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Keywords:

  • alcoholism;
  • opioid analgesics;
  • tobacco use disorder;
  • cancer;
  • substance abuse

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

BACKGROUND:

The objectives of this retrospective study were to determine the frequency of undiagnosed alcoholism among patients with advanced cancer who were referred to palliative care and to explore its correlation with alcoholism, tobacco abuse, and use of illegal drugs.

METHODS:

The authors reviewed 665 consecutive charts and identified 598 patients (90%) who completed a screening survey that was designed to identify alcoholism, the Cut Down, Annoyed, Guilty, Eye Opener (CAGE) questionnaire, including 100 consecutive patients who had CAGE-positive and CAGE-negative results. Data on tobacco and illegal drug use, the Edmonton Symptom Assessment Scale, and the morphine equivalent daily dose were collected.

RESULTS:

The frequency of CAGE-positive results in this palliative care population was 100 of 598 patients (17%). Only 13 of 100 patients (13%) in that CAGE-positive group had been identified as alcoholics before their palliative care consultation. Compared with CAGE-negative patients, CAGE-positive patients were younger (aged 58.6 years vs 61.3 years; P = .07), predominantly men (68 of 100 patients vs 51 of 100 patients; P = .021), more likely to have a history of tobacco use (86 of 100 patients vs 48 of 100 patients; P < .001), more likely to be actively using nicotine (33 of 100 patients vs 9 of 100 patients; P = .02), and more likely to have a history of illegal recreational drug use (17 of 100 patients vs 1 of 100 patients; P < .001). Pain and dyspnea were worse in patients who had a history of nicotine use. Both CAGE-positive patients and patients who had a history of tobacco use more frequently were receiving strong opioids at the time of their palliative care consultation.

CONCLUSIONS:

The current findings suggested that alcoholism is highly prevalent and frequently under diagnosed in patients with advanced cancer. CAGE-positive patients were more likely to have a history of, or to actively engage in, smoking and illegal recreational drug use, placing them at risk for inappropriate opioid escalation and abuse. Cancer 2011;. © 2011 American Cancer Society.

Alcoholism is a devastating disease that can cause suffering in both patients and their families.1, 2 In the general population, the frequency of alcoholism is approximately 8%3; however, it is often under diagnosed.4 It also has been reported that alcoholic patients use tobacco and other illicit drugs more frequently.5 In cancer patients, alcoholism reportedly occurs in up to 28% of patients.6, 7 Previous research on the frequency of alcoholism in 2 cohorts of 100 consecutive cancer patients who were admitted to a palliative care unit indicated alcoholism rates of 28% and 27%, respectively.7

It has been noted that patients who have a history of alcohol or drug use are susceptible to addiction when prescribed opioid analgesics8; whereas, in patients without such a history, the use of opioids to control cancer pain very rarely results in abuse or addiction. In the United States, there is an epidemic of prescription drug abuse. In 2009, roughly 21.8 million Americans aged ≥12 years used illicit drugs, including marijuana, cocaine, heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics, for conditions other than their intended medical use.9 The number of individuals dependent on opioid analgesics has increased from 1.5 million to 1.9 million.9 Before physicians prescribe opioid analgesics, it is imperative that a thorough assessment is conducted that includes a screen for alcohol and drug abuse.10

In our outpatient Supportive Care Clinic, all patients are screened routinely for alcoholism using the Cut Down, Annoyed, Guilty, Eye Opener (CAGE) questionnaire, a 4-item survey that is a simple to administer as a screening tool.11 This questionnaire asks the following:

  • Have you ever felt the need to cut down on drinking?

  • Have you ever felt annoyed by criticism of your drinking?

  • Have you ever had guilty feelings about your drinking?

  • Have you ever taken a morning eye opener?

The objectives of the current study were to determine the frequency of undiagnosed alcoholism in our patient population with advanced cancer and to study the correlation between CAGE-positive patients (those who answered “yes” to at least 2 questions on the CAGE questionnaire), a current or past history of smoking tobacco, and the use of illegal drugs and sedatives, hypnotics, and anxiolytics (SHA). In addition, we examined the characteristics of patients who had a history of tobacco use with regard to demographics, symptom burden, and opioid use.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

