Olgumuz çok yüksek doz (yaklaşık 3gr) amitriptilin almıştı. Bu vakanın acil servisimizde değerlendirilmesi sırasında teknik nedenlerden dolayı amitriptilin düzeyi çalışamamamız bir eksiklik olmuştu. Yüksek dozda alıma bağlı olarak respiratuar depresyon, bilinç kaybı, ritm bozuklukları ve nöbet gelişmişti. Olgu acil serviste çok hızlı değerlendirilmişti. Acil tıp yaklaşımına uygun olarak hava yolu, solunum ve dolaşımının desteklenmiş olması bu olguda hayat kurtarıcı olmuştur. Uygulanacak spesifik tedavi bu yaklaşımdan sonra gelmektedir.
Trisiklik antidepresan zehirlenmelerinde tüm vakalara 1 gr/kg dozunda aktif kömür verilmesi önerilmektedir1. Bizim olgumuzda da aktif kömür verilmişti. Bilincin kapalı olması nedeniyle aspirasyon riski de olduğundan aktif kömür verilmesi ön planda düşünülmeyebilirdi ancak olgunun havayolu kontrolü entübasyonla sağlandığı için nasogastrik sonda ile iki doz aktif kömür verildi.
Bikarbonat tedavisi de bu tür vakalarda önerilmektedir1. 1-2 mEq/kg dozunda puşe verilmesi ve kan PH değerleri 7.50-7.55 oluncaya kadar tekrarlayan dozlarda yapılması da bazı kaynaklarda önerilmektedir1. Bizim olgumuzda ise 2mEq/kg dozunda olacak şekilde 100 mEq bikarbonat puşe edilmiş olup kan PH değerlerinde yükselme olmaması üzerine tekrar aynı dozlarda 2 kez daha bikarbonat verilmişti. Ancak hemodializ sonrası hem asidozun düzelmesi hem de sinüzal taşikardi dışında EKG bulgularının normale gelmesi ile bikarbonat tedavisi verilmedi.
Olgunun dirençli hipotansiyonu nedeniyle 10 ml/kg olacak şekilde izotonik sıvılar verildi. Takiplerinde tansiyonları normal düzeylere geldi. Yapılan sıvı ve bikarbonat tedavilerinin başarılı olduğunu düşünmekteyiz ancak derin asidozun devam etmesi üzerine hemodializ kararı verildi. Trisiklik antidepresanlarla olan zehirlenmelerde hemodializ ya da hemoperfüzyon uygulamalarının halen tartışmalı bir tedavi şekli olduğu söylenebilirse de bu olguda faydalı olduğu kanaatindeyiz ve trisiklik antidepresanların proteinlere bağlanma oranlarının yüksek olmasına rağmen etkin bir uzaklaştırma yöntemi olabileceğini düşünmekteyiz5,6,7. Bazı yayınlarda yüksek doz amitriptilin alımı sonrası derin koma, kardiyotoksisite bulguları olan vakaların hemoperfüzyon uygulanması sonrası klinik durumlarının düzeldiği ve tamamen iyileşerek taburcu edildiği belirtilmektedir. Bu vakalarda hemoperfüzyon öncesi ve sonrası Trisiklik antidepresan düzeyleri anlamlı şekilde farklı bulunmuştur7,8. Ancak yeterli çalışmaların olmaması nedeniyle hemoperfüzyon veya hemodializ uygulaması rutin olarak önerilmemektedir. Ancak direçli metabolik asidoz ve anormal EKG bulguları mevcutsa erken dönemde hemodializ yapılması gerektiğini düşünmekteyiz.
Epileptik nöbetler yüksek dozda alım sonrasında görülürken genellikle tonik klonik tarzda olmaktadır. Trisiklik antidepresan kan plazma düzeyi 1000 ng/ml üzerinde olduğunda kardiyotoksisite ve nöbet gelişeceği belirtilmektedir1. Bizim olgumuzda myoklonik tarzda nöbetler görüldü. Dört doz IV Diazepam la müdahale etmemize rağmen nöbetlerin kontrolü zor olmuştu. Tekrarlayan nöbetlerde fenobarbital önerilmekte olup bizim vakamızda nöbetlerin kontrolü ancak endotrakeal entübasyon ve nöromuskuler blokaj sonrası sağlanmıştır1. Bazı yayınlarda amitriptilin alımı sonrası ortaya çıkan epileptik nöbetli vakalar rapor edilmiştir8,9.
