Anticonvulsants??diabetic neuropathic pain???

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Anticonvulsants??diabetic neuropathic pain???

• ???? R2???

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????

• Anticonvulsants?diabetic neuropathic pain????????
• ?anticonvulsants??diabetic neuropathic
  pain??,???anticonvulsant??????

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????

• 1960???,?????anticonvulsants???neuropathic
  pain,?diabetic neuropathy,trigeminal
  neuralgia,post-herpetic neuralgia??
• Diabetic neuropathic pain?????????,????DM??,??????
  ?anticonvulsants??,???????diabetic neuropathic
  pain?????,?????,??????????anticonvulsants?diabetic
  neuropathic pain????

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Diabetic peripheral neuropathy

• 15 DM pt have S/S of neuropathy
• DMgt25 years? affect nearly 50 pt
• Pathogenesis unknown
• Hyperglycemia
• Microvascular diasease
• Treatment TCAs, NSAID, anticonvulsants, opioids,
  topical anesthetic agents, nerve block

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????

• anticonvulsants?diabetic neuropathic
  pain?????,?????anticonvulsants ???????

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????

• ????
• Neuropathy
• anticonvulsant, anticonvulsants, carbamazepine,
  oxcarbazepine, valproate, phenytoin, lamotrigine,
  vigabatrin, gabapentin, topiramate
• Clinical trial (PubMed)
• ????
• ACP Journal Club -- 1
• Cochrane Database of Systematic Reviews -- 1
• Cochrane Central Register of Controlled Trials,
  PubMed -- 15

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? ?
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????(I)

• Cochrane Database of Systematic Reviews
• Anticonvulsant drugs for acute and chronic pain
  (2000)
• Diabetic Neuropathy Four placebo-controlled
  studies
• one with carbamazepine (Rull 1969), two with
  phenytoin (Chadda 1978, Saudek 1977), and one
  with gabapentin (Backonja 1998)).
• Rull (Rull 1969) and Chadda (Chadda 1978) found
  that with two weeks' treatment between 30 and 50
  more patients improved on anticonvulsant than on
  placebo.
• Saudek 1977, using phenytoin (300 mg/day) for 23
  weeks of treatment found no difference in mean
  pain intensity compared with placebo
• Backonja (Backonja 1998) reported a 60
  improvement on a global scale for patients on
  gabapentin (up to 3.6 grams per day) after four
  weeks' treatment in a study of 165 participants.
• one active control study comparing carbamazepine
  200 mg versus a nortriptyline 10 mg/fluphenazine
  0.5 mg combination (Gomez -Perez 1996). Only mean
  data were reported and the authors could not show
  a difference between the two treatments although
  it is stated that all patients improved
• Conclusion gabapentin is effective in
  post-herpetic neuralgia and diabetic neuropathy
  but does not appear to be superior to
  carbamazepine, a cheaper alternative in many
  countries. There were, however, no direct
  comparisons between these two drugs

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????(II)

• ACP journal (2002)
• Review Anticonvulsant drugs relieve chronic but
  not acute pain
• 6 drugs carbamazepine (12 trials), phenytoin (6
  trials), sodium valproate (2 trials), gabapentin
  (2 trials), clonazepam (1 trial), and lamotrigine
  (1 trial)
• Carbamazepine, phenytoin, and gabapentin were
  more effective than was placebo in relieving the
  pain of diabetic neuropathy
• all caused such minor side effects as drowsiness,
  dizziness, constipation, nausea, and ataxia
  (numbers needed to harm NNHs ranged from 3 to
  4). The NNHs for major harm were not
  statistically significant for any drug

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????-Carbamazepine

• 3 randomized clinical trial
• 2 with placebo (Rull, 1969 Wilton, 1974)
• More effective then placebo
• 1 with nortriptyline and fluphenazine
  (Gomez-Perez, 1996)
• Both drugs improvements from baseline, but no
  significant difference between 2 drugs
• Dose 300-1000mg/d
• Adverse events (up to 70) Somnolence,
  dizziness, gait disturbance
• Withdrawal rate 0-7

