Depression is a comorbid disabling syndrome that affects approximately 15% to 25% of cancer patients.[
Definitions: Depression is suspected when a number of specific symptoms are observed (affect, sleep disturbance, thought patterns). These are specified in the categorization of psychiatric/behavioral disorders in the Diagnostic and Statistical Manual of Mental Disorders, 4th and 5th editions.[
Assessment and management of these symptoms require an understanding of the various pathways and the evidence-based treatment options.
Normally, a patient's initial emotional response to a diagnosis of cancer is brief, extending over several days to weeks, and may include feelings of disbelief, denial, or despair. This normal response is part of a spectrum of depressive symptoms that range from normal sadness to adjustment disorder with depressed mood to major depression.[
Possible Medical Causes of Depressive Symptoms in People With Cancer
A survey in England of women with breast cancer showed that among several factors, depression was the strongest predictor of emotional and behavioral problems in their children.[
Just as patients require ongoing evaluation for depression and anxiety throughout their course of treatment, so do family caregivers. In a study of family caregivers of patients in the palliative phase of illness, both male and female caregivers experienced significantly more anxiety than did a sample of non-caregivers, while there was an increased incidence of Hospital Anxiety and Depression Scale–defined depression among women.[
There are many myths about cancer and how people cope with it, such as the following:
Some people may have more difficulty adjusting to the diagnosis of cancer than others do and will vary in their responses to the diagnosis. Sadness and grief are normal reactions to the crises faced during cancer. All people will experience these reactions periodically. Because sadness is common, it is important to distinguish between normal degrees of sadness and depressive disorders. An end-of-life care consensus panel review article describes details regarding this important distinction and illustrates the major points using case vignettes.[
Major depression is not simply sadness or a blue mood. Major depression affects approximately 25% of patients and has recognizable symptoms whose diagnosis and treatment are essential because they have an impact on quality of life.[
Depression and anxiety disorders are common among patients receiving palliative care and contribute to a greatly diminished quality of life in these patients.[
Participants diagnosed with a depressive or anxiety disorder had the following characteristics:
They also reported more severe distress about physical symptoms, social concerns, and existential issues, suggesting significant negative impact on other aspects of their quality of life.[
The importance of psychological issues was underscored by another study conducted in terminally ill cancer patients (n = 211) with life expectancies of less than 6 months.[
In multiple regression analysis, four variables predicted perception of burden to others:
No association between sense of burden to others and actual degree of physical dependency was found, implying that this perception is mainly mediated through psychological distress and existential issues. A subanalysis of patient groups from different settings suggested that these findings were consistent across the inpatient and outpatient settings, with some minor variations.[
The emotional response to a diagnosis of cancer (or cancer relapse) may begin as a dysphoric period marked by increasing turmoil. The individual will experience sleep and appetite disturbance, anxiety, ruminative thoughts, and fears about the future. Epidemiological studies, however, suggest that at least one-half of all people diagnosed with cancer will successfully adapt.
Markers of successful adaptation to a diagnosis of cancer include the following:[
Some studies suggest an association between maladaptive coping styles and higher levels of depression, anxiety, and fatigue symptoms.[
One study conducted in a group of 86 mostly late-stage cancer patients suggested that maladaptive coping styles and higher levels of depressive symptoms are potential predictors of the timing of disease progression.[
Preliminary data suggest a beneficial impact of spirituality on associated depression, as measured by the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being questionnaire and the Hamilton Depression Rating Scale.[
The following indicators may suggest a need for early intervention:
As shown by a study of adult cancer patients (n = 48) and their adult relatives (n = 99), family functioning is an important factor that impacts patient and family distress. Families that were able to act openly, express feelings directly, and solve problems effectively had lower levels of depression, and direct communication of information within the family was associated with lower levels of anxiety.[
Risk factors may be different, especially pain and other physical symptoms.[
Evidence-based recommendations have described various approaches to the problems of cancer-related fatigue, anorexia, depression, and dyspnea.[
The pathophysiology of cancer-related depression remains unclear and probably encompasses many mechanisms. A study of patients with advanced metastatic cancer showed that both plasma interleukin-6 (IL-6) concentrations and hypothalamic-pituitary-adrenal axis dysfunction were markedly higher in patients with clinical depression.[
Although the etiology of depression is largely unknown, many risk factors for depression (such as those listed below) are known.
In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.
Symptoms and Risk Factors
There are two major classifications of symptoms for major depression: neurovegetative and emotional-cognitive. In cancer patients whose neurovegetative symptoms may be affected by the disease process or treatment, assessing the emotional-cognitive symptoms of their depression is likely to be more diagnostic and prevent false-positive results. Symptoms include the following:
Cognitive symptoms may express themselves as repeated and ruminative thoughts such as "I brought this on myself," "God is punishing me," or "I'm letting my family down," and as fatalistic expectations concerning prognosis, despite realistic evidence to the contrary. Such thinking may predominate or may alternate with more realistic thinking, yet remain very stressful. Some individuals will share negativistic thoughts freely, and family members may be aware of them. Other patients will not volunteer such thinking but will respond to brief inquiries such as the following (other examples are listed in Table 1):
It is possible for a physician or nurse to ask these types of questions without becoming engaged in providing counseling themselves. Merely asking these questions will express concern and increase the likelihood that the patient will be receptive to suggestions for further counseling.
These questions can be followed by a statement such as, "Many people with cancer sometimes have these feelings. You are not alone. But talking to someone else about them can greatly help. I'd like to suggest that you consider doing that. Would you be willing to talk to someone who has a lot of experience helping people cope with the stress of having cancer?"
