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The Cochrane Database of Systematic... May 2019This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the efficacy... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the efficacy of amitriptyline for neuropathic pain is now dealt with in a separate review. Amitriptyline is a tricyclic antidepressant that is widely used to treat fibromyalgia, and is recommended in many guidelines. It is usually used at doses below those at which the drugs act as antidepressants.
OBJECTIVES
To assess the analgesic efficacy of amitriptyline for relief of fibromyalgia, and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with reference lists of retrieved papers, previous systematic reviews and other reviews, and two clinical trial registries. We also used our own hand searched database for older studies.
SELECTION CRITERIA
We included randomised, double-blind studies of at least four weeks' duration comparing amitriptyline with placebo or another active treatment in fibromyalgia.
DATA COLLECTION AND ANALYSIS
We extracted efficacy and adverse event data, and two study authors examined issues of study quality independently. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both. For efficacy, we calculated the number needed to treat to benefit (NNT), and for harm we calculated the number needed to treat to harm (NNH) for adverse events and withdrawals. We used a fixed-effect model for meta-analysis.
MAIN RESULTS
We included seven studies from the earlier review and two new studies (nine studies, 649 participants) of 6 to 24 weeks' duration, enrolling between 22 and 208 participants; none had 50 or more participants in each treatment arm. Two studies used a cross-over design. The daily dose of amitriptyline was 25 mg to 50 mg, and some studies had an initial titration period. There was no first or second tier evidence for amitriptyline in the treatment of fibromyalgia. Using third tier evidence the risk ratio (RR) for at least 50% pain relief, or equivalent, with amitriptyline compared with placebo was 3.0 (95% confidence interval (CI) 1.7 to 4.9), with an NNT) of 4.1 (2.9 to 6.7) (very low quality evidence). There were no consistent differences between amitriptyline and placebo or other active comparators for relief of symptoms such as fatigue, poor sleep, quality of life, or tender points. More participants experienced at least one adverse event with amitriptyline (78%) than with placebo (47%). The RR was 1.5 (1.3 to 1.8) and the NNH was 3.3 (2.5 to 4.9). Adverse event and all-cause withdrawals were not different, but lack of efficacy withdrawals were more common with placebo (12% versus 5%; RR 0.42 (0.19 to 0.95)) (very low quality evidence).
AUTHORS' CONCLUSIONS
Amitriptyline has been a first-line treatment for fibromyalgia for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against years of successful treatment in many patients with fibromyalgia. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline will be one option in the treatment of fibromyalgia, while recognising that only a minority of patients will achieve satisfactory pain relief. It is unlikely that any large randomised trials of amitriptyline will be conducted in fibromyalgia to establish efficacy statistically, or measure the size of the effect.
PubMed: 35658166
DOI: 10.1002/14651858.CD011824 -
Drug Delivery and Translational Research Apr 2022Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical...
Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical properties of the molecule, amitriptyline is also a promising candidate for delivery as a topical analgesic. Here we report the dermal delivery of amitriptyline from a range of simple formulations. The first stage of the work required the conversion of amitriptyline hydrochloride to the free base form as confirmed by nuclear magnetic resonance (NMR). Distribution coefficient values were measured at pH 6, 6.5, 7, and 7.4. Solubility and stability of amitriptyline were assessed prior to conducting in vitro permeation and mass balance studies. The compound demonstrated instability in phosphate-buffered saline (PBS) dependent on pH. Volatile formulations comprising of isopropyl alcohol (IPA) and isopropyl myristate (IPM) or propylene glycol (PG) were evaluated in porcine skin under finite dose conditions. Compared with neat IPM, the IPM:IPA vehicles promoted 8-fold and 5-fold increases in the amount of amitriptyline that permeated at 24 h. Formulations containing PG also appear to be promising vehicles for dermal delivery of amitriptyline, typically delivering higher amounts of amitriptyline than the IPM:IPA vehicles. The results reported here suggest that further optimization of topical amitriptyline formulations should be pursued towards development of a product for clinical investigational studies.
Topics: Administration, Cutaneous; Amitriptyline; Analgesia; Analgesics; Animals; Excipients; Propylene Glycol; Skin; Skin Absorption; Swine
PubMed: 33886076
DOI: 10.1007/s13346-021-00982-x -
Australian Prescriber Oct 2017
Review
PubMed: 29109601
DOI: 10.18773/austprescr.2017.056 -
Annals of the Academy of Medicine,... Apr 2020Amitriptyline (AMT) is a tricyclic antidepressant. In this review, we evaluate the clinical and epidemiological profile, pathological mechanisms and management of... (Review)
Review
INTRODUCTION
Amitriptyline (AMT) is a tricyclic antidepressant. In this review, we evaluate the clinical and epidemiological profile, pathological mechanisms and management of AMT-associated movement disorders.
MATERIALS AND METHODS
A search for relevant reports in 6 databases was performed. Studies that reported patients developed only ataxia or tremor after AMT use were excluded.
