STUDY PURPOSE: To describe an evidence-based approach to the use of psychosocial interventions to manage anxiety and depression in adults with cancer

TYPE OF STUDY: Combined systematic review and meta-analysis

• FINAL NUMBER OF STUDIES INCLUDED = 13
• TOTAL PATIENTS INCLUDED IN REVIEW = Not stated
• SAMPLE RANGE ACROSS STUDIES: Not described
• KEY SAMPLE CHARACTERISTICS: Not described

PHASE OF CARE: Active treatment

APPLICATIONS: Late effects and survivorship

Nine of the 13 publications reached positive conclusions about the efficacy of psychosocial interventions for depression in patients with cancer. Positive supporting evidence yielded recommendations for behavioral therapy, counseling/psychotherapy, and either of these approaches combined with education, relaxation training for patients not undergoing surgery, and cognitive-behavioral therapy.  

Six of eight publications reached positive conclusions about the efficacy of psychosocial interventions for anxiety. Recommended are behavioral interventions for patients undergoing treatment, relaxation training for patients not undergoing surgery, and cognitive-behavioral therapy in the post-treatment period.

1. Psychoeducation for new patients with cancer reported significantly less anxiety and depressive symptoms (p < 0.001) as well as greater satisfaction with their care than usual care (p < 0.01).
2. Patients randomized to problem-solving therapy demonstrated significantly less depression (p < 0.05), and results were maintained through a one-year follow-up period.
3. Stress-management techniques of paced abdominal breathing, progressive muscle relaxation with guided imagery, and the use of coping self-statements were briefly taught and provided to patients via print and audiovisual materials prior to beginning chemotherapy. Significantly less anxiety and depression (p < 0.05) was found versus usual care.
4. Cognitive therapy evaluated against a wait-list control in women with breast cancer who had clinically significant depressive symptoms demonstrated significantly less depression postintervention (p < 0.01), with even a further reduction occurring during the six-month follow-up period.
5. Group cognitive-behavioral therapy was offered to early-stage breast cancer survivors post treatment; the efficacy of this intervention in an randomized controlled trial compared with no-intervention controls indicated that the intervention group reported significantly (p < 0.05) less depression immediately postintervention and at two-year follow-up.

• Gaps regarding benefits of psychosocial interventions for diverse demographic, disease, and treatment characteristics. Men and ethnic and racial minorities were underrepresented, and most studies were based on several different types of cancer, usually early stage. 
• Inconsistency in the evaluation of interventions, the number and timing of outcome assessments, and outcome measures used
• Inadequate reporting of study methodology 
• Lack of research on patients experiencing clinically significant anxiety or depression (most patients studied were experiencing low levels when recruited)

Future research is needed, particularly focusing on men, minorities, patients with advanced disease, and patients who have completed treatment. Studies must include patients experiencing significant depression and/or anxiety prior to intervention. Combinations of interventions should also be studied. Last, timing for screening and intervening is important, but current data specify only “vulnerable times” rather than evidence to guide practice.

This was a preliminary trial evaluating effectiveness of two types of homeopathy for treatment of menopausal symptoms in breast cancer survivors.

At the initial visit, a homeopathic practitioner conducted a homeopathic evaluation of each participant and prescribed an individualized homeopathic medication that best matched the symptom profile for that participant. A homeopathic pharmacist randomized the participants tothree treatment groups:

1. A placebo combination medicine and a verum single remedy
2. A verum combination medicine and a placebo single remedy
3. Two placebo medications

All study medications were donated by the Standard Homeopathic Company. The treatments were identical in taste, appearance, and odor and were dispensed in identical containers. The combination medicine was Hyland’s Menopause, which is sold over-the-counter in the United States. It contained three homeopathic medicines: Amyl nitrate, Sanguinaria canadensis, and Lachesis.

Participants were mailed a one-week daily hot flush diary to complete during the week prior to call.

Eighty-three (83) participants completed the initial homeopathic visit and were randomized into the three treatment groups. Of this total, 28 patients (33.7%) withdrew, including 11 who reported no relief from hot flashes, 7 who had a cancer recurrence or withdrew because of other illness, 5 who said the study was inconvenient, and 4 who were lost to follow up. Sixty-six (66) participants completed at least six months of the study (80.5%).