It is preferable at this time both to encourage patients to seek out someone already known to them and to inform them about other resources in the community. Particularly for patients who have completed cancer treatment and who have manageable physical symptoms, higher perceived availability of social support has been associated with fewer depressive symptoms.[
Evaluation of depression in people with cancer includes careful assessment of the following:
Limited data suggest that depressive symptomatology in cancer patients undergoing cytokine therapy with interferon-alfa and interleukin-2 may be mediated by changes in availability of neurotransmitter precursors.[
A prospective study of terminally ill Japanese patients who were assessed for psychiatric illness by structured clinical interview at the time of registration (baseline) and again at admission to a palliative care unit (follow-up) found that 5 (42%) of the 12 patients diagnosed with adjustment disorder at baseline progressed to major depression at follow-up. Only the Hospital Anxiety and Depression Scale (HADS) was significantly predictive of psychiatric diagnoses at follow-up.[
Screening and Assessment for Depression
Because of the common underrecognition and undertreatment of depression in people with cancer, screening tools can be used to prompt further assessment.[
The following screening tools are commonly used:
One study of women with newly diagnosed breast cancer (n = 236) successfully utilized brief screening instruments such as the Distress Thermometer and the Patient Health Questionnaire to identify women requiring further assessment to detect clinically significant levels of distress and psychiatric symptoms.[
In a study of 321 women with newly diagnosed stage I to stage III breast cancer, the ability of the single-item Distress Thermometer to specifically predict depression, as measured by a self-report questionnaire of the nine Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) symptoms for major depressive disorder, was investigated. Sensitivity and specificity characteristics were evaluated, and the optimal cutoff score of 7 was identified, resulting in a sensitivity of 0.81 and a specificity of 0.85 for detecting depression. Therefore, individuals scoring 7 or above will undergo a more thorough psychosocial evaluation.[
The Impact Thermometer, a modification of and accompaniment to the Distress Thermometer, has improved specificity for the detection of adjustment disorders and/or major depression, as compared with the Distress Thermometer. The revised tool has a screening performance comparable to that of the HADS and is brief, potentially making it an effective tool for routine screening in oncology settings.[
It is important that screening instruments be validated in cancer populations and used in combination with structured diagnostic interviews.[
In a study of 2,141 German cancer patients, the HADS and the PHQ-9 had similar sensitivity (89% and 83%, respectively) and specificity (43% and 61%, respectively) for detecting DSM-IV major depressive disorder at suggested cutoffs based on receiver operating characteristic curves.[
Other brief assessment tools for depression can be used. To help patients distinguish normal anxiety reactions from depression, assessment includes discussion about common symptoms experienced by cancer patients. Depression is reassessed over time.[
| a Adapted from Roth et al.[
|How well are you coping with your cancer? Well? Poorly?||Well-being|
|How are your spirits since diagnosis? During treatment? Down? Blue?||Mood|
|Do you cry sometimes? How often? Only alone?||Mood|
|Are there things you still enjoy doing, or have you lost pleasure in things you used to do before you had cancer?||Anhedonia|
|How does the future look to you? Bright? Black?||Hopelessness|
|Do you feel you can influence your care, or is your care totally under others' control?||Helplessness|
|Do you worry about being a burden to family/friends during cancer treatment?||Guilt|
|Do you feel others might be better off without you?||Worthlessness|
|Physical symptoms (evaluate in the context of cancer-related symptoms)|
|Do you have pain that isn't controlled?||Pain|
|How much time do you spend in bed?||Fatigue|
|Do you feel weak? Fatigue easily? Rested after sleep? Any relationship between how you feel and a change in treatment or how you otherwise feel physically?||Fatigue|
|How is your sleeping? Trouble going to sleep? Awake early? Often?||Insomnia|
|How is your appetite? Food tastes good? Weight loss or gain?||Appetite|
|How is your interest in sex? Extent of sexual activity?||Libido|
|Do you think or move more slowly than usual?||Psychomotor slowing|
Organic Mood Syndromes or Mood Syndromes Related to Another Medical Condition (MSRAMC), as they are referred to in the DSM, 5th edition (DSM-5),[
To make a diagnosis of depression, the clinician confirms that these symptoms have lasted at least 2 weeks and are present on most days. The diagnosis of depression in people with cancer can be difficult because of the problems inherent in distinguishing biological or physical symptoms of depression from symptoms of illness or toxic side effects of treatment. This is particularly true of individuals who are receiving active treatment or those with advanced disease.
The following cognitive symptoms are probably the most useful in diagnosing depression in people with cancer:
One German study comparing cancer patients who had a current affective disorder with those who had a single depressive symptom found loss of interest, followed by depressed mood, to yield the highest power of discrimination between the two groups on multivariate analysis.[
The evaluation of depression in people with cancer also includes:
More than 90% of patients indicate that they prefer to discuss emotional issues with their physician, but more than one-quarter of patients feel that the physician must initiate any discussion of that topic.[
Suicidal ideation is not uncommon among patients with cancer and, when it occurs, is frightening for the individual, the health professional, and the family. In one study of 354 health care providers working with oncology patients in Germany, 83.3% reported that they had at least one patient with suicidal ideation in the past year, and 59% reported having one to three suicidal patients annually. This experience was distressing for 88.1% of providers. In addition, over 20% of providers reported feeling overwhelmed when confronted with a suicidal patient.[
Suicidal statements may range from an offhand comment resulting from frustration or disgust with a treatment course—"If I have to have one more bone marrow aspiration this year, I'll jump out the window"—to a reflection of significant despair and an emergent situation—"I can no longer bear what this disease is doing to all of us, and I am going to kill myself." Exploring the seriousness of the thoughts is imperative. If the suicidal thoughts are believed to be serious, it is imperative that a referral to a psychiatrist or psychologist is made immediately and attention is given to the patient's safety.[
The most common form of depressive symptomatology in people with cancer is an adjustment disorder with depressed mood, sometimes referred to as reactive depression. This disorder is manifested when a person has a dysphoric mood that is accompanied by the inability to perform usual activities.[
It is also important to distinguish between fatigue and depression, which are often interrelated. The different mechanisms that give rise to these conditions can be treated separately.[
The decision to initiate therapy for depression depends on the probability that the patient will recover spontaneously in the next 2 to 4 weeks, the degree of functional impairment, and the severity and duration of the depressive symptoms.[
For the following reasons, referral of individuals for a psychiatric consultation should be considered:[
There is a dearth of randomized, placebo-controlled trials assessing the risks and benefits of antidepressants in patients with cancer and depression or depressive symptoms. Furthermore, these studies are limited by methodological challenges and a lack of broad representation of children, adolescents, older adults, and minority groups.[
A survey of prescribing patterns in outpatient oncology settings over a 2-year period found that antidepressants were prescribed for about 14% of patients.[
Because of the relative paucity of data regarding antidepressant use in oncology settings, there is considerable variability in practice patterns related to prescribing antidepressants for cancer patients. Although studies generally indicate that about 25% of all cancer patients are depressed, one study found that only 16% of cancer patients were receiving antidepressant medication.[
Antidepressants are divided into several classes on the basis of their underlying mechanisms. Most inhibit uptake of neurotransmitters; some also have a direct impact on cell receptors (refer to Table 2).
