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9 Articles in Volume 8, Issue #4
Chronic Daily Headache
Confidentiality, Choice, and the Question of Autonomy
Head and Neck: Temporal Arteritis and Temporal Tendonitis Co-morbidity
Laser Acupuncture as a Pain Relief Modality
Long-term Therapy Using Short Acting Opioids for Chronic Non-cancer Pain
New Daily Persistent Headache (NDPH)
Opioids in Patients with Renal or Hepatic Dysfunction
Pain Management and Terminal Illness
The Biopsychosocial Approach

Long-term Therapy Using Short Acting Opioids for Chronic Non-cancer Pain

A cohort study explores the role of conditioning factors, dosage stability, opioid agreement violations, patient satisfaction, and the patient’s own estimated improvement in overall quality of life.

Opioids can, and do, play a role in the modulation of pain.1-3 Opioid therapy for chronic non-cancer pain appears to have gained in popularity,4,5 if not acceptance, in the past decades but remains controversial.6 Indeed, Brennan, Carr and Cousins7 went so far as to conclude “Opioids remain the drugs of choice for the treatment of moderate to severe pain, regardless of etiology.” There are a variety of routes of administration including oral, buccal, transdermal, intravenous (IV), and intrathecal (IT). Oral opioids are perhaps the most frequently used in the clinical setting and may be conveniently classified as short acting (SA) such as immediate release, or long acting (LA) such as sustained released, controlled released, and extended release.

A number of ‘guidelines’ regarding long term opioid therapy have been proposed.8-12 They often recommend the use of LA over SA opioids. It has always been assumed that LA opioids: (a) provide more consistent and stable serum levels, and therefore more stable analgesia, (b) enhance compliance secondary to reduced frequency of dosing, (c) are less likely to be ‘abused’ as they are not as often associated with euphoria, and (d) less likely to activate an ‘addiction’ process or pattern of abuse. The initial use of SA opioids to establish baseline requirements followed by a transition to LA opioids is often urged.9-12

Recent issues of Practical Pain Management have highlighted the use of LA opioids in the treatment of chronic pain. Tennant13 outlines an approach for transitioning from SA to LA. He notes concern over the potential problem of excessive acetaminophen intake given its frequent use in combination with the SA opioids such as codeine, hydrocodone, oxy-codone, and propoxyphene. Four indications, including failure to control pain with eight or more doses per day, are outlined for converting from SA to LA. He states however, “The failure to control severe, chronic pain with short acting opioids invariably occurs in a patient who complains of severe, constant, persistent pain.” Sustained blood levels of an opioid, which is presumably associated with pain relief, is listed among the advantages of LA preparations. Schneider14 offers support for the use of LA opioids citing acetaminophen use, plasma levels, com-pliance, dosing frequency, euphoria and sleep as issues with SA opioids. Schneider also notes the common use of SA in addition to LA for “breakthrough” pain. Time of day, patient activity, weather, mood, life stresses are listed as possible sources of breakthrough pain.

Although proponents of the use of LA opioids assert their advantages,8 Chou et al,15 in a systematic review of studies comparing SA to LA, found the data to be inconclusive at best. One plausible reason for this apparent lack of benefit of LA over SA opioids may be based in the recognition that the efficacy of opioids appears to be related to a variety of factors other then their pharmacodynamic and pharmacokinetic properties. For example, age of the patient and type of pain (nociceptive or neuropathic),16 gender,17 history of substance abuse,18 cognitive functioning,19 and co-morbid psychopathology20 have each been shown to influence the analgesic effect of opioids in general.

