Antidepressants

PHASE OF CARE: Multiple phases of care

Of 677 articles, 22 were selected for a full review. Following consensus, only two were found eligible for key question 1. In one RCT, mianserin had significant antidepressant effects compared to a placebo. In the second RCT, desipramine and paroxetine no were more efficacious than a placebo. Of 1,149 articles, 52 articles were selected for full review for key question 2, but none met the inclusion criteria.

The results of this systematic review highlight the paucity of RCTs evaluating the efficacy and tolerability of antidepressants for the treatment of MDDs in women with breast cancer. No RCTs for psychotherapeutic approaches were identified for this systematic review, emphasizing the lack of data for the treatment of MDDs in patients with breast cancer. Further research is needed on the treatment of MDDs based on clinical experience.

• The results of the two eligible RCTs were mixed.
• They had small samples and significant risk of bias.
• The authors did not include unpublished results, and the review only focused on depression-related outcomes.

Psychological distress is an unmet need in patients with breast cancer and needs to be researched further.

To quantify the overall effect of antidepressants in the treatment of depressive symptoms in patients with cancer

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed and Cochrane library

KEYWORDS: Depressive or depression and cancer

INCLUSION CRITERIA: Double-blind randomized trials, presence of depression or depressive symptoms in patients with cancer determined by diagnostic criteria or depression rating scale, primary outcome was reduction in severity of depressive symptoms, published between 1980–2010

EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED: N = 5,959

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane collaboration tool for risk of bias

• N (studies) = 9
• SAMPLE RANGE ACROSS STUDIES: 35–177
• TOTAL PATIENTS INCLUDED IN REVIEW: 722

Six trials compared antidepressants to placebo. In head-to-head comparison trials, fluoxetine was not superior to desipramine, no difference was seen between paroxetine and amitryptiline, and mirtazapine had a greater effect than imipramine. Overall effect size in meta-analysis was RR = 1.56 (95% CI 1.07 = 2.28, p = .021) in favor of antidepressants. Only three studies reported the number of patients with side effects, and many studies had a lot of missing data and high dropout rates or low samples.

Findings suggest that antidepressants are beneficial for depression and depressive symptoms in patients with cancer. However, the strength of this finding is limited due to limitations in studies included in this meta-analysis.

A low volume of studies was included. Average risk of study bias was unclear. Differing depression scales and criteria for depression response were used across studies. Most studies had small sample sizes for analysis. Study duration ranged from five weeks to six months.

This analysis provides some support for effectiveness of antidepressants in treatment of depression and depressive symptoms in patients with cancer. Nurses need to be aware of adverse side effects of antidepressants that may make other symptoms worse, such as nausea and cognitive impairment. Most studies reviewed did not analyze antidepressant side effects, so the real tolerability of antidepressants in patients with cancer is not clear. Patients may benefit from antidepressants but need to be monitored for side effects of this treatment.

• FINAL NUMBER STUDIES INCLUDED = 21, and 19 in meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,007
• SAMPLE RANGE ACROSS STUDIES: 19-549
• KEY SAMPLE CHARACTERISTICS: Varied tumor types, ages ranged from 18-89 years

Antidepressants were effective in reducing distressing symptoms (SMD = -0.229, p = 0.018) and major depression or depressive symptoms (SMD = -0.285, p = 0.001).  All types of antidepressants showed some efficacy, although tricyclic antidepressants did not show efficacy across two small studies. SSRIs and manserin were effective. Quality of life measures were also improved. There was significant heterogeneity. Analysis showed significant efficacy was correlated with length of follow up (p < 0.001). Antidepressants did not differ from placebo in terms of acceptability, using drop-out rate as a proxy of acceptability.

Antidepressants of all types demonstrated overall efficacy for improvement in depressive symptoms as well as other distressing symptoms. SSRIs and manserin showed the best results

Overall quality of reports was graded as low to moderate. Several studies included funding by drug companies, suggesting sponsorship bias as the funder role was not described.  There was significant heterogeneity

Findings from this analysis show that antidepressants, particularly SSRIs and manserin, were tolerable and effective in reducing depressive symptoms in patients with cancer. Findings also suggest that efficacy may increase over time, pointing to the potential need for sufficient duration of treatment. It is important that nurses screen for symptoms of depression among patients with cancer, and facilitate relevant treatment.

STUDY PURPOSE: Assess effects of antidepressants among people with cancer for treatment of depression

There was no differences between antidepressants as a class and placebo in five RCTs, no difference between groups comparing different antidepressants, and no difference in drop-out rates between placebo and antidepressants

The findings did not provide strong evidence for efficacy of antidepressants.

Study quality was generally low with unclear risk of bias in multiple aspects of the study design and implementation. In five studies, risk of bias due to conflict of interest was questionable. There was no difference found between SSRIs and tricyclic antidepressants. Studies included were all conducted prior to 2009.

This particular analysis did not demonstrate efficacy of antidepressants in patients with cancer for management of depressive symptoms. There were multiple limitations in this analysis due to the low quality of the studies included.

To provide an evidence-based review of empiric literature, about depression in patients with cancer, that focuses on occurrence, assessment, and treatment

The search examined literature published January 1966–September 2001 and cited in PubMed, PsycINFO, CINAHL, or BIOSIS Citation Index.

Common interventions for depression are behavioral and cognitive counseling. Because hundreds of articles exist about these topics, the review was limited to several meta-analyses of psychosocial interventions. Some measured emotional adjustment or distress rather than depression. All studies cited were conducted prior to 1998. Eleven randomized, controlled trials of medication treatment for depression in patients with cancer were identified. Tools for measuring depression included the Hamilton Depression Rating Scale, Clinical Global Impression, Hospital Anxiety and Depression Scale, and Montgomery-Asberg Depression Rating Scale. Descriptive reports—but no randomized, controlled trials—were found regarding complementary treatments.

Eleven randomized, controlled trials of medication treatment for depression in patients with cancer included data from 755 patients, averaging 58 patients per study.

Some data exist regarding the efficacy of psychosocial and pharmacologic treatments for depression in people with cancer. Studies conforming to usual practices of antidepressant trials demonstrated benefit. Studies measuring at less than five weeks tended to show less benefit. Randomized, controlled trials of alternative or complementary interventions were not found.