• Inclusion criteria:
  • Women with a history of breast cancer who had completed all surgery, chemotherapy, and radiation treatment.
  • Tamoxifen use was allowed.
  • Participants had a history of hot flashes for at least one month, with an average of at least three hot flashes per day in the week prior to beginning treatment.
• Exclusion criteria:
  • Other medications for the treatment of hot flashes, including specific vitamin regimens, herbs, estrogen or progestational agents, antidepressants, or sleep medications were not permitted.
  • Concurrent chronic health problems such as rheumatoid arthritis, asthma, heart disease, and inflammatory bowel disease and corticosteroid use.
  • Those expected to receive additional chemotherapy or radiation treatment within the next year were not allowed to participate.
  • Women who were pregnant or planned to become pregnant in the next year were also excluded.

Participants stratified by age (younger or older than 50 years), breast cancer staging, and use of tamoxifen.

The study was a randomized, double-blinded, placebo-controlled trial. Participants received controlled an individualized homeopathic single remedy, homeopathic combination medicine, or a placebo.

Homeopathic providers saw or called participants every two months for one year.

No significant difference was reported for the primary outcome measure, the hot flash severity score, or in the total hot flashes among the three groups in the univariate model adjusted for baseline, time, and tamoxifen use over the period of 1 year. The single remedy group had a lower severity score and fewer hot flashes as a whole, which was most marked during the first three months of the study, with a positive trend (p = 0.1) at three months compared to placebo. However, in the combination homeopathy group not receiving tamoxifen, there was a statistically significant increase in the hot flash severity score compared to placebo (p= 0.01) and a highly significant difference when compared to single homeopathic remedy (p= 0.001). Similarly, there was a highly significant increase in the total number of hot flashes in the combination group compared to placebo (p = 0.006) and compared to single remedy (p=0.002) in the group not receiving tamoxifen. There was also a statistically significant increase in headaches in the group receiving the homeopathic combination at 6 months (p = 0.04) and 12 months (p = 0.03). In the multivariate analysis, which included baseline values, time, age, last month in the study, and treatment group, the same statistically significant relationships between treatment group and tamoxifen/no tamoxifen were found for both severity score and total number of hot flashes.

The small sample size precludes definitive answers. Difficulty in retaining participants for one year was a major problem. Use of three arms made treatment decisions difficult, although the average number of remedy changes found over the one-year study period is not unusual in homeopathic practice. Use of the homeopathic combination medicine in an ongoing daily regimen, rather than as it is used in current over-the-counter treatment, was a major flaw in this study.

To assess the efficacy and adverse effects of a ketamine burst protocol for pain relief in patients with refractory pain

Patients received IV ketamine at three dose levels (100, 300, and 500 mg per 24 hours) over 3–5 days in inpatient palliative care settings. All other medications remained, and benzodiazepines or haloperidol could be used to minimize adverse psychotomimetic events. Maintenance doses of 24 opioids and breakthrough pain opioid dosing could be reduced as appropriate for pain control. Data were collected on pain scores and total opioid intake during ketamine infusions and for 48 hours post infusion.

• The sample consisted of 44 patients.
• The median age was 61 years, with a range of 35–82 years.
• The sample was 52% female and 48% male.
• The majority of primary malignancies were lung, breast, colorectal, head and neck, mesothelioma, and multiple myeloma.
• Patients had various types of pain, including neuropathic (64%), pain from bony metastases (25%), and somatic pain (32%).
• All patients had pain scores of 4 or more at baseline, using a verbal rating scale.
• Pretreatment morphine-dose equivalents for opioid intake ranged from 3–1,050 mg per 24 hours.

This was a multisite study conducted in an inpatient setting in Australia.

This was an open-label, prospective study.

Patients were assessed based on the European Cooperative Oncology Group (ECOG) performance status, National Cancer Institute (NCI) Common Toxicity Criteria, and a pain verbal rating scale (which was not described).

• In all, 77% of patients required 300 mg or more of ketamine and 41% required 500 mg per 24 hours. Half of the participants were classified as responders to the ketamine.
• The longest documented response was 3 months in one patient; 11 patients continued with defined response for 2 weeks.
• More than half (61%) of patients experienced low-grade adverse effects. All grade 3 and 4 side effects occurred in patients who needed at least  300 mg per 24 hours of ketamine.
• Injection site toxicity was the most frequent grade 3 toxicity, and the most frequent grade 4 toxicity was hallucinations. No responding patient required withdrawal because of neurological adverse events.

