| Past psychiatric illness |
| Family history of psychiatric illness |
| Younger age (<45 years) |
| Having young children |
| Limited social support |
| Substance use |
| Single status |
| Pain |
| Physical disability |
| Poor family coherence |
| Financial strain |
| Source: Adapted from reference 10 |
Psychotherapeutic options
Behavioral therapies can diminish symptoms of depression, according to a review of studies and practice guidelines on managing depression in cancer patients.17 Group interventions, in particular, can be valuable. Anderson et al18 found that group cohesion, member connectedness, and more sessions correlated with decreased psychological distress.
Psychoeducation aims to provide medical information and discuss cancer’s causes, prognosis, and treatment strategies. Group settings can help improve communication and problem-solving skills. In a randomized controlled trial (RCT) of 203 women with breast cancer, psychoeducational group treatment reduced depression, anger, and fatigue.19
Cognitive-behavioral therapy (CBT) helps patients identify and restructure negative thoughts and increase positive, adaptive behaviors. Hunter et al20 noted significant improvement in depressed mood, anxiety, and sleep in 17 women experiencing menopausal symptoms who received group CBT after completing breast cancer treatment. In 1 study, 124 patients with metastatic breast cancer who received 8 weekly sessions of group CBT reported reduced depression and mood disturbance and improved self-esteem compared with a no-therapy control group.21
Supportive-expressive therapy (SET) is a manual-based therapy that focuses on increasing social support, improving symptom control, and enhancing communication between the patient and treatment team. Affective expression helps lead the therapist to issues that should be addressed. Evidence on the effectiveness of SET for patients with breast cancer is mixed. A study of 357 women with breast cancer who were randomly assigned to 12-week group SET or an educational control condition found no evidence that SET reduced distress.22 However, a trial of 485 women with advanced breast cancer who were randomly assigned to group SET plus relaxation therapy or relaxation therapy alone showed that SET improved quality of life, including protection against depression.23
Mindfulness-based stress reduction (MBSR) is a standardized form of meditation and yoga. Clinicians teach patients visualization, breathing exercises, and meditation to help them become aware of the body’s reaction to stress and how to regulate it. In an RCT of 84 female breast cancer survivors, a 6-week MBSR program diminished depressive symptoms, improved physical functioning, and reduced fear of cancer recurrence.24
Evidence for antidepressants
SSRIs. Expert consensus guidelines on treating depression in women recommend an SSRI as a first-line agent.25 In RCTs, fluoxetine, paroxetine, and sertraline were more effective than placebo in treating depression and related symptoms specifically in women with breast cancer (Table 2).26-28
The interaction between SSRIs and chemotherapy agents is a concern. Tamoxifen decreases the rate of death from breast cancer in hormone receptor positive breast cancers.29 Endoxifen, a potent anti-estrogen, is an active metabolite of tamoxifen via cytochrome P450 (CYP) 2D6. Goetz et al30 demonstrated that women with decreased or inhibited metabolism via CYP2D6 had significantly shorter times to