|CYP = cytochrome P450 enzyme; GI = gastrointestinal; IR = immediate release; MAOI = monoamine oxidase inhibitor; NDRI = norepinephrine-dopamine reuptake inhibitor; SNRI = serotonin-norepinephrine reuptake inhibitor; SR = sustained release; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant; XL = extended release.|
|a All antidepressants carry a boxed warning about the risk of suicidal thinking and behavior, risk of mania, and risk of drug-drug interaction when combined with MAOIs (refer to the MAOIssection of this summary for more information).|
|b Refer to the Serotonin-norepinephrine reuptake inhibitors (SNRIs)section of this summary for more information about side effects associated with SNRIs.|
|Medication||Starting Dose (mg/day)||Maintenance Dose (mg/day)||Comments|
|Citalopram||10–20||20–40||Better safety-tolerability profile than other antidepressants.|
|Potential for QTc prolongation (dose increase limited in patients with cardiac issues).|
|Escitalopram||5–10||10–20||Better safety-tolerability profile than other antidepressants.|
|Fluoxetine||10–20||20–60||Minimal risk of serotonin discontinuation syndrome due to long half-life.|
|Significant inhibitor of CYP2D6.|
|Fluvoxamine||25–50||100–300||Better anxiolytic properties than other SSRIs.|
|Significant inhibitor of CYP1A2 and CYP3A4.|
|Paroxetine||10–20||20–60||High risk of serotonin discontinuation syndrome.|
|Modest anticholinergic properties.|
|Significant inhibitor of CYP2D6.|
|Sertraline||25–50||100–200||Higher risk of GI side effects.|
|Dose-dependent inhibition of CYP2D6.|
|Vilazodone||10||20–40||Risk of GI side effects.|
|Possibly less risk of sexual dysfunction, but evidence inconclusive.|
|Medication||Starting Dose (mg/day)||Maintenance Dose (mg/day)||Comments|
|Desvenlafaxine||50||50–100||Positive impact on hot flashes.|
|Duloxetine||30||30–60||First-line treatment in patients with comorbid neuropathic pain (in doses as high as 120 mg).|
|Higher risk of GI side effects and hypertension.|
|Risk of hepatotoxicity.|
|Levomilnacipran||20||40–120||More-potent noradrenergic effects, activating effects.|
|Useful for comorbid cognitive and pain symptoms.|
|Increased risk of cardiovascular side effects, sweating, and urinary hesitancy.|
|Venlafaxine (IR and XL)||37.5–75||150–225||First-line treatment in patients with comorbid hot flashes.|
|Higher risk of serotonin discontinuation syndrome.|
|Medication (only most commonly used TCAs included below)||Starting Dose (mg/day)||Maintenance Dose (mg/day)||Comments|
|Amitriptyline||10–25||150–300||Marked sedation and anticholinergic effects.|
|Clomipramine||25||100–250||More serotonergic effects, less sedation, and fewer anticholinergic effects than other TCAs.|
|Minimal anticholinergic effects.|
|Doxepin||10–25||75–300||Marked sedation and anticholinergic effects.|
|Moderate anticholinergic effects.|
|Medication||Starting Dose (mg/day)||Maintenance Dose (mg/day)||Comments|
|Bupropion (IR, SR, and XL)||100–150 (SR and XL)||150–450||Stimulating effects and lack of sexual dysfunction.|
|Dose-dependent seizure risk (rare), insomnia, headaches, and weight loss.|
|SR and XL commonly used to avoid anxiogenic effects and higher seizure risk associated with IR.|
|Medication||Starting Dose (mg/day)||Maintenance Dose (mg/day)||Comments|
|Mirtazapine||7.5–15||30–45||Frequently used in cancer patients with comorbid insomnia and cachexia. Known for its antinausea effects.|
|Decreased elimination in elderly.|
|Sedation, weight gain, and dizziness.|
|Risk of hepatotoxicity and neutropenia.|
|Trazodone||25–50||50–200||Primarily used as adjunct to other antidepressants. Useful for comorbid insomnia and anxiety.|
|Marked sedation and anxiolytic effects.|
|Risk of orthostatic hypotension, dizziness, and priapism (rare).|
|MAOIs /Psychostimulants as adjunctive treatments to antidepressants/ Other adjunctive treatments||Refer to the text belowfor more information.|
The following sections describe the major antidepressant classes, their underlying mechanisms of action, their safety/tolerability profiles, and their potential use in cancer patient populations.[
Selective serotonin reuptake inhibitors
SSRIs are most commonly used in patients with cancer because they have better safety-tolerability profiles than other antidepressants. SSRIs block the reabsorption of serotonin (also called 5-hydroxytryptamine or 5-HT) by the presynaptic neurons by blocking the serotonin transporters. This causes more serotonin to be available to bind to the receptors of the postsynaptic neuron. Medications such as citalopram, escitalopram, and paroxetine work primarily by serotonin transporter blockade. Other SSRIs have additional mechanisms underlying their antidepressant effects. For example, fluoxetine binds to a specific serotonin receptor called the 5-HT2c receptor, sertraline blocks dopamine transporters, and vilazodone has partial agonism at the 5-HT1a serotonin receptor. The drugs in this class are similar in terms of their effectiveness. The most common side effects associated with this class of medications include:
However, the drugs differ in severity of these side effects and can have additional effects related to their impact on other neurobiological systems such as:
SSRIs generally undergo hepatic metabolism, renal elimination, and differ significantly in terms of their half-lives. The half-life of the specific SSRI depends on the half-lives of the parent compound and the metabolite. The serotonin discontinuation syndrome, a syndrome associated with abrupt discontinuation of SSRIs, is related to the half-life of the SSRI and its active metabolites (refer to the Serotonin discontinuation syndrome section of this summary for more information). The shorter the half-life of the SSRI and its metabolites, the higher the risk of serotonin discontinuation syndrome.