Findings suggest that use of a ketamine burst infusion may be helpful for pain relief in some patients with cancer-related refractory pain.

• The sample size was small, with fewer than 100 patients.
• No comparison or control group was included.
• Opioid intake and episodes of breakthrough pain were not reported, although these were stated as outcomes of interest in the study.
• Refractory pain was defined as at least 4 on the rating scale, but duration of pain was not described in the population.
• Use of adjuvant pain medications was not described; therefore, subgroup analyis could not be done based on other medication intake.
• Statistical analysis of findings was not included.

In patients with pain that is not effectively controlled by other means, approaches such as ketamine infusions may have some benefit. More research in ketamine use is warranted. Although some patients responded and had a duration of effect as long as three months, 50% of patients did not respond as defined. Use of this approach requires hospitalization with continuous infusion and monitoring.

To examine research about the effectiveness of therapeutic touch in decreasing the pain and anxiety of patients with cancer

• Databases searched were PubMed, CINAHL, and the Cochrane Library.
• Search keywords were healing touch, therapeutic touch, cancer, and pain and anxiety.
• Studies were included if they
  • Researched the use of therapeutic touch in the context of any type of cancer.
  • Used therapeutic touch as the independent variable and pain or anxiety as the dependent variable.
• Exclusion criteria were not cited.
• Although the initial search strategy did not include the search keywords healing touch or Reike, these terms were included later.

• The study does not cite the number of studies retrieved or how authors assessed the studies for inclusion.
• Studies were organized, according to the quality of the evidence, by using the seven-level rating system that Melnyk proposed.

• Authors included 12 studies in the analysis.
• Sample size across all 12 studies was 6,066 patients. The range of sample sizes was 9–5,457.

• Authors identified only one study as a level 1 study. This study, a systematic review of 18 studies, concluded that, though evidence showed therapeutic touch to be a promising intervention, the evidence to support recommending therapeutic touch was inadequate.
• Three studies reported positive results, demonstrating that therapeutic touch was associated with significant improvement in physical and psychological health.
• The analysis yielded no results regarding the direct effect of therapeutic touch on pain or anxiety. Studies in this regard, three cohort or case control studies, were of low quality. Authors assessed them as level 3 nonrandomized controlled trials. One of these trials reported significant reduction (p = 0.03) of measured anxiety during the perioperative period.

The authors report that research relating to therapeutic touch indicates that the therapy helps to reduce pain and anxiety; however, the evidence that the research provides is very weak. Few studies showed statistically significant results, and several studies did not directly measure either variable. The rating scale used does not take sample size into account. As a result, a study rated level II included only 20 patients. Even with this rating scale, most studies analyzed were of low quality. Although the purpose of this study was to summarize the research, the authors incorporated opinion and review articles that were in support of therapeutic touch.

The evidence to support the efficacy of therapeutic touch, as a means of reducing the pain and anxiety of patients with cancer, is weak because the research about this topic is of low quality. Many investigators believe that therapeutic touch and related interventions are promising for patients with cancer and that the interventions pose little risk. Delivering these interventions requires training, however. Some authors have noted that, compared to inexperienced practitioners, experienced practitioners achieve more significant results. Therapeutic touch is something to consider as an adjunctive treatment for the pain and anxiety of patients with cancer. However, therapeutic touch must be administered by a trained and experienced practitioner. Well-designed and appropriately powered research of the efficacy of therapeutic touch is warranted.

STUDY PURPOSE: To examine the current amount and quality of evidence for the standard treatment of lower limb lymphedema (LLL) after treatment for gynecologic cancers

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 3
• TOTAL PATIENTS INCLUDED IN REVIEW = 55
• SAMPLE RANGE ACROSS STUDIES: 54–158 participants
• KEY SAMPLE CHARACTERISTICS: The review addressed women who had prior radiation, chemotherapy, surgery, or lymph node removal for the diagnosis of a gynecologic cancer and received standard care: complex decongestive therapy (CDT)

PHASE OF CARE: Late effects and survivorship

The evidence was weak (IIIC) but did show an overall decreased volume of limb(s) after CDT.

