Depression and Anxiety in Cancer Patients – Causes, Symptoms and Treatment

Depression and anxiety are mental disorders commonly seen in cancer but often neglected despite their effects on quality of life, treatment adherence, survival rates and treatment costs.

Regardless of cancer’s course or whether it can be cured, %20 of cancer patients may experience depression and %10 anxiety.

Depression is important not only because it impedes treatment adherence and reduces cancer survival, but also because it increases suicide risk.

The clinical update below addresses the frequency, causes and treatment of depression and anxiety in cancer.

How Common Are Depression and Anxiety in Cancer?

A systematic review and meta-analysis found major depression in %15 of cancer patients, minor depression in %20 and anxiety in %10. Severe anxiety symptoms were also found in 2/3 of patients with depression.

Although rates vary by cancer type, major depression is estimated in lung cancer at %13, gynecological cancers at %11, breast cancer at %9, colorectal cancers at %7 and genitourinary cancers at %6.

The highest anxiety levels were reported by patients with lung, gynecological and hematological (blood and lymph) cancers. Evidence attributes differences in depression and anxiety rates across cancers to differences in disease course, pain, effects on body image, tumor-specific neuropsychiatric effects and treatment-specific side effects.

Although considerably more common than in the general population, among cancer patients with depression, %73 cannot receive effective psychiatric treatment and only % 5 can see a mental health professional. Anxiety usually does not occur alone but accompanies depression. Treating depression therefore often also resolves anxiety.

Which Cancer Patients Are at Greater Risk of Depression and Anxiety?

Younger age, social deprivation and female sex (for lung and colorectal cancers) have been identified as depression risk factors in cancer. Anxiety is associated with previous anxiety disorders and trauma, and with metastases in some cancers; no relationship was found with age, sex or socioeconomic status.

Those tending to blame themselves for having cancerwere found more likely to experience depression than those considering other causes. The severity of mental disorder was associated with restricted functioning and low social support.

Patients with a history of mental disorders require particular attention after diagnosis because distress may recur or worsen. Those with prior post-traumatic stress disorder may be retraumatized during pelvic, breast or rectal examinations; recurrent depression may recur after mastectomy (breast cancer surgery); and bipolar patients started on corticosteroids may experience manic or depressive episodes.

What Causes Depression and Anxiety in Cancer?

Two main pathways explaining depression and anxiety in cancer have been described:

1. The effects of biological, psychological and social factors, explained by the biopsychosocial model; 
2. Cancer and treatment neuropsychiatric effects. Distress caused particularly by treatment effects may be missed because it begins rapidly and disappears when treatment stops.

Biopsychosocial Causes of Depression and Anxiety

Depression and anxiety mostly arise from psychological responses to diagnosis, treatment, recurrence, end-of-life care or becoming a survivor after cancer. Treatment-related losses in particular, such as loss of organs, hair or sexual function , survival expectations and effects on work and social life can cause prolonged psychological stress leading to depression and anxiety. Even the perception of illness can produce symptoms. This is thought to result from prolonged stimulation of the hypothalamic-pituitary-adrenal axis, the brain–adrenal gland pathway regulating stress responses and closely linked to the endocrine (hormonal) system.

Among biological factors, common conventional chemotherapy side effects such as nausea, vomiting, hair loss, mucositis (mouth sores) and peripheral neuropathy (nerve damage with abnormal sensations at hand and foot tips) may act as chronic stressors and create a predisposition to depression .

Health anxietyinvolves fear of serious illness caused by misinterpreting bodily symptoms. It is very understandable in patients in remission (who have completed treatment), especially after delayed initial diagnosis. However, when anxiety is disproportionate to the threat or disrupts daily life, it constitutes an anxiety disorder and requires treatment.

Direct Neuropsychiatric Effects of Cancer or Its Treatments

There are no clear data on how many depression and anxiety cases can be explained by direct biological effects of cancer or its treatments. Tumor-specific studies suggest this proportion is very low.

Depression and Anxiety by Cancer Site

Examples particularly include pancreatic cancer (depression associated with substantial cytokine release) and lung cancer (endocrine paraneoplastic syndromes associated with anxiety and depression); many cancers are known to cause depression and anxiety.

Among pancreatic cancer patients, 70% experience depression, %50 anxiety and %30 both; symptoms may occur in advanced disease or even months before cancer diagnosis.

Levels of tumor-secreted cytokine IL-6 are directly associated with depression severity.

Small-cell lung cancer patients develop inappropriate ADH syndrome in %15 of cases, and a large proportion experience depressed mood due to hyponatremia (severely low blood sodium).

A third example is depressed mood caused by malignant hypercalcemia (severely elevated blood calcium), affecting %1 of cancer patients in the United Kingdom. This may result from a substance produced by non-small-cell lung, myeloma, sarcoma, breast, kidney, gynecological, and head and neck cancers (ectopic parathyroid hormone-related peptide), or from certain tumors’ bone metastases .

Depression and Anxiety Associated with Cancer Treatments

Neuropsychiatric problems caused by conventional chemotherapy, hormone suppression, new immunotherapies, targeted therapies (smart drugs), radiotherapy and surgery are not very well recognized by clinicians.

For example;

• Studies of prostate cancer treatment with androgen (male hormone) suppression therapy reported higher depression and anxiety rates after 9 months than at baseline.
• High-dose steroids (cortisone) may cause mania and hypomania, whereas long-term low-dose use may cause depression.
• Among solid tumor patients treated with the small-molecule targeted therapy buparlisib, %37 developed mood disorders such as depression.
• Among people receiving radiotherapy for head and neck cancer, %10 develop hypothyroidism (low thyroid hormone), and 2/3 of this group are expected to develop depressive symptoms.
• Of patients receiving pelvic (lower abdominal) radiotherapy, %14 experience depression symptoms because impaired gastrointestinal absorption causes vitamin B12 deficiency .
• Premenopausal women having their uterus and/or ovaries removed prophylactically because of high hereditary cancer risk, or as cancer treatment, were found at high long-term risk of depression and anxiety disorders.

