8 Prescribing Guidelines
Overdose deaths involving prescription drugs are rising, and the reasons are multifactorial. Data are incomplete, but good evidence points to several likely contributing factors. To minimize harm when prescribing opioids and other psychotherapeutics, observe the following guidelines:
1. Assess patients for risk of abuse before opioid therapy and manage accordingly
Problem: Overuse of prescriptions has been shown to cause harm and may be a factor contributing to overdose deaths (1-2).
Suggestion: Pain providers may use one of several available tools before prescribing for opioids ever takes place to assess patients for their risk of developing problematic drug-taking behaviors. Tools recommended by experts in the field include the Opioid Risk Tool (ORT) and the Screener and Opioid Assessment for Patients with Pain (SOAPP)(3-4). If risk factors are revealed, implement a plan according to the level of risk: e.g., for high-risk patients, this might include referral for further psychological evaluation and co-management with a chemical dependency expert prior to initiating an opioid trial; for low-to-moderate but at-risk patients, a structured monitoring and close follow-up plan should be agreed upon, documented and followed. All patients, no matter how low the apparent risk, should be treated with “universal precautions,” modeled after the infectious disease paradigm (5).
2. Watch for and treat co-morbid mental disease when it occurs
Problem: Mental health problems such as depression and anxiety disorders frequently occur together with chronic pain (6-7), causing some patients to misuse their analgesics or psychotherapeutic medications, or mix their medications with alcohol or illicit drugs to relieve emotional distress. These behaviors place the patient at high risk for drug-drug interactions and related toxicity.
Suggestion: It is important to assess for the presence of mental health disorders before initiating opioid therapy. When indicated, treating clinicians should consult with experts in mental health fields to coordinate care. Patients with a dual diagnosis of chronic pain and psychiatric co-morbidity should be treated for both problems simultaneously. Patients sometimes independently seek care from multiple sources without volunteering this information; be proactive and seek out this information when taking a history at each visit. Know what is being prescribed and by whom to coordinate care and manage medication use as safely and effectively as possible.
3. Use conventional conversion tables cautiously when rotating (switching) from one opioid to another
Problem: Equianalgesic conversion tables only serve as general guides to determine the equivalent doses of different opioids (8-9). Their use in determining a safe and effective dose of a substitute opioid requires additional consideration for every patient’s individual circumstances.
Suggestion: When rotating from one opioid to another, consider slowly decreasing one opioid while slowly titrating the new opioid to effect. This process takes time but may be safer than switching all at once. If you are not experienced in switching opioids in patients on long-term opioid therapy, seek consultation from a clinician with this expertise.
4. Avoid combining benzodiazepines with opioids, especially during sleep hours
Problem: Benzodiazepines will enhance the respiratory-depressant effects of opioids (10-11).
Suggestion: When possible, consider using an alternative to benzodiazepines for anxiety disorders. When a sleep aid is indicated, avoid benzodiazepines and use alternative treatments, like an anticonvulsant or a low dose of trazodone. For a patient with a neuropathic pain disorder, a low dose of a tricyclic antidepressant at bedtime may be dually beneficial; use caution in older patients, monitoring for excessive anticholinergic effects.
5. Methadone should be started at a very low dose and titrated slowly regardless of whether the patient is opioid tolerant or not.
Problem: Methadone's half life ranges from 5 to 150 hours, although its analgesic effect usually lasts only 6 hours (12). This unusual pharmacokinetic profile can contribute to an unpredictable accumulation of methadone during the first few weeks of treatment. Until steady state is reached, and especially during sleep, this is a time of particular vulnerability to respiratory depression.
Suggestion: Consider starting patients on 10 mg or less per day (13), in divided doses (q8h) and increase total daily dose by no more than 25% to 50% no more frequently than weekly. If you are not experienced prescribing methadone, consult with a clinician who is.
6. Assess for sleep apnea in patients on high daily doses of methadone or other opioids and in patients with a predisposition
Problem: Recent data have shown a high prevalence of sleep apnea in patients on chronic opioid therapy (10, 14-15). The data suggest a dose relation, and the sleep apnea can be life threatening on moderate-to-high doses of opioids.