One frequently overlooked area is that of conditioning and learning. Siegal and his colleagues21 have explored the role of conditioning factors, particularly classical conditioning, as they relate to the development of opioid tolerance. Opioid therapy is likely to continue when the ingestion of a drug is reinforced by the reduction of a negative state such as pain, anxiety, depression, and/or the onset of a positive state such as reduced pain, euphoria, sedation, or improved function. Stimuli, either external (exteroceptive) to the patient such as size, color, or shape of the pill, or internal to the patient (interoceptive) such as sense of well being, autonomic changes, may become associated with the drug that is producing these desirable states. By virtue of the classical conditioning process, these stimuli become capable of eliciting some or all aspects of the final drug-induced outcome. Stimuli associated with the onset of the drug-induced effect have been labeled as drug onset cues (DOCs) and those with the taking of the drug as self-administration cues (SACs). Thus, patients often insist that the ‘brown, square pill works better than the white, triangular one,’ even when they are similar compounds. It is these conditioned properties of opioids that may lead to positive expectations so often responsible for the well recognized ‘placebo’ response. Indeed, some 30-50% of the analgesic response to various drugs has been attributed to the placebo effect when studied in an ‘open-hidden’ paradigm.22

The present study intended to extend the evaluation of SA opioids in the long term treatment of chronic non-cancer pain by examining a cohort of patients using SA opioids for several years. Furthermore, the possible role of conditioning factors was explored by seeking information regarding DOCs. The patients were ‘self-selected’ as a result of: (a) preferring SA opioids to previously trialed LA, or (b) satisfied with the results of SA opioids and not wishing to change.

Method

Subjects. Patients were selected from those treated in a multidisciplinary outpatient private practice setting in Birmingham, Alabama. The clinic has a pharmacologically-based pain management com-ponent. Patients are referred from a variety of sources. The study cohort was made up of the first 50 patients returning for follow up visits, on or after January 2005, noted to be on a single short acting opioid agent for at least one year. Patients were informed that we were interested in obtaining more detailed information as to the effects of their opioid therapy. Their participation was voluntary and their continued treatment would not be affected by whether they agreed to participate or not. In addition, all analyses and reports would involve ‘group’ versus individual data. This interaction was documented in the chart and a consent form indicating they had been so informed was signed. Each of these 50 patients agreed to participate. Three patients were ultimately excluded from the analysis because of inadequate or incomplete data.

Procedure. The majority of patients in the clinic were physician-referred for chronic non-cancer pain management. Self-referrals were also accepted. Nearly all of the patients had an extended history of pain and had been trialed on one or more opioids. Each patient was evaluated by one of the clinic physicians and a psychologist. The interview included specific questions regarding any history of illicit drug and/or alcohol use. Patients were classified as ‘current users’ if they reported using an illicit drug in the last six months, ‘recent users’ if during the last one to five years, and ‘remote users’ if the last use was more that 5 years ago. Baseline urine drug screens (UDS) were obtained on each patient.

“The present study intended to extend the evaluation of SA opioids in the long term treatment of chronic non-cancer pain by examining a cohort of patients using SA opioids for several years.”

The clinic’s ‘medication agreement’ listing 22 items was reviewed and signed. Included among these items were prohibitions against early refills, unsanctioned self-adjustment, use of illicit drugs/ alcohol, obtaining medicine from multiple providers, use of unauthorized medicines, ‘sharing’/hoarding/selling medicines, replacement of lost or stolen medicines, operating a vehicle/machinery if feeling impaired, and non-compliance with scheduled office visits. Patients were also informed of the UDS policy and protocol. A departure from any one of these items was considered a ‘violation/ infraction’ of the agreement. The consequences of a violation/infraction varied depending on the seriousness, type, frequency and degree of the infraction/ violation and the patient’s alcohol/drug (A/D) history. As defined in the agreement, patients could be discharged, counseled, or referred for an addiction evaluation and/or treatment. Each of the patients in the present study demonstrating a violation via an abnormal UDS responded to corrective action. Subsequent UDS was appropriate and they were compliant with other recommended treatment. Therefore, each was continued in the clinic. In general, patients were seen approximately each 2-4 weeks during dosage titration and each 1-3 months once on a stable dose of medicine.