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
SNRIs increase levels of both 5-HT and norepinephrine (NE) in the synapse by blocking reuptake of these neurotransmitters by their respective transporters. SNRIs differ in their blockade of 5-HT and NE transporters, depending on their affinity for these transporters. Venlafaxine is primarily serotonergic at lower dosages, with mixed 5-HT and NE effects at higher dosages. Duloxetine and desvenlafaxine are known to block both 5-HT and NE transporters at low dosages, while levomilnacipran has the highest noradrenergic effects at lower dosages, compared with other SNRIs. These different 5-HT and NE effects may be associated with differential efficacy and side effect profiles in different patient populations. For example, serotonergic effects may be more beneficial in the treatment of depression with comorbid anxiety, while noradrenergic effects may be more beneficial in the treatment of depression with atypical features such as hypersomnia, lack of energy, and lack of motivation.
Many of the SNRIs are also known for their positive impact on pain syndromes, including neuropathic pain associated with chemotherapy. Like SSRIs, SNRIs can cause GI side effects and sexual side effects. Other side effects associated with SNRIs result from their anticholinergic and antihistamine properties and include the following:
The precise underlying mechanisms of these side effects remain unknown. Other side effects of SNRIs include dose-related diastolic hypertension and increased risk of cardiovascular side effects, primarily resulting from their noradrenergic effects. For this reason, a baseline electrocardiogram (ECG) is recommended in some cases. SNRIs are also associated with increased risk of headaches and excessive sweating. Certain SNRIs, specifically venlafaxine and desvenlafaxine, are known to treat hot flashes associated with menopausal symptoms. Similar to SSRIs, SNRIs also carry a risk of serotonin syndrome and serotonin discontinuation syndrome with abrupt discontinuation.
Similar to SNRIs, TCAs also increase levels of both 5-HT and NE in the synapse by blocking reuptake of these neurotransmitters by their respective transporters. TCAs are converted to secondary amine metabolites by demethylation in the liver. Both the primary amines and their secondary amine metabolites are active compounds. The secondary amine active metabolites of imipramine (desipramine) and amitriptyline (nortriptyline) are much more potent NE reuptake inhibitors.
TCAs are not commonly used as first-line agents due to high risk of cardiotoxicity and neurotoxicity, including risk of seizures. Use of TCAs requires extreme caution because overdoses of even small amounts can be fatal. A baseline ECG is recommended to evaluate for preexisting cardiac conduction abnormalities. Other side effects include risk of weight gain and anticholinergic effects. These side effects are more prominent with TCAs than SNRIs.
TCAs are primarily used as adjuncts in the treatment of refractory depression and in the treatment of comorbidities such as headaches, neuropathy, and insomnia. TCAs also carry a risk of serotonin syndrome and serotonin discontinuation syndrome with abrupt discontinuation.
Serotonin discontinuation syndrome
A discontinuation syndrome has been associated with stoppage of serotonergic antidepressants, both SSRIs and SNRIs.[
The syndrome is generally self-limiting but in rare cases requires medical attention. The treatment may include re-initiation of serotonergic medications at lower dosages, with gradual taper of these medications over a longer period. Gradual tapering of all serotonergic medications, especially medications with short half-lives such as paroxetine, is strongly recommended to avoid discontinuation syndrome. When taper schedules are recommended, it is also critical to consider individual patient factors such as history of discontinuation syndromes.
Serotonin syndrome [
Careful review of all medications is recommended before any serotonergic medication is added to a patient's medication regimen.
Norepinephrine-dopamine reuptake inhibitors
Bupropion is the only medication with this mechanism of action. It blocks the dopamine transporter while its primary metabolite, 6-hydroxybupropion, is a potent NE reuptake inhibitor. Bupropion may be more effective in the treatment of atypical depression (i.e., depression with fatigue and hypersomnia). It is a unique alternative to SSRIs and SNRIs for treating persons with depression and cancer, especially when depression is accompanied by fatigue. Unlike serotonergic antidepressants, bupropion is not associated with sexual dysfunction; therefore, it may be useful in treating patients who wish to remain sexually active and those who have experienced sexual dysfunction with other antidepressants.
Bupropion is available in three formulations based on frequency of administration:[
The sustained- and extended-release formulations are used more frequently because of the ease of administration and less risk of certain side effects, such as anxiety and seizures. The risk of seizures with bupropion is low but can be increased substantially by predisposing factors such as the following:[
Bupropion should be avoided in patients with malignant diseases involving the brain and histories of cranial trauma or seizure disorder,[
Antidepressants with mixed pharmacological properties
The antidepressants in this category have multiple pharmacological properties, including combinations of blockade of monoamine transporters and direct receptor agonist or antagonist properties.[
Mirtazapine is an alpha-2 adrenergic receptor antagonist, blocks several serotonin receptors (5-HT2a, 5-HT2c, and 5-HT3), and is a potent H1 histamine receptor antagonist. Its blockade of presynaptic alpha-2 adrenergic receptors causes the release of NE which, in turn, causes the release of 5-HT. This increase in NE and 5-HT and blockade of 5-HT2c and 5-HT3 receptors have been associated with mirtazapine's antidepressant effects. The potent antihistaminic effects of mirtazapine can cause significant sedation; in addition, its blockade of histaminic and 5-HT2c receptors has been associated with increased appetite/weight gain, and its blockade of 5-HT3 receptors causes mild antiemetic effects. Mirtazapine has minimal risk of drug-drug interactions because it does not have significant impact on cytochrome P450 enzymes. The sedation and increased appetite/weight gain side effects can be beneficial in patients with cancer struggling with insomnia and cachexia.
Mirtazapine is frequently used for cancer patients, specifically for the treatment of depression with comorbid insomnia and weight loss. It is also useful in this patient population because of the following:
Mirtazapine is associated with agranulocytosis/neutropenia and increased liver enzymes in rare cases. Monitoring of blood counts and liver enzymes is necessary, especially when patients are at risk of these side effects because of comorbid conditions and other cancer treatments. In rare cases, mirtazapine carries the risk of serotonin syndrome (refer to the Serotonin syndrome section of this summary for more information), primarily when taken in combination with other potent serotonergic medications; it is not associated with serotonin discontinuation syndrome.