RESULTS
A total of 48 reports on 200 cases were found. AMT-associated movement disorders included myoclonus (n = 26), dyskinesia (n = 11), dystonia (n = 8), stutter (n = 5), akathisia (n = 3) and restless legs syndrome (n = 1). For less well-defined cases, 99 patients had dyskinesia, 19 had psychomotor disturbances, 3 had myoclonus, 11 had dystonia, 12 had Parkinsonism and 1 each had akathisia and extrapyramidal symptoms. Mean and standard deviation (SD) and median ages were 45.40 years (SD 16.78) and 40 years (range 3.7-82 years), respectively. Over half were women (58.13%) and the most common indication was depression. Mean and median AMT doses were 126 mg (SD 128.76) and 75 mg (range 15-800 mg), respectively. In 68% of patients, onset of movement disorders was <1 month; time from AMT withdrawal to complete recovery was <1 month in 70% of cases. A weak negative linear correlation (r = -0.0904) was found between onset of movement disorders and AMT dose. AMT withdrawal was the most common treatment.
CONCLUSION
Amitriptyline is associated with various movement disorders, particularly myoclonus, dystonia and dyskinesias. Stutters and restless legs syndrome are some of the less common associations.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Humans; Movement Disorders
PubMed: 32419008
DOI: No ID Found -
American Journal of Men's Health Mar 2018Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with... (Meta-Analysis)
Meta-Analysis Review
Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with amitriptyline comes from only one clinical trial and several case reports from three decades ago. In the current study, a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) related to amitriptyline and sexual dysfunction (SD) was performed. The frequency, gender-difference, types, disease-specificity and time course of SD, and the relationship between SD and nonsexual adversity were studied. A total of 14 publications, including 8 qualified randomized clinical trials, were eligible. The frequency of SD in overall, male and female patients was 5.7, 11.9 and 1.7%, respectively. SD was six-fold higher in men than women. The frequency of SD was 6.9% in depressive patients compared with 0.8% in non-depressive patients ( p = .008), and gradually decreased at 8 weeks after treatment ( p = .02). Amitriptyline impacted arousal and libido more than orgasm and ejaculation in male patients but mainly libido in female patients. SD was significantly correlated with insomnia linearly whereas somnolence and nausea dually. Therefore, amitriptyline-associated SD mainly occurs in depressive and male patients, disturbs each phase of the sexual response cycle in men but mainly libido in women, gradually decreases under long-term treatment, and can be predicted by the co-existence of insomnia, somnolence or nausea during treatment. Clinicians should caution and tailor the gender and disease vulnerability of amitriptyline in their practice.
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Depression; Humans; Male; Sexual Dysfunctions, Psychological
PubMed: 29019272
DOI: 10.1177/1557988317734519 -
Frontiers in Pain Research (Lausanne,... 2022Burning mouth syndrome (BMS) is defined by chronic oral burning sensations without any corresponding abnormalities. Besides amitriptyline, aripiprazole has been reported...
Burning mouth syndrome (BMS) is defined by chronic oral burning sensations without any corresponding abnormalities. Besides amitriptyline, aripiprazole has been reported as a possible medication to manage BMS. However, especially for elderly patients, the adverse events of these medications would be a problem. The aim of the present study was to investigate the differences in the effectiveness and adverse events of amitriptyline and aripiprazole in very elderly patients with BMS. This is a retrospective comparative study of 80 years old and older patients with BMS who were initially treated with amitriptyline or aripiprazole and who were new outpatients of our department from April 2017 to March 2020. All clinical data, including sex, age, comorbid physical diseases, comorbid psychiatric disorders, the prescribed doses (initial, maximum, and effective dose), prognosis, and adverse events, were collected from their medical charts. Each medication was selected considering their medical history. Amitriptyline was prescribed in 13 patients (11 women, 82.3 ± 2.1 years old) and aripiprazole was prescribed in 27 patients (26 women, 84.2 ± 3.8 years old). There were no significant between-group differences in sex, age, duration of illness, pain intensity, salivation, and psychiatric comorbidity at the first examination. Amitriptyline clinically improved more patients (7 patients, 53.8%) with the effective dose of 10 (7.5, 15.0) mg than aripiprazole (11 patients, 40.7%) of which the effective dose was 1.0 (0.5, 1.5) mg, although there were no significant between-group differences. The adverse events of amitriptyline were found in 9 patients (69.2%) and most patients had constipation (46.2%). For aripiprazole, 7 patients (25.9%) showed adverse events, most of them reported sleep disorder (11.1%). Amitriptyline had significantly longer duration taking medication ( = 0.021) and lower discontinuation ( = 0.043) despite of higher occurrence rate of adverse events ( = 0.015) compared to aripiprazole. These results suggest that both psychopharmacotherapies with a low dose of amitriptyline and aripiprazole are effective for the very elderly patients with BMS. Furthermore, aripiprazole may have some advantages in the adverse events compared to amitriptyline; however, the low dose amitriptyline monotherapy may have more benefit in the effectiveness and tolerability over prudent collaboration with primary physicians.