When Does a Cancer Patient Experience Depression and Anxiety?

The Stage of Cancer Symptoms and Signs

Depression and anxiety may be the first signs of tumors with direct biological effects on mood. Cancer diagnosis within one month after anxiety begins is three times as common as in the general population. This rate is particularly high above age 65. Among people over 50 presenting to psychiatry with first-time depression, every 54 include 1 expected to receive a cancer diagnosis within 1 year, particularly of cancers with neuropsychiatric effects.

Cancer Diagnosis and Treatment Stage

Estimated depression rates are highest in the initial cancer treatment period. Hopelessness, a depression criterion, may lead to refusal of treatment. Among breast cancer patients, %50 receive a diagnosis of depression, anxiety or both within the first year after diagnosis; after 5 years, this falls to around %15.

Severe depression may sometimes arise suddenly during conventional chemotherapy, particularly taxane -based treatment, and may persist for up to 18 months after completion.

Depression and Anxiety After Cancer Treatment

For some patients, frequent appointments, tests and treatments interrupt adjustment to cancer. This process, postponed partly through unconscious protective denial, may emerge when treatment ends. After surgery and chemotherapy, depression and anxiety may surface when a person first feels the significance of facing a serious, life-threatening disease and potentially struggling with long-term physical changes.

Discharge also means losing ties to an institution providing regular support, so increased anxiety is often seen during this period.

End-of-Life Period

Contrary to common belief, depression and anxiety rates in end-of-life care (%25 and %10, respectively) are not higher than in active cancer treatment.

Depression and Anxiety in Cancer Survivors

People remaining in remission five years after diagnosis are called cancer survivors .However, even after treatment ends, vulnerability to psychological stress continues as they adjust to this identity.

Anxiety frequency in this group (%18) is significantly higher than in healthy controls, and this may persist for 10 years. Severe fear of recurrence is reported by %17 of long-term breast cancer survivors and is associated with depression and low quality of life.

Treatment of Depression and Anxiety in Cancer

1. Identifying Underlying Causes

Identifying and treating underlying biological problems causing depression (such as B12 deficiency, hypothyroidism, inappropriate ADH syndrome or hypercalcemia) and reversible causes (such as use of another chemotherapy agent) will resolve symptoms.

Similarly, identifying and treating factors maintaining depression, such as pain, will reduce its severity. Where tumors respond well and chemotherapy cannot be changed, depression should be treated according to standard depression guidelines.

2. Stepped Care

Standard treatment guidelines can be used for depression and anxiety in cancer, but the following points need particular emphasis.

Psychological Treatments

Cognitive-behavioral therapies are important for understanding thoughts, feelings and behaviors causing and maintaining depression and anxiety. Access varies geographically. Some major cancer centers in the United States, Australia, France, Germany, Britain and our country provide specialist counseling and clinical psychology support within cancer treatment in an integrated manner. Where cancer services cannot provide this integrated care, contact should be sought with mental health professionals to address adherence, complex illness perceptions, coping with side effects, adjustment to bodily changes and end-of-life issues.

Drug Treatments

Medication for depression and anxiety in cancer is not recommended as first-line treatment, either alone or in combination.

Antidepressant or anti-anxiety medication selection should consider clinical parameters and all possible side effects, particularly chemotherapy interactions and existing or expected bone marrow suppression.

First-line treatments for depression and anxietyinclude sertraline and citalopram, preferred because of low interaction risks and good tolerability.

3. Considerations for Psychiatric Medication Use in Cancer

• Because of hyponatremia (low sodium) risk, caution is needed when prescribing SSRIs (selective serotonin reuptake inhibitors), particularly to older patients, especially women. 
• Monoamine oxidase inhibitor (MAO inhibitor) antidepressants should be avoided because of interaction risks with opioid painkillers and anesthetics.
• Tamoxifenusers should avoid fluoxetine and paroxetine because they inhibit its conversion to the active metabolite; venlafaxine and citalopram should be preferred instead.
• Because of bone marrow suppression risk, in patients with low white blood cell counts , mirtazapine and mianserin require caution/avoidance; in those with thrombocytopenia (low platelets), SSRIs require caution/avoidance because they may predispose to bleeding.
• In patients at risk of epileptic seizures, tricyclic antidepressants should be avoided because they may lower seizure threshold, particularly clomipramine, dosulepin and high-dose amitriptyline. Sertraline is recommended here because it does not trigger seizures.
• Because of serotonin syndrome risk, great caution is needed when starting serotonergic psychiatric drugs, such as SSRIs and SNRIs, in patients taking serotonergic drugs such as fentanyl, tramadol or ondansetron.
• In patients with chemotherapy-related nausea, starting an SSRI antidepressant may initially worsen nausea, which should be considered.

4. Recommendations for Treating Depression and Anxiety in Cancer

• Vitamin B12 supplementation is recommended for patients with depressive symptoms after gastrectomy (stomach cancer surgery) or pelvic radiation.
• Fluoxetine is recommended for depression following antifolate chemotherapies such as methotrexate or pemetrexed.
• Gastroprotective agents are added for patients taking SSRIs to prevent gastrointestinal bleeding. Particular caution is needed in bone marrow-suppressed patients at higher bleeding risk.
• Sedating antidepressants such as mirtazapine may help patients with weight loss and insomnia.
• Venlafaxine, with its dual effect, is recommended for depression in breast cancer patients taking tamoxifen, particularly those experiencing hot flashes.