Trazodone is a 5-HT2a and 5-HT2c receptor antagonist and weak serotonin reuptake inhibitor. It can be very beneficial as an adjunct in the treatment of depression with comorbid insomnia and anxiety. It has potent sedative effects even at low dosages because of its blockade of histamine, 5-HT2c receptors, and alpha-1 receptors. Trazodone is primarily used at low dosages (25–150 mg) to treat insomnia with or without depression/anxiety. Only high dosages (150–600 mg) of trazodone are associated with antidepressant effects. However, such high dosages carry a high risk of side effects, especially risk of significant daytime sedation, dizziness due to orthostatic hypotension, and other cardiovascular risks.
MAOIs increase all three monoamines (dopamine, serotonin, and NE) simultaneously because of their inhibition of MAO enzymes. The older MAOIs cause irreversible inhibition of both MAO-A and MAO-B enzymes. These medications can be highly effective, especially in the treatment of refractory depression and anxiety symptoms. However, MAOIs are primarily used as last resort because of their risk of serious side effects, multiple drug-drug interactions, and the significant dietary restrictions patients must adhere to when using these medications.
Several classes of medications are contraindicated or used with extreme caution with MAOIs because of the risk of serious and even lethal interactions due to serotonin syndrome and hypertensive crisis. Such classes of medications include the following:
Opioids with serotonergic properties, such as meperidine and methadone, should also be avoided with MAOIs. Patients taking MAOIs must follow strict dietary restrictions to avoid potentially fatal hypertensive crises. Avoiding foods that contain significant amounts of tyramine (e.g., aged cheese and meats) is critical when these medications are taken. The hypertensive crisis with MAOIs is related to the rapid increase in NE levels because of lack of tyramine processing by the MAO enzymes. Other common side effects include orthostatic hypotension, dizziness, anticholinergic side effects, and headaches.
MAOIs include selegiline, phenelzine, and tranylcypromine. Selegiline, a reversible MAOI, is available as a transdermal patch. At low dosages, it is primarily a selective MAO-B inhibitor and therefore does not require dietary restrictions (up to 9-mg doses). Because of selegiline's transdermal delivery, at higher doses it still bypasses most of the MAO-A enzyme in the gut while inhibiting both MAO-A and MAO-B in the brain needed for antidepressant effects. However, patients receiving high doses are required to follow dietary restrictions because of the potential for inhibition of MAO-A enzyme in the gut. Higher doses carry warnings for drug-drug interactions and other side effects similar to those for older MAOIs.
In patients with cancer, the use of MAOIs is limited to highly refractory cases due to additional cancer and cancer treatment–related risk factors (e.g., cardiovascular comorbidities due to certain cancer treatments and the use of pain medications such as tramadol and methadone). In most cases, MAOIs are prescribed and managed by psychiatric clinicians in this patient population because of the multiple risks noted earlier. At a minimum, significant involvement of psychiatric prescribers and pharmacy consultation are strongly recommended during initiation and management of MAOIs.
A patient may show improvement with the primary antidepressant treatment, but this improvement may be inadequate from a clinical standpoint because of significant residual symptomatology affecting the patient's well-being and functioning. In such cases, certain augmentation strategies may be helpful.[
Benzodiazepines can be used to effectively treat the anxiety that may be associated with depression. In patients receiving antidepressant medications and benzodiazepines concomitantly, the latter drugs may be discontinued after patients' depressive symptoms begin to abate; however, both agents can be continued safely if needed. Benzodiazepines cannot be stopped abruptly because withdrawal symptoms with possible seizures may occur. The dose of benzodiazepines is tapered slowly, at a rate of approximately 25% every 3 to 4 days.
Clinical experience suggests that analeptic agents (e.g., methylphenidate and dextroamphetamine) are useful at low doses for patients whose symptoms include the following:[
These agents are usually prescribed at low dosages and as adjuncts to antidepressants. Analeptic agents are particularly useful for patients with advanced cancer who have a limited life expectancy (weeks to a few months). Psychostimulants often demonstrate antifatigue effects within a few days of starting treatment. They can be helpful in countering the sedating effects of opioids.
Adverse effects associated with analeptic agents include neuropsychiatric side effects such as insomnia, mood lability, anxiety, agitation, anorexia, and even psychotic symptoms. They are also associated with adverse cardiovascular effects such as hypertension and arrhythmia. A baseline ECG is recommended. These medications can also lower the seizure threshold. Finally, there is a risk of developing tolerance, misuse, and dependence on these medications. Considering risks and benefits is critical when the use of these medications is being contemplated. These medications, in appropriate cases and when used in optimal dosages, can have a significant positive impact on a patient's quality of life, especially for those with advanced cancers.
Adjunctive medications to treat medical and psychiatric comorbidities
Medical and psychiatric comorbidities (e.g., neuropathy, menopausal symptoms, and trauma symptoms) may play a role in depression severity. Such conditions frequently have a bidirectional interaction with depression, with one exacerbating the other and vice versa. Medications other than antidepressants that can treat medical/psychiatric comorbidities may play a crucial role in the management of depression in patients with psychiatric comorbidities. For example, gabapentin can be used as an adjunct to antidepressants to target comorbid neuropathic pain, menopausal symptoms, and anxiety symptoms.
Adjunctive medications in treatment-refractory cases
Evidence from the non-cancer (general psychiatry) literature suggests a role for other medications and medication classes as adjuncts to antidepressants in treatment-refractory cases.[
Buspirone is primarily used as an adjunct to treat comorbid anxiety symptoms. Some of these medications (e.g., antipsychotic medications and lithium) are associated with a significant burden of side effects. Referral to and/or extensive involvement of psychiatric clinicians is strongly recommended for treatment-refractory cases, especially if these medications and medication classes are considered as adjuncts.
Antidepressant medication selection and management
Several general, cancer-related, and cancer treatment–related factors play an important role in the choice and management of antidepressants in cancer patients.[
The predominance or lack of specific symptoms of depression (e.g., fatigue, insomnia, and cognitive difficulties) and related psychiatric comorbidities (e.g., anxiety disorders) play a role in the selection of an antidepressant.[
Avoiding side effects
Patients with cancer frequently struggle with multiple physical and psychological adverse effects related to their cancer and cancer treatments. It is critical to select antidepressants to avoid further worsening of their health status, either by addition of side effects due to antidepressants or exacerbation of existing issues. For example, patients with cancer may be struggling with issues concerning their sexual function. Antidepressants exacerbating sexual dysfunction can heighten distress, which can worsen depression. Some patients may struggle with the GI side effects of their cancer and cancer treatments. Certain antidepressants with known risks for significant GI side effects such as nausea and diarrhea (e.g., sertraline and duloxetine) may need to be avoided in these patients.