Urine Drug Screens (UDS). Urine drugs screens (UDS) were obtained (a) at the initial visit, (b) unannounced approximately once a year at the patient’s usual office visit, (c) in response to aberrant behavior, such as loss of prescription/ medication, evidence of intoxication, or excessive sedation. If a UDS was positive for an illicit substance, subsequent UDSs were more frequent. Some patients were contacted and instructed to present at times other then their regular visit for a ‘pill count’ and ‘random’ UDS. Specimens were provided in the office restroom next to the nurse’s office, but were not ‘observed.’ Each specimen was sent to the same lab for gas chromatography/mass spectroscopy (GC/MS) confirmation.

Attention was given to the temperature and color of the specimen as well as specific gravity and creatinine levels as possible indicators of an adulterated specimen. We did not encounter any apparent adulterated or invalid specimens. In fact, it was not uncommon for the patients to acknowledge the probable presences of an illicit drug, especially marijuana (THC) upon providing the specimen, even before the results were obtained.

Data Collection. Patient demographics, duration of pain and treatment, A/D history, agreement violation/infractions, UDS results and medications prescribed were obtained via chart review. A structured interview was administered by the clinic nurse during the patient’s regular office visit. The interview elicited information regarding the following areas: (a) number of pain pills (per month; most, least, and usual number/ day), (b) when taken (fixed time i.e., each 6 hours, as recommended in the agreement; based on pain severity or interference; other), (c) time between taking the pill and onset of effect, (d) drug onset cue(s) (DOC; energized, dulling of pain, decreasing of pain, sleepy, groggy, euphoria, other), (e) percent relief of pain (0-100%), (f) duration of relief (hours), (g) means of detecting when the medication has worn off, (h) percent improvement in quality of life (QoL; 0-100%), (i) ‘tolerance’ (medication works as well now as when first taken?), (j) pain ratings (highest, lowest, average, 0-10 numerical pain rating, NPR), and (k) overall level of satisfaction with treatment (not satisfied, satisfied, very satisfied). Information was also obtained from the Medical Visit Questionnaire23 completed at each visit, and/or by clinician interviews. The structured interview allowed for the information to be collected in a more comprehensive and efficient manner.

Patient and Opioid Characteristics
Patients 47
Patients with A/D history 11/47 (23%)
Age Mean=53.4 (range 32-77; s.d.8.9)
Male 29/47 (69%)
Pain duration Mean=11.9 years (range 3-28)
Pain Location
Low back 39.0%
Low back/leg(s) 29.3%
Low back/neck 7.3%
Neck 7.3%
Head/face 4.9%
Generalized (Fibromyalgia) 4.9%
Leg 2.4%
Knee 2.4%
Foot 2.4 %
Opioid
hydrocodone 37/47 (78.7%)
pentazocine 4/47 (8.5%)
tramadol 3/47 (6.4%)
oxycodone 2/47 (4.3%)
propoxyphene 1/47 (2.1%)
How Taken
Time contingent 29/47 (61.7%)
As needed (ie prn) 13/47 (27.7%)
When pain interferes with activity 4/47 (8.5%)
Other 1/47 (2.1%)
Table 1. Patient characteristics, opioids prescribed, and the manner in which they were taken.
Opioid Dosing
Pills/day: 4.1 (range 3.1-4.5)
Months at present dose 30.8 (range 12-96)
Onset of Relief
0-20min 17/47(36.2%)
20-30 21/47(44.7%)
45+ 9/47 (19.1%)
Drug Onset Cues
Decrease in pain 9/47 (39.9%)
Sleepiness 4/47 (8.5%)
Decrease/dulling of the pain 18/47 (37.8%)
Euphoria 0/47
Energized 5/47 (10.5%)
Duration of Relief (hours)
Mean 3.2 hours
1 or less 5/47 (10.6%)
1-2 hours 4/47 (8.5%)
2-3 hours 23/47 (48.9%)
2-3/3-4 3/47 (6.4%)
4-5hours 10/47 (21.3%)
5 hours+ 2/47 (4.3%)
Table 2. Data regarding the dosing parameters including the number of pills per day and the average number of months at a specific dose are noted. The percent of patients reporting various times to onset of pain relief, the associated drug onset cue(s), and duration of pain relief are also given.