Suggestion: Patients who require greater than 50 mg of methadone or greater than 150 mg morphine equivalent of other opioids should be referred for formal sleep apnea evaluation. So should those with a predisposition for sleep apnea (e.g.,“Pickwickian” physiognomy, history of snoring or apneic episodes reported by sleep partner). If sleep apnea is moderate-to-severe, seek consultation regarding the best treatment options. At-risk patients may require inpatient evaluation to monitor for and determine safety of opioid therapy.
7. Tell patients on long-term opioid therapy to reduce opioid dose during upper respiratory infections or asthmatic episodes
Problem: Respiratory infections or asthma attacks can decrease the margin of safety during long-term opioid therapy.
Suggestion: Patients should be advised to reduce their daily opioid doses, particularly their evening doses, by at least 30% during events with acute respiratory tract compromise.
8. Avoid using long-acting opioid formulations for acute post-operative or trauma-related pain
Problem: Long-acting or sustained-release opioids, including transdermal patches (16), were not designed to treat acute post-operative or trauma pain.
Suggestion: These medications should be reserved for patients who have developed tolerance to opioids.
References:
1. Paulozzi LJ, Budnitz DS, Xi Y. Increasing deaths from opioid analgesics in the United States. Pharmacoepidemiology and Drug Safety 2006;15(9):618-627.
2. Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guide for Practitioners. 1st ed. North Branch, MN: Sunrise River Press; 2007.
3. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the opioid risk tool. Pain Med2005 Nov-Dec;6 (6):432-42.
4. Butler SF, Budman SH, Fernandez K, Jamison RN. Validation of a screener and opioid assessment measure for patients with chronic pain. Pain. 2004 Nov;112(1-2):65-75.
5. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005 Mar-Apr;6(2):107-12.
6. Ohayon MM Specific characteristics of the pain/depression association in the general population. J Clin Psychiatry. 2004;65 Suppl 12:5-9.
7. Arnold LM, Hudson JI, Keck PE, Auchenbach MB, Javaras KN, Hess EV. Comorbidity of fibromyalgia and psychiatric disorders. J Clin Psychiatry. 2006 Aug;67(8):1219-25.
8. Leavitt SB. Methadone safety stressed by FDA; report from Pain Treatment Topics provides clinical guidance. Pain Treatment Topics e-briefing 2006;1(2).
9. Ripamonti C, De Conno F, Groff L, et al. Equianalgesic dose/ratio between methadone and other opioid agonists in cancer pain: Comparison of two clinical experiences. Annals of Oncology 1998; 9:79-83.
10. Webster LR, Choi Y, Desai H, Grant BJB, Webster L. Sleep-disordered breathing and chronic opioid therapy. Pain Med. Published article online: 30-Jul-2007
doi: 10.1111/j.1526-4637.2007.00343.x
11. Mikolaenko I, Robinson CA Jr, Davis GG. A review of methadone deaths in Jefferson County, Alabama. Am J Forensic Med Pathol. 2002 Sep;23(3):299-304.
12. Leavitt SB. Methadone analgesia safety overview & patient instructions handout. Pain Treatment Topics 2006. Available at:
http://www.pain-topics.org/pdf/Methadone_Safety_Overview&Handout.pdf. Accessed 2/25/08.
13. Webster LR. Methadone-related deaths. J Opioid Manage 2005 Sep-Oct;1(4):211-7.
14. Farney RJ, Walker JM, Cloward TV, Rhondeau S. Sleep-disordered breathing associated with long-term opioid therapy. Chest 2003; 123(2):632-639.
15. Wang D, Teichtahl H, Drummer O, Goodman C. Cherry G, Cunnington D, Kronborg I. Central sleep apnea in stable methadone maintenance treatment patients. Chest 2005; 128 (3): 1348-1356.
16. Waknine Y. Deaths related to fentanyl patch misuse spark second public health advisory. Medscape Medical News, Dec. 21, 2007. Accessed 2/25/08 at http://www.medscape.com/viewarticle/567891.
