To provide clinical practice guidelines for the evaluation and treatment of distress — a normal feeling of vulnerability to a feeling that leads to disabling problems, such as depression and anxiety — in adult patients with cancer

• Evidence-based guidelines    
• Consensus development involving a panel composed of physicians, psychiatrists, psychologists, and social workers

• Phases of care: multiple phases 
• Clinical application: palliative care

Results were not stated.

Recommended standards of care include

• Screening all patients for distress, at initial visits and appropriate intervals
• Distress management according to guidelines
• Having committees to implement standards, provide relevant education and training to healthcare professionals
• Having mental health professionals and certified chaplains available
• Providing a distress-thermometer screening tool
• Identifying at-risk patients and periods of increased vulnerability, to define appropriate screening intervals

Evaluation should include measures relating to level of distress, behavior symptoms, psychiatric history and medications, pain and symptom control, body image and sexuality issues, impaired capacity, safety, potential medical causes, and psychological disorders.

Management algorithms should be provided for dementia, delirium, mood disorder, psychotic disorder, adjustment disorder, anxiety disorder, personality disorder, and substance-related disorder.

Treatments identified for use include psychotherapy, anxiolytics, antidepressants, psychoeducation, cognitive behavioral therapy, social work and counseling interventions, spiritual counseling and ethics, and palliative care consultation according to algorithms.

• The evidence is mainly \"lower level,\" and recommendations are primarily consensus-based. 
• The panel did not include a nursing member.
• Many recommendations tend to focus on approaches to care for patients with significant mental disorders or for those referred to a mental health team. 
• The guidelines provide limited suggestions regarding low-level distress associated with physical symptoms.

The guidelines provide recommended pathways regarding assessment and management of distress. They do not provide a nursing perspective or identify a role for nursing in patient management.

RESOURCE TYPE: Consensus-based guideline

PHASE OF CARE: Not specified or not relevant

• Recommends psychological interventions with or without antianxiety or antidepressants to treat anxiety
• Recommends psychological interventions with or without antidepressants to treat depression
• Provides algorithms for social work counseling and chaplain interventions

Limited information on the quality of evidence was retrieved. All recommendations were mainly consensus based.

This guideline provides very general level treatment algorithms based on the results of an initial distress screening, and recommends further assessment and intervention determination if overall distress is 4 or above on the distress thermometer.

The guidelines recommend the following for management of opioid-induced constipation.

Preventive Measures:

• Take polyethylene glycol or a combination of stool softener and stimulant laxative daily.
• Maintain adequate fluid intake.
• Maintain adequate fiber intake. Compounds such as psyllium are not recommended because they are unlikely to control opioid-induced constipation.

If Constipation Occurs:

• Rule out other causes and begin treating.
• Titrate stool softeners and laxatives as needed.
• Consider coanalgesics to enable opioid dose reduction.

Persistent Constipation:

• Consider the addition of agents such as magnesium hydroxide, bisacodyl, rectal suppository, lactulose, and sorbitol.
• Use enemas.
• Consider methylnaltrexone 0.15 mg/kg subcutaneously daily.

Recommendations were identified as having low-level evidence and uniform consensus.

These guidelines do not provide any information about search strategy or any specific evaluation of evidence. Notes state that most direct evidence is of low quality, but recommendations do result from unanimous consensus.

The guidelines provide detailed recommendations regarding:

• Screening and assessment
• Management of pain in opioid-naive as well as opioid-tolerant patients
• Ongoing care of adult patients with cancer and related pain management
• Comprehensive pain assessment and use of pain ratings
• Interventions for specific types of pain syndromes
• Opioid prescribing, titration, and ongoing management
• Management of adverse effects related to opioids
• Psychosocial support and patient and family education
• Nonpharmacologic interventions.

In general, opioids are first-line interventions. The NCCN guidelines suggest that antidepressants and anticonvulsants can be first-line treatments for adjuvant pain, although the recommendation for using them as such is still based on anecdotal experience or guidelines relating to patients who do not have cancer.