Results

The patient and pain characteristics are outlined in Table 1. The majority of patients were male (62%) with an average age of 55.4 years and a pain duration of over 11 years. Over 78% of the patients reported pain in the low back, or low back/leg(s). Hydrocodone (7.5mg or 10mg/pill) was prescribed to more then 78% of the patients. Nearly 62% percent (29 of 47) reported taking their opioid on a fixed time basis, 27.7% (13 of 47) as needed for pain, 8.5% (4 of 47) when pain interfered with function, and 2.1% (1 of 47) ‘other’ basis.

The data obtained relating to opioid dosing, onset and duration of relief are given in Table 2. The average number of pills/day was 4.1, with stable dosing for an average of 30.8 months. Eighty percent of patients noted relief within 30 minutes of dosing. A “decrease in pain” alone or in combination with a “dulling of the pain” were identified as DOCs in 78%. None of the patients selected “euphoria” as a DOC. The average duration of pain relief was 3.2 hours/pill. The loss of effect was heralded by ‘increased pain’ in 96% (45 of 47). Nearly 81% (38 of 47) indicated that the opioid was working well now as it did when first introduced.

Table 3 outlines the overall outcomes. The mean for the “highest”, “lowest”, and “average” pain ratings were 8.8, 3.7, and 5.1, respectively. The average reported “subjective pain relief overall” was 56.8%, and average estimated “overall improvement in quality of life” was 64%. Over 95% of patients reported they were “satisfied” or “very satisfied” with treatment. Approximately 28% (13 of 47) of patients were working full time.

A total of 134 UDSs (average of 2.9/patient) were analyzed. More than 70% of patients (34 of 47) were free of any abnormality, violation, or infraction. Of the 28.7% (13 of 47) that registered an ‘abnormal’ UDS, 15.4% (2 of 13, or 4.3%; 2 of 47 of the total cohort) were positive for an illicit drug; one for THC the other for cocaine. Another 15.4% (2 of 13) were positive for unauthorized or non-prescribed drugs, and 54% (7 of 13; 7 of 47, or 14.9% of the total cohort) were negative for the prescribed opioid. When questioned, these seven patients reported omitting their morning and/or evening dose secondary to concerns over driving safely ‘in the city or on the expressway.’ They denied any problems driving in their home community but admitted to apprehension in busy and unfamiliar areas. Once counseled about the importance of consistent dosing and having someone else drive if they were uncertain, subsequent UDS was appropriate. Other infractions included unsanctioned self-adjustment (1 of 13) and overuse of the opioid as indicated by running-out prior to the next prescription due date (1 of 13). Of the 18 females in the cohort, 33.3% (6 of 18) compared to 24.1% (7 of 29) of males had a violation. Of these, 83% (5 of 6) were negative for the prescribed opioid, only 17% (1 of 6) were positive for an illicit drug.

Overall Outcomes
Mean pain rating (0-10/10)
Highest 8.8 (range=7-10)
Lowest 3.7 (range=0-8)
Average 5.1 (range=1-8)
Overall Improvement (0-100%)
Pain 56.8%
Qol 64%
Satisfaction Level
Very satisfied 14/47 (29.8%)
Satisfied 31/47 (66%)
Not satisfied 2/47 (4.2%)
Working 13/47 (28%)
Urine Drug Screening (mean /pt=2.9)
Normal 34/47 (70%)
Abnormal 13/47 (28.7%)
Illicit 2/13 (THC=1; cocaine=1)
Unauthorized drug present 2/13
Negative for prescribed drug 9/13
Patient with alcohol/drug history free of any violation: 9/11 (81%)
Table 3. Outcome including average pain rating, overall improvement in pain, overall improvement in quality of life (QoL) and degree of patient satisfaction are noted. The frequency of normal and abnormal urine drug screens (UDS) as well the number of patients with a reported alcohol/drug history the remained free of any violation are summarized.