Sonuç olarak, trisiklik antidepresanlarla olan zehirlenmelerde klinik olarak ağır koma durumlarında bile acil serviste uygulanacak ilk müdahalelerle mortalite oranı önemli ölçüde azaltılabilir. Epileptik nöbetler ve solunum depresyonu özellikle yüksek doz alımlarda ortaya çıkmakta olup, bikarbonat ve sıvı tedavileri halen önemini korumakta olup, derin asidoz ve hipotansiyon uzun süre devam ederse mortalite artabilir. Tartışmalı bir konu olan hemodializ ve hemoperfüzyon uygulamaları ise durumu ağır vakalar için akılda tutulmalıdır. Ayrıca tüm semptomatik vakalar hastaneye yatırılmalı asemptomatik olanlar ise en az 6 saat gözlem altında tutulmalıdır.
LAROXYL, amitriptilin adı verilen etkin madde içeren bir ilaçtır. Her draje 10 mg amitriptilin içerir. Drajeler pastel kırmızı renkli ve kokusuzdur.
LAROXYL 30 adet draje içeren beyaz opak şişe ambalajlarda bulunur.
LAROXYL trisiklik antidepresan adı verilen ilaç grubuna aittir. Bu ilaçlar beyindeki kimyasal maddelerin düzeyini değiştirerek depresyon semptomlarını (belirti) düzeltir.
LAROXYL aşağıdaki durumların tedavisinde kullanılır;
• Depresyon semptomlarının tedavisinde
• LAROXYL depresyon belirtilerinin giderilmesinde, özellikle endojen depresyonun tedavisinde kullanılır
SUT DEĞİŞİKLİĞİNDE ANTİDEPRESANLARIN ÖDENME KOŞULLATINDA YAPILAN DEĞİŞİKLİK HK.
SNRI, SSRE, RIMA, NASSA grubu antidepresanlar, psikiyatri, nöroloji, geriatri uzman hekimlerinden biri tarafından veya bu hekimlerden biri tarafından düzenlenen uzman hekim raporuna dayanılarak tüm hekimlerce reçete edilebilir. Bupropiyon HCl (Ek: RG-18/06/2016- 29746/ 11 md. Yürürlük: 25/06/2016), vortioksetin (Ek: RG- 25/07/2014- 29071/ 20 md. Yürürlük: 07/08/2014) ve agomelatin yanlızca major depresif bozukluk tedavisinde, psikiyatri veya nöroloji uzman hekimleri tarafından veya bu hekimler tarafından düzenlenen uzman hekim raporuna dayanılarak tüm hekimlerce reçete edilir şeklinde düzenlenmiştir.
Trisiklik,tetrasiklik,SSRI grubu antidepresanlar aşağıda tabloda belirtilmiştir.Bilgilerinize sunarız.
