To review systematically the efficacy of psychotherapeutic and antidepressant interventions for cancer patients with depression or symptoms of depression

• Databases searched were PubMed, CINAHL, Cochrane Library, Database of Abstracts and Reviews of Effects (DARE), Cochrane Database of Systematic Reviews (CDSR), Cochrane Controlled Trials Register (CCTR), PsycARTICLES. In addition, investigators searched reference lists manually.
• Search keywords were terms relevant to depression and cancer from articles relevant to the review and medical subject headings (MeSH) per the National Library of Medicine. Intervention terms included antidepressant agents, SSRI, fluoxetine, and cognitive therapy.
• Studies included were randomized controlled trials involving pharmacologic and psychotherapeutic interventions for depression in adult patients with cancer. All study reports were in English.
• Excluded were studies involving the combination of pharmacologic and psychotherapeutic interventions, interventions involving complementary or alternative medicine, or educational strategies.
   

• Investigators retrieved a total of 164 studies.
• Evaluation included assessment by Cho and Bero's instrument for measuring methodological quality.

• The final number of studies assessed was 24, with the following sample range across studies:
  • Pharmacologic: N = 892, with a range of 40–549.
  • Psychotherapeutic: N = 2,518, with a range of 36–450.
• Participants in the studies had multiple and different disease sites.
   

• Results reflected 6 pharmacologic trials and 18 trials involving psychotherapeutic interventions.
• None of the trials using antidepressants reported avoiding or monitoring use of cointerventions.
• One trial found paroxetine to be effective in cases of major depression; one found paroxetine to be effective in reducing symptoms of depression.
• One trial reported that fluoxetine was ineffective in patients who presented with major depressive disorder, and response was not significantly higher than that with placebo. Two other trials reportedly showed the effectiveness of fluoxetine in reducing symptoms of depression.
• The majority of psychotherapeutic trials involved use of cognitive behavioral therapy. Other interventions were social support, counseling, support, and education and psychotherapy.
• Two studies examined the use of computer-based assessment and care planning. Most did not control for co-interventions and aimed at treatment of depression.
• Symptoms were measured at various time points and with various instruments. Of assessed studies, 42% demonstrated some significant improvement in depression as measured.

Some evidence suggests that antidepressants are effective in reducing symptoms of depression in patients with cancer, and overall tolerability of antidepressants appeared to be good. Cognitive behavioral therapy was effective in reducing symptoms of depression. An intervention that might be effective is the social-support group.

• Almost none of the assesed trials monitored, avoided, or reported cointerventions that could impact symptoms of depression.
• Most psychotherapeutic trials were single-center trials, a fact that limits generalizability.
• Patients recruited to participate in many of the studies did not have significant psychological morbidity.
• Many pharmacologic studies did not report tolerability data.
• Overall, few studies examined the use of antidepressants in patients studied. No studies were conducted of palliative care patients.

Findings suggest that antidepressants, cognitive behavioral interventions, and support group interventions can have a positive impact on symptoms of depression in patients with cancer. Variability in findings suggests that these interventions are likely to be of most benefit to patients who actually have clinically defined symptoms of depression. There is a need for further research of the efficacy of antidepressants in the patients studied.  Studies in this area should include data regarding use of any cointerventions for depression.

To determine the effectiveness of audiotapes on self-care behaviors, state anxiety, and the use of self-care behaviors and to describe the occurrence and intensity of common side effects in patients with breast cancer

Two 20-minute audiotapes provided information on nutritional management of side effects, exercise, and relaxation techniques along with written transcripts that were professionally developed at a fifth-grade reading level. All participants received standard education for the clinic but not standardized education. The experimental group received audiotapes and transcripts via mail and were provided with a cassette player if they did not have one at home. All participants were interviewed three times via telephone.

The study reported on 70 women with newly diagnosed stage I or II breast cancer starting the first cycle of chemotherapy treatment. Most of the women were receiving docorubicin and cyclophosphamide.