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????-Phenytoin

• 2 randomized clinical trial(Chadda, 1978 Saude,
  1977)
• Conflicting result

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????-Sodium valproate

• 2 randomized clinical trial(91 pt)(Kochar, 2002
  2004)
• Significant improvement then placebo
• SF-MPQ 5?3.41 (1 month)
• VAS 6 ?3, SF-MPQ 19.47?9.66, PPI 2.71?1.33 (3
  months)
• Side effect nausea2, sedation1, liver change2
• Dose 1200mg, 1000mg/d

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????-Gabapentin I

• 4 randomized clinical trial
• 3 with placebo, 1 with morphine, 1 with
  amitriptyline
• Backonja, 1998 (165pt)
• 900 titrated to 3600mg/d
• Significant pain relief than placebo, improvement
  of sleep, mood (pain score 6.4?3.9
  placebo6.5?5.1)
• Pain relief was observed during 2nd week when
  dose reached 1800mg/d
• Dizziness 24, somnolence 23, headache 11,
  diarrhea 11
• Gorsen, 1999 (40 pt)
• 900mg/d
• Ineffective at dose of 900mg/d

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????-Gabapentin II

• Morello, 1999 (28 pt)
• Gabapentin 900-1800mg, or Amitriptyline 25-75 mg
  /d
• No significant different in pain relief
• No significant difference in occurrence of
  adverse effects (17 in amitriptyline, 18 in
  gabapentin)
• Gilron, 2005 (57pt)
• Gabapentin (3200mg), Morphine(120mg), combine(G
  2400mg, M 60mg), placebo
• Gabapentin and Morphine combined achieved better
  analgesia at lower dose of each drug
• Adverse effect
• Combination contipation?than gabapentin, dry
  mouth?than morphin

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????-Lamotrigine

• 1 randomized clinical trial (53 pt)(Eisenberg,
  2001)
• Lamotrigine attenuates painful diabetic
  neuropathy at a daily dose of 200-400mg then
  placebo (NPS 6.4?4.2, MPQ, PDI, BDI unchanged)
• Maximal pain reduction37, 12 pt 50 pain
  reduction
• Adverse events similar to placebo (exception 2
  rash developed)

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????-Topiramate

• 2 randomized clinical trial
• Topiramate diabetic neuropathic pain study group,
  2004 (3 trial)(1259 pt)
• 100mg, 200mg, 300mg
• 1 effective, 2 no significant (placebo effect
  high, 38 and 48)
• Overall no significant more effective than
  placebo
• 16 31 discontinuation due to adverse events
• Raskin, 2004 (12weeks, 323 pt, 400mg)
• ½ - 30, 1/3 - 50 pain reduction
• Reduced pain and body weight more effective than
  placebo
• Adverse event nausea, somnolence, dizziness,
  paresthesia, cognition dysfunction, appetite
  decrease
• 48 dropout rate

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????-Oxcarbazepine

• 1 open-label trial (30pt)(Beydoun, 2004)
• Significant improvement in total pain score, and
  present pain intensity (VAS score 66.3?34.3,
  48.3)
• Dose up to 1200mg/d (mean 814mg)
• Adverse events(gt10) drowsiness, dizziness,
  headache, nausea, vomiting, diarrhea

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??(I)

• ??????carbamazepine, sodium valproate,
  lamotrigine, gabapentin???diabetic neuropathic
  pain??????????,???????????anticonvulssants?????
• Topiramate, phenytoin???????????????,??diabetic
  neuropathic pain????????
• Oxcarbazepine, vigabatrin??RCT?????diabetic
  neuropathic pain????
• ??anticonvulsants (gabapentin, topiramate,
  oxcarbazepine),??????adverse effects?dizziness,
  somnolence, sedation????
• Sodium valproate?Lamitrigine??????,????????

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??(II)

• ????diabetic neuropathic pain,anticonvulsants?????
  ?????,?????????????????
• ?????????anticonvusants?????,?????,??anticonvulsan
  ts??????,?????????????????,???????anticonvulsants?