Adverse drug reactions and debrisoquine/sparteine (P450IID6) polymorphism in patients with fibromyalgia.
OBJECTIVE
To assess the frequency of adverse drug reaction in patients with fibromyalgia in relation to medications prescribed for this condition. To evaluate the potential role of the P450IID6 phenotype in the pathogenesis of these adverse drug reactions.


METHODS
Thirty-five patients with fibromyalgia were assessed using a structured questionnaire with demographic and clinical data and perceived adverse drug reactions. A sample of 60 patients with rheumatoid arthritis and 62 patients with localized back pain served as controls. The P450IID6 phenotype was determined for each of the fibromyalgia patients.


RESULTS
Overall, 141 patients had used NSAID and 79 (56%) of them reported adverse effects. Antidepressant drugs were used by 68 patients and 35 (51%) patients had adverse effects. Muscle relaxant drugs were used by 48 patients and 15 (31%) of them reported side effects. Analgesics were used by 122 patients and 22 (18%) had experienced adverse effects. Statistical differences in the frequency of adverse effects were found with antidepressant drugs in the fibromyalgia group, compared with rheumatoid arthritis (p=0.01) and back pain (p=0.02). Four of the 35 patients (11.4%) had a metabolic ratio (M.R.) greater than 0.30 (log M.R.= -0.52) indicative of the poor metabolizers (PM) phenotype. M.R. varied from 0.005 (log M.R. = -2.30) to 4.99 (log M.R. = 0.70).


CONCLUSIONS
The problem of adverse drug reactions in fibromyalgia patients does not appear to correlate with the PM phenotype of the P450IID6 oxidative enzyme. It also is unlikely that altered xenobiotic detoxification attributable to this PM phenotype would have a significant role in the development of fibromyalgia.
Skeith
K J
KJ
Division of Rheumatology, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Hussain
M S
MS
Coutts
R T
RT
Ramos-Remus
C
C
Avina-Zubieta
J A
JA
Russell
A S
AS
D000328:Adult; D000700:Analgesics / Q000009:adverse effects* / Q000627:therapeutic use; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology; D001416:Back Pain / Q000188:drug therapy / Q000201:enzymology; D002170:Canada; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003647:Debrisoquin / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000928:Antidepressive Agents; D018501:Antirheumatic Agents; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin