Starting Opioids

See “A Comprehensive Algorithm for Management of Neuropathic Pain” for guidelines on which medications should be tried prior to trying an opioid regimen. If adequate trials of non-opioid and non-medication treatments have not resulted in significant functional improvement, opioid analgesia may be indicated.

After an assessment of patient risk using the ORT or SOAPP, consideration of what type of opioid to prescribe includes patient pain characteristics and prior exposure to opioids.

Short acting (Immediate Release) opioids:

• Indication: No opioid tolerance/opioid naive; intermittent severe pain; breakthrough pain

Source: http://dailymed.nlm.nih.gov

Long acting opioids:

• Indication: Opioid tolerance exists; constant significant pain is present (around the clock pain, protracted pain for hours); to stabilize pain relief when patient using multiple doses of  immediate release opioids.
• Long-acting opioids should be titrated in a conservative and measured way (until a stable dose is reached) at interval visits if only partially effective.

Source:  http://dailymed.nlm.nih.gov

Variability

Variability in methadone treatment exists on an individual level because of genetic polymorphisms in the Cytochrome P450 enzyme pathways and the use of co-administration of medications that can impact the metabolism of methadone.  Methadone is metabolized through Cytochrome P450 3A4 and 2B6 pathways. The types of medications that inhibit these pathways such as the SSRIs can cause greater methadone side effects (sedation, etc.).  Medications that induce these pathways like rifampin can cause the methadone to be less effective due to lower blood levels.

High methadone doses can contribute to QTc prolongation. However, these risks for QTC prolongation can be managed with proper baseline and follow-up ECG monitoring.  Some benefits that make methadone a better choice than others are that it has no ceiling, meaning you can always keep increasing the dose so long as you check the ECG results. Another benefit is the price because it is one of the least expensive opioids on the market.  It is the only opioid with a long-acting dose in liquid form for oral consumption. The other major benefit is several studies have shown that methadone is effective to treat neuropathic pain because it acts as an n-methyl-d-aspartate receptor antagonist.

Additional Testing for Chronic Pain Patients

Patients on an NSAID who are older than 65 or have a history of heart failure, liver disease, diabetes, or concurrent nephrotoxic drugs should have a creatinine within the past 3 months of initiation and 2-4 weeks thereafter.

Acetaminophen should be limited to ≤ 2 gm/day in cirrhosis and chronic alcohol use (>3 drinks per day).

Tramadol should be avoided in patients with a history of seizures, or in patients on SSRIs (can increase the risk of seizures). If used in a patient with a history of seizures, additional monitoring is required.

Regarding antidepressants, patients receiving a tricyclic antidepressant (TCA) equivalent to 100 mg amitriptyline or 50 mg nortriptyline or 75 mg venlafaxine should have well-controlled blood pressure at baseline, and at recheck within the first 2 weeks. TCAs should not be used in patients 65 years or older.

Patients taking methadone should have electrocardiogram taken at baseline since methadone has been associated with electrocardiographic abnormalities such as QT prolongation and cardiac arrhythmia.

Sources:

These recommendations are based on expert consensus.

Altier N, et al. Management of chronic neuropathic pain with methadone: a review of 13 cases. Clin J Pain. 2005; 21:364-369.

Finn S, Tuckwiller S. Feds act on methadone deaths. West Virginia Gazette. July 23 2006.

Foley KM. Opioids and chronic neuropathic pain. NEJM. 2003; 348:1279-1281.

Gagnon B, et al. Methadone in the treatment of neuropathic pain. Pain Res Manage. 2003; 8:149-154.

Google Search: ‘Methadone deaths.’ December 2007.

Increase in poisoning deaths caused by non-illicit drugs–Utah, 1991-2003. MMWR Weekly. 2005; 54:33-36.

Morley JS, et al. Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Pall Med. 2003; 17:576-587.

Moulin DE, et al. Methadone in the management of intractable neuropathic non cancer pain. Can J Neuro Sci. 2005; 32:340-343.

Nichloson AB. Methadone for cancer pain: Review. Cochrane Database of systematic reviews. 2004;2:CD003971.

US Department of Health and Human Services – Division on Pharmacologic Therapies. Report on Methadone Mortality. 2007.