Eleven of the patients (23.4%) reported a history of drug and or alcohol abuse. One was classified as a ‘current user’, six as ‘recent users’ (alcohol=4; THC and alcohol=1; THC=1), and four as ‘remote users’ (alcohol=2; THC=1; alcohol and THC=1). About 82% (9 of 11) of patients admitting to a history of alcohol/drug abuse pre-treatment were free of any violation/ infraction. The exceptions were the admitted cocaine user in the ‘current user’ group and a THC user in the ‘remote group.’

Discussion

Overall, the outcomes from this cohort of patients taking SA opioids on a long term basis for chronic non-cancer pain approximate those reported from studies examining similar patient populations utilizing LA opioids, with or without SA ‘breakthrough’ opioids.14,24-26 In addition, pain relief was achieved at relatively low dosages. These data also compare favorably with those from other cohort studies of three years or more treatment duration.27 The 56% subjective level of improvement falls into the ‘much improved’ category.28 The relatively high (95.7%) patient satisfaction level and reported improved QoL is comparable to other studies that have examined patient satisfaction as an outcome.26,29,30 In addition, each patient in the present study that was working at the onset of treatment continued doing so.

The incidence of positive UDSs for illicit drugs (4.3% of total cohort and 9.8% of patients reporting a A/D history), is less then the 16.3%,31 and the 16% and 20% for hydrocodone and methadone treated patients respectively,32 reported by others. A recent study by Fleming et al33 noted that 24% of 771 adults receiving daily opioid therapy in primary care settings wherein SA opioids were prescribed to 63.2% of patients, yielded a UDS positive for illicit drugs. Therefore, the use of SA opioids alone does not necessarily result in a higher rate of illicit drug use. Indeed, extractability variables,34 psychosocial factors and A/D history,35 as well as sedating oneself, use of opioids for non pain reasons, increasing doses without authorization, and feeling intoxicated while taking opioids,33 appear to correlate with substance abuse and reactivation of an addiction process as much or more then the type of opioid, degree of pain, or analgesia.

That 9 of 11 (82%) patients admitting to a history of alcohol/drug abuse were free of any violation for nearly three years, is greater than would be expected based of the report by Dunbar and Katz36 which noted 11 of 20 (55%) to be compliant. In addition, these authors noted that those patients relapsing into patterns of abuse did so early on in the one year study. The difference noted in the present study may be attributable to the ‘self-selected’ nature of the cohort. However, none of the patients approached to participate in the study was excluded on the basis of a prior violation/infraction. The fact that patients with a substance abuse history were required to have more frequent follow-up visits and that most of them were managed by a clinic physician with an addiction/ psychiatry and pain medicine background, may have contributed to this relatively high rate of compliance. Furthermore, the patients that did demonstrate a violation responded to corrective action including increased frequency of clinic visits, referral to Alcoholics Anonymous/ Narcotics Anonymous groups, and titration of their opioid dose pending a ‘clean’ UDS. As noted by Ballantyne,37 summarily discharging or abandoning such patients may only encourage further maladaptive behavior.

Most noteworthy is the degree of patient satisfaction, overall pain relief, and increased QoL, despite an estimated duration of pain relief of only 13.1 out of 24 hours (3.2 hours x 4.1 pills/day). This would seem contrary to the assertion regarding the necessity—assuming it can be achieved—of 24 hour relief and reduced dosing frequency. When questioned, the patients in the present study highlighted the importance of the predictability and detectability of pain relief. For them, it was more important to have confidence that the drug would, in fact, work when needed. This appeared to be one of the means by which they coped; knowing their increased pain could and would be lessened when they were ready. This combined sense of control and positive expectancy appeared to improve their tolerance for pain. This is consistent with the literature showing increased tolerance for pain under conditions of perceived controllability.38,39 This is also consistent with Siegal’s21 assertion regarding the relevance of DOCs. A decrease or dulling of the pain was readily detectable, with 81% reporting relief within 30 minutes, as was the ‘wearing off’ of relief. This responsiveness to detectability may explain why some patients, even though they are taking substantial amounts of oral, transdermal, or intrathecal opioids, still seem to require or benefit from SA ‘breakthrough’ opioids.