To determine, by means of a meta-analysis and systematic review, the effectiveness of treatment with antidepressants in people with depression in the context of physical illness

• The Cochrane Register of Clinical Trials, MEDLINE,^® EMBASE, PsycINFO, ClinicalTrials.gov, Current Controlled Trials Register, LILACS, CINAHL,^® PSYNEX, AMED, and the pharmaceutical industry trials registers of GlaxoSmithKline and Eli Lilly were consulted.
• The following inclusion criteria were used: any type of antidepressant used; patients older than 18 years, with depression in the context of a physical illness; and depression defined as diagnosis of major depressive disorder, adjustment disorder, or dysthymic disorder, according to DMS-IV or ICD-10 or scores indicative of a diagnosis on validated tools. The main comorbidity was a physical health problem with a biological underpinning, not just symptoms. The control condition was a placebo.
• The study was excluded if patients had psychiatric comorbidity or if the study involved trials in which antidepressants were prescribed to treat symptoms other than those of depression.
   

• A total of 2,230 references were retrieved.
• Risk of bias was evaluated with Cochrane handbook criteria.
   

• 51 studies were included.
• Studies included patients with stroke, AIDS, Parkinson disease, cancer, chronic obstructive pulmonary disease, diabetes, myocardial infarction, renal failure, heart failure, epilepsy, and chronic prostatitis. Age range was 33–82.
• Four of the trials involved patients with cancer, mostly women with breast cancer. In those trials, the age range of the 254 patients was 35–91.
   

Most of the studies involved use of tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs); three studies looked at mirtazapine. In 25 studies providing data on short-term response, odds of response were greater with antidepressants (OR = 2.33, 95% CI, 1.8–3.0, p < 0.00001). Across 20 studies (N = 1,214 patients), at six to eight weeks antidepressants were more effective than placebo in reducing symptoms of depression (SMD = 0.66, 95% CI, –0.94 to –0.38, p < 0.00001). Analysis of medium-term response at 9–18 weeks showed odds of response were greater with antidepressant drugs than placebo (OR = 2.08, 95% CI, 1.33–3.24, p = 0.00001). Long-term response ( > 18 weeks) was better with antidepressants than placebo (OR = 2.13, 95% CI, 1.31–3.47, p = 0.002). Heterogeneity had a low impact on the meta-analysis reported. In the short term, fewer patients receiving placebo dropped out of the study. Most frequent adverse events were dizziness, dry mouth, headache, nausea, constipation, insomnia, sexual dysfunction, sedation, hypotension, and appetite change. No trials studied patients with advanced cancer,

Antidepressants were superior to placebo for treatment of depression in people with a physical illness.

The large number of studies were of relatively low quality, which may have inflated the effect sizes calculated. Depression was presumed to be similar across physical diseases. No subgroup analysis was conducted for different diseases.

Findings showed that treatment with antidepressants is superior to use of placebo in patients with physical illnesses who have moderate or major depressive disorders in the context of the physical illness. Antidepressants may benefit patients with cancer who have moderate to major depression. Applicability of antidepressants for patients with advanced cancer is unknown. Nurses should be aware of the side effects of antidepressants and how they may contribute to various disease or treatment symptoms.

• FINAL NUMBER STUDIES INCLUDED = 9
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,169
• KEY SAMPLE CHARACTERISTICS: The nine final RCTs were published between 1985 and 2011. Eight of these studies contained a placebo group compared to a group receiving an active drug; one trial compared patients receiving an active drug to patients receiving no treatment. Six studies included multiple cancer types, but three studies reported only patients with breast cancer. Most (83%) of the patients were female, and the mean age of all patients was 54.3 years old. The duration of treatment ranged from 4–12 weeks; attrition was greater than 20% for all but two of the studies. 

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Elder care, palliative care

The three effective antidepressants were mianserin, paroxetine, and fluoxetine. The mianserin group had a lower dropout rate than the placebo group, but with non-significant difference; higher depression response rate. Paroxetine group had higher dropout rate than placebo but with non-significant difference. The fluoxetine group had a significantly higher dropout rate when compared to a placebo. Paroxetine and fluoxetine were not associated with higher depression response rates when compared to a placebo. The evidence for the efficacy and tolerability of different antidepressants remains scarce for cancer-related depression, suggesting a great need for further randomized, controlled trials with placebo controls.

Opening database search dates varied. Heterogeneity among the studies complicated comparisons, causing small sample studies to be left out of at least two analyses. Only nine studies met the final criteria for inclusion, suggesting a need for research addressing the efficacy and tolerability of antidepressant use in patients with cancer and symptoms of depression.

Further research in patients with cancer and depression is needed to determine the best treatment guidelines. Mianserin showed the best results in these studies; however, it was reported that it is not available for sale in the United States. Research using other antidepressant drugs is needed. For example, tricyclic antidepressants and monoamine oxidase inhibitors should be studied. Paroxetine and desipramine did not show promising results in reducing depression in these studies.

To evaluate the efficacy of pharmacologic and nonpharmacologic treatments for depression in patients with cancer

Literature review of works, published through June 2005, conducted by the Supportive Care Guidelines Group (Ontario). Databases searched were MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Database.

Authors identified seven pharmacologic randomized control trials and four nonpharmacologic trials.

Pharmacologic trials: Three trials detected significant differences (symptom improvement) among treatment groups on a measure of depression. Two compared the antidepressant mianserin to placebo. The third, which compared use of alprazolam to muscle relaxation, found reduction in symptoms of depression with the use of alprazolam. Two studies compared active treatments—fluoxetine versus desipramine and paroxetine versus amitriptyline. They found improvement of symptoms of depression in all groups, with no differences in treatment efficacy. The remaining two trials found no significant differences among patients randomized to fluoxetine versus placebo; however, only low-dose fluoxetine was evaluated in one of the studies, and both studies were for a short duration, only five weeks.

Nonpharmacologic trials: Two of the four studies reported greater improvement in symptoms of depression in the intervention groups rather than in groups with usual care. Interventions included an orientation program with educational information and a multicomponent intervention. One of the remaining studies found that adjuvant psychotherapy did not significantly affect patients’ Hospital Anxiety and Depression Scale (HADS) subscores for depression. The final study found no significant difference among patients receiving cognitive-existential group therapy plus relaxation and those receiving relaxation therapies alone.

The evidence of treatment effectiveness for depressive disorders in patients with cancer is limited and of modest quality.

At present, treatment guidelines must be based on limited evidence and on data derived from the general population, other medically ill populations, and on expert opinions.