The NCCN guidelines provide comprehensive algorithms for pain management, from screening to ongoing maintenance. The guidelines recommend considering a variety of nonpharmacologic interventions. Psychosocial support, including coping-skills training, is recommended, as is comprehensive patient and family education. The guidelines provide useful information and an overview of the full range of pain management. The work points to the ongoing need to consider multiple adjuvant and supportive interventions to achieve pain relief that works for the individual patient.

NCCN categories of evidence and consensus are described. Unless otherwise stated, all recommendations are reported to be category 2A, indicating a low level of evidence and uniform NCCN consensus. Specific process for evidence rating and consensus development is not described in the document. In addition, a search strategy was not described.

The NCCN guidelines document recommends universal screening for pain and provides an algorithm for comprehensive assessment and management approaches based on etiology of pain and current status with regard to pharmacologic management.

For opioid-naïve patients:

• Rapidly titrate short-acting opiods for moderate and severe pain, and consider for mild pain.
• Consider nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for mild pain.
• Consider addition of co-analgesics for all pain levels based on the specific pain syndrome.

For opioid-tolerant patients:

• An algorithm is provided for dose increases based on timing of peak effect and patient response. Initial calculation for titration is 10%–20% of the previous 24-hour dose, and if pain is unchanged or increased, an increased dose of 50%–100%.

For all cases, recommendations include:

• Regular pain medication dosing with rescue medications as needed
• Ongoing reassessment and regimen modification to manage pain and minimize adverse effects

For specific pain syndromes:

• Inflammation–A trial of NSAIDS or glucocorticoid
• Nerve compression or inflammation–A trial of glucocorticoid
• Bone pain without emergency–NSAIDS titrated to effect, consideration of nerve block or local radiation therapy for local pain, trial of biphophonates, hormonal or chemotherapy, and radioisotopes for diffuse bone pain
• Neuropathic pain–A trial of antidepressants, anticonvulsants, or topical agents

The major limitations of these guidelines are:

• Recommendations are mainly consensus based
• Recommendations are associated with low levels of evidence

The NCCN guidelines document provides comprehensive decision making algorithms for assessment, severity grading, and management of cancer-related pain. The guidelines also provide assessment tools, titration schedule examples, and conversion tables for medications and conversion to transdermal fentanyl. An additional offering are suggestions regarding the management of a variety of opioid adverse effects. (A trial of adjunctive medications are suggested for neuropathic pain as a pain management approach.)

RESOURCE TYPE: Evidence-based guideline

PHASE OF CARE: Multiple phases of care

One hundred seventy-one articles were retrieved via aPubMed search. No information was provided regarding which articles were selected as relevant to these guidelines, and no discussion of any method used for rating the quality of included evidence exists.

Limited database used. Recommendations are a combination of evidence- and consensus-based suggestions, and most nonpharmacologic interventions are by consensus.

Provides multiple evidence- and consensus-based recommendations for prophylaxis and the management of nausea and vomiting due to chemotherapy or radiation therapy. Recommendations provide a list of chemotherapy agents, including oral agents and categorization as to emetic potential.

RESOURCE TYPE: Evidence-based guideline

DATABASES USED: Not provided

KEYWORDS: Not provided

INCLUSION CRITERIA: Not provided

EXCLUSION CRITERIA: Not provided

PHASE OF CARE: Multiple phases of care

Not provided.

The guidelines recommends no prophylaxis for those with a low risk of infection; consideration of bacterial, fungal, and viral prophylaxis for intermediate risk (anticipated neutropenia 7–10 days), considerations of fluoroquinolone prophylaxis, antifungal prophylaxis until resolution of neutropenia, and viral prophylaxis during neutropenia in high-risk patients (e.g., anticipated neutropenia longer than 10 days, allogeneic HCT, acute leukemia induction or consolidation). It provides a recommended vaccination schedule for patients undergoing HCT, recommends annual influenza vaccine and pneumococcal vaccine to newly diagnosed patients based on individual assessment, and suggests fluoroquinolone prophylaxis in patients at high risk for mucositis.

• Provides limited information about search strategies and evidence base
• Most recommendations reported to be low quality evidence and high consensus

The guidelines provide general recommendations for prevention and management of infection, and useful algorythms for work up and management of signs and symptoms of infection by site.

The objective of this study was to assess the efficacy of a rapid titration of either morphine or midazolam for reduction of dyspnea.