The setting was outpatient chemotherapy clinics operated by a university center in satellite clinics in rural areas of southeastern United States that covered 29 counties.

The design was an experimental, randomized, clinical trial.

• The Spielberger State-Trait Anxiety Instrument and modified Nail Self-Care Diary were used.
• Anxiety and self-care measures were recorded in diaries (nausea, fatigue, taste change, difficulty sleeping).

• Women who used the audiotapes demonstrated effective self-care behaviors over time, whereas the control group appeared to experiment to find effective self-care behaviors.
• Anxiety was high in both groups, but the symptoms decreased among women who received audiotapes and telephone calls.
• The most frequently experienced side effects were fatigue, nausea and vomiting, and taste changes.
• The number of women reporting nausea and vomiting decreased by half from the first to second self-care diaries.
• More self-care behaviors were used for nausea and vomiting than any other side effect that patients experienced.
• Prescription medications were the most frequently used self-care behavior and were effective over time.

• Informational audiotapes are effective teaching tools.
• Self-care behaviors can be taught and can be effective in managing side effects.

• The amount and type of information received in clinics and from community was not controlled.
• A limitation of the study was its small sample size.
• The telephone intervention may have had a substantial effect on patients’ behaviors. The questions asked during the phone interview reinforced self-care behaviors in the experimental group and provided information to women in the control group that they may not have had otherwise.
• The age of the population (half were younger than age 50) should be considered.
• The intervention was expensive; costs were incurred when developing the audiotapes in a studio with a professional speaker.

To present the short-term effects of a web-based computer-tailored intervention on quality of life, anxiety, depression, and fatigue in cancer survivors

A stand-alone web-based computer-tailored intervention (Cancer Aftercare Guide: KNW) was applied that aims to increase cancer survivor quality of life by providing personalized information and support on specific topics by promoting lifestyle changes. The eHealth intervention was based on principles of the problem-solving theory (PST) and cognitive behavioral theory (CBT). The KNW consists of eight training modules on topics of return to work, fatigue, anxiety, depression, social relationship and intimacy, physical activity, diet, and smoking cessation. After online registration, the computer randomly assigned participants to the intervention or waiting control group. Both groups had to complete questionnaires at 3, 6, and 12 months from baseline. The 6 and 12 month measures revealed the effectiveness. Participants filled in baseline questionnaires, modules were selected by the program, and the information was tailored to the participant, resulting in a personalized action plan. After 30 days, participants were invited to a second session to evaluate goal attainment and to set new goals.The program was unrestricted so that participants could self-select modules they wished to use and skip assignments.

• N = 419   
• AGE = 18 years or older
• MALES: 19%, FEMALES: 81%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Any cancer survivor
• OTHER KEY SAMPLE CHARACTERISTICS: Off treatment for at least four weeks but no longer than 56 weeks; no recurrence; no serious psychiatric, medical, or cognitive impairment

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

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Elder care

Randomized, controlled trial comparing the KNW intervention with a waiting list control group

• Global health status scale
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• Hospital Anxiety and Depression Scale (HADS)
• Checklist Individual Strength

With the exception of treatment type, the intervention and control group were comparable. Participants in the intervention group used an average of 2.22 modules from first login to last use of 10.67 weeks. The authors indicated that the KNW intervention had a significant effect on increasing emotional and social functioning (p = 0.022, p = 0.011) and decreased depressions and fatigue (d = 0.019, p = 0.007, d = 0.020, p = 0.02) six months after baseline. The only effect for fatigue occurred in participants who used the module Fatigue (p = 0.009). No significant differences existed between groups for anxiety. For those who used the therapist face-to-face component, available effect sizes ranged from 0.26 to 0.38.

While the use of the web-based intervention showed statistically significant results, the effect sizes for depression, anxiety, and social functioning were extremely small. The module use and program were not fully automated and offered direct therapist contact. The authors reported substantially higher effect sizes with therapist contact, raising the question of overall effectiveness of the web-based content.