TRİSİKLİK ANTİDEPRESANLAR | TETRASİKLİK ANTİDEPRESANLAR | SSRI GRUBU ANTİDEPRESANLAR |
Amitriptilin (Laroxyl) | Mianserin (Tolvon) | Fluoksetin (Prozac) |
Klomipramin (Anafranil) | Moprotilin (Ludiomil) | Fluvoksamin (Faverin) |
İmipramin (Tofranil) | Paroeksetin (Paxil) | |
Opipramol (İnsidon) | Sitalopram (Cipram) | |
Sertralin (Lustral) | ||
Essitalopram (Cipralex) |
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Gunseli Acet,1Arzu Kaya,2Semra Akturk,3 and Gurkan Akgol2
1Department of Physical Medicine and Rehabilitation, Malatya Training and Research Hospital, Malatya, Turkey
Find articles by Gunseli Acet
2Department of Physical Medicine and Rehabilitation, Firat University Faculty of Medicine, Elazig, Turkey
Find articles by Arzu Kaya
3Department of Physical Medicine and Rehabilitation, Inonu Univesity Faculty of Medicine, Malatya, Turkey
Find articles by Semra Akturk
2Department of Physical Medicine and Rehabilitation, Firat University Faculty of Medicine, Elazig, Turkey
Find articles by Gurkan Akgol
Author informationArticle notesCopyright and License informationDisclaimer
1Department of Physical Medicine and Rehabilitation, Malatya Training and Research Hospital, Malatya, Turkey
2Department of Physical Medicine and Rehabilitation, Firat University Faculty of Medicine, Elazig, Turkey
3Department of Physical Medicine and Rehabilitation, Inonu Univesity Faculty of Medicine, Malatya, Turkey
Correspondence: Dr. Semra AKTURK. Turgut Ozal Tip Merkezi, Fiziksel Tedavi ve Rehabilitasyon Klinigi 1. Kat, Malatya, Turkey. Tel: +90 422 - 341 06 60 e-mail: moc.liamtoh@krutkayakarmes
Received 2017 Mar 20; Accepted 2017 Jul 4.
Copyright : © 2017 by Istanbul Northern Anatolian Association of Public Hospitals
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
The present study is a comparison of the effectiveness of amitriptyline and pregabalin on the symptoms of fibromyalgia patients.
A total of 71 female patients aged ≥18 years were included in this study. The patients were divided into 2 groups. Pregabalin (n=36) or amitriptyline (n=35) treatment was initiated at daily oral dose of 450 mg and 25 mg, respectively for the indicated number of patients. The patients were evaluated at the start of treatment and at the end of 12 weeks. The Fibromyalgia Impact Questionnaire, Fatigue Severity Scale, Modified Fatigue Impact Scale, Hospital Anxiety Depression Scale, Nottingham Health Profile, Mini Mental State Test, and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were administered to all study participants. Pain at all tender points was measured using a pressure algometer.
Significant improvement was observed in both groups after 12 weeks of treatment (p<0.05). Percent change in LANSS was greater in the pregabalin group compared with the amitriptyline group. Tender point pressure pain thresholds and total myalgic score improved significantly in both groups (p<0.05); however higher percentage change in these parameters was achieved in the amitriptyline group when compared with the pregabalin group (p<0.05).
Both drugs improved pain, fatigue, sleep disorder, disability, psychological evaluation, and cognitive function; however, amitriptyline was more effective at reducing experimentally measured pain than neuropathic pain. According to these results, preference for pregabalin may be recommended in fibromyalgia patients whose primary complaint is neuropathic pain.
Keywords: Amitriptyline, fibromyalgia, neuropathic pain, pregabalin, pressure pain threshold
Fibromyalgia syndrome (FMS) is a chronic, extra-articular, rheumatic syndrome characterized by widespread musculoskeletal system pain and tender points at specific anatomical points [1]. Its prevalence ranges between 2% and 7% in the population [2]. Although trauma, infection, autoimmune, genetic, endocrinological, and emotional factors have been emphasized in the etiology of FMS, its exact etiology is still not known [3, 4]. Abnormalities in central mechanisms may explain its etiopathogenesis. Sleep disorders, psychological function, disorders in pain modulation, biochemical changes in the central nervous system, and neuroendocrinological dysfunction play roles in abnormalities of central mechanisms [5–8]. Abnormalities in the mechanisms of tryptophan, which is a serotonin precursor, are seen in these patients. As a neuropeptide, substance P is a primary nociceptive afferent modulator, and plays a role in the regulation of immune functions. In FMS patients, plasma substance P level is within normal limits; however, the level in cerebrospinal fluid was found to be 3 times higher than that of normal control subjects [9].