• FINAL NUMBER STUDIES INCLUDED = 8
• TOTAL PATIENTS INCLUDED IN REVIEW = 589
• SAMPLE RANGE ACROSS STUDIES: 33–181
• KEY SAMPLE CHARACTERISTICS: Included patients with hepatitis C. One study in melanoma

PHASE OF CARE: Active antitumor treatment

Analysis showed that antidepressant treatment reduced overall incidence of depressive disorder (OR = 0.42, p < 0.001). Only one trial was done in which patients with a history of depression were excluded.

Prophylactic use of antidepressants was associated with reduced incidence of depression in patients receiving interferon alpha monotherapy.

• There was only one study in patients with cancer.

Depression has been identified as an adverse effect of treatment with interferon alpha. This study showed that pre-emptive treatment with antidepressants can reduce the incidence of this effect. Nurses need to be aware of depression associated with interferon alpha treatment, and assess patients for depression, especially if they have a history of depressive symptoms. Long-term effects in patients with cancer are unknown, since there is limited evidence for this group of patients.

To determine which treatments are effective for patients with diagnoses of both cancer and depression

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE, EMBASE, EMBASE Classic, PsycINFO,Cochrane centeral register–all to 2012

INCLUSION CRITERIA: Randomized controlled trial, adult patients, cancer diagnosis, diagnosis of major depression, trial evaluated treatments for depression, depression outcomes were assessed with a standardized measure. Patients with additional psychological diagnoses were included if results were analyzed separately for depression.

EXCLUSION CRITERIA: None specified

TOTAL REFERENCES RETRIEVED: N = 8,442

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane risk of bias tool used for quality evaluation

• N (studies) = 7
• SAMPLE RANGE ACROSS STUDIES: 46–200

Three trials of antidepressants were included. Two used mianserin, and one compared amitriptyline and paroxetine. One trial of mianserin showed superiority to placebo. No difference in depression outcomes was seen between amitriptyline and paroxetine. One trial of psychological treatment compared eight one-hour sessions of behavioral activation therapy with problem-solving therapy. No differences in depression outcomes were seen. One trial of combined antidepressants and psychological treatment showed better outcomes compared to usual care.

Limited evidence exists for treatment of depression among patients with cancer from this review. Limited evidence exists that antidepressant drugs alone or in combination with psychological treatments are effective.

Twenty-five trials were excluded because they did not use standard psychiatric DSM or ICD criteria for depression. Risk of performance bias was high, and other ratings of bias were deemed unclear. No studies included involved use of newer and more commonly used antidepressants.

This review provides little evidence regarding interventions that are effective for treatment of depression in patients with cancer.

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 compare the tolerability and efficacy of two different titrations of paroxetine in a population of patients with cancer who have depression

Patients who were randomized to slow up-titration started paroxetine 2.5 mg/day, increasing the daily dose by 2.5 mg each third day, until 10 mg/day was reached on day 8. On day 9, the dosage was increased to 15 mg/day, and on day 11, patients reached the full dose of 20 mg/day.

Patients who were randomized to standard up-titration started with 10 mg/day of paroxetine and increased the daily dose to 20 mg/day on day 8.

• The sample size was 20.
• The median age of the slow up-titration group was 60 (range = 40–78), and the median age of the standard up-titration group was 64 (range = 43–78).
• The sample was 30% male and 70% female.
• Cancer types included breast (30%), lung (20%), colorectal (20%), hematologic (10%), head and neck (6.7%), gastric (3.3%), dermatologic (3%), and others (6.7%).
• 46.7% had no active disease, 30% had local active disease, and 23.3% had metastatic disease. 
• For inclusion, patients had to have any stage of cancer and a major depressive disorder or adjustment disorder with depressed mood. By DMS criteria, 30% had major depression and 50% had adjustment disorder with depressed mood.

• Single site
• Outpatient setting  
• Turin, Italy
   

• Active treatment
• Late effects and survivorship
   

Open randomized trial  

• Dosage Record and Treatment Emergent Symptom Scale
• Subjective Side Effects From Medication Scales
• Hospital Anxiety and Depression Scale
• Montgomery Asberg Depression Rating Scale (MADRS)
• European Organization for Research and Treatment of Cancer–Quality-of-Life Questionnaire Core 30
• Hamilton Rating Scale for Anxiety (Clinical Global Impression and Patient Global Impression of Improvement)
   

Both treatment groups showed a significant mood improvement. A significantly higher rate of patients in the slow up-titration group2, compared to the standard titration group, showed no side effects after two weeks (p = 0.005). A total of 46.7% of subjects used in the intent-to-treat analysis were considered responders, according to MADRS results. Nine patients (30%) dropped out because of side effects that included gastrointestinal problems, dizziness, confusion, restlessness, and tremors. The majority of side effects appeared within the first two weeks.

Slow paroxetine up-titration is better tolerated and at least as effective as the standard paroxetine up-titration in patients with cancer who have depression. Fewer than half the patients in the final sample were identified as responders to treatment, and a third discontinued the treatment because of the drug's side effects.

• The sample was small, containing fewer than 30 participants.
• No control group was used. 
• The drop-out rate was high. 
• At baseline patients' severity of depressive symptoms at baseline varied.

Slow up-titration is better tolerated and may support patient compliance.

A large proportion of patients had side effects that caused them to discontinue treatment. In the general population, side effects from antidepressants are associated with discontinuation of treatment. In patients with cancer who may already have significant symptom burden, the benefits of antidepressant treatment need to be considered in this context.

Among patients with cancer, it is not yet clear which patients actually benefit from medication to counter depressive symptoms.

To compare the effectiveness of two psychotropic medications, mirtazapine and imipramine, on distressing somatic symptoms (i.e., pain, nausea, vomiting, decreased appetite, and sleep disturbance) of cancer as well as symptoms of depression and anxiety.

Patients self-selected to receive psychotropic medication and supportive psychotherapy (intervention group) or supportive psychotherapy only. Those who elected to take medication were randomly enrolled to receive mirtazapine or imipramine. Mean dosage of mirtazapine ranged from 5 to 30 mg/day, depending on the visit. Mean dosage of imipramine ranged from 5 to 100 mg/day, depending on the visit. Each group was then assessed at three visits:  baseline and three and six weeks after therapy had begun.