Patients were randomized to receive oral morphine or oral midazolam. Starting dose of morphine was 3 mg, and midazolam was 2 mg. Two steps of 25% increases in dosage were given as needed to achieve 50% reduction in symptoms and to establish the “effective dose” for the follow-up period. Dyspnea relief was assessed 30 minutes after each medication dose during the rapid titration phase. In the follow-up phase, the effective dose was taken every four hours around the clock while awake. Breakthrough dyspnea was managed with rescue doses, and the dose was adjusted daily during the five-day follow-up period based upon need.

• The study reported on a sample of 63 participants.
• The mean age in the morphine arm was 55 years, with a range of 30–80 years.
• The mean age in the midazolam arm was 59 years, with a range of 36–82 years.
• Gender distribution was not reported.
• Of the participants, 16 of 63 had lung cancer, 15 of 63 had breast cancer, 6 of 63 had head and neck cancer, and 26 of 63 had other cancers.
• Other clinical contributing risk factors for dyspnea were present in most patients.
• Exclusion criteria included active or uncontrolled COPD, noncompensated heart failure, and severe renal or hepatic failure.

The study was conducted in a single outpatient setting in Buenos Aires.

Patients were undergoing end-of-life and palliative care.

The study was a random-assignment, single-blind intervention trial.

• Mini-mental status (MMS) exam for cognitive ability to participate in trial
• Dyspnea numeric rating scale (NRS) of 0–10 for breathlessness in which 0 means no breathlessness and 10 means worst possible breathlessness (used to establish baseline dyspnea and for follow-up phase)
• Dyspnea descriptors patients used first to characterize their dyspnea
• Semi-structured questionnaire for healthcare providers regarding possible active causes of dyspnea for each patient, dyspnea syndromes, and treatment or diagnostic approaches
• Dyspnea relief five-point scale (used only during rapid titration phase): none, slight, moderate, a lot, complete

• No serious adverse events required drug discontinuation, but about 50% in both arms developed mild somnolence.
• All patients in both arms of rapid titration were alleviated of dyspnea and continued into the follow-up phase
• Median intensity for dyspnea at baseline was 9 on NRS, and day one showed a significant decrease in dyspnea in both arms (morphine [9–6] and midazolam [9–4.5, p < .001]). Subsequent days continued to decrease or stayed low.
• The midazolam arm maintained significantly lower dyspnea levels as compared to the morphine arm on days three to five (p < .0002).
• Therapeutic failure (defined as less than 50% reduction in breathlessness) was seen in 20% of those on morphine and 0% of those on midazolam.

Midazolam alone or in combination with opioids may be beneficial for dyspnea management.

• The study had a limited sample size of less than 100 patients.
• Patients were eliminated if their symptoms were rated greater than or equal to 3/10, which is inconsistent with the stated criteria of moderate to severe dyspnea.
• Only patients and caregivers were stated to be blinded.
• No clear description was provided of whether patients could tell the difference in medications used.
• Patients were ambulatory and followed daily in the clinic; findings here may not apply to individuals with worse performance status.
• Though stated that patients could use rescue doses, no discussion ofuse of rescue medication took place between groups.
• Whether this was dypsnea at rest or dyspnea on exertion was unclear.
• Some patients on midazolam were also on opiods for other reasons, but no differentiation was made of these patients, and the number of the sample involved with use of both drugs was not described.

Midazolam may be useful in the management of dyspnea, but well designed clinical trials are needed to establish supporting evidence for this intervention.

To assess the role of midazolam as adjunct therapy to morphine in patients with advanced cancer with severe dyspnea during their last week of life

 Patients randomly were assigned to one of three treatment groups.

• Group Mo (n = 35): morphine 2.5 mg every four hours around the clock (ATC) for opioid-naive patients or 25% above the daily dose for those receiving baseline opioids with midazolam 5 mg rescue doses for breakthrough dyspnea (BD)
• Group Mi (n = 33): midazolam 5 mg every four hours ATC with 2.5 mg morphine rescue doses for BD
• Group MM (n = 33): morphine ATC (same dose as Group Mo) plus midazolam 5 mg every four hours ATC with morphine 2.5 mg rescue doses for BD

All drugs were given subcutaneously through a butterfly needle in the infraclavicular space. Random assignments were performed using a random number generator in 1:1:1 ratio in blocks of nine.