Despite the accepted and common recommendation to use CDT for LLL treatment, few studies support this in an evidence-based environment.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• Poor or awkward wording at times and structuring of the writeup, which were perhaps because of a typo/discrepancy between the titles initially identified as numbering 121 (in first paragraph of the Results section) and then 120 listed in Figure 1 flowchart
• The number of final studies included was listed as “5,” then changed to “3” without a clear explanation in the Results writeup, making it difficult to review.
• The graded evidence was weak (IIIC per results), and no randomized trials existed.
• One of the studies seemed to focus more on quality of life, and the clinical outcomes were secondary (Kim and Park, 2008).

The value of this review is that it highlights the limited evidence and research attempted, to date, for standard LLL treatment. More research is needed in this area, particularly randomized, clinical trials. Hopefully, this encourages nurses to initiate research to better support evidence-based practice and interventions for women with LLL.

To investigate the effectiveness of a dietary supplement amino acid jelly containing coenzyme Q10 and L-carnitine in controlling fatigue in patients with breast cancer

A dietary supplement containing branched chain amino acids coenzyme Q10 and L-carnitine was given orally once daily for 21 days at a dose of 125 g. Patients in the control group received usual care. Study assessments were conducted on day 1 and day 22, and fatigue was measured on days 8 and 15.

• N = 57  
• MEDIAN AGE = 50 years
• AGE RANGE = 22–70 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients had breast cancer; 89% had recurrence, and 86% had metastases. All were receiving chemotherapy, with varied regimens.

• SITE: Multi-site  
• SETTING TYPE: Not specified    
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

• Open-label, multicenter, randomized, controlled trial

• Brief Fatigue Inventory (BFI)
• Hospital Anxiety and Depression Scale (HADS)
• European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30)
• EORTC QLQ-BR-23

Fatigue initially increased from baseline to day 8 and then declined in both groups. The mean change in worst level of fatigue was greater with the intervention (p = 0.005). The mean reduction in current level of fatigue was greater with the intervention (p = 0.0009). No differences existed between groups in average feeling of fatigue or anxiety and depression scores.

The dietary supplement tested here may have some benefit in controlling fatigue among patients with breast cancer during chemotherapy.

• Small sample (< 100)
• Risk of bias (no blinding)
• The study was underpowered.
• No placebo control
• Baseline fatigue levels were not reported, so whether baseline fatigue was clinically relevant is unknown.

These findings suggest that a dietary supplement of branched chain amino acids coenzyme Q10 and L-carnitine may be helpful for the management of fatigue. Further research is needed to confirm this potential.

To evaluate whether all patients undergoing highly emetogenic chemotherapy (HEC) need an NK₁ and to evaluate the effects of aprepitant on patients who experience chemotherapy-induced nausea and vomiting (CINV) in the first course of therapy

Patients received standard antiemetics consisting of IV granisetron on day 1 and dexamethasone on days 1–3 when given highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Patients who needed aprepitant experienced CINV and received aprepitant prophylactically for the subsequent courses of chemotherapy. Other agents for rescue antiemesis were allowed. Pharmacists visited patients on days 1–6 to assist them with completing diaries to record symptoms.

• N = 77
• MEAN AGE = 67 years
• AGE RANGE = 38–85 years
• MALES: 83.1%, FEMALES: 16.9%
• KEY DISEASE CHARACTERISTICS: Of the patients, 93.5% had lung cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Of the patients, 36.4% were receiving HEC and the rest were receiving MEC.

• SITE: Single site  
• SETTING TYPE: Not specified  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

• Retrospective, descriptive

• Eleven-point numeric rating scale for nausea
• Functional Living Index-Emesis (FLIE)

Eighteen patients (23%) needed aprepitant after the first course of chemotherapy. Those receiving HEC who needed aprepitant experienced a significant improvement in the prevention of CINV (p = 0.018) and had less need for rescue medications (p = 0.001). Those receiving MEC also experienced an improvement in CINV after the use of aprepitant, although the difference was not statistically significant. Most improvement was seen in the delayed phase. Though vomiting was reduced, no significant improvement in nausea was observed. About 50% of patients required rescue antiemetics with the first course of chemotherapy.