• The sample was comprised of 53 patients with cancer (35%–38.5% male, 61.5%–65% female).
• Median age was 43 to 47.5 years (range 26–56).
• All cancer types were included; no information about cancer stage was provided. 
• In each group, median time since diagnosis ranged from 6.5 to 8 months.
• All patients had an additional psychiatric diagnosis. All had cancer; were undergoing chemotherapy; and had been diagnosed with major depressive disorder, adjustment disorder, and/or anxiety disorder.

• Single site
• Outpatient
• Large oncology research and training hospital in Turkey

Patients were undergoing the active treatment phase of care.

The study used a prospective, repeated measures design.

• Patient sociodemographic information    
• Pain, nausea, and vomiting (evaluated by single-symptom scale)
• Weight
• Appetite (evaluated by single item)
• Hamilton Rating Scale for Depression (HRSD) (three items to assess sleep disturbance)
• Hospital Anxiety and Depression Scale (HADS), Turkish version

• Among the three visits, no significant differences were observed with regard to the degree of pain, nausea, vomiting, or appetite in the mirtazapine, imipramine, and control groups, and nor did differences exist in terms of the scores relating to the degree of pain, nausea, vomiting, appetite, weight, or insomnia, among the mirtazapine, imipramine, and control groups.
• In the mirtazapine group, the initial, middle, and late insomnia scores improved between the first and second and first and third visits. In the control and imipramine groups, no significant change occurred in insomnia scores between visits.
• In the imipramine group, a significant difference was seen in weight at the three visits. Median weight decreased from the second to third visit.
• In the mirtazapine group, statistically significant differences were noted in the mean total, anxiety, and depression HADS scores at each visit. Especially notable were score changes between the first and second visit. In the imipramine and control groups, no differences were found in the total, anxiety, and depression HADS scores across visits. 

Mirtazapine is effective in resolving insomnia and in reducing the symptoms of anxiety and depression in patients with cancer who have depression, anxiety, or adjustment disorders.

• The study had a small, heterogeneous sample, with less than 100 patients.
• The study had a high drop-out rate; by six weeks, 10 of 20 patients had dropped out of the control group, 4 of 20 had dropped out of the mirtazapine group, and 4 of 13 had dropped out of the imipramine group.
• The study had no control group or random assignment and presented no information about confounding factors. 
• Patients were not controlled for use of concomitant medications to treat the somatic symptoms being evaluated.

Mirtazapine may be useful in treating anxiety, depression, and insomnia in patients undergoing chemotherapy for cancer who have clinically relevant anxiety or depression. More systematic research, such as placebo-controlled studies, is required.

To evaluate the risk-benefit profile of the use of mirtazapine for the treatment of depression in patients with cancer

Patients were enrolled who presented for psychiatric evaluation and treatment of depression and met DSM-IV criteria for major depression (HAM-D-17 score > 18). Patients started a drug therapy of mirtazapine, 15 mg/day day orally; the dose was increased to 30 mg/day in the fourth week of therapy if patients were not responding and had no adverse effects. All patients continued receiving the minimum dose for 24 weeks, but the use of other medications was not controlled. Patients were assessed at the initial visit and at the end of weeks 4, 12, and 24. Adverse effects were noted during routine assessments.

• A total of 19 patients completed 24 weeks of follow-up and evaluation for treatment efficacy.
• The mean age was 55.47 (SD = 11.04; range = 22–69 years).
• 12 patients were female and 7 were male.
• Various types of cancer were represented, including breast, brain, gynecologic, liver, hematologic, and larynx/nasopharynx.
• The study states that most had advanced cancer, but stages were not reported.
• Most patients were receiving some form of cancer treatment (e.g., chemotherapy, radiation therapy, tamoxifen). Five patients were not receiving any cancer treatment during the study period.

• Unspecified but assumed to be outpatient
• Turkey

Active treatment

Open-label (no blinding) longitudinal study

• 17-item Hamilton Rating Scale for Depression (HAM-D-17)
• Clinical interview by psychiatrist
• Routine blood tests (heme panel and biochemistry) performed weekly during the first 12 weeks of therapy, then monthly

Clinical efficacy was defined as a greater than 50% reduction in HAM-D-17 scores (defined as a positive treatment response). Patients with HAM-D-17 scores of 8–18 were defined as partial responders. Patients with HAM-D-17 scores less than 8 and a period of at least two months without significant symptoms of depression met the criteria for remission. All patients obtained at least a 50% reduction in HAM-D-17 scores, which improved from baseline to one month and were maintained for the duration of the study (24 weeks) (p < 0.001). HAM-D-17 scores significantly decreased from baseline to one month (p < 0.001). The drug was well tolerated, and no one required discontinuation of therapy. Minimal adverse effects were reported, including mild to moderate hand tremor, fatigue, weight gain, and restless leg syndrome.

The study provides preliminary evidence that (open-label) the drug mirtazapine is safe, efficacious, and tolerated.

• The sample was small, containing fewer than 30 participants.
• The study was open-label, with no placebo control.
• The potential for selection bias existed.
• The findings could be confounded by the lack of control over the type of cancer therapy and the time lapse since cancer treatment.

This particular agent may have antiemetic effects, which may be desirable in this patient population, and it had a minimal side-effect profile. Future research should include a randomized, controlled trial examining mirtazapine versus selective serotonin reuptake inhibitors in this patient population.

To observe the longitudinal effects of antidepressant medication in a cohort of patients with advanced cancer

Of the 628 patients with advanced cancer in the study, 25% were receiving antidepressants for a median of 9.5 weeks. Patients were followed for six months or until death. Consecutive patients in the daycare unit were eligible for inclusion. Patients completed study assessments at baseline and at eight, 16, and 24 weeks. A patient self-report was used to identify patients taking antidepressants.

• N = 628  
• AVERAGE AGE = 66
• MALES: 33%, FEMALES: 67%
• KEY DISEASE CHARACTERISTICS: Advanced cancer; any tumor type
• OTHER KEY SAMPLE CHARACTERISTICS: Enrolled in hospice

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Hospice day units, northwest England

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Elder care and palliative care 

Observational

• Patient Health Questionnaire (PHQ-9) 
• Edinburgh Depression Scale (EDS)

Patients who stated that they took antidepressants had significantly higher depression scores on both measures. A subgroup analysis was completed for those with the highest PHQ-9 scores, assuming that effects might be seen in those with greater depression levels. However, there were no differences in results between those taking and not taking antidepressants.