• Baseline sample/group differences of import
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results 
• Measurement/methods not well described

eHealth interventions, such as web-based PST or CBT approaches, may be useful for improving quality of life in cancer survivors. Further research is necessary to target the desired information and to provide support specifically for fatigue, anxiety, and depression in cancer survivors. The findings showed much greater size of effects with direct therapist intervention, suggesting that an eHealth system may be best used as an initial step in a multicomponent intervention with additional steps, in which increasing intervention is provided based upon patient need and response.

To assess the evidence regarding massage as a means of improving the physical and psychological well-being of patients with cancer

• Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE, Allied and Complementary Medicine (AMED), System for Information on Grey Literature (SIGLE), PsycINFO, and CancerLIT. Investigators also searched dissertation abstracts.
• Year of publication, as defined by the search strategy, varied by database. The most recent date was September 2006.
• Search keywords were massage, aromatherapy, therapeutic touch, essential oil, volatile oil and cancer or neoplasm or oncolog* or palliate* or terminal or hospice.
• Studies were included in the review if they
  • Were randomized controlled trials (RCTs)
  • Involved adult patients with cancer who were receiving care in any healthcare setting
  • Included any type of massage, with a systemic goal, provided by a therapist with a recognized qualification
  • Produced patient-reported outcomes, reported by means of reliable and valid assessment tools, of physical or psychological symptoms and quality of life
  • Included the means by which the reliability and validity of assessment tools were evaluated.
• Studies were excluded if the purpose of the massage was a specific localized physical effect without a specific systemic aim. For example, a study involving prostatic massage to obtain a semen sample was excluded.

After elimination of duplicates from the initial search, investigators considered 1,321 references. Of these, investigators chose 10 studies for analysis, using the Jadad scoring approach and CONSORT Statement to appraise study quality. Investigators also used sample size and duration of follow-up to evaluate studies. Given the range of massage techniques and patients, meta-analysis was impossible. Three investigators reviewed studies independently.

• The review reported on 386 patients from nine studies.
• One of the initial references was a duplicate report of a single study.
• One study was based on personal communication, rather than a final published report.
• Study samples included more females than males.
• Various cancer diagnoses were represented.
• Sample sizes ranged from 6 to 87 participants.
• Samples included patients receiving surgery, radiotherapy, chemotherapy, and combined treatments.

• Patients were assessed 4–16 times, with all patients assessed before and after the intervention or control period.
• Follow-up was limited. One study assessed patients three weeks after the last massage.
• Five trials assessed psychological outcomes, including outcomes related to anxiety and depression.
• Seven trials assessed physical symptoms and quality of life.
• One study found a significant post-massage decrease in pain for males only. One study found a significant reduction in pain after massage but not after the control period. One study showed pain reduction after the first and third massage, but not after the second and fourth, and a nonsignificant trend of greater pain improvement in the massage group than in the group that did not receive massage.
• One study showed significant reduction of depression with massage, and one study showed no change.
• Three studies demonstrated significant post-massage improvement in anxiety.
• One study associated massage with short-term reduction in nausea.
• One study associated massage with reduction in fatigue.
• One study associated massage with improvement in quality of life.
• Most studies reported decreases in anxiety and other psychological benefits; however, results relating to depression were equivocal across studies.
• Adverse effects included a single case of skin rash in one trial and, in another trial that involved the use of essential oils, a higher incidence of digestive problems.

The authors stated that results were inconclusive; however, reported results showed that massage had a preponderantly positive effect in regard to anxiety reduction.

• This review did not discuss the patients' treatment phase, so effects relating to specific groups of patients were unspecified.
• Authors did not know how and if variations in massage style affected outcomes.
• Trials that included the use of oils used different oils, so the authors could draw no conclusions regarding the effect of aromatherapy.
• No evidence was available to assess long-term effects of massage. Authors found that research of long-term effects, as reported in the studies, was of low quality.
• Although inclusion criteria demanded that all studies be RCTs, results suggest that one study did not include a separate control group.

