduced and whether there was an improvement in function.12  


Overall, the study found that a small but significant proportion of individuals benefited from using amitriptyline. Therefore, the study protocol suggested that amitriptyline can potentially provide a new avenue of treatment for knee osteoarthritis. 


  1. Amitriptyline: a medicine used to treat pain and prevent migraine [Internet]. 2020 [cited 25 March 2022]. Available from: 
  2. Amitriptyline: an antidepressant medicine [Internet]. 2022 [cited 25 March 2022]. Available from: 
  3. Amitriptyline Interactions [Internet]. 2022 [cited 25 March 2022]. Available from: 
  4. Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020;29:100587 
  5. Conaghan PG, Peloso PM, Everett SV, Rajagopalan S, Black CM, Mavros P, et al. Inadequate pain relief and large functional loss among patients with knee osteoarthritis: evidence from a prospective multinational longitudinal study of osteoarthritis real-world therapies. Rheumatology (Oxford). 2015;54(2):270–7 
  6. Dawson L, Wluka AE, Wang Y, Cicuttini FM. Obesity, arthritis and gout. In: Bray G, Bouchard C, editors. Handbook of Obesity. New York: Dekker & Co; 2014. 
  7. Nelson AE, Allen KD, Golightly YM, Goode AP, Jordan JM. A systematic review of recommendations and guidelines for the management of osteoarthritis: the chronic osteoarthritis management initiative of the U.S. bone and joint initiative. Semin Arthritis Rheum. 2014;43(6):701–12
  8. Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil. 2010;18(4):476–99
  9. Leopoldino AO, Machado GC, Ferreira PH, Pinheiro MB, Day R, McLachlan AJ, et al. Paracetamol versus placebo for knee and hip osteoarthritis. Cochrane Database Syst Rev. 2019;2(8)
  10. da Costa BR, Reichenbach S, Keller N, Nartey L, Wandel S, Jüni P, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2017;390(10090):e21–33 
  11. Thorlund JB, Turkiewicz A, Prieto-Alhambra D, Englund M. Opioid use in knee or hip osteoarthritis: a region-wide population-based cohort study. Osteoarthr Cartil. 2019;27(6):871–7
  12. Wluka A, Urquhart D, Teichtahl A, Hussain S, Forbes A, Arnold C et al. Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double blind, placebo-controlled trial. BMC Musculoskeletal Disorders. 2021;22(1).  



Author: Murielle Nsiela

MSc Graduate in Medical Engineering - Bachelor's degree, Pharmaceutical Science, Keele University, Staffordshire UK

MSc in Medical Engineering Design, Keele University Modules included: Advanced engineering applications, Engineering for medical applications report, Bioreactors and Growth environment, Creative engineering design, Experimental research methodology and research projects

BSc (Hons) Pharmaceutical Science, Technology and Business, Keele University Modules included: Core topics in pharmaceutical science, Laboratory studies - tabletting and liposomes report, applied Pharmaceutical Science 2, Pharmaceutical research project

Klarity logo in white
Klarity is a citizen-centric health data management platform that enables citizens to securely access, control and share their own health data. Klarity Health Library aims to provide clear and evidence-based health and wellness related informative articles.