The observational findings of this study suggest that antidepressant medication had little impact in reducing depression scores for patients attending Hospice daycare service.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Other limitations/explanation: Hospice day treatment; other treatments in use as well as antidepressants; difficult to determine what was the cause of change; patient self-report only used to identify those taking antidepressants and was not corroborated with medical records or any other source information

This observational study did not show that antidepressants reduced depression among patients receiving Hospice care. However, there were several study design and measurement limitations. The role and effectiveness of antidepressants may vary among patients at different phases in the trajectory of cancer.

To determine whether prophylactic use of the antidepressant escitalopram oxalate would decrease the incidence of depression in patients receiving primary therapy for head and neck cancer

Patients were randomized and stratified by sex, site, stage (early vs. advanced), and the primary means of treatment (radiation or surgery). During the study, patients received either escitalopram or placebo. This was dosed at one tablet (10 mg if escitalopram) and increased by one tablet during the second week. This was the study dose until week 16. At this point, all patients were “weaned” by 10 mg per week, then “medication” was discontinued. Patients were reassessed at 20, 24, and 28 weeks.

• N = 125 
• MEAN AGE: 63.5 years
• MALES: 118 (79.7%), FEMALES: 30 (20.3%)
• KEY DISEASE CHARACTERISTICS: Newly diagnosed head and neck cancer (newly diagnosed or recurrent stage II–IV epidermoid cancer of head and neck)
• OTHER KEY SAMPLE CHARACTERISTICS: Patient must be willing to participate and must be non-depressed (excluded if cognitively impaired, had advanced cancer or limited life expectancy of less than six months, met diagnostic criteria for mental illness, or undergoing treatment for depression or anxiety).

• SITE: Multi-site  
• SETTING TYPE: Outpatient   
• LOCATION: Nebraska Methodist Cancer Center, University of Nebraska Medical Center

PHASE OF CARE:  Active antitumor treatment

APPLICATIONS: Elder care, palliative care

Randomized, double-blind, placebo-controlled

• Quick Inventory of Depressive Symptomology-Self Rated (QIDS-SR)
• Mini-International Neuropsychiatric Interview (MINI)
• Quick Inventory of Depressive Symptomology-Clinician (QIDS-C)

Prophylactic escitalopram reduced the rate of depression in patients with head and neck cancer undergoing treatment. Rate of depression was 10% with escitalopram and 24.6% among those on placebo (p = .04). The rate of depression was significantly higher in patients receiving radiation as their primary therapy as compared to  surgery. Those patients who received drug reported better overall and health-related quality of life throughout the trial and during three consecutive months following drug cessation. Due to unacceptable side effects of medication, 12.8% withdrew from the study.

Escitalopram used in the setting of head and neck cancer immediately following diagnosis can have a positive effect on depression, possibly preventing depression from occurring. It also positively affects quality of life and ability to cope with cancer treatments, possibly enabling patients to continue with treatments.

Subject withdrawals ≥ 10%

Nurses do not have influence as to what the practitioner prescribes for patients (i.e., escitalopram). However, they can suggest it to practitioners. Some oncology practitioners are reluctant to prescribe anti-depressants, as they feel that this is outside their scope of practice. However, consideration is also generally recommended in professional guidelines. Depression may be underdiagnosed in patients with cancer; nurses can advocate for patients by raising attention to the problem in clinical practice. Initial and ongoing assessments for this patient population is imperative based on the high risk for depression. Results should be reported to the provider so patients who are exhibiting signs of depression can be addressed.

To determine whether prophylactic treatment with the antidepressant citalopram hydrobromide can prevent major depression in patients undergoing treatment for head and neck cancer

The intervention consisted of 40 mg citalopram hydrobromide (a selective serotonin reuptake inhibitor). Medication began with 20 mg/day for week 1 and increased to 40 mg/day until week 12; after week 12, the dosage decreased to 20 mg/day for one week and then the drug therapy was stopped. Data were collected at baseline and at weeks 4, 8, 12, and 16 as well as at any time during the study.

• A total of 23 patients participated in the study (13 in the intervention group and 10 in the control group).
• Mean patient age was 61 years. The age range was 43–81 years.
• Eleven patients were female, and 12 were male.
• Patients were diagnosed with head and neck cancer only, mostly stage III or IV.
• No group differences existed in patients' age or sex, in tumor grade or type, in location of cancer, or in the number of treatment modalities.
• Patients began cancer treatment (surgery and/or radiation with or without chemotherapy) at baseline.

• Single site
• Outpatient
• Nebraska

Active treatment

Prospective, randomized, placebo-controlled trial with double blinding

• Hamilton Rating Scale for Depression (HRSD)
• Psychiatric interview using Mini-International Neuropsychiatric Interview I (MINI) for depression
• University of Washington disease-specific Quality-of-Life Questionnaire (UW-QOL)
• Clinician Global Impression-Severity (CGI-S) scale for global assessment of depression severity

During the 12 weeks of the study, 5 out of 10 taking the placebo and 2 out of 12 taking citalopram met the cutoff criteria for depression (measured by HRSD). However, the difference was statistically insignificant (Fisher exact test, p = 0.17). At the end of the study, of those receiving citalopram 15% were at least mildly ill in terms of global mood state as measured by the CGI-S scale; 60% of those in the control group were at least mildly ill as measured by the same means. Quality of life, measured by the UW-QOL, deteriorated in both groups from baseline to week 16, but less deterioration occurred in the citalopram group (p = 0.14).

Prophylactic treatment with citalopram hydrobromide may decrease the incidence and severity of depression during head and neck cancer therapy.

• The sample size was small, with fewer than 30 participants.
• Because of the small sample size and the inclusion of subjects from only one setting, the external validity and detection of intervention effect may be skewed.
• A priori sample estimation was set at N = 80, and the sample size of this study was much smaller. (Personnel factors led to early conclusion of the study.) As a result, researchers were unable to draw meaningful conclusions.

The risk of major depressive disorder can be very high in patients with head and neck cancer who are undergoing active treatment. Prevention of depression may be an attainable goal, although more research in this area is needed.

Patients with malignant melanoma received paroxetine or a placebo two weeks prior to initiation of interferon alfa, continuing for the first 12 weeks of therapy. Study tablets contained 10 mg paroxetine; both groups took one tablet daily for a week, followed by 2 tablets daily for a week. Two weeks after the initiation of interferon alfa (four weeks after beginning paroxetine or placebo), the dosage of the study medication could be increased up to four tablets per day at the discretion of the study psychiatrist. The average number of tablets at the maximal dose for each group was 3.1. Patients were evaluated at baseline and at regularly scheduled intervals for the first 12 weeks of therapy.

