Low Dose Neuropathic Pain Drugs Only Work in Combo – and then only a Bit

Neuropathic pain drugs by self have mediocre effects – often dropping pain by </= 2/10 points. At low dose Imipramine 75 mg/day and Pregabalin 300/day did not have significant benefit but the combo dropped VAS by One more than placebo – nothing to write home about however.

Pain. 2015 May;156(5):958-66. doi: 10.1097/j.pain.0000000000000143.
Imipramine and pregabalin combination for painful polyneuropathy: a randomized controlled trial.
Holbech JV(1), Bach FW, Finnerup NB, Brøsen K, Jensen TS, Sindrup SH.

  • Double bllind trial
  • “Polyneuropathy diagnosis had to be confirmed by clinical signs and QST or
    electrophysiological tests or skin biopsy.”
  • Selection included a big proportion of “idiopathic” cases:


  • Imipramine 75 mg and pregablin 150 mg twice daily was titrated up over 1 week though over 70 were given Imipramine 25 mg or pregabalin 75 md/day [that was probably way too little)



  • Pregabalin and imipramine by self have NO statistical benefit even.
  • The combo had only a difference on VAS of about ONE which is statistically significant but barely clinically significant.

Comments – Like the Canadian study that found only 23.5% of neuropathic pain patients came under control with standard meds, this confirms that unless pushed to high dose, neuropathic pain drugs are almost useless. Mind you, in Fibromyalgia, 2/10 will respond substantially to Pregabalin or Duloxetine so golden cases could occur with Neuropathic cases as well. By the way, I have extended the response graph to zero so you can really see how little it does – in their article it looked better but really isn’t. I see new patients who are treated like they are nuts because their pain does not come under control and that is so sad.  Opioids will bring down pain 20-30% only unless they are “golden” cases. Had one really told she was nuts because her fentanyl patches were expected to last 3 days and her behaviour was like a drug shopper. Fentanyl patches DO NOT last 3 days – 3rd day most subjects will report having to use rescue meds so I have tehm change canada goose pas cher canada goose pas cher

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