We previously reviewed the electronic charts of 665 consecutive patients who attended our Supportive Care Clinic at the University of Texas MD Anderson Cancer Center for the first time before January 2007 to identify 100 consecutive CAGE-positive patients.12 The CAGE questionnaire is a simple, 4-item screening survey for alcoholism.11 Two positive answers (CAGE-positive) have sensitivity >90% and specificity >95% to detect alcoholism13; however, this questionnaire does not distinguish between current versus past alcohol use. For the purpose of our study, a patient was considered CAGE-positive when he or she answered “yes” to at least 2 questions. Demographics, date of advanced cancer diagnosis, symptom scores, and opioid use also were collected for 100 consecutive CAGE-negative patients and 100 consecutive CAGE-positive patients.12

For the current study, we retrospectively reviewed the medical records of the previously identified 100 CAGE-positive patients and 100 CAGE-negative patients and systematically recorded any documentation of alcoholism or alcohol abuse as noted in the electronic medical records before the initial palliative care consultation in our Supportive Care Clinic. A history of tobacco abuse (including active use), any documented use of illegal drugs (marijuana, intravenous drug abuse, cocaine, etc), and ≥1 SHA listed in patients' medication records at the time of palliative care consultation were noted.

Symptoms were recorded for the initial visit to our center using the Edmonton Symptom Assessment Scores (ESAS), a validated tool to assess 9 symptoms (pain, nausea, drowsiness, dyspnea, anxiety, depression, anorexia, sleep, and fatigue) and general feelings of well being on a scale ranging from 0 to 10.14, 15 A total symptom distress score (range, 0-90) is calculated as the sum of the first 9 symptom scores. The total daily opioid dosage was calculated for the first visit by converting the total opioid dosage during 24 hours to an equivalent dose of oral morphine (morphine equivalent daily dose [MEDD]) using standard equianalgesic conversion tables.16

Summary statistics were generated to describe the demographic and clinical characteristics of the patients as well as the frequency and proportion of cancer patients who screened positive with the CAGE questionnaire during the study period. Variables to be analyzed included symptom burden (as measured by the ESAS), opioid dosage, use of tobacco or illegal recreational drug use, and demographic variables, such as age, sex, and ethnicity. To determine whether there were significant differences between groups, we used a 2-sample t test when the data were distributed approximately normally, the Wilcoxon 2-sample test if the data were skewed, and chi-square tests for dichotomous variables.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

CAGE information was available for 598 of 665 patients (90%); and 100 patients had positive CAGE results (17%). Characteristics of CAGE-negative and CAGE-positive patients are summarized in Table 1.

Table 1. Patient Demographic and Clinical Characteristics in Patients With Negative Versus Positive Results on the Cut Down, Annoyed, Guilty, Eye Opener (CAGE) Alcoholism Questionnaire
 No. of Patients (%) 
CharacteristicCAGE-Negative, N=100CAGE-Positive, N=100P
  1. MEDD indicates morphine equivalent daily dose.

Men51 (51)68 (68).05
Race   
 White76 (76)74 (74) 
 African American9 (9)17 (17) 
 Hispanic11 (11)8 (8) 
 Asian2 (2)1 (1) 
 Other2 (2)0 (0) 
Median age [range], y61.3 [52.3-71.2]58.6 [51.2-64.7].07
Type of cancer   
 Lung18 (18)19 (19) 
 Gastrointestinal24 (24)23 (23) 
 Urologic7 (7)8 (8) 
 Breast6 (6)5 (5) 
 Gynecologic7 (7)6 (6) 
 Head/neck17 (17)24 (24) 
 Hematologic4 (4)3 (3) 
 Other17 (17)12 (12) 
History of tobacco use48 (48)86 (86)<.001
Active tobacco use9 (9)33 (33).02
History of illegal drug use1 (1)17 (17)<.001
On strong opioids before palliative care consultation29 (29)47 (47).05
Median MEDD at consultation [range]60 [47.5-200]100 [50-150] 
Use of ≥1 sedative, hypnotic, anxiolytic34 (34)42 (42) 

CAGE-positive patients were predominantly men, and we noted a trend toward younger age. CAGE-positive patients were significantly more likely to have a history of tobacco abuse and active nicotine use, and they more frequently were on strong opioids at the time of palliative care consultation. No differences in the use of ≥1 SHA were noted between the 2 groups.

Only 13 of the 100 CAGE-positive patients (13%) had medical documentation of a history of alcohol abuse or alcoholism before palliative care consultation (Table 2). Four patients were identified by the consulting psychiatric team, and 2 were identified by an oncology fellow who was trained in palliative care and had incorporated the CAGE questionnaire into his routine clinical assessment.