A pharmacological agent that completely resolves all symptoms and ensures complete well-being is not yet available for patients with fibromyalgia. Treatments are most frequently targeted at symptoms using non-standardized methods [10]. Depression medications, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin, and noradrenalin reuptake inhibitors have been demonstrated to be effective at reducing pain, depression, and fatigue in patients with fibromyalgia [11]. Tricyclic antidepressants are believed to be effective in fibromyalgia treatment by influencing the reuptake of amines, such as serotonin and epinephrine, by inducing the production of endogenous opioids, and regulating central motor activity, thereby improving symptoms of depression. Amitriptyline is an important member of this class of antidepressants. Its analgesic mechanism has not been fully explained yet; however, it has been demonstrated to have greater effectiveness in providing relief for patients with fibromyalgia than selective serotonin reuptake inhibitors, independent of its antidepressant effects. It has been proposed that the inhibition of noradrenaline reuptake, N-Methyl-D-aspartic acid receptor antagonism, and the blockade of muscarinic receptors and ion channels may contribute to the analgesic effect of amitriptyline [12–14].
It has been demonstrated in various studies that pregabalin is effective in the treatment of fibromyalgia [15–17]. In 2007, it was the first medicine approved by the US Food and Drug Administration for fibromyalgia treatment. It exerts its effect by binding to alpha-2 delta subunits of voltage-sensitive calcium channels and slowing the entry of calcium into neurons It does not interact with benzodiazepine or gamma-aminobutyric acid (GABA)-A and GABA-B receptors. Since it does not bind to these receptor sites, it also does not interact with other antiepileptics, antidepressants, or analgesics, and it can be used safely in drug combinations [16].
The aim of this study was to compare the effectiveness of amitriptyline, with established efficacy in patients with fibromyalgia, with that of pregabalin, the use of which in the treatment of fibromyalgia has become increasingly prevalent in recent years.
The present study was approved by the Fırat University Faculty of Medicine ethics committee and was conducted in accordance with the Declaration of Helsinki. Written, informed consent was obtained from all participants.
Among admissions to Fırat University Hospital Physical Medicine and Rehabilitation outpatient clinic, a total of 71 female patients aged ≥18 years (mean age: 39.2±8.96 years in the amitriptyline group and 36.5±6.68 years in the pregabalin group) having predominantly neuropathic pain pattern diagnosed as FMS based on the diagnostic criteria of the American College of Rheumatology were included in this study. Patients who had previously been operated on for lumbar herniated disc, those who had recently received physical therapy, or pregabalin or antidepressant treatment within the previous 2 months, patients with inflammatory or malignant diseases, pregnant patients, cases with severe psychological disorders or systemic disease were not enrolled in the study.
Demographic data (age, gender, marital status, socioeconomic status, type of employment, educational level, smoking/alcohol use, body mass index) of the patients were recorded. All participants underwent systemic examination and laboratory assessment of complete blood count, routine biochemical analysis, erythrocyte sedimentation rate, rheumatoid factor, C-reactive protein level, presence of Brucella, and thyroid function was performed. Body mass index was measured using Tanita BC-418MA scale with Segmental Body Composition Analyzer (Tanita Corp., Tokyo, Japan).
The patients were randomly divided into 2 groups. Pregabalin (n=36) or amitriptyline (n=25) therapy was initiated at daily 150 mg and slowly increased to 450 mg oral dose, and 10 mg to 25 mg, respectively, in the indicated number of patients. The patients were evaluated monthly over the course of 3-month treatment for effects using the Visual Analogue Scale (VAS) for pain, assessment of sleep quality, and side effects of the treatment.
At baseline and at the conclusion of 12 weeks, clinical evaluations were performed in both groups using several measurement tools. Functional evaluation was performed with the Fibromyalgia Impact Questionnaire (FIQ), impact of fatigue on daily activities was measured with the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS), quality of life was assessed with the Nottingham Health Profile (NHP), risk for anxiety and depression was evaluated with the Hospital Anxiety Depression Scale (HADS), cognitive function was measured with the Mini Mental State Examination (MMSE), neuropathic pain was gauged using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), and a global scoring of severity of pain estimated separately by the patient and the physician using the VAS. VAS and sleep quality evaluations were performed at 4-week intervals.