Caution should be exercised in the use of SA opioids for breakthrough pain particularly if it is determined to be secondary to psychological factors or volitional behavioral. Because of the conditioning factors noted above, some patients may respond preferentially to the SA breakthrough opioid, taking 2-4 per day, essentially displaying little or diminished benefit from the baseline LA opioid because of the lack of detecability, i.e. DOC. This could be one explanation for the relative weak correlation between opioid serum levels, and pain relief, as judged by patients reported ability to drive and function, in long term treatment with chronic non-cancer pain.40,41 In addition, providing SA breakthrough opioids could inadvertently reinforce “chemical coping” on the part of the patient. Utilizing stress management, cognitive behavior therapy, activity pacing, proper goal setting, modalities such as ice in combination with regular exercise and stretching would appear more appropriate.

The apparent lack of tolerance over the three year period is also contrary to expectations for SA opioids. This is further surprising given the data on opioid-induced hyperalgesia (OIH).42,43 Perhaps one of the hallmarks of a ‘SA responder’ is their resilience to the development of tolerance or hyperalgesia. The mechanism is obviously unclear, but the repeated reinforcement of the effect via classical and operant conditioning may mitigate the usual extinction process that can be part of an associative or behavioral tolerance. Perhaps SA responders are more sensitive to, and aware of, the opioid effects and therefore more easily and strongly conditioned. This conditioning effect may compensate for any nonassociative or pharmacological tolerance as shown by Siegal21 in his studies on situation-specific tolerance.

When seen at their clinic visit, patients were frequently asked to estimate:

  1. the delay of onset— the time between taking the drug and a detectable reduction in pain,
  2. magnitude or degree of pain relief— how much does the medicine reduce your pain (0-100%), and
  3. duration of relief— how long does it take before the effect of the medicine has worn off.

Prolonged delay of onset, reduced magnitude of relief, and decreased duration of relief, may suggest tolerance or OIH. Pharmacological tolerance can be demonstrated by return of analgesia after increasing the opioid. OIH may be indicated by patients reporting minimal pain relief, even after dosage adjustment, but an unwillingness to discontinue their medicine. In such cases, the medicine appears to be preventing the pain from getting worse rather than making it better. Indeed, the patient may experience a worsening of their primary or baseline pain and/or the development of areas of secondary pain, both potential clinical indicators of OIH.42,44,45 This pattern could be tantamount to the continued use of alcohol/drugs in the dependent patient to avoid negative affective states versus their initial effect of producing a positive effect.

These data should be interpreted with caution. They do not represent an indictment against LA opioids nor an endorsement of SA. Rather, clinicians should be encouraged to approach patients in a ‘single subject or N=1’ fashion.46 Rule- governed behavior,47 where all non-cancer chronic pain patients undergoing extended therapy with opioids should be treated with LA opioids,48 assumes a data base that does not appear to exist.

Whereas Chou15 failed to find evidence supporting one type of opioid to be superior to the other, the present data suggests that there may be a subpopulation of patients differentially responsive to SA opioids. Indeed, Jamieson et al24 noted several patients reported a preference for SA oxycodone over LA morphine. Futhermore, they noted that those patients varying their dose from week to week reported less pain and better mood without any overall dose escalation.

Future research in the area of opioid responsivity and/or preference may benefit from exploring the role of psychological and conditioning factors mentioned above. It is, of course, unclear as to what percent of patients might respond to one type of opioid over another. Indeed, the present group of patients represents but a fraction of the more than 2000 patients treated with opioids, including transdermal and intrathecal, in our clinic. It is estimated that less than 20% of our patients are treated by SA opioids alone. It is impossible to know the true percentage of ‘SA responder’ as they could be intermixed in those who seem to require or benefit from SA opioid for ‘breakthrough pain’.

“Jamieson et al24 noted several patients reported a preference for SA oxycodone over LA morphine. Futhermore, they noted that those patients varying their dose from week to week reported less pain and better mood without any overall dose escalation.”