40 adult patients with malignant melanoma that had been resected but was estimated to have a greater than 50% chance of recurrence

Single site

Randomized, double-blind study

• Hamilton Rating Scale for Depression
• Carroll Rating Scale for Depression
• Hamilton Rating Scale for Anxiety
• Neurotoxicity Scale

• Major depression symptoms developed in 2 of 18 patients (11%) in the paroxetine group  and 9 of 20 (45%) in the placebo group.
• Paroxetine treatment significantly decreased the likelihood that interferon alfa therapy would have to be discontinued because of severe depression.

The sample size was small. One disease group and one site were involved in the study.

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.

To investigate the effectiveness and tolerability of open-label treatment with escitalopram in patients with breast cancer who have major depressive disorder

Patients received escitalopram at 5 mg/day in week 1. After week 1, the dose was adjusted to 5–20 mg/day. Patients were evaluated at baseline, 1, 2, 4, 8, and 12 weeks.

• A total of 79 patients participated in the study. 
• Patients' mean age was 49.1 years.   
• The sample was 100% female.
• All patients had a breast cancer diagnosis.
• Patients met the criteria for a current major depressive episode and scored 16 or higher on the Hospital Anxiety and Depression Scale.
   

Outpatient settings in the Republic of Korea
 

Transition phase after initial treatment

Prospective study

• Hamilton Depression Rating Scale (HAMD) 
• Functional Assessment of Cancer Therapy Breast (FACT-B)
• MD Anderson Symptoms Inventory
• Clinical Global Impression-Severity (CGI-S)
• Distress Thermometer (DT)
   

62 patients were included in the efficacy analysis, and only 45.6% completed the full 12-week study. Dropouts occurred because of lack of efficacy, no symptom improvement, side effects, and unspecified reasons. 34% of the sample dropped out due to lack of effectiveness or no change in symptoms.

Significant decreases were seen at week 1 and forward in HAMD (p < 0.001), DT (p < 0.001), and CGI-S (p < 0.003). FACT-B scores improved after week 2 (p = 0.011). No differences were observed in baseline scores between responders and nonresponders.

No serious adverse events were reported. The most common side effects were dry mouth, drowsiness, constipation, and increased sweating. Sleep disturbance, shortness of breath, and sadness were improved, but pain, fatigue, and anorexia did not improve.

Escitalopram reduced depression in some patients with breast cancer who had major depressive disorder.

• The sample size was small, fewer than 100 participants.
• No control group was used, and the study had an open-label design. 
• The drop-out rate was more than 30% because of lack of effect. 
• The study was, as the authors said, \"underpowered.\"
   

Escitalopram may be an effective treatment for symptoms of depression in some patients with breast cancer; however, about a third of patients in the study did not experience an effect. Nurses should be aware of side effects that may worsen existing symptoms.

To investigate the safety and efficacy of fluvoxamine to treat anxiety and depression in patients with gynecologic cancer

For eight weeks patients were treated with escalating doses:

• Week 1: 25 mg once daily
• Week 2: 50 mg once daily
• Week 3: 50 mg twice daily
• Week 4: 50 mg three times daily
• Week 5 and onward: Dosing varied according to each patient's condition. 

Subjects were evaluated at two, four, six, and eight weeks.

• The study reported on a sample of 10 female patients.
• Median patient age was 53 years, with a range of 33–66 years.
• All patients had gynecologic cancers and were diagnosed at least two weeks prior to study entry.
• All patients had a HADS score of at least 11, indicating clinically relevant conditions. Mean HADS score was 19.
• Five patients had a diagnosed adjustment disorder, and five patients had major depression.

• Single site
• Setting not specified
• Japan

Patients were undergoing active antitumor treatment.

Prospective trial design 

• Hospital Anxiety and Depression Score (HADS)
• Short Form 36 Health Survey (SF-36)

Compared to HADS anxiety and depression scores at baseline, the scores were significantly lower after four weeks of treatment (p < 0.05) and remained significantly lower. After eight weeks, researchers noted significant improvements in SF-36 scores for vitality, mental health, and emotional role functioning (p < 0.05). No adverse effects of treatment were reported.

Fluvoxamine treatment of patients with gynecologic cancer who had clinically relevant anxiety and depression appears to reduce anxiety and depression. The small study sample precludes firm conclusions.

• The sample size was small, with fewer than 30 participants.
• The study had risks of bias because it had no control group, no blinding, and no random assignment.
• All patients had, at baseline, significant depression and anxiety, so findings cannot be generalized to patients with levels of these symptoms that are not clinically relevant. The follow-up period was only eight weeks; longer-term safety and efficacy are unknown.

Fluvoxamine as provided appeared to be effective in management of clinically relevant anxiety and depression in women with gynecologic cancer. Studies of anxiety and depression are often done with patients who do not have clinically significant problems in these areas at baseline, often making findings nonsignificant. This study provided some support for effective use of medication in patients with clinically relevant levels of anxiety and depression. The sample was very small, and the study design had multiple risks of bias. To determine which groups of patients can benefit from treatment, larger, well-designed trials are warranted.

To investigate the efficacy and tolerability of duloxetine in patients with cancer with mood disorder

Consecutive patients with diagnosed mood disorder started a regimen of duloxetine. They received an initial dose of 30 mg/day for one week, then 60 mg daily. If response was poor after one month, the dose was increased to 120 mg. Benzodiazepines were allowed as needed during the first two weeks. Study assessments were done at baseline, week 4, and week 12. Analysis compared results pertaining to those who had cancer and to those who did not.

• The study reported on a sample of 37 patients, 23 with cancer.
• Mean patient age was 63.6 years (SD = 10.9 years).
• The sample was 44.7% male and 45.3% female.
• Cancer types were not reported.

• Single site
• Outpatient setting
• Italy

Prospective observational design

• Hospital Anxiety and Depression Scale (HADS)
• State-Trait Anxiety Inventory
• EORTC questionnaire

Overall, 20% of patients dropped out of the study. Of the patients with cancer, 15% dropped out due to agitation, insomnia, or tachycardia. Analysis showed similar response over time of those with and without cancer diagnoses. Depression and anxiety by all measures declined at all follow-up times (p < 0.001).

Duloxetine was effective in reducing anxiety and depression in patients with and without cancer. The majority of patients tolerated the medication well.