The presence or absence of certain medical comorbidities can drive antidepressant selection.[
Antidepressants, even from the same class, can have significant pharmacological differences. They can differ in their absorption; half-lives, including half-lives of their active metabolites; and metabolism via an impact on different cytochrome P450 enzymes. These differences can play an important role, depending on cancer types and cancer treatments.
Consideration of pharmacodynamic and pharmacokinetic interactions with concomitant medical and psychiatric medications is critical when an antidepressant is being contemplated. For example, highly sedating antidepressants, such as mirtazapine, are not desirable in combination with sedating concomitant medications, such as opioids and benzodiazepines. Potent 2D6 cytochrome P450 enzyme inhibitors, such as paroxetine and duloxetine, are not recommended for patients receiving tamoxifen because of concerns about their impact on the efficacy of tamoxifen (because of the inhibition of tamoxifen's conversion to endoxifen, its active metabolite).
Antidepressant trials for patient and biological family members
Information collected from patients and family members about experience with antidepressants (i.e., positive responses or negative experiences such as side effects) can be crucial in the selection of an antidepressant. Genetic background (e.g., serotonin transporter polymorphism) shared by the patient and biological family members may play a role in responsiveness to specific medications or medication classes. Information about successful or failed antidepressants for biological family members can play an important role in antidepressant selection.
The availability of antidepressant formulations may play a crucial role in antidepressant selection for certain patient populations with cancer. For example, patients with head and neck cancers may have difficulty swallowing because of the disease, its treatment, or both. In such cases, the use of antidepressants in liquid form (e.g., citalopram and fluoxetine) or parenteral form (e.g., amitriptyline injection) may be necessary.
Certain cancers can affect medication absorption (e.g., GI cancers) or metabolism (e.g., liver and kidney cancers). Antidepressant selection may therefore be driven by the pharmacokinetic profile of individual antidepressants to circumvent any issues. In some cases, antidepressant dosages may need to be adjusted beyond recommended guidelines to derive maximum therapeutic benefit.
Initial titration and management
Generally, there is a long latency period (3–6 weeks) from initiation of antidepressant medications to the onset of a therapeutic response.[
It is recommended that an antidepressant be continued for at least 1 year for a major depressive episode. Continuation of an antidepressant beyond 1 year depends on several factors, including a patient's psychological status at that time, their psychiatric history, their cancer and cancer treatment status and, more important, their thoughts about and experience with the antidepressant. As in the initiation, decisions are individualized according to the risks-benefits-alternatives principle and patient choice.
Switching or discontinuing antidepressants
Switching from one antidepressant to another or discontinuing antidepressants is frequently indicated because of intolerable adverse effects or lack of treatment response. Several factors play a role in the strategies employed during switching or stopping an antidepressant. These factors are primarily driven by the risk of serotonin syndrome (refer to the Serotonin syndrome section of this summary for more information) and serotonin discontinuation syndrome (refer to the Serotonin discontinuation syndrome section of this summary for more information). Such factors include antidepressant-dependent factors and patient- or illness-related factors:[
Patient- or illness-related factors
Generally, when antidepressants are switched, either (1) discontinuing one antidepressant followed by initiating the new one or (2) gradual cross-tapering between the two antidepressants is recommended. However, given the lack of controlled evidence, the switching strategy is highly individualized and driven by the pharmacological properties of both antidepressants and specific patient- and illness-related factors.[
Switching from a serotonergic antidepressant with a longer half-life (or one that has an active metabolite with a longer half-life, e.g., fluoxetine) to another serotonergic antidepressant may carry the risk of developing serotonin syndrome, depending on when one medication is stopped and the second one is started. (Refer to the Serotonin syndrome section of this summary for more information.) The risk of serotonin syndrome in these cases will also depend on the doses of both medications and the schedule of cross-taper.[
For the discontinuation of serotonergic antidepressants, it is strongly recommended that antidepressants be tapered gradually to minimize the risk of serotonin discontinuation syndrome. (Refer to the Serotonin discontinuation syndrome section of this summary for more information.)
As with switching antidepressants, specific medication-related factors and patient- or illness-related factors need to be considered when patients are tapered off antidepressants, but the precise taper strategy is highly individualized. The half-life of antidepressants is a critical factor in stopping antidepressants. Generally, the shorter the half-life of an antidepressant, the higher the risk of discontinuation syndrome. (Refer to Table 3 for a list of antidepressants and the risk of serotonin discontinuation syndrome.)
|MAOI = monoamine oxidase inhibitor; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant; + = low risk; ++ = moderate risk; +++ = high risk.|
|a Risk based on half-life of antidepressant.|
|Fluoxetine||Very long half-life; generally, no taper required|
|Clomipramine||++||Most serotonergic TCA|
|Bupropion||Minimal to no risk|
|Mirtazapine||Minimal to no risk|
|Trazodone||Doses <150 mg/d carry minimal to no risk|
Educating patients about what to expect, close clinical monitoring, and frequent reassurance are crucial during the switching or discontinuing of antidepressants. Consultation with pharmacy or psychiatric services is generally recommended for switching or stopping. In a minority of cases, despite gradual tapering, patients may experience severe withdrawal symptoms, sometimes lasting several weeks. In such cases, immediate consultation with psychiatric services is strongly recommended.