Pressure pain threshold (PPT) measurements were taken from tender points (18 points), and control points (3 points: midpoint of the forehead; distal one-third dorsal aspect of the dominant forearm, and nail of the thumb of the dominant hand) before and after the treatment using a manual algometry device (Force Dial model FDK 40 Push Pull Force Gage; Wagner Instruments, Riverside, CT, USA). Pressure was applied with 1 kg increase per second. Skin temperature was measured using Scantemp Pro 440 infrared thermometer (Cardinal Health, Inc., Dublin, OH, USA).
The FIQ was administered to measure the health status of the patients. This disease-specific measure of global health status has been validated for a Turkish population with FMS [18]. The FIQ is a 10-item, self-administered test that measures physical function, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well-being. As score approaches maximum total of 100 it indicates more severe symptoms and disability.
The FSS is the most frequently used questionnaire to evaluate the effect of fatigue on daily activities. Validation and reliability studies for Turkish version were performed by Armutlu et al. The scale consists of 9 statements, each of which is scored between 1 (I don’t agree at all), and 7 (I strongly agree). The FSS score is the average value of score for all 9 statements. A higher score reflects a more severe state of fatigue [19, 20].
The HADS is a self-assessment scale used to determine risks for, level of, and changes in severity of anxiety and depression. It comprises a total of 14 questions, 7 related to anxiety and 7 concerning depression.
Health-related quality of life of the patients was evaluated with the NHP, which contains 38 items in 6 domains related to level of energy (3 items), pain (8 items), emotional reactions (9 items), sleep (5 items), physical mobility (8 items), and social isolation (5 items). Items in each domain are assigned a weight; the total score for each domain is 100; a score of 0 indicates good subjective health status, while 100 indicates poor subjective health status. Total NHP total score is obtained by averaging the 6 domain scores.
The LANSS scale evaluates symptoms of neuropathic pain and responsiveness to treatment. Sensitivity and specificity in the discrimination between neuropathic and non-neuropathic pain have been evaluated in a local patient population [21].
Functions of orientation, registration, attention and calculation, recall, and language are measured with the MMSE questionnaire, which consists of 11 questions and has a total possible score of 30 points. Score <24 points indicates cognitive impairment [22–24].
Statistical analyses were performed using SPSS for Windows, Version 15.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were used to summarize the distribution of patient and control group demographic characteristics. For intragroup comparisons of measurements performed at baseline and after 12 weeks of therapy, parametric Student’s t-test was used. McNemar’s test was used for intragroup comparisons of rates, and intergroup comparisons were performed using parametric Student’s t-test. For intergroup comparisons of measurements with ordinal and nominal variables, chi-square test was used. Pairwise comparisons of multiple measurements were assessed with Student’s t-test, with a limit of significance of 0.016 (0.05/number of comparisons [n=3] = 0.016). For other comparisons, limit of significance was accepted as p=0.05.
A total of 66 patients (amitriptyline group, n=32; pregabalin group, n=34) completed the study. No significant intergroup difference was found with respect to age, body mass index, or level of formal education (p>0.05).
Pre- and post-treatment measurements of VAS and MFIS physical, cognitive, and psychosocial function subscale scores were significantly different in the amitriptyline group (Group 1) (p=0.00). NHP, FIQ, and VAS scores of the patients in the amitriptyline group are provided in Table 1. A significant difference was seen in post-treatment LANSS score, or measurement of anxiety and depression parameters of the patients in Group 1 (p<0.05). No significant difference was found between pre- and post-treatment MMSE scores or sum of 3 PPT control point scores (p>0.05).