• The study had small sample sizes, with samples of fewer than 30 and fewer than 100, respectively.
• The study had risks of bias due to no control group, no blinding, and no random assignment.
• Participant withdrawals were ≥ 10%.

Findings suggest that antidepressant use by patients with cancer who also have clinically relevant mood disorders can improve symptoms of anxiety and depression. Note: Most antidepressant studies that show a positive impact involve use by patients who have clinically relevant mood disorders at baseline.

To examine the effectiveness and safety of sertraline on somatic and emotional symptoms of depression and on the quality of life of cancer patients

The intervention was a 12-week trial with a flexible-dose regimen of sertraline (a selective serotonin reuptake inhibitor). Patients started the regimen with a dose of 25 mg/day, with a possible increase to 100 mg/day. The treatment response was assessed at baseline (T0), at week 4 (T1), and at week 12 (T2).

• N = 35.
• Mean age = 51.97 (SD = 13.26; 23–72 years).
• 30 female, 5 male.
• Cancer type and stage: diverse. Majority: breast cancer (54%).
• All patients underwent chemotherapy during the study and were diagnosed with mood disorder at baseline.

Single site (outpatient)

Active treatment

Open-label noncomparative prospective pilot study

• Hospital Anxiety and Depression Scale (HADS) for depression and anxiety
• Montgomery-Asberg Depression Rating Scale (MADRS) for depression
• Mini-Mental Adjustment to Cancer (mini-MAC) scale for psychological response to the diagnosis of cancer
• Clinical Global Impression (CGI) for severity of psychological illness
• Dosage Record and Treatment Emergent Symptom (DOTES) scale for the adverse effects of the clinical treatments and their possible relation to the drug used
• Quality of Life (QL) index for quality of life

Mean daily dose of sertraline was 57.50 (±18.74) mg at T1 and 57.41 (±18.10) mg at T2. Both mean depression scores, HADS and MADRS, and HADS anxiety scores significantly decreased during the 12 weeks of the study (all p's < 0.05). Mean mini-MAC scores show that hopelessness and anxious preoccupation decreased significantly at T2, compared with scores at T0 (p < 0.05). Quality of life improved over time (p < 0.05). CGI improved over the treatment period; however, no statistical tests were involved. No severe adverse effects were observed. 6 patients reported varying degrees of side effects (e.g., nausea, agitation, insomnia, dizziness).

Sertraline may be effective; a more definitive conclusion requires stronger evidence.

• Small sample: < 100.
• Internal validity is limited because of the lack of a control group, the lack of control over the lapse of time since the beginning of cancer therapy, and the small sample size.
• External validity is limited because the sample size was small and testing occurred in one setting only.
• Minor flaws include lack of information regarding measurements of validity and reliability.

Nurses can tell patients that sertraline may be an option in the treatment of symptoms of depression during chemotherapy.

The guideline provides an algorithm for the screening and assessment of anxiety, a care map for anxiety in adults with cancer, an algorithm for the screening and assessment of depression, a care map for depression in adults with cancer, the Patient Health Questionnaire (PHQ 9) symptom depression scale and generalized anxiety disorder (GAD) items, and selected measures for depression and anxiety (modified).

• Before the implementation of guidelines, referral systems and resources should be identified and available in each institution.
• The guidelines are designed for healthcare providers, patients, family members, and caregivers to guide in the screening, assessment, and treatment approaches of adult patients with cancer who have anxiety and depression at any stage of the cancer continuum, regardless of cancer type, disease stage, or treatment modality. 
• All patients with cancer and cancer survivors should be evaluated for the symptoms of anxiety and depression with validated instruments at periodic times during the cancer care. Treatment recommendations are based on the levels of symptoms. Follow-up care and reassessment are important in this setting to monitor for follow-through, compliance with referrals, and pharmacologic management. If compliance is poor, develop a plan. After eight weeks of treatment, if symptoms are not improved or poor compliance is noted, alter the treatment course and add a psychological or pharmacologic intervention. The guidelines recommend that individual psychological interventions be delivered by a licensed mental health professional, which may include cognitive and behavioral strategies, education and relaxation strategies, group psychosocial interventions, and physician-prescribed antidepressants. 

• A guideline that has been adapted from another country often can't lend itself to different policies or cultural influences.
• Some of the recommendations were removed from the original guideline because of references to the Edmonton Symptom Assessment Scale screening measure, which is not widely used in the United States.

Nurses play a vital role in the early screening, assessment, and treatment of patients who may have significant symptoms of anxiety and depression. By screening and making appropriate referrals, we can impact the emotional, interpersonal, and financial costs for patients and reduce the economic impact for providers and the healthcare system.

RESOURCE TYPE: Evidence-based guideline

PHASE OF CARE: Multiple phases of care

Several clinical practice guidelines and two meta-analyses of 21 RCTs and some integrative reviews were included. Guideline quality was assessed with the AGREE II instrument, and a systematic review quality was assessed with the Assessment of Multiple Systematic Reviews (AMSTAR) tool.

• Screening of patients with cancer for depression is very important to guide treatment.
• Psychoeducation and providing information about the nature of depression and its impact in cancer outcomes are important. Optimizing cancer-related symptom management
• Pharmacologic or psychosocial interventions either alone or in combination have beneficial effects.
• A stepped care model that suggests low intensity interventions (i.e., physical activity programs, group-based peer support, and self-help programs) for mild -to-moderate depression and high-intensity interventions (i.e., group cognitive behavioral therapy, behavioral couples’ therapy, and individual or group supportive-expressive psychotherapies) for severe depression were recommended.
• Collaborative care (active collaboration between the oncologist or primary care provider and a patient care manager nurse, social worker, or psychologist) should be considered.
• Referral to psychosocial specialist when needed
• Selection of psychological therapy should be based on patient factors and local resource availability. This recommendation is based in consensus. 
• Antidepressants should be considered for severe depression, not for mild depression related to high risk–benefit ratio.

Some recommendations were consensus-based.

A quick reference algorithm for the initial management of depression in patients with cancer and the stepped care model for delivering care interventions depending on the severity of depression are great tools nurses and other healthcare professionals can use in their clinical practice while managing depression.

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.

PHASE OF CARE: Late effects and survivorship

All recommendations were based on lower level evidence and consensus.

Physical activity and memory aids were recommended for cognitive impairment. SSRIs and SNRIs were recommended for depression as first-line treatment, and benzodiazepines were recommended as first-line treatment for anxiety. Physical activity, cognitive behavioral therapy, psychoeducation, and the consideration of psychostimulants were recommended for fatigue.