Most antidepressant prescribing is directed at the treatment of an existing depressive disorder or significant depressive symptoms. However, one study supports the use of antidepressants to prevent depression in patients receiving high-dose interferon for adjuvant therapy of malignant melanoma.[
In a double-blind study of patients receiving high-dose interferon, 2 of 18 patients in the paroxetine group developed depression during the first 12 weeks of therapy, compared with 9 of 20 patients in the placebo group (relative risk [RR] = 0.24; 95% confidence interval [CI], 0.08–0.93). Moreover, there were significantly fewer treatment discontinuations in the paroxetine group (5% vs. 35%, RR = 0.14; 95% CI, 0.05–0.85).[
Suicide risk of antidepressant medications
Over the past few years, significant concerns have been raised about the risk of suicidal thinking and behavior with the use of antidepressants in children, adolescents, and young adults. In October 2004, the U.S. Food and Drug Administration (FDA) mandated pharmaceutical companies to add a boxed warning to the labeling of all antidepressants suggesting increased risk of suicidality in pediatric patients who were taking antidepressants. The FDA revised this boxed warning in May 2007 to include young adults younger than 25 years.[
The meta-analysis that led to the initial boxed warning in pediatric patients concluded that the antidepressants are associated with a twofold increase in suicidal ideation and behavior compared with the placebo in children and adolescents.[
Concerns have been raised that the unintended consequence of the warnings will be overly restricted use of antidepressants among those who benefit the most and, hence, an increase in suicidality that the warning seeks to prevent.
In summary, the risks-benefits-alternatives principle favors appropriate use of antidepressants with careful monitoring for suicidality. None of the studies that led to the boxed warning included or focused on patients being treated for cancer. Clinical experience and results of small clinical trials suggest that antidepressants can be safely administered to adult cancer patients, although there are no large controlled clinical trials to support this position. When antidepressants are prescribed for patients with cancer, implementation of a careful monitoring plan should be considered by individuals with expertise, and consultation referral made for patients who do not respond as anticipated or who present other concerns.
Traditionally, depressive symptomatology was managed with insight-oriented psychotherapy, which is quite useful for some people with cancer. For many other people, these symptoms are best managed with some combination of crisis intervention, brief supportive psychotherapy, and cognitive-behavioral techniques.
Psychotherapy for depression has been offered in a variety of forms. Most interventions have been time limited (range, 4–30 hours), have been offered in both individual and small-group formats, and have included a structured educational component about cancer or a specific relaxation component.[
Cognitive-behavioral psychotherapy has been one of the most prominent types of therapies studied. Cognitive-behavioral interventions focus on the following:
Understanding and altering one's thoughts can change emotional reactions and accompanying behaviors. For example, frequent, intrusive, uncontrollable thoughts about loss, life changes, or death can cause poor concentration and precipitate feelings of sadness, guilt, and worthlessness. In turn, these feelings can result in increased sleep, withdrawal, and isolation. A cognitive-behavioral intervention focuses on the intrusive thoughts, often challenging their accuracy or rationality and noting specific patterns of cognitive distortions. Simultaneously, patients develop specific cognitive coping strategies that are designed to alter emotional reactions and accompanying behaviors. The result is improved coping, enhanced adjustment, and better overall quality of life.
Other goals of psychotherapy include:[
Consultation with a cleric or a member of a pastoral care department may also help some individuals.
Specific goals of these therapies include the following:
Cancer support groups can be useful adjunctive therapies in the treatment of cancer patients.[
Support groups can be found through the Cancer Support Community, the American Cancer Society, and many other community resources, including the social work departments of medical centers and hospitals.
Empirical studies of the efficacy of psychotherapy
Psychotherapy as a treatment for depression in the general adult mental health population has been extensively researched and found to be effective.[
One well-designed randomized clinical trial of a cognitive-behavioral intervention for depressed cancer patients investigated the effect of problem-solving training on symptoms of depression.[
Between-session homework with tasks relevant to each step was assigned, and patients were provided with a written manual and encouraged to refer to it as problems arose. One hundred thirty-two adult cancer patients were randomly assigned to the problem-solving treatment (PST), PST with a significant other, or a wait-list control. Overall results showed that PST (alone or with a significant other) improved problem-solving abilities and clinically significantly decreased symptoms of depression.[
Current Clinical Trials
Demographics and Statistics
Epidemiological studies conducted across several countries indicate that cancer is a risk factor for suicide.[
Certain clinical and sociodemographic risk factors for suicide have been identified in patients with cancer.[
Suicide risk also differs by social and structural health determinants. An investigation of more than 5.3 million individuals with cancer across 635 counties included in the SEER 18 database found that among the 6,357 of these individuals who died of suicide, the standard mortality ratio (SMR) of suicide among those in the lowest-income counties, compared with those in the highest-income counties, was significantly higher (SMR, 1.94; 95% confidence interval [CI], 1.76–2.13 vs. SMR, 1.30; 95% CI, 1.26–1.34)[
Another consistent risk factor is related to the time since diagnosis. Studies have consistently found higher risk of suicide in the first year after diagnosis, especially in the first 3 to 5 months.[
Certain cancer types have been associated with higher suicide risk, including the following cancer types:[
Other risk factors include nonlocalized disease and aggressive or advanced cancer with a survival rate of fewer than 5 years.[
In a study of Japanese patients (n = 220) who had cancer and who were diagnosed with major depression after being referred for psychiatric consultation, approximately 50% reported suicidal ideation. In a retrospective analysis of predictors of suicidal ideation, researchers found that those with more symptoms of major depression and poorer physical functioning were significantly more likely to report suicidal ideation.[
Risk factors for suicide in the cancer population are as follows:[
In addition, veteran survivors with head and neck cancer are at a particularly high risk for suicide. In a study of 7,803 U.S. veteran survivors of head and neck cancer (98.4% male; mean age, 65 years)[
Suicide assessment occurs frequently along the cancer continuum. Components of suicide assessment include the following:[
Hopelessness is a powerful predictor of suicidal ideation and completed suicides in the general population and in cancer patients.[
However, these tools are not validated for cancer patients.[
Other complicating factors in suicide assessment include the demoralization syndrome and desire for hastened death.[
The relationships between suicidal ideation and the desire for hastened death, requests for physician-assisted suicide (refer to the Requests for Hastened Death section in the PDQ summary on Last Days of Life for more information), and/or euthanasia are complex and poorly understood.[
Patients who are found to be suicidal require careful further assessment (refer to Table 4). The risk of suicide increases if the patient reports ideation (i.e., thoughts of suicide) plus a plan (i.e., description of the means). Risk continues to increase to the extent that the plan is lethal.[
Factors to consider in assessing lethality include:
For the cancer patient reporting suicidal ideation, it is essential to determine whether the underlying cause is the following:[