Table 2. Documentation of Alcoholism Before Palliative Care Consult Among Patients with Positive Results on the Cut Down, Annoyed, Guilty, Eye Opener (CAGE) Alcoholism Questionnaire (n=100)
Medical Source Documenting of AlcoholismNo. of Patients (%)
Primary oncology team7 (7)
Oncology fellow trained in palliative care2 (2)
Consulting psychiatry team4 (4)
Total13 (13)

In addition, CAGE-positive patients were more likely to have a documented history of illegal recreational drug use (17 of 100 CAGE-positive patients vs 1 of 100 CAGE-negative patients; P < .001) (Table 2). Four of the 18 patients had a documented history of polysubstance abuse. Of the 18 patients who had a documented history of illegal drug use, the specific drug was noted as follows: marijuana (11 patients), intravenous drug abuse (5 patients), cocaine (5 patients), hydrocodone addiction (1 patient), methamphetamine (1 patient), heroin (1 patient), and a history of unspecified substance abuse (1 patient).

Characteristics of patients according to their history of tobacco use are summarized in Table 3. Men and patients with lung tumors were significantly more likely to have a history of tobacco use. Patients who had a history of nicotine use were more likely to be on strong opioids on initial palliative care consultation, but no difference was noted in the MEDD or in the frequency of being prescribed ≥1 SHA between the 2 groups (Table 3).

Table 3. Patient Demographic and Clinical Characteristics by History of Tobacco Use Status
 No. of Patients (%) 
CharacteristicNo Tobacco Use, N=66 (%)History of Tobacco Use, N=134 (%)P
  1. MEDD indicates morphine equivalent daily dose; CAGE, the Cut Down, Annoyed, Guilty, Eye Opener alcoholism questionnaire.

Men25 (38)94 (67).001
Race   
 White47 (71)103 (77) 
 African American7 (11)19 (14) 
 Hispanic10 (15)9 (7) 
 Asian1 (1)2 (1) 
 Other1 (1)1 (1) 
Median age [range]58.9 [50.6-68.4]59.8 [51.8-69.4] 
Type of cancer   
 Lung1 (1)36 (27).001
 Gastrointestinal18 (27)29 (22) 
 Urologic6 (9)9 (7) 
 Breast5 (8)6 (4) 
 Gynecologic8 (12)5 (4) 
 Head/neck13 (20)28 (21) 
 Hematologic0 (0)7 (5) 
 Other15 (23)14 (10) 
On strong opioids before palliative care consultation17 (26)59 (44).01
Median MEDD [range]100 [50-400]90 [50-150] 
CAGE-positive status14 (21)86 (64)<.001
Use of ≥1 sedative, hypnotic, anxiolytic23 (35)53 (40) 

Patients who had a history of tobacco use had significantly higher pain expression and levels of dyspnea (Table 4). A nonsignificant trend toward higher fatigue also was noted in patients who had a history of tobacco use.

Table 4. Median Baseline Symptom Distress by History of Tobacco Use
 Median Symptom Distress Score (Interquartile Range) 
SymptomNo Tobacco History, N=64Tobacco History, N=128P
Anxiety3 (1-5)4 (0-6) 
Appetite4 (1-7)5 (3-7.5) 
Depression2 (0-5)3 (0-5) 
Drowsiness3.5 (1-6)4 (1-7.5) 
Fatigue6 (3-8)7 (4-8).06
Nausea0 (0-2)0 (0-3) 
Pain4 (2-7)5.5 (3-8)<.05
Sleep4 (2-6)4 (2.5-7) 
Dyspnea1 (0-4)3 (0-6)<.05
Well being5 (3-6)6 (4-8) 

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

The current data suggest that alcoholism frequently is undocumented in patients with advanced cancer. In our study, healthcare professionals had noted that only 13 of 100 (13%) CAGE-positive patients were alcoholics before palliative care consultation. A previous study reported that 9 of 28 patients (32%) and 8 of 24 patients (33%) who were diagnosed as alcoholics during 1989 and 1992, respectively, had been identified as alcoholics in the medical charts before assessment by the CAGE questionnaire.7 The CAGE questionnaire is a useful tool with which to screen for alcoholism in a palliative care population.