• Mainly consensus for most recommendations
• Limited database use  
• Full results of search not provided

This guideline gave numerous recommendations and suggestions for various aspects of patient needs. Most recommendations were consensus-based.

Comprehensive, evidence-based guidelines were developed to assist healthcare professionals in providing optimal psychosocial care. The guidelines are multidisciplinary in focus, with recommendations applicable to diverse treatment settings.

Evidence was presented using levels I, II, III-1, III-2, III-3, and IV rating system with level I representing the gold standard.

 Clinically relevant recommendations supported by level I and II evidence about depression include the following.

• Referring high-risk patients to specialized psychological services to minimize the likelihood of developing significant distress (level I)
• Using a range of psychoeducational interventions to decrease distress (level I)
• Managing depression by incorporating a combination of supportive psychotherapy, cognitive and behavioral techniques, and pharmacotherapy (levels I, II)
• There is no evidence that any particular antidepressant is superior to another in the management of depression in people with cancer (level I).
• Other therapies that may improve depression are art, music, painting, reading, poetry, wellness programs, meditation, hypnosis, acupuncture, relaxation, exercise, prayer, and laughter. (levels I, II, III-3, IV).

The treatment of depression should incorporate psychotherapeutic interventions and the use of medication.

Evidence of the efficacy of antidepressant medication in treating depression in patients with cancer is clear.

No evidence suggests that any particular antidepressant is superior to another.

• The sedating properties of tricyclics may be beneficial to some patients, as may their potentiation and enhancement of opioid analgesia in those with pain.
• Their anticholinergic side effects may aggravate stomatitis, exacerbate constipation, and affect cardiac rhythm.
• Patients with cancer may respond to a lower dose of tricyclic antidepressants.
• Selective serotonin reuptake inhibitors have been demonstrated to be effective in treating depression in patients with cancer.
• The long half-life of fluoxetine makes it less desirable in patients with hepatic or renal dysfunction where sertraline or paroxetine is preferable.

Objectives were to

• Present evidence that will contribute to the improvement of palliative care at the end of life.
• Answer questions regarding critical elements.
• Identify patients who could benefit from palliative approaches.
• Identify treatment strategies that work for pain, dyspnea, and depression.
• Identify elements important in advance care planning, collaboration and consultation, and assessment and support aspects helpful to caregivers.

Included were patients with any disabling or symptomatic condition at the end of life.

The guideline was based on a systematic evidence review, done by others, in an Agency for Healthcare Research and Quality evidence report. The guideline does not address nutritional support, complementary and alternative therapies, or spiritual support because evidence related to these areas does not often appear in the literature. Specific procedures for grading the evidence and recommendations are not described.

The guideline was developed for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Evidence and recommendations were graded using the clinical practice guidelines grading system (GRADE).

Databases searched were MEDLINE and the Database of Abstract Reviews of Effects (January 1990–November 2005); citations from the review by the National Consensus Project for Quality Palliative Care (2003) also were searched.

Search keywords were cancer, congestive heart failure, and dementia. The full description of search terms is published elsewhere.

The guideline outlines the strength of GRADE recommendations and includes a brief description of the supporting evidence for each recommendation.

Critical Elements for End-of-Life Care: Elements identified are preventing and treating pain and other symptoms; supporting families and caregivers; ensuring continuity of care; ensuring respect for patients as people and informed decision making; ensuring well-being, including consideration of existential and spiritual concerns; and supporting function and duration of survival.

Identifying Patients Who Could Benefit From Palliation: No evidence tools have been validated or effectively shown to predict optimal timing. Decisions should be based on each patient's symptoms and preferences.

Treatment Strategies:

• Pain
  • Evidence is strong in support of the use of nonsteroidal anti-inflammatory drugs, opioids, bisphosphonates, and radiotherapy or radiopharmaceuticals for pain, with bisphosphonates used for bone pain specifically.
  • Insufficient evidence exists to evaluate the usefulness of acupuncture or exercise for pain control.
  • Palliative care teams may be moderately beneficial in providing pain management.
• Dyspnea
  • Evidence shows a valuable effect of morphine.
  • Nebulized opioids show no additional benefit over oral opioids.
  • Evidence regarding the use of oxygen is equivocal.
  • Studies that evaluated facilitated communication or palliative care consultation showed no effect.
• Depression
  • Evidence suggests that long-term use of tricyclic antidepressants, selective serotonin reuptake inhibitors, and psychosocial interventions are beneficial for patients with cancer who are depressed.
  • Evidence is mixed regarding the benefit of guided imagery and exercise in the defined patient population.
  • Evidence showed that care coordination had no effect.

Important Elements for Advance Care Planning: Evidence shows that extensive multicomponent interventions, goal-oriented interviews with palliative care providers, and proactive communication involving skilled discussants can reduce unnecessary services, without causing harm, and increase the use of advance directives.

Collaboration and Consultation: Use and patient-centered outcomes improve when multidisciplinary teams include nurses and social services providers, address care coordination, and use facilitated communication.

Supporting Caregivers: Evidence regarding the effects of palliative care teams for caregivers is mixed.

The following were graded as strong recommendations with moderate quality of evidence.

• Patients with serious illness at the end of life should be regularly assessed for pain, dyspnea, and depression.
• For patients with cancer, clinicians should use therapies with proven effectiveness to manage pain. These therapies include nonsteroidal anti-inflammatory drugs, opioids, and bisphosphonates.
• Clinicians should use therapies with proven effectiveness to manage dypsnea. These therapies include opioids (for unrelieved dyspnea) and oxygen (for the relief of short-term hypoxemia).
• Clinicians should use therapies with proven effectiveness to manage depression in patients with cancer. These therapies include tricyclic antidepressants, selective serotonin reuptake inhibitors, and psychosocial interventions.
• Clinicians should ensure that advance care planning occurs for all patients with serious illness. Such planning includes the preparation of advance directives.

• Several authors had grants from the Agency for Healthcare Research and Quality or pharmaceutical companies.
• Financial support for this guideline was entirely from the American College of Physicians.

The guideline provides clear guidance in several areas of end-of-life care and symptom management and identifies the relevant evidence and strength of the evidence. The guideline may not apply to all patients and is not intended to override clinical judgment. In addition to recommending medication interventions for depression, the guideline recommends psychosocial interventions.