Comparison of parameters in the amitriptyline group
Parameters | Before treatment | After treatment (3 months) | p |
---|---|---|---|
VAS-pain | 7.77±1.65 | 3.37±1.76 | 0.00 |
FIQ-pain | 7.72±1.71 | 3.56±1.82 | 0.00 |
FIQ-morning fatigue | 8.32±1.34 | 3.39±2.31 | 0.00 |
FSS | 5.77±1.04 | 4.14±1.28 | 0.00 |
NHP-fatigue | 91.86±23.68 | 33.55±37.92 | 0.00 |
NHP pain | 66.22±26.29 | 24.64±15.46 | 0.00 |
FIQ-anxiety | 6.15±2.54 | 1.25±1.79 | 0.00 |
FIQ-depression | 5.81±2.68 | 1.29±1.66 | 0.00 |
NHP-physical activity | 34.51±28.18 | 8.55±14.18 | 0.00 |
NHP-sleep | 54.46±33.70 | 11.84±16.45 | 0.00 |
NHP-social isolation | 26.41±37.13 | 7.1413±13.28 | 0.001 |
NHP-emotional reaction | 10.97±19.75 | 2.15±3.88 | 0.005 |
HADS-depression | 8.94±2.90 | 6.94±1.96 | 0.000 |
HADS-anxiety | 10.17±2.06 | 8.20±1.90 | 0.000 |
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In the pregabalin group, significant differences were observed in the patient self-assessment and the physician’s global evaluation (VAS) of the patient, and in the pain subscale scores of the NHP and FIQ (p<0.05). Group scores are provided in Table 2. Pre- and post-treatment LANSS neuropathic pain scale scores were significantly different in the pregabalin group (p=0.00). A significant difference was also found in pre- and post-treatment total PPT score of tender points and total myalgic score (p<0.05).
Comparison of parameters in the pregabalin group
Parameters | Pre-treatment | Post-treatment (3 months) | p |
---|---|---|---|
VAS | 8.04±1.44 | 4.27±1.83 | 0.000 |
NHP-pain | 72.70±21.14 | 30.20±15.85 | 0.000 |
FIQ-pain | 7.91±1.65 | 4.50±1.80 | 0.000 |
NHP-pain | 78.37±35.32 | 34.44±38.21 | 0.000 |
FIQ-fatigue | 8.33±1.72 | 4.14±1.64 | 0.000 |
FIQ-morning fatigue | 8.04±2.10 | 3.67±1.78 | 0.000 |
NHP-physical activity | 38.57±25.59 | 16.53±20.51 | 0.000 |
NHP-sleep | 33.60±35.64 | 10.72±18.73 | 0.000 |
NHP-social isolation | 12.06±19.97 | 5.54±18.46 | 0.071 |
NHP-emotional reactions | 5.60±11.09 | 2.80±9.82 | 0.174 |
HADS-depression | 8.36±2.63 | 7.02±2.08 | 0.000 |
HADS-anxiety | 9.41±1.93 | 7.26±1.60 | 0.000 |
FIQ-anxiety | 5.94±2.94 | 1.67±1.95 | 0.000 |
FIQ-depression | 4.91±3.076 | 1.60±1.74 | 0.000 |
MFIS-physical function | 21.80±6.54 | 14.32±5.04 | 0.000 |
MFIS-cognitive function | 21.91±7.85 | 14.73±5.66 | 0.000 |
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A significant intergroup difference was seen in post-treatment assessments of the FIQ pain subscale, and the HADS anxiety measurement score (p<0.05). Pre- and post-treatment VAS and NHP pain subscale score was not significantly different between groups (p>0.05). Pre- and post-treatment NHP, FIQ, modified fatigue impact scale and VAS scores are presented in Table 3. No significant difference was found between pre- and post-treatment LANSS score (p>0.05), while the percent change was significantly different between groups (p<0.05); a greater degree of improvement was seen in the pregabalin group compared with the amitriptyline group. In the tender point pressure and total myalgic score percent change, however, there was a significant difference between the groups in favor of the amitriptyline group (p<0.05) (Table 4). No significant intergroup difference was found in the rate of pre- and post-treatment symptoms associated with FMS (p>0.05).