Study Limitations

There are a number of limitations to this study. Most importantly, the patient cohort is essentially self-selected by virtue of our inclusion criteria. This limits the generalization of the findings. It may also have contributed to the relatively high rate of compliance, patient satisfaction, pain relief, and low incidence of illicit drug use. The absence of pre-treatment measures does not allow for a pre-post opioid therapy analysis. We are, therefore, limited to drawing conclusions based upon the patient’s recall of their ‘baseline’ levels of pain and function. To the extent that recall of remote pain and function may be overestimated—that is recalled as being more severe than it really was—the data would be biased towards a more positive outcome. As with many such self-report studies, it is difficult to rule out response bias on the part of the patient given that the interview was conducted by the clinic nurse and in the clinic setting. Despite being informed that their participation and responses would have no effect on their continued treatment, the potential for the patient wanting to ‘please’ the staff by reporting enhanced level of relief, compliance, functioning and satisfaction can not be overlooked. There was also an element of recall as to the pain ratings and DOCs since the previous clinical visit that may affect the accuracy of their statements. This variable might have been managed by the use of a real-time diary system. Using a single-item, self-report measure for assessing improvement in pain and quality of life, although not uncommon, may be overly simplistic. Such single-item measures may lack sensitivity and specificity leading to a more favorable impression of the therapeutic effectiveness of SA opioids.

 

Future studies should employ a larger group of patients. A more detailed assessment of patient characteristics, expectations, SA opioid ‘responsivity’, and opioid treatment history should be undertaken. Inclusion and exclusion criteria should be clearly delineated, and multidimensional assessments of pre-opioid levels of pain and function obtained. Reliance on patient recall in determining treatment outcome should be minimized. The sensitivity of other research protocols, such as a crossover designs, should be explored as to their ability to detect these SA responders. Evaluating patients’ beliefs or self-statements about the effects of their opioids and why they were satisfied, despite the limited duration of relief, might help to understand the mechanism(s) involved. Finally, the area of ‘long term opioid therapy’ is in need of more studies, extending two years or more, to properly evaluate therapeutic effects and side-effects that may not manifest themselves in the span of a few weeks of months.

Summary

While long acting (LA) opioids are generally recommended or preferred to short acting (SA) for long term therapy, there have been very few studies involving short acting (SA) opioids on a long term basis. The present study examined a cohort of 47 patients undergoing treatment for chronic non-cancer pain with short acting (SA) opioids. Data were obtained from chart review and patient interviews. Emphasis was placed on exploring the role of conditioning factors such as drug onset cues (DOC), dosage stability, opioid agreement violations, patient satisfaction, and patient estimated improvement in overall quality of life (QoL). The results showed highly stable dosing over the average treatment duration of more than 30 months, with some patients extending to 96 months. Patients’ rated overall improvement approximated 56% despite an average duration of pain relief of only 13.1 hours per day. Nearly 90% of patients indicated they were ‘satisfied or very satisfied’ with treatment. Seventy percent of all patients, and 81% of the 11 patients with a reported history of drug or alcohol abuse, had no agreement violations. The most frequently sited DOCs were decrease in pain or dulling of the pain. Detectability and predictability of the drug effect appeared important. Efficacy, patient satisfaction, and treatment violation outcomes compared favorably with other studies using LA opioids. These data are discussed in the context of a more empirical approach to selecting a LA or SA opioid and the possible existence of a subgroup of chronic pain patients that may be ‘SA’ responders.

Conclusion

In conclusion, we speculate that there may be a subpopulation of chronic non-cancer pain patients that can be effectively treated with SA opioids. Furthermore, that the clinical outcomes and incidence of drug abuse may well be comparable to those found with LA opioids. The hypothesized importance of perceived detect-abillity is obviously theoretical, but appears to fit the present data. Admittedly, the results of this study may be skewed by the fact that the cohort was self selected and may well represent an ‘optimal effect sample.’ Never-the-less, there may be a rationale for taking a more empirical and flexible approach regarding the selection of a LA versus SA opioid for long term therapy.

Last updated on: April 7, 2015
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