Pregabalin vs amitriptyline: safety and efficacy in neuropathic pain treatment

Pegabalin:

1.Efficacy and safety of pregabalin for treating neuropathic pain associated with diabetic peripheral neuropathy: a 14 week, randomized, double-blind, placebo-controlled trial:

Significant reductions in pain were observed in patients treated with pregabalin at 300 and 600 mg/day vs. placebo (P < 0.05). Improvements in weekly pain scores were observed as early as week 1 and were sustained throughout the study period (300 and 600 mg/day difference from placebo at study end-point, -0.63 and -0.74, respectively). Pregabalin produced significant improvements in weekly sleep interference scores, the short-form McGill Pain Questionnaire, the Medical Outcomes Study-Sleep Scale, the 36-item Short-Form Health Survey scale, and the Patient and Clinical Global Impression of Change. Patient impressions of numbness, pain and paraesthesia were also significantly improved. Regarding treatment responders, 29.1 and 35.6% of patients treated with 300 and 600 mg/day, respectively, reported ≥ 50% improvement in mean pain scores (vs. 21.5% for placebo). Pregabalin was well tolerated; somnolence (26%), dizziness (24%), peripheral oedema (13%) and weight gain (11%) were the most common adverse events and generally were reported as mild to moderate.

The two higher doses of pregabalin had similar responder rates of roughly 47%, whereas the placebo rate was 18%. These doses were also tied to significant improvements in sleep and quality of life. Improvements in pain and sleep were noted within 1 week of treatment and persisted throughout the study. A total dose of 300 mg/day has also been found effective in improving pain scores, sleep interference, and other secondary outcomes.

Conclusion:Pregabalin was effective in reducing pain and improving sleep disturbances due to pain, and was well tolerated in Japanese patients with painful DPN.

2. Amitriptyline vs. pregabalin in painful diabetic neuropathy: a randomized double blind clinical trial:

Good, moderate and mild pain relief were noted in 21 (48%), 6 (13%) and 7 (15%) patients on pregabalin and 15 (34%), 5 (11%) and 12 (27%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physician's global assessment, McGill pain questionnaire, Likert pain scale and Patient Global Impression of Change showed no significant difference between the treatments, although improvement with both treatments was seen from the first week. Of the 52 adverse events reported, 34 (65.4%) were with amitriptyline, drowsiness being the commonest [in 19 (43%) patients]. Pregabalin caused adverse events in 18 (25%), of which drowsiness was the most common in nine (20%) patients. The preferred pregabalin dose was 150 mg twice daily.

Conclusion:As there are few differences between the two treatments in efficacy, pregabalin 150 mg twice daily might be the alternative choice as it is associated with fewer adverse effects

3.Comparative Study of Clinical Efficacy of Amitriptyline and Pregabalin in Postherpetic Neuralgia:

we found a clinically significantly better response with pregabalin compared to amitriptyline

 The study included 50 patients, 32 (64%) male and 18 (36%) female, randomized to receive either amitriptyline or pregabalin (n=25 each). Amitriptyline was administered in a dose of 25 mg once daily and pregabalin in a dose of 75 mg twice daily. Inclusion criteria were as follows: postherpetic neuralgia of more than 1 month duration; pain of at least moderate severity; and patient age 40 years or older and no pregnancy. Patients with a history of any serious diseases (renal, cardiac, hepatic or seizure) were excluded. Total treatment period spanned 8 weeks, with patient follow up visits at 2, 4 and 8 weeks to assess the degree of improvement in pain perception and any adverse reaction. Patients with four herpes zoster types were included in this study, of which thoracic type predominated (54%). Other types were cervical in 12 (24%), trigeminal in 8 (16%) and lumbosacral in 3 (6%) patients. Prodromal symptoms before herpes zoster were reported by 66% of study patients. Satisfactory improvements of pain perception at the end of 8 weeks (>75%) were noticed in pregabalin group, which was statistically significant (χ2=10.08; P<0.05).Dry mouth was the commonest complication in amitriptyline group and dizziness in pregabalin group.

If pregabalin dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum interval of 1 week.

“In the United States, the Food and Drug Administration (FDA) has approved pregabalin for adjunctive therapy for adults with partial onset seizures, management of postherpetic neuralgia and neuropathic pain associated with spinal cord injury and diabetic peripheral neuropathy, and the treatment of fibromyalgia.[7] Pregabalin has also been approved in the European Union”.

Adverse drug reactions associated with the use of pregabalin include:

·         Very common (>10% of patients): dizziness, drowsiness.

·         Common (1–10% of patients): blurred vision, diplopia, increased appetite, euphoria, confusion, vivid dreams, changes in libido (increase or decrease), irritability, ataxia, attention changes, abnormal coordination, memory impairment, tremors, dysarthria, parasthesia, vertigo, dry mouth and constipation, vomiting and flatulence, erectile dysfunction, fatigue, peripheral edema, drunkenness, abnormal walking, weight gain, asthenia, nasopharyngitis, increased creatine kinase level.

·         Infrequent (0.1–1% of patients): depression, lethargy, agitation, anorgasmia, hallucinations, myoclonus, hypoaesthesia, hyperaesthesia, tachycardia, excessive salivation, sweating, flushing, rash, muscle cramp, myalgia, arthralgia, urinary incontinence, dysuria, thrombocytopenia, kidney calculus

·         Rare (<0.1% of patients): neutropenia, first degree heart block, hypotension, hypertension, pancreatitis, dysphagia, oliguria, rhabdomyolysis, suicidal thoughts or behavior

Amitriptyline:

Disadvantages:

·         risk of fatality in overdose

·         narrow therapeutic index

·         strong anticholingergic properties, and as a result severe anticholingergic side effects

·         sedation and mental or motor impairment

·         can lower the seizure threshold

·         cardiotoxicity

·         weight gain (greater increase in weight than with nortriptyline, desipramine, zimelidine, and imipramine) 39, 24

·         possible decreased amount of REM sleep

Amitriptyline was not approved by US FDA for this use.

References:

1.Bansal D, Bhansali A, Hota D, Chakrabarti A, Dutta P. Amitriptyline vs. pregabalin in painful diabetic neuropathy: a randomized double blind clinical trial. Diabet Med. 2009 Oct;26(10):1019-26. doi: 10.1111/j.1464-5491.2009.02806.x.Available from: http://www.ncbi.nlm.nih.gov/pubmed/19900234

2Arun Achar1, Partha Pratim Chakraborty2, Samiran Bisai3, Asish Biswas4,Tapobrata Guharay5. Comparative Study of Clinical Efficacy of Amitriptyline and Pregabalin in Postherpetic Neuralgia. Acta Dermatovenerol Croat. 2012;20(2):89-94.

3.Satoh J, Yagihashi S, Baba M, Suzuki M, Arakawa A, Yoshiyama T, Shoji S.Efficacy and safety of pregabalin for treating neuropathic pain associated with diabetic peripheral neuropathy: a 14 week, randomized, double-blind, placebo-controlled trial. Diabet Med. 2011 Jan;28(1):109-16. doi: 10.1111/j.1464-5491.2010.03152.x.Available from: http://www.ncbi.nlm.nih.gov/pubmed/21166852

4.Amitriptyline HCL (Elavil). Last updated: April 12, 2012.Available from: http://www.emedexpert.com/facts/amitriptyline-facts.shtml