Two studies included in the review used a crossover design, and one of these showed significant results after massage but not after the control period. This suggests that crossover design may be particularly applicable to this area of research and that the effects of massage are immediate and time sensitive.

The intervention was a four-week course of one-hour aromatherapy massage offered in National Health Service cancer care settings in the United Kingdom. Patients were recruited and randomized to the intervention group or the control group. The primary variable was change in anxiety and/or depression between full case and borderline and noncase at 10 weeks postrandomization. Diagnostic assessments were tape-recorded, and regular consensus meetings were held to ensure consistency of the diagnostic rating. The secondary variable was self-reported anxiety using the State Subscale of the State Anxiety Inventory (SAI).

• The sample was comprised of 288 participants.
• Participants had a diagnosis of cancer, with prognosis of more than three months.

Four cancer centers and one hospice in England (National Health Service cancer care settings)

A longitudinal, randomized controlled trial design was used.

State Anxiety Inventory (SAI)–State Subscale measured at 6 and 10 weeks

Patients receiving aromatherapy massage experienced a significant improvement in anxiety at two weeks after intervention, and this was maintained at six weeks after intervention. The reduction of anxiety (by SAI) in the patients receiving usual care plus aromatherapy massage was at a confidence interval of 95% (p = 0.04) both at 6 weeks and 10 weeks.

The results of this trial suggest that aromatherapy massage is an effective therapeutic option for the short-term management of mild to moderate anxiety in patients with cancer.

The study required specialized training in aromatherapy massage.

To test the hypothesis that thalidomide is superior to placebo in terms of weight gain in patients with cachexia caused by esophageal cancer

Patients with advanced esophageal cancer who were not in active disease treatment were recruited at multidisciplinary team meetings at an individual site and randomly assigned to receive either placebo or 200 mg of thalidomide daily. Total body weight, lean body mass, resting energy expenditure measurements, and blood samples (complete blood count, biochemistry, tumor necrosis factor [TNF]-alpha, and interleukin 1-beta)  were taken at baseline and after six weeks of therapy. At two and four weeks, triceps skinfold thickness, mid-arm circumference, disease progression symptoms, adverse drug reactions, Karnofsky Performance Status score, and Piper Fatigue Scale questionnaire data were collected.

• The study reported on 22 patients.
• Mean patient age was 68 years, with a range of 57.7–80.2 years.
• The sample was 82% male and 18% female.
• Patients were diagnosed with incurable advanced esophageal cancer.
• Patients were excluded if they were in active treatment (surgery, chemotherapy, or radiation) but were eligible if treatment had taken place no less than four weeks prior.

The study site was not stated, but it appears to be a single site in an outpatient setting located in the United Kingdom.

• Patients were undergoing the end-of-life phase of care.
• The study has clinical applicability for end-of-life care.

A randomized, placebo-controlled trial design was used.

• Calibrated electronic scales to measure total body weight
• Dual-energy x-ray absorptiometry to measure lean body mass
• Triceps skinfold thickness
• Mid-arm circumference
• Karnofsky Performance Status index (performance indices)
• Piper Fatigue Scale Questionnaire    
• Blood: complete blood count, chemistries, TNF-alpha, and interleukin 1-beta
• Disease progression symptoms
• Adverse drug reaction information
• Indirect calorimetry via a vented hood apparatus to measure resting energy expenditure

At the end of the six-week study period, neither lean body mass nor total body weight changed from baseline in the treatment or in the placebo group. Mid-arm muscle circumference did not show changes at two or four weeks. None of the body composition endpoints showed any significant difference between groups (p > 0.05). The placebo group had a statistically significant increase in resting energy expenditure (p = 0.04), which was not shared with the treatment group.  

Survival was not different between the two groups. The median Karnofsky performance score was 10 points higher at baseline for the placebo group and did not change during the study, but this was not significant. The treatment group's median Karnofsky score dropped by 10 points. The Piper fatigue score did not change in either group.

TNF-alpha scores remained the same for both groups pre- and post-treatment. The interleukin 1-beta scores increased in the placebo arm.