Not all patients receiving HEC or MEC need an NK₁ to prevent CINV. Aprepitant was effective in preventing vomiting in patients who had CINV during the first course of chemotherapy.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• No information regarding rescue medications used is provided.

The findings suggest that all patients may not need NK₁s for complete control of CINV; however, no evidence predicts which patients will or will not experience CINV without an NK₁. Current guidelines recommend triplet antiemetics for HEC. Further work to identify the factors that would predict the patients who need NK₁s would be helpful to potentially provide control of CINV without the high cost of NK₁s.

To evaluate the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-HT3 receptor antagonist, and dexamethasone compared to standard therapy with a 5-HT3 receptor antagonist and dexamethasone

Chemotherapy-naïve patients receiving a carboplatin-based therapy were randomized to standard antiemetic regimens of a 5-HT3 receptor antagonist plus dexamethasone or a triple antiemetic regimen of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant.  

• N = 134  
• AGE = ≥ 20 years
• MALES: 82%, FEMALES: 18%
• KEY DISEASE CHARACTERISTICS: Chemotherapy-naïve patients with stage IIIB or IV ​non-small-cell lung cancer (NSCLC) who received moderately emetogenic, carboplatin-based chemotherapy (either carboplatin/taxol or carboplatin/pemetrexed)
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusion criteria: nausea and vomiting within 24 hours or use of antiemetic agents within 48 hours before administration of chemotherapy; use of pimozide; uncontrolled diabetes mellitus; asymptomatic brain metastasis; GI obstruction; or an active gastric ulcer

• SITE: Multi-site    
• SETTING TYPE: Outpatient  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care 

Multi-center, randomized, open-label, parallel-group, phase-II trial

Daily questionnaire regarding the frequency of vomiting and scoring of nausea during five days. Physicians recorded any additional antiemetic therapies used during the study period.

The aprepitant group had a better overall complete response (CR) of 80% (95% CI 69%–88%); the control group had a CR rate of 67% (95% CI 55%–77%). The difference is not significant. Rescue antiemetics were given to 15% of the aprepitant group and 28% of the control group. Adding aprepitant to patients receiving carboplatin/pemetrexed (with or without bevacizumab) had an overall CR of 84% in the aprepitant group versus 57% in the control group and a 87% CR in the aprepitant group versus 59% in the control group in the delayed phase of chemotherapy. The aprepitant group had a reduced need for rescue antiemetics compared to the control group (16% versus 36%, p = 0.04). Adding aprepitant to patients receiving carboplatin/paclitaxel did not reduce the use of rescue antiemetics.

Triple antiemetic therapy did not demonstrate a significant improvement in CR and decrease in chemotherapy-induced nausea and vomiting events in the overall and delayed phases of therapy when compared to standard use of 5-HT3 and dexamethasone as an antiemetic regimen in patients with stage IIIB–IV NSCLC being treated with carboplatin-based chemotherapy (considered moderately emetogenic chemotherapy). The addition of aprepitant to the regimen of carboplatin/pemetrexed (with or without bevacizumab) improved the overall response rate and delayed phase response in addition to decreasing use of rescue antiemetics.

• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions are not described that would influence results.
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: High percentage of male to female study participants overall may reduce generalizability to general population. Patients on carboplatin/paclitaxel regimen received a high-dose steroid (12 mg) IV to prevent anaphylaxis; this may influence the effectiveness of the antiemetic regimen.

There may be benefit to adding aprepitant to antiemetic regimens for patients with NSCLC being treated with carboplatin/pemetrexed. This benefit was not demonstrated when aprepitant was added to carboplatin/paclitaxel regimens.

To evaluate the effectiveness and safety of adding metoclopramide to the standard ondansetron and dexamethasone antiemetic regimen for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) among patients receiving cisplatin-based therapy

Patients were randomized (stratified by gender and age group) to a treatment or control group. All patients received ondansetron and dexamethasone prior to cisplatin and on the four subsequent days (days 2-5). Patients received either 20 mg of metoclopramide or placebo orally four times daily on days 2-5. Rescue treatment (including metoclopramide) was allowed based on the decision of the primary physician. On day 2, blinded data collectors documented the first emetic episode and frequency of emesis, severity of nausea and vomiting, side effects, and rescue antiemetic medications. On day 5, patients reported satisfaction of emetic treatment and quality of life.

