1. 2009;12;259-267Prevalence of Side Effects of Prolonged Low or Moderate Dose Opioid Therapy with Concomitant Benzodiazepine and/or Antidepressant Therapy in Chronic Non-Cancer Pain
   Observational Study
   Laxmaiah Manchikanti, MD, Kavita N. Manchikanti, BA, MS IV, Vidyasagar Pampati, MSc, and Kimberly A. Cash, RT.

BACKGROUND: Opioid use in the management of chronic pain is widespread in chronic pain settings. Opioid prescriptions for non-cancer pain and overall opioid sales have been soaring with the increasing nonmedical use of opioids in the United States. Prolonged use of high dose opioids has been associated with adverse consequences including tolerance, abuse, addiction, hyperalgesia, hormonal effects, and immunosuppression.

Studies of high dose therapy have shown pain relief with a 30% decrease in the intensity of pain and that only 44% of the patients continue the treatment between 7 and 24 months. However, there is no data available on the prevalence of side effects associated with low or moderate dose opioid use in chronic non-cancer pain when administered in conjunction with interventional techniques.

OBJECTIVE: To evaluate the prevalence of side effects, of low or moderate dose opioid therapy with or without benzodiazepines, antidepressants, and their combinations.

METHODS: The evaluation was conducted by interviewing 1,000 patients on stable doses of opioids, with or without benzodiazepines, antidepressants, and their combinations. Patients were categorized into 4 groups with Group 1 receiving opioids only (n = 143), Group 2 receiving opioids and benzodiazepines (n = 159), Group 3 receiving opioids and antidepressants (n = 113), and Group 4 received opioids, benzodiazepines, and antidepressants (n = 118).

RESULTS: Inclusion criteria was met in 533 patients receiving opioid therapy for longer than 6 months. The incidence of side effects in Group 1 was 18%, in Group 2 was 8%, in Group 3 was 17%, and in Group 4 was 14%. The most frequent complications were in patients receiving methadone (52%) followed by oxycodone (41%) and morphine (36%). Patients receiving hydrocodone had the least incidences of side effects with 7.5%. There were no significant differences noted based on the duration of therapy, age of the patient, and gender. Severe side effects accounted for only 14 of 137 instances.

LIMITATIONS:  Limitations of this study include the inability to incorporate multiple other drugs due to complicated nature with multiple groups and data collection and analysis. The other limitation is that the proportion of patients receiving methadone, oxycodone, morphine, and propoxyphene was low compared to hydrocodone with 77% of the patients.

CONCLUSION:  Moderate or low dose opioid therapy in conjunction with or without benzodiazepines, antidepressants, or in combinations are associated with minor side effects.