Patients with advanced esophageal cancer taking thalidomide to increase body weight or lean muscle mass did not benefit positively from the intervention. There were many treatment arm drop-outs, mostly due to drug toxicity. All but two study arm patients who were able to complete the study required a dose reduction of thalidomide. Forty-seven percent of treatment patients were unable to complete the six-week study, whereas 94% of the placebo arm patients did complete it.

• The study had a small sample size and was conducted in a group of patients with a high rate of mortality and morbidity. The study was powered for 17 patients in each arm to be clinically significant, and this number was not met.
• Treatment patients had a lower Karnofsky performance score at baseline compared to placebo patients.
• Preliminary data from a pilot study used to design this study were gathered from patients with esophageal cancer who had not yet received treatment, suggesting an earlier intervention in their disease course and giving more favorable data to the intervention.
• The burden of treatment was so high that it interfered with data collection.

In this small study, the benefit of thalidomide for patients with advanced esophageal cancer was eclipsed by the drug’s adverse reactions and side effects. Quality of life was not enhanced and was actually negatively impacted. Although patients with advanced disease are often concerned about anorexia and weight loss, this study did not demonstrate benefit to the introduction of thalidomide in the end stages of life for patients with esophageal cancer.

The objective of the study is to assess the benefit of nebulized furosemide on breathlessness and respiratory function in patients with cancer.

Patients were assigned to receive 40 mg nebulized furosemide, nebulized 0.9% saline, and no treatment on three consecutive days in random order. Subjects were familiarized with the equipment and surrounding on day one of study and underwent assessments before and after administration of the assigned treatment. Spirometry was administered before and after nebulizer treatments. Following 10 minutes of rest, subjects underwent a reading test and arm exercise test and then rated their sensation of breathlessness intensity on a Borg scale. On nontreatment days, patients also underwent spirometry before and after the arm exercise test. Patients finally were asked if they had perceived benefits from the nebulized saline or furosemide treatments and whether they noted a difference between the two.

• The study reported on a sample of 15 patients.
• The mean age was 66 years.
• Of the sample, eight were females and seven were males.
• Patients had primary non-small cell lung (7), secondary lung cancer (breast) (2), pancreatic cancer (1), thymus cancer (1), uterine cancer (1), unknown (1), or mesothelioma (2).
• Participants experienced increased breathlessness on low levels of exertion or at rest, as patients with chronic obstructive pulmonary disease were accepted in the study if they had stable disease and breathlessness was cancer-related.
• Patients were excluded if breathlessness could be relieved by drainage of a pleural effusion or blood transfusion.

The study was conducted on a single-site, inpatient palliative care unit in England.

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

• Dyspnea Exertion Scale (range 0–5)
• Spirometric values [to compare forced expiratory volume (FEV1) and forced vital capacity (FVC) before and after intervention]
• Number Reading Scale (to measure breathlessness at rest)
• Arm exercise test (to measure breathlessness on minimal physical exertion)
• Borg Scale

All 13 patients who completed the arm exercise test experienced increased breathlessness, but no significant difference between exercise duration and Borg score at maximum equivalent workload between the furosemide, saline, and no treatment group were observed. Average score at maximum equivalent workload indicated no significant difference among the three treatments. Six of 15 patients perceived improved ventilation following nebulized treatment, with 3 preferring saline, 1 preferring furosemide, and 2 finding either treatment equally beneficial.

Results do not support benefit of nebulized furosemide in patients with cancer-related breathlessness.

• The study had a small sample size of less than 30.
• No standard or constant minimally effective dose or volume nebulized furosemide and saline treatment were established in the study that could have served as a basis for comparing dosing adequacy.
• Baseline performance scores were not established at the beginning of the study to determine activity level and ability to perform ADLs.
• Data are relevant/significant to individuals with primary or secondary lung cancer or mesothelioma and otherwise not truly representative/generalizable to other symptomatic groups (because breathlessness and treatment response in the study group may be related to or dependent on underlying cancer pathology).
• Patients could not have been blinded to nontreatment days.
• Although the authors state that treatments were prepared by a pharmacist, they appear to have been delivered by someone else, so no treatment days also could not have been blinded from investigators.