Comparison of pretreatment and post-treatment clinical parameters between the amitriptyline and pregabalin groups
Parameters | Pre-treatment | Post-treatment | ||||
---|---|---|---|---|---|---|
Amitiriptyline (n=35) | Pregabalin (n=36) | p | Amitiriptyline (n=32) | Pregabalin (n=34) | p | |
VAS | 7.42±1.67 | 8.04±1.44 | * | 4.26±1.93 | 4.27±1.83 | * |
NHP-pain | 66.22±26.29 | 72.70±21.14 | * | 24.64±15.46 | 30.20±15.85 | * |
FIQ-pain | 7.72±1.71 | 7.91±1.65 | * | 3.56±1.82 | 4.50±1.80 | 0.04 |
MFIS-pf | 21.22±6.66 | 21.80±6.54 | * | 14.62±4.46 | 14.32±5.043 | * |
NHP-fatigue | 91.86±23.68 | 78.37±35.32 | * | 33.55±37.92 | 34.44±38.21 | * |
FIQ-fatigue | 8.41±1.62 | 8.3333±1.72 | * | 3.9375±1.79 | 4.14±1.64 | * |
NHP-pa | 34.51±28.18 | 38.57±25.59 | * | 8.55±14.18 | 16.53±20.51 | * |
HADS-depression | 8.94±2.90 | 8.36±2.63 | * | 6.94±1.96 | 7.02±2.08 | * |
HADS-anxiety | 10.17±2.06 | 9.41±1.93 | * | 8.20±1.90 | 7.26±1.60 | 0.031 |
MMSE | 24.82±3.15 | 25.44±2.96 | * | 25.56±3.25 | 26.32±2.55 | * |
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Percent change in tender point and total myalgic scores between groups
Parameters | Amitriptyline (n=35) | Pregabalin (n=36) | P |
---|---|---|---|
Percent change tender point score | -0.197±0.14 (-0.61–0.09) | -0.098±0.12 (-0.47–0.17) | 0.005 |
Percent change total myalgic score | -0.160±0.13 (-0.58–0.06) | -0.079±0.11 (-0.44–0.16) | 0.012 |
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The most frequently reported side effects of all patients in both groups were dizziness and sleep disorders. Dizziness was more frequently seen in the pregabalin group (Figure 1). Changes over time in side effects experienced and VAS scores can be seen in Table 5.
Assessment of side effects and VAS (pain and sleep) changes in the groups at first, second, and third month
Parameters | First month | Second month | Third month | |||
---|---|---|---|---|---|---|
Amitiriptyline % | Pregabalin % | Amitiriptyline % | Pregabalin % | Amitiriptyline % | Pregabalin % | |
Sleep disorders | 17.1 | 5.6 | 15.2 | 2.7 | 8.3 | 2.7 |
Dizziness | 5.7 | 16.7 | 5.7 | 13.8 | 2.8 | 6.2 |
Dyspepsia | 0 | 2.8 | 0 | 2.8 | 0 | 2.8 |
Cardiac disorders | 0 | 0 | 2.8 | 0 | 2.8 | 0 |
Sleep+cardiac disorders | 5.7 | 0 | 5.7 | 0 | 5.7 | 0 |
Dizziness+dyspepsia+sleep disorders | 0 | 5.6 | 0 | 5.6 | 0 | 5.6 |
p | p | p | ||||
Pregabalin VAS (pain) | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
Pregabalin VAS (sleep) | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
Amitiriptyline VAS (pain) | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
Amitiriptyline VAS (sleep) | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
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In the present study we observed that the effects of both pregbalin and amitriptyline were similar with respect to effectiveness on pain, fatigue, sleep disorders, disability, psychological factors, and cognitive function; however, amitriptyline was more effective at relieving experimental pain, while pregabalin was more helpful for neuropathic pain.
Since fibromyalgia patients describe widespread clinical manifestations, an overlap with neuropathic pain has been suggested. Hyperalgesia, allodynia, and paresthesia seen in neuropathic pain can also be observed in FMS. In almost all of these patients, impairment of central pain mechanism, neuroendocrinological abnormalities, and abnormal activation in the nociceptive domain of the brain are seen. These multiple abnormalities strongly suggest that fibromyalgia is a neuropathic pain syndrome [25, 26].
A serotonin deficiency proposed in the etiology of FMS may account for the pain and sleep disorders observed, which are important features of this syndrome [27]. Most frequently, antidepressants are used in the treatment of fibromyalgia, and among them the tricyclic antidepressant amitriptyline is most often administered. Generally, the analgesic effects of tricyclic antidepressants are accepted to be an acute effect independent of antidepressant effects, and only require a low dose [28].
