Effexor useful for pain d/t peripheral diabetic neuropathy

Specialties Geriatric


Thought others might find this letter of particular interest if you have a patient with peripheral diabetic neuropathy who currently has an ineffective pain control regimen. I copied it from medscape.com. I would bet dollars to donuts many of our GP's are not aware of this treatment possibility.

Venlafaxine in the Treatment of Painful Peripheral Diabetic Neuropathy in a Uremic Patient Undergoing Hemodialysis

Mehmet Emin Yilmaz, MD, Ali Kemal Kadiroglu, MD, Ismail Hamdi Kara, MD, Suber Dikici, MD

Medscape General Medicine 4(3), 2002. © 2002 Medscape

Posted 08/21/2002

In recent anecdotal reports by Kiayias and colleagues,[1] Lithner,[2] and Davis and Smith,[3] venlafaxine was reported to be effective in the symptomatic treatment of pain with diabetic neuropathy. These observations are in accordance with a similar finding we made in a uremic patient with painful peripheral diabetic neuropathy.

Diabetic neuropathy is a chronic complication of diabetes mellitus. It occurs in either peripheric or autonomic neuropathy. Distal sensorial and autonomic polyneuropathy are the most frequently observed clinical forms of diabetic neuropathy. In type 2 diabetics, both distal sensorial and autonomic neuropathy are seen in 4% of cases in the first 5 years after diagnosis, rising to 15% of cases after 20 years.[4,5]

In young adult patients with type 2 diabetes, diabetic neuropathy is a very rare state at the time of diagnosis. Diagnosis of neuropathic pain is often easily made from information gathered on neurologic examination and from patient history.[4,6,7]

Clinical presentation of painful peripheral diabetic neuropathy usually occurs in distal lower extremities, typically as burning, numbness, and throbbing. These symptoms increase in the evening. Studies from the diabetes control and complications trial and the UK Prospective Diabetes Study Group (UKPDS) have shown that improved glycemic control (maintaining HbA1c levels in the 7-8.5 range) can prevent or delay the onset of diabetic neuropathy in both type 1 and type 2 patients. The UKPDS study did not show a statistically significant difference in diabetic neuropathy as a subcategory. However, by grouping all diabetic complications, the authors were able to demonstrate a significance (P = .03).[6]

Because control is difficult to achieve, this condition remains very common and difficult to treat. Treatment of neuropathic pain may be difficult because selection of an appropriate pharmacologic agent is highly variable. Some drug options include: anticonvulsants, antiarrhythmics, local anesthetic agents, opioids, topical agents, and tricyclic antidepressants.[7-9]

The antidepressant venlafaxine is a potentially useful new serotonin-noradrenaline receptor inhibitor drug that is better tolerated and may also be an effective analgesic.[10,11] Venlafaxine inhibits the reuptake of the neurotransmitters serotonin and noradrenaline, weakening dopamine in the brain synapse, but does not inhibit the muscarinic, histaminergic, and adrenergic receptors. It is metabolized via CYP2D6 and CYP3A4 in the liver. Therefore, no serious toxic side effects are seen with ordinary dosage in renal insufficiency. The most common side effects are nausea, somnolence, and dizziness.[9,12,13]

In this case, venlafaxine extended-release capsules (Effexor XR; Wyeth) were administered to a 33-year-old female patient with a 2-year history of type 2 noninsulin-dependent diabetes mellitus (NIDDM). She complained of bilateral numbness, burning, and pain in her feet, which increased at night. The pain was so severe that the patient was unable to wear shoes or slippers. The patient used conventional analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs, but the pain did not resolve. After 6 months of these symptoms, diagnoses of NIDDM and diabetic neuropathy were made. After neurologic examination, deep tendon reflexes were hypoactive, and there was sock-shaped hypoesthesia. The intensity of the pain was evaluated by Visual Analog Scale (VAS).[14]

The patient marked 7 in the numeric scale, which corresponds to severe pain in the descriptive pain scale. The differential diagnosis was made with uremia, vitamin B12 and folic acid deficiency, and alcohol abuse. The patient was given glipizide (Glucotrol XL; Pfizer) 10 mg/day, amitriptyline (Laroxyl; Roche) 10 mg 3 times a day, and an 1800 kcal/day diet that consisted of protein 1.2 g/kg/day. Additionally, potassium and sodium were restricted. The patient's pain resolved slightly after this course of treatment but maintained a VAS = 3. Chronic renal failure developed after 1 year. Creatinine clearance gradually decreased below 15 mL/minute. Hemodialysis was administered 3 times/week. The painful peripheral diabetic neuropathy continued during this period as the doses of amitriptyline were being gradually increased to 75 mg/day. The authors administered extended-release venlafaxine to a maximum dosage of 75 mg/day. In uremia patients, with this dosage, serum levels cannot build up and become toxic because the drug is metabolized in the liver.

After 5 days, the patient's symptoms resolved and the pain was relieved. The pain was reevaluated by VAS and the patient marked zero on the numeric scale, indicating no pain. Due to the pain relief, the patient stopped taking venlafaxine, but in a short time the pain recurred on VAS 5. The patient resumed the drug regimen and experienced complete pain relief in 5 days. The patient continued to take the medication and was not using any other analgesic concurrently. Venlafaxine was tolerated well and there were no side effects.

In conclusion, we observed that venlafaxine may be useful in the treatment of painful peripheral diabetic neuropathy in uremic patients.


1 Article; 2,334 Posts

I am on Effexor XL 225 mg/day as part of the program from my pain management clinic. It has been of enough help for radicular pain that I have been able to avoid increasing my pain meds for about 6 months.


1,961 Posts

Really? Interesting. I learn something new everyday. Thanks for the info!



1,961 Posts

BTW - do you take that dose at night Nancy? In my experiences in giving it, it makes the person taking it very sleepy, in much smaller doses.

Just curious.



1 Article; 2,334 Posts

Actually I have to take it all in the morning...I wake up every 2 hours if I take it at bedtime.

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