Results do not support the use of nebulized furosemide in the management of dyspnea.

Patients were studied on three consecutive days and were given nebulized saline on day 1, lignocaine 100 mg on day 2, and then lignocaine 200 mg on day 3. Lignocaine is the same as lidocaine hydrochloride (name used in the United States).

• The sample was comprised of six patients with cancer (four with lung cancer and two with breast cancer); all patients were breathless at rest but had stable symptoms for two weeks. Four patients had coexisting lung disease.
• Age ranged from 66 to 76 years.
• Oxygen saturation ranged from 78% to 98%.

Vital signs were measured and pulse oximetry was performed at baseline and 10, 20, and 30 minutes following treatment. Forced expiratory volume in the first second (FEV1) was measured before and 30 minutes after treatment. A visual analog scale (VAS) measured work of breathing and distress of breathing at baseline and 10, 20, 30, and 60 minutes following the intervention.

No significant differences in vital signs or FEV1 existed between treatments. Two patients developed a wheeze after the 200-mg dose of lignocaine, but no bronchodilator was required. The rate of breathing effort decreased after all three treatments, with no significant differences between treatments. The distress of breathing decreased after saline and increased slightly but was statistically significantly (p < 0.025) with both doses of lignocaine. No benefit was seen with inhaled lignocaine.

• The study had a small sample size (N = 6).
• The authors stated that the sample was limited because most patients were either too unhealthy or insufficiently stable to participate in the study.

• FINAL NUMBER STUDIES INCLUDED = 7
• TOTAL PATIENTS INCLUDED IN REVIEW = 135
• SAMPLE RANGE ACROSS STUDIES: Not provided
• KEY SAMPLE CHARACTERISTICS: Postmastectomy

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Palliative care

This review demonstrated a lack of high-quality research on neural blockades for PPBCS, which is predominantly a neuropathic pain syndrome.

• This review found that the studies included for the analysis were of low quality because of the case studies included (n = 4; 56%).
• Only two randomized, controlled trials were included.

Because of the low quality of the included studies and the small number of randomized, controlled studies of studies in this review, little evidence for neural blockades for PPBCS can be used for nursing at this time point.

To determine the efficacy of oral morphine in bringing relief from cancer pain; to assess the incidence and severity of side effects associated with oral opioids

• Databases searched were MEDLINE; EMBASE; Cochrane Central Register of Controlled Trials (CENTRAL); Cochrane Pain, Palliative and Supportive Care Group Trials Register; and Oxford Pain Relief Database. In addition, investigators performed manual searches of 40 key journals that list pain-related trials.
• Search keywords were analgesics, opioid (*administration and dosage), morphine, (*administration and dosage), neoplasms (*complications) pain (*drug therapy, radiotherapy), randomized controlled trials (RCT). Investigators searched for studies relating to humans, adults, and children.
• Studies were included if they
  • Were RCTs.
  • Had been published as full journal articles.
  • Compared an oral morphine preparation to placebo, active control, or alternative route of morphine.
  • Included adults or children with cancer pain that required opioids for treatment.
• Studies were excluded if they were quasi-randomized studies, included 10 or fewer participants, did not assess pain as an outcome measure, focused on pain unrelated to cancer.

The search retrieved 133 studies; 62 met inclusion criteria. After elimination of duplicates, the group for analysis included 54 studies. There were insufficient data to perform meta-analysis. Study quality was evaluated using the Jadad scale. Overall, the quality of studies was high, with a median score of 4 on a five-point scale. Studies included comparisons of modified- and immediate-release opioids, comparisons of morphine versus other drugs, and comparisons of the effects of morphine delivered by different routes and delivery mechanisms.

The 54 studies involved a total sample of 3,749 participants. Sample range was 11–699.