Gabapentin, which is an anticonvulsant also used to treat neuropathic pain, was compared with amitriptyline, and both drugs were found to be effective in pain management. Gabapentin was found to be more effective on paroxysmal stabbing pain [29]. The effect of pregabalin on chronic pain syndromes has been reported to be comparable to that of gabapentin [14]. A study of 529 patients with fibromyalgia investigated the effect of pregabalin on pain, fatigue, and quality of life. Daily dose of 150 mg, 300 mg, and 450 mg pregabalin was compared with a placebo, and at the end of 8 weeks of treatment, a decrease in all painful sensations was reported in all of the pregbalin groups. It was reported that in patients using daily dose of 450 mg pregabalin, painful sensations decreased more dramatically compared with the other groups, and at daily dose of 300 mg and 450 mg, sleep quality and fatigue improved markedly relative to the placebo group [16].
In our study, in both the pregabalin and amitriptyline groups, considerable improvement was seen in parameters of pain; however, the percent of change, which indicated decrease in the severity of pain, did not differ significantly between groups. The present study included patients with prominent neuropathic complaints. The LANSS was used to evaluate neuropathic pain pattern. LANSS scores improved significantly in both the amitriptyline and pregabalin group, yet intergroup comparisons revealed greater improvement in the pregabalin group.
Morning fatigue is found in 75% to 80% of patients with fibromyalgia [30–32], though severity varies. A similar percentage of patients complains of poor sleep or sleep disorders [33]. Antidepressants demonstrate important effects on sleep quality and the fatigue seen in FMS [1]. An important difference in the NHP sleep subscale scores was observed with respect to restless sleep in both amitriptyline and pregabalin users. Neither treatment was superior in terms of improvement in sleep problems or morning fatigue.
In another study performed to investigate the effect of pregabalin on anxiety disorders, effectiveness in the short term was demonstrated relative to placebo. Pregabalin was also found to be more effective in patients who partially responded to atypical antipsychotic drug quetiapine [34]. In our study, we observed comparable, favorable effects for both pregabalin and amitriptyline on anxiety and depression in patients with fibromyalgia.
The most important side effects of pregabalin are somnolence and dizziness. They are typically observed within the first 1 to 2 weeks of starting the drug therapy, and are more marked among the elderly [17, 35]. Among the most frequently seen side effects of tricyclic antidepressants are anticholinergic effects, such as dry mouth and constipation, and postural hypotension, sedation, and weight gain [36]. In our study, consistent with literature findings, the most frequently seen side effects of pregabalin users were dizziness (8.5%) and sleep disorders (2.8%); however, none of the patients discontinued the treatment due to these side effects. In the amitriptyline group, the most frequent side effects were sleep disorders (8.5%) and dizziness (2.8%). Dizziness was more common in the pregabalin group than the amitriptyline group. Generally, tolerance developed in 2 to 3 weeks, and these complaints decreased at control visits.
In our study, PPTs and skin temperature were measured at all fibromyalgia control and tender points using an algometer and an infrared thermometer, respectively. In both the amitriptyline and pregabalin groups, control point scores did not change after treatment relative to baseline, while tender point and total myalgia scores improved in both groups. Tender point PPTs, which are considered a laboratory (experimental) assessment of pain, decreased more dramatically in the amitriptyline group after the treatment.
The main limitation of this study is the small number of participants and the inability to prolong the follow-up period due to strict exclusion criteria of the study.
In conclusion, based on the data we gathered in this study, we can say that neither drug is superior in terms of effectiveness on systemic symptoms of myalgia. However, we can state that amitriptyline is more effective in decreasing experimental pain, whereas pregabalin is more effective in relieving neuropathic complaints. Accordingly, a preference for pregabalin may be recommended for FMS patients primarily complaining of neuropathic pain.
Conflict of Interest: None declared.
Financial Disclosure: The authors declared that this study has received no financial support.
Authorship contributions: Concept – G.Acet, A.K. Data collection &/or processing – G.A; Analysis and/or interpretation – G.Acet; Writing – S.A.
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