Alcoholism is strongly linked with other addictive substances, including tobacco and illicit drugs,5 and the aberrant use of these substances to help cope with life stressors is defined as chemical coping.17 Our findings suggest that, although the vast majority of cancer patients are started on strong opioids by their oncologist or primary care providers, they often undergo less stringent screening for risk factors for chemical coping. Cancer patients are living longer, and those with chronic pain may be treated with opioids for prolonged periods. In the past, assessment of risk factors for addiction may have been overlooked in patients with cancer, because it was believed they had a short life expectancy. Identifying patients who are at risk for chemical coping has important clinical implications, including the need for close monitoring of opioid use, consideration for early referral to pain specialists or palliative care physicians, and management by an interdisciplinary team to avoid inappropriate escalation, neurotoxicity, and side-effects of strong opioids. Before prescribing pain medications, clinicians need to carefully screen for behaviors that place patients at risk for addiction or chemical coping, including past history of alcohol, prescription drug, or nonprescription drug abuse.10

Our study also reveals that CAGE-positive patients more frequently have a history of, and are actively using, tobacco and illegal nonprescription drugs. The relation between smoking behavior, symptom burden, and opioid use has not been well characterized in patients with advanced cancer. Our findings are consistent with the clinical observation that suggests tobacco use is associated with higher opioid use. In addition, patients with a history of opioid addiction reportedly had a 3-fold or greater increased frequency of tobacco use.18

Both alcohol and nicotine are readily available and legal. Relative to the general population, individuals who smoke are 4 times more likely to be addicted to alcohol, and alcoholic patients are 3 times more likely to be dependent on nicotine.19 Alcohol and nicotine have different mechanisms of action. Although nicotine activates the nicotinic acetylcholine receptors in specific brain regions, whereas alcohol acts on several different molecular receptors, recent research suggests that both drugs may share the ability to modulate the endogenous opioid system.20 A history of abuse of either alcohol or tobacco may indicate an individual's predisposition to chemical coping.

In 2009, the prevalence of smoking in the general population aged ≥12 years in the United State was 27.7%.8 Currently, smoking tobacco is less socially acceptable than in years past. Recent nicotine use or active smoking behavior may indicate a stronger risk factor for chemical coping and addiction. In population-based studies, smokers generally report more severe, widespread pain compared with nonsmokers.21, 22 Our study confirmed that patients who had a history of tobacco abuse had more severe symptoms of pain and dyspnea and also were more likely to be prescribed strong opioids before palliative care consultation; however, the MEDD in smokers and nonsmokers did not differ significantly.

Several studies suggest that patients who cope chemically tend to express a higher degree of symptoms.12, 23, 24 In a study conducted by our group, we noted that CAGE-positive patients were referred earlier to palliative care; were more likely to be on opioid therapy upon referral; and had increased pain, sleep, dyspnea, decreased well being, and total symptom distress at baseline.12 A history of both alcohol and tobacco abuse places patients at risk for chemical coping, and health care professionals should cautiously adjust opioid therapy based not only on a patient's pain expression but also on assessments of their level of physical and mental function. It is unclear whether or not increased ratings of symptoms by cancer patients who have a history of substance abuse may be attributed to central sensitization, increased nociceptive input from the underlying cancer, or a combination of both.

The CAGE questionnaire can help screen patients for alcoholism but is not diagnostic; for that reason, CAGE-positive patients should undergo formal evaluation and diagnosis using Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for definitive diagnosis. Our study was a retrospective review, which limited our ability to determine the actual frequency of use of opioid and SHA. Therefore, our findings are preliminary, and further prospective studies are needed to examine the association between alcohol and tobacco use with chemical coping in cancer patients.

In conclusion, the current data suggest that alcoholism is highly prevalent and frequently undocumented in patients with advanced cancer. CAGE-positive patients were more likely to have a history of, or actively engage in, smoking and illegal recreational drug use, placing them at risk for chemical coping. The CAGE questionnaire is a useful tool for detecting alcoholism, which often is under diagnosed. Patients with history of tobacco abuse expressed more pain and dyspnea and were prescribed strong opioids more frequently at their initial palliative care consultation. Before prescribing opioids, clinicians need to carefully screen for behaviors that place patients at risk for chemical coping, including alcohol and nicotine use.

FUNDING SOURCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

Eduardo Bruera is supported in part by National Institutes of Health grants RO1NR010162-01A1, RO1CA1222292.01, and RO1CA124481-01. Egidio Del Fabbro is supported in part by grant PEP-08-299-01-PC1 from the American Cancer Society.

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES
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