• N = 101
• KEY DISEASE CHARACTERISTICS: Patients with advanced cancer experiencing severe dyspnea during their last week of life
• OTHER KEY SAMPLE CHARACTERISTICS: Eligible patients had to have low performance status (PS = 4), severe dyspnea, and life expectancy less than one week and had to be coherent (more than 23/30 on the mini-mental state examination [MMSE]).

• Randomized, single-blind

• Modified Borg scale was performed at baseline and 24 and 48 hours after randomization.
• The number of breakthrough dyspnea episodes was recorded daily.
• MMSE was used to monitor cognitive impairment daily.
• Pulse oximetry also was monitored.
• Common Toxicity Criteria for Adverse Events v2.0 was used to score adverse events.
• Study endpoints were dyspnea intensity (measured by Borg scale), dyspnea relief (yes-no) after the intervention, and number of episodes of breakthrough dyspnea requiring rescue medication.
• Side effects from rescue medication also were monitored.

A significant correlation existed between dyspnea and anxiety at baseline and 24 and 48 hours. No correlation existed between dyspnea and anxiety and the other variables. No significant difference was found in oxygen saturation among the groups. Also, the groups did not differ significantly with respect to dyspnea intensity. Dyspnea relief at 24 hours was 69% Mo, 46% Mi, and 92% MM (p = 0.0004 for MM versus Mi, p = 0.03 for MM versus Mo). Patients with no dyspnea relief were 12.5% Mo, 26% Mi, and 4% MM (p = 0.04 for MM versus Mi). Percentage of breakthrough dyspnea episodes were 34.3% Mo, 36.4% Mi, and 21.2% MM (p = not significant) at 24 hours and was 38%, 38.5%, and 21.2%, respectively, at 48 hours. Authors asserted that clinicians should prescribe the combination.

The addition of midazolam to morphine improved the control of baseline dyspnea.

• Single blinding was a potential limitation.
• The physician’s knowledge of the drug regimen that patients were receiving may have influenced the need for administering rescue medication for breakthrough dyspnea.

More evidence, in addition to this one randomized, uncontrolled trial, is needed to validate findings.

To investigate whether the oral antidepressant fluoxetine affected symptoms of depression, adjuvant treatment completion, or quality of life

Intervention was daily oral fluoxetine (20 mg) for 6 months. Fluoxetine is a selective serotonin reuptake inhibitor. Data were collected at baseline, 3 months, and 6 months.

• The sample size was 180 (90 in the intervention group and 90 in the control group).
• Patients' mean age was 55.9 (range = 37–85).
• All patients were female.
• Patients had stage I or II breast cancer only.
• Patients had symptoms of depression but not a diagnosis of depression.

Four community outpatient settings

Active treatment

Prospective, randomized, placebo-controlled trial with double blinding

• The Functional Assessment of Cancer Therapy-General (version 3) for quality of life.
• The completion of adjuvant treatment was recorded.
• 11-item brief Zung Self-Rating Depression Scale for depressive symptoms.
• Two-question screening survey (TQSS) at baseline, to screen patients with symptoms of depression.

The use of fluoxetine for six months in each adjuvant therapy group (chemotherapy alone, hormonal therapy alone, chemotherapy plus hormonal therapy), was associated with, compared to the control group:

• An improvement in quality of life (p < 0.01 in each group)
• A higher completion of adjuvant treatment (p < 0.01 in each group)
• A reduction in symptoms of depression (p < 0.01 in each group).

An antidepressant may be effective for patients with early-stage breast cancer who have symptoms of depression and who are receiving adjuvant treatment. Given study limitations, more evidence is needed.

• The time lapsed since cancer therapy was unknown.
• The number of patients who showed a significant improvement in each measurement was statistically tested. However, it is unclear how the significant improvement was determined. Data for both the main outcome measures (quality of life and depression) were not reported.
• No data were recorded about reliability, validity, sensitivity, or specificity for TQSS.
• The study included patients with early-stage breast cancer only, and the size of each adjuvant therapy subgroup was small.

Oncology nurses can inform patients that oral fluoxetine may be an option for decreasing symptoms of depression.