McMaster University

Michael G. DeGroote
National Pain Centre

Scope of Search

Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain

Cluster 4: Treating Specific Populations with LTOT

R20. Recommendation Statement

No. Recommendation Keyword
R20 Patients with a psychiatric diagnosis are at greater risk for adverse effects from opioid treatment. Usually in these patients, opioids should be reserved for well-defined somatic or neuropathic pain conditions. Titrate more slowly and monitor closely; seek consultation where feasible (Grade B). Co-morbid psychiatric diagnoses
  • R20. Discussion
  • R20. Summary of Peer-Reviewed Evidence

R20. Discussion

1. Extra Considerations for CNCP Patients with Co-morbid Psychiatric Conditions

CNCP patients with psychiatric disorders are more likely to receive opioids than CNCP patients without psychiatric disorders (Sullivan 2005, Breckenridge 2003, Fishbain 2004). Yet evidence suggests that patients with depression or anxiety are less likely to benefit from opioids, due to a diminished response to opioids or an enhanced perception of pain, or both (Wasan 2005, Levenson 2008, Riley 2008).

In patients with active psychiatric disorders affecting pain perception, opioids should, in most cases, be reserved for well-defined somatic or neuropathic pain conditions. For example, fibromyalgia patients have a high prevalence of depression and anxiety, and a nociceptive or neuropathic cause for fibromyalgia pain has not been found. Opioids have little effect on functional status of these patients, in particular, strong opioids; (see Recommendation 4).

2. Increased Risks with Co-morbid Psychiatric Conditions

  • Substance Abuse: Patients with psychiatric disorders have a higher prevalence of substance abuse (Becker 2008, Edlund 2007, Sullivan 2006, Manchikanti 2007, Wilsey 2008).
  • Sedation and Falls: Opioids increase the risk of sedation and falls in patients on psychotropic drugs, and they increase the lethality of overdose and suicide attempts (Voaklander 2008).
  • Overdose: Patients with psychiatric disgnoses are frequently on benzodiazepines, and concurrent benzodiazepine use is a common feature in opioid overdoses (White 1999, Cone 2003, Burns 2004, Man 2004).
  • Depression: Opioid use is associated with a higher prevalence of depression.

3. Prescribing Cautions for Co-morbid Psychiatric Conditions

  • Titrate more slowly in CNCP patients with co-morbid psychiatric disorders.
  • Consultation with a psychiatrist might be advisable for patients on LTOT who have a concurrent psychiatric illness, particularly if the illness has not fully responded to treatment. They may be able to comment on a) the role of the illness on the patient’s pain perception, and b) the advisability of benzodiazepine tapering.
  • Use structured opioid therapy (see Recommendation 21), with a specific treatment agreement, conservative dosing, frequent dispensing, and monitoring for aberrant drug-related behaviours.
  • Closely monitor the patient’s mood and functioning.
  • Consider tapering if opioid effectiveness is inadequate.

    opioid effectiveness = improved function or at least 30% reduction in pain intensity

    Short-term studies have documented improvements in mood and pain with opioid tapering (see Appendix B-12 for a tapering protocol).

R20. Summary of Peer-Reviewed Evidence

1. Need for careful patient selection, cautious opioid prescribing, and opioid tapering when indicated:

1.1 Patients on chronic opioid therapy have a higher prevalence of depression and other psychiatric conditions than the general population.

A large population-based study found that self-reported regular opioid use was strongly associated with both mood and anxiety disorders (Sullivan 2005).

Another study found that patients with low back pain who were receiving opioids were more likely to be depressed than those receiving only NSAIDs (Breckenridge 2003). Other studies have had similar results (Fishbain 2004).

1.2 Patients with anxiety or depression may have diminished analgesic response to opioid therapy, and/or a heightened perception of pain.

One study found that depressed patients with discogenic back pain had diminished analgesic response to opioids (Wasan 2005).

Another study of patients with sickle cell disease found that the severity of pain, functional disability and use of opioids were correlated with the patient’s depression and anxiety. The association held for both crisis days and non-crisis days, and even after controlling for hemoglobin type (Levenson 2008). In a recent review of the literature, the most consistent finding is that depression and anxiety are associated with increased risk for drug abuse and decreased opioid efficacy (Riley 2008).

1.3 Opioid tapering is associated with improved mood and pain intensity.

For more details see Recommendation 13.

In one study, patients attending a multidisciplinary pain program were classified into no opioid, low-dose opioid or high-dose opioid groups. Both opioid groups had higher depression scores than the non-opioid group. The opioid groups were tapered off their medication. By six months, all groups improved in mood and function. Interestingly, all three groups had similar mood ratings at six months, even though the opioid group had more depression at baseline (Townsend 2008).

2. Need for monitoring of substance use and mood:

2.1 Patients on LTOT who have psychiatric disorders are more at risk for substance misuse and dependence than patients on LTOT without psychiatric disorders.

A large national cross-sectional survey (United States) found that depression, panic disorder, social phobia and agoraphobia were associated with non-medical use of prescription opioids (Becker 2008). Another cross-sectional survey found higher rates of opioid misuse and problematic drug use among patients on opioid therapy; these rates were mediated by higher rates of psychiatric disorders (Edlund 2007). An earlier study had similar results (Sullivan 2006). A study of 500 chronic pain patients on opioids documented that anxiety and depression was associated with significantly higher rates of opioid abuse and illicit drug use (Manchikanti 2007). A study of chronic pain patients presenting to the emergency department for prescription refills documented that a) a high proportion (81%) were abusing their opioids, and b) of these, a high proportion had depression and anxiety (Wilsey 2008).

2.2 Patients on LTOT are at higher risk for completed suicide.

One case control study found that patients on chronic opioid therapy are at greater risk for suicide than control patients (Voaklander 2008). This likely reflects the association between depression and opioid use for chronic pain. Nonetheless, it indicates that physicians should assess their patients for depression and suicidal ideation, and opioids should be dispensed in small amounts for patients at risk.