Prompt identification and treatment of major depression is essential in lowering the risk of suicide in cancer patients. Risk factors, particularly hopelessness (which is an even stronger predictive factor for suicidal ideation and completed suicides than is depression), requires careful assessment.[
Establishing rapport is of prime importance in working with suicidal cancer patients as it serves as the foundation for other interventions. The clinician must believe that talking about suicide will not cause the patient to attempt suicide. On the contrary, talking about suicide legitimizes this concern and permits patients to describe their feelings and fears, providing a sense of control.[
A crisis intervention–oriented psychotherapeutic approach that mobilizes as much of a patient's support system as possible is initiated.[
| a Adapted from Roth et al.[
|Most people with cancer have passing thoughts about suicide such as, "I might do something if it gets bad enough."||Acknowledge normality by opening with a statement recognizing that a discussion does not enhance risk|
|Have you ever had thoughts like that? Any thoughts of not wanting to live or wishing your illness might hasten your death?||Level of risk|
|Do you have thoughts of suicide? Have you thought about how you would do it? Do you intend to harm yourself?||Level of risk|
|Have you ever been depressed or made a suicide attempt?||History|
|Have you ever been treated for other psychiatric problems or have you been psychiatrically hospitalized before getting diagnosed with cancer?||History|
|Have you had a problem with alcohol or drugs?||Substance dependence|
|Have you lost anyone close to you recently? (Family, friends, others with cancer.)||Bereavement|
In clinical practice, the goal of management of suicidal patients is to attempt to prevent suicide that is driven by desperation due to poorly controlled symptoms. Prolonged suffering due to poorly controlled symptoms can lead to such desperation. Thus, effective symptom management is critical to decrease psychological distress in suicidal cancer patients.[
At times, it may be important to limit access to potentially lethal medications for patients considered at risk of suicide. When potentially lethal medications are limited, it is important to weigh the impact on symptom management against the impact on suicide risk because poorly controlled symptoms may contribute to risk. Furthermore, suicidal patients will often have other means available to complete suicide attempts and these must also be evaluated. Strategies to lessen suicidal risk include frequent contact to reassess suicidal risk and symptom control, as well as regular delivery of limited quantities of medications facilitating rapid dose titration for effective management of poorly controlled symptoms when necessary. For patients receiving parenteral or intrathecal opioids, programmable pumps with limited access to programming and locked, inaccessible cartridges may provide an element of safety.
Strategies to lessen suicide risk in cancer patients include the following:
Information concerning the incidence of depression in healthy children is limited. One study of children seen in a general practice showed that 38% had problems that required major intervention by a psychiatrist. Another study of children aged 7 to 12 years showed a 1.9% incidence of depression. If applied to the general population of the United States, these results show that 40,000 12-year-olds are depressed. Teachers have estimated that as many as 10% to 15% of their students are depressed. The Joint Commission on Mental Health of Children states that 1.4 million children younger than 18 years need immediate help for disorders such as depression; only one-third of these children receive help for their disorder.[
Most children cope with the emotional upheaval related to cancer and demonstrate not only evidence of adaptation but positive psychosocial growth and development. A minority of children, however, develops the following psychological problems:[
These children require referral to and intervention by a mental health specialist.
In one of the first studies of depression in childhood cancer, 114 children and adolescents were studied, and 59% were found to have mild psychiatric problems.[
A study of long-term cancer survivors and their mothers, comparing the survivors with a group of 92 healthy children, showed that most former patients were functioning within normal limits. Not surprisingly, children with severe late effects had more depressive symptoms.[
Most cancer survivors demonstrate general resiliency and successful psychological adjustment to the disease and its treatment. Despite evidence for successful adaptation, most studies document psychological difficulties in a significant subset of cancer survivors.
Assessment and Diagnosis of Pediatric Depression
The term depression refers to a symptom, a syndrome, a set of psychological responses, or an illness.[
Depression should be considered whenever any behavior problem persists. Depression does not refer to transitory moments of sadness, but rather to a disorder that affects development and interferes with realization of the child's innate potential.[
Some manifestations of depression in a school-aged child include the following:[
Differentiating these symptoms from behavioral responses to normal developmental stages is important.
Assessment of depression includes determination of the child's:[
A comprehensive assessment for childhood depression is the basis for accurate diagnosis and treatment. Evaluation of the child and family situation focuses on the pediatric health history, behaviors observed by the practitioner or reported by others (e.g., parents and teachers), interviews with the child, and judicial use of tests such as the Beck Depression Inventory or the Child Behavior Checklist.[
In discussing the diagnosis of childhood depression, experts stress the importance of understanding childhood depression as an entity distinct from depression in adults because developmental issues in childhood are distinctly different from those of adulthood.[
A model of childhood affective disorders uses the following explicit criteria:[
Management of Pediatric Depression
Treatment regimens implemented for childhood depression reflect theoretical models, etiology, and manifestations of the disorder.[
As is the case with depression in adult cancer patients, there are few, if any, revealing trials of antidepressants in children with cancer. One author described rapid clinical response to low doses (<2 mg/kg/d) of imipramine or amitriptyline for eight depressed children with cancer.[
The combined use of tricyclic antidepressants and neuroleptics in the management of three children with severe symptoms of depression and anxiety has been reported. The children studied were in the terminal phases of their disease and were treated with a combination of low-dose amitriptyline and haloperidol. Levels of anxiety and depression were decreased, and this intervention allowed the patients and their families to deal with issues involved in death and dying.[
Refer to the subsection on Depression and Suicide in the PDQ summary on Pediatric Supportive Care for information on pediatric considerations for suicidality and cautions about the use of selective serotonin reuptake inhibitors.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added text about a large study of patients with breast, colorectal, gynecologic, and prostate cancers in Scotland, United Kingdom, which found that having major depression was associated with worse survival (cited Walker et al. as reference 19 and level of evidence II).
Suicide Risk in Cancer Patients
Added Nugent et al. as reference 13 and level of evidence III.
Added text about a study of U.S. veteran survivors of head and neck cancer, which found that their rates of suicidal self-directed violence and death by suicide were higher than those associated with male sex and older age.
This summary is written and maintained by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about cancer-related depression and suicide risk in both the adult and the pediatric populations. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Depression are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Supportive and Palliative Care Editorial Board. PDQ Depression. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/coping/feelings/depression-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389407]
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Last Revised: 2022-04-19
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