• Fifteen studies compared modified-release morphine to immediate-release morphine. The trials showed that both forms were similar in terms of pain relief provided and adverse effects experienced.
• Twelve studies compared various doses or dose intervals of modified-release morphine. The trials revealed no significant differences across products in terms of pain intensity, rescue analgesia, or adverse effects.
• Thirteen studies compared modified-release morphine with other opioids, including oxycodone, hydromorphone, transdermal fentanyl, dextropropoxyphene, tramadol, and methadone.
  • Comparisons of modified-release morphine with oxycodone showed that both resulted in adequate analgesia. Studies revealed some differences in side-effect profiles.
  • In a comparison of modified-release hydromorphone and modified-release morphine, both achieved satisfactory pain control. Authors noted no difference regarding the use of rescue medications.
  • Comparisons of oral morphine and transdermal fentanyl showed no significant differences between treatments in regard to pain control. However, more patients receiving fentanyl required upward-dose titration and more rescue medication. Transdermal fentanyl was associated with less sedation and less constipation. Dose-equivalency determination appeared to be problematic in one trial.
  • One small study found that, compared with morphine, dextropropoxyphene was associated with fewer side effects and lower doses needed for pain relief
  • One study of tramadol versus morphine in opioid-naive patients revealed that both medications resulted in satisfactory analgesia but that tramadol was more effective in treating neuropathic pain.
  • One study, which compared methadone to oral morphine, showed that a greater number of adverse events were associated with methadone than with oral morphine.
• Six studies compared immediate-release morphine to other opioids, including Brompton cocktail, methadone, tramadol, oxycodone, and oral transmucosal fentanyl citrate.
  • Comparisons of oral morphine to Brompton cocktail showed no difference between treatments and demonstrated that cocaine did not enhance analgesia.
  • One comparison involving morphine and methadone showed that both drugs achieved pain control but that more patients on morphine complained of dry mouth and that more patients on methadone complained of headache.
  • Tramadol and morphine use resulted in a pain decrease to similar intensities.
  • One study, which compared morphine to immediate-release oxycodone, revealed that the two achieved similar control of pain. The most frequent side effect of both was sedation. Oral morphine was associated with more nausea than was oxycodone.
  • In one study, patients could use either morphine capsules or oral transmucosal fentanyl (OTFC) for breakthrough pain. OTFC was more successful than morphine at reducing pain intensity, and the majority of patients preferred OTFC.
• The studies showed no significant difference in pain control or adverse events between oral and rectal administration or between tablets and oral suspension.
• Compared to naproxen, morphine was associated with greater use of rescue medication.
• The studies showed that oral morphine and epidural morphine produced a similar level of pain relief. The epidural route was associated with fewer side effects but more technical problems.
• Oral morphine and morphine suppositories provided a similar level of pain control. Studies showed no difference in the adverse effects associated with these two interventions.
• Various studies compared different medication routes or morphine to nonopioids. Across studies there was a 6% withdrawal rate due to adverse effects.

The literature demonstrates the effectiveness of morphine with titration to effect. The range of doses used in studies varied widely, with the maximum dose recorded being 2000 mg/day. Mean daily dose was 110–250 mg/day. This shows effectiveness over a wide range and that oral morphine, at the correct dose for the individual, is as effective as other opioids and morphine adminstered through nonoral routes. Limited evidence shows that transdermal fentanyl is faster than oral morphine at dealing with breakthrough pain. Some evidence shows that transmucosal fentanyl may be superior to oral morphine in the treatment of breakthrough pain and that fentanyl patches are associated with fewer side effects at the same level of analgesia. Oxycodone, hydromorphone, and morphine provide comparable pain control and are associated with similar adverse events. A small number of patients appear to develop intolerable side effects as the result of using oral opioids. Findings support the effectiveness of various forms of opioids for pain control, and the appropriateness of dose titration across a wide range, with specific medication selected according to each patient's responses and preferences.

These findings show that titrating to pain relief, using modified-release opioids, is possible.