• The study consisted of 162 patients.
• Just more than half (51%) of patients were 50 years old or older.
• The sample was 73% male and 27% female.
• The majority of patients (74%) had been diagnosed with head and neck cancer. Other cancers included gastrointestinal tract (10%), lung (5%), and sarcoma (5%).
• All patients received more than 50 mg/m² of cisplatin for their first dose.

The study was conducted at a single site, inpatient setting in Thailand.

All patients were in active antitumor treatment.

This was a randomized, double-blinded, placebo-controlled study.

• Measurement instruments for the first emetic episode, frequency of emesis, side effects, and rescue antiemetic medication were not reported in the article. 
• Common Terminology Criteria for Adverse Events, version 3.0, was used to measure severity of nausea and vomiting. 
• The Functional Living Index Emesis was used to document patient-reported satisfaction and quality of life.

• Before random assignment to the study, significantly more patients in the placebo group (30%) required rescue antiemetic medication for treatment of acute emesis (p = 0.04), and significantly more placebo group patients received metoclopramide as a rescue antiemetic (p = 0.02).
• No differences were found among treatment and placebo groups for patients who developed CINV, the severity of CINV, time to first emetic episode, or impact of CINV on daily life.  The only difference noted between groups was the proportion of patients that required rescue antiemetic medication, with significantly less medication used in the treatment group versus the placebo group (p = 0.05). 
• Metoclopramide was well tolerated with no difference in toxicities among the two groups.  Only one patient receiving metoclopramide had extrapyramidal effects.

No antiemetic benefit was found by adding metoclopramide to the standard ondansetron and dexamethasone regimen during cisplatin-based therapy; however, results are difficult to interpret because of a significant number of control patients receiving metoclopramide prior to the start of the study.

• Notable baseline sample group differences existed.
• Patients were allowed to receive metoclopramide for treatment of acute emesis prior to study randomization; therefore, some patients in the placebo group received metoclopramide and were not technically a control group.

A high number of patients in the placebo group developed anticipatory vomiting prior to the start of treatment, which illustrates the importance of performing thorough assessments prior to the start of chemotherapy and providing education prior to the start of the next course of chemotherapy.

To investigate potential analgesic benefits of 4 g paracetamol daily for palliative patients with cancer requiring high-dose opioids

Patients received usual medications plus 4 g paracetamol or placebo for five days each in random order. Primary outcome, effect on pain, was assessed using daily diaries, including a numeric rating scale ranging from 0 (no pain) to 10 (unbearable pain) and recording numbers of breakthrough analgesics. Patients also indicated in which part of the study their pain was better controlled.

• The study reported on 22 patients who completed the study.
• Mean patient age was 56.3 years (range = 28–79 years).
• The sample was 55% male and 45% female.
• Patients had a variety of cancer types.
• Baseline pain score was greater than or equal to 2, and patients were using at least 200 mg daily morphine equivalents.

• Multisite
• Both inpatient and community-based patients from Brisbane South Palliative Care Service and Mt. Olivet Palliative Care Service in Brisbane, Australia

The study used a randomized, double-blind, placebo-controlled, crossover design.

• Numeric rating scale (0–10)
• Patient-generated daily diary
• Mini-Mental State Examination

There were no significant order or treatment-by-the-order interaction effects for any variable. There were no significant differences in pain when assessed with placebo compared with paracetamol. No change approached clinically significant levels, with a mean difference in rated pain of 0.16, and mean difference of 0.42 for a number of breakthrough medications. Fifteen patients were undecided whether paracetamol improved pain.

Data from this study do not support the common practice of adding regular paracetamol (acetaminophen) daily to high-dose opioids to enhance pain control in the palliative setting.

The study had a small sample, with less than 30 participants.

There is a growing body of evidence suggesting that some patients do not receive any additional benefit from adding paracetamol or acetaminophen to strong or high-dose opioids. Pain management interventions should be individualized. Unwarranted exposure to potential side effects/toxicities and costs should be avoided when possible by eliminating paracetamol or acetaminophen in those individuals in whom no benefit has been demonstrated.