PubMed: 35295804
DOI: 10.3389/fpain.2022.809207 -
European Review For Medical and... May 2024Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite the contradicting recommendations. There is a need to inform the scientific community regarding first-line pain control among patients with PPDN. This meta-analysis assessed pregabalin and amitriptyline effects on PPDN.
PATIENTS AND METHODS
We searched PubMed, MEDLINE, Cochrane Library, EBSCO, and Google Scholar; the terms used were amitriptyline, pregabalin, painful diabetic neuropathy, antidepressant, gabapentinoids, quality of life, and adverse events. Boolean operators like AND, and OR were used. Six hundred and thirty-one studies were retrieved, and 37 full texts were screened. However, only six randomized controlled trials fulfilled the inclusion and exclusion criteria.
RESULTS
No significant statistical differences between amitriptyline and pregabalin regarding pain score and significant pain reduction (odd ratio, -0.82, 95% CI, -2.21-0.58, and odd ratio, 1.16, 95% CI, 0.76-1.76 respectively). Quality of life, total adverse events, and drug discontinuation were not different between the two drugs (odd ratio, 0.89, 95% CI, -2.11-3.89, odd ratio, 0.98, 95% CI, 0.52-1.85, and odd ratio, 0.51, 95% CI, 0.08-3.15, respectively).
CONCLUSIONS
No significant statistical differences between amitriptyline and pregabalin regarding their effects on pain and quality of life. The drugs showed similar total adverse events and drug withdrawal. Further larger real-world studies are needed.
Topics: Pregabalin; Amitriptyline; Humans; Diabetic Neuropathies; Analgesics; Quality of Life
PubMed: 38856135
DOI: 10.26355/eurrev_202405_36296 -
American Family Physician Aug 2016Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects... (Review)
Review
Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient's goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.
Topics: Administration, Topical; Amines; Amitriptyline; Analgesics; Analgesics, Opioid; Anesthetics, Local; Capsaicin; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; Humans; Isosorbide Dinitrate; Lidocaine; Phenols; Pregabalin; Sensory System Agents; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Tapentadol; Tramadol; Transcutaneous Electric Nerve Stimulation; Vasodilator Agents; Venlafaxine Hydrochloride; gamma-Aminobutyric Acid
PubMed: 27479625
DOI: No ID Found -
Journal of Traditional Chinese Medicine... Aug 2014To comprehensively evaluate the effectiveness of acupuncture as a treatment for fibromyalgia syndrome. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To comprehensively evaluate the effectiveness of acupuncture as a treatment for fibromyalgia syndrome.
METHODS
Two review authors independently selected the trials for the Meta-analysis, assessed their methodological quality and extracted relevant data. A quality assessment was conducted according to the Cochrane Review Handbook 5.0. RevMan 5.0.20 software was used in the statistical analysis.
RESULTS
A total of 523 trials were reviewed and 9 trials were selected for Meta-analysis. (a) Compared acupuncture with sham acupuncture, there was a significant difference in the visual analogue scale, but no difference in the pressure pain threshold. Additionally, and there was a difference in the fibromyalgia impact questionnaire and the multidisciplinary pain inventory after 4 weeks of treatment, but no difference after 7 weeks of therapy. There was no difference in the numerical rating scale in weeks 3, 8 and 13. (b) Acupuncture versus drugs. There were differences in the VAS after 20 days of acupuncture and moxibustion treatment comparing with the drug amitriptyline, and after 4 weeks of acupuncture and moxibustion treatment comparing with the drug fluoxetine and amitriptyline. There were also differences in the number of tender points when comparing acupuncture with amitriptyline or fluoxetine. There was no difference in total efficiency when comparing acupuncture with amitriptyline after 4 weeks of treatment, but there were differences between the two groups 45 days after treatment. There were also differences in total efficiency comparing acupuncture with fluoxetine, and when comparing 4 weeks post-treatment of acupuncture with a combination of amitriptyline, oryzanol and vitamin B. (c) A comparison of acupuncture, drugs and exercise with drugs and exercise showed PPT differences in months 3 and 6. There was no difference between the two comparison groups after follow-up visits in months 12 and 24.
CONCLUSION
Compared with sham acupuncture, there was not enough evidence to prove the efficacy of acupuncture therapy for the treatment of fibromyalgia. Some evidence testified that the effectiveness of acupuncture therapy for fibromyalgia was superior to drugs; however, the included trials were not of high quality or had high bias risks. Acupuncture combined with drugs and exercise could increase pain thresholds in the short-term, but there is a need for higher quality randomized controlled trials to further confirm this.
Topics: Acupuncture Therapy; Fibromyalgia; Humans; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 25185355
DOI: 10.1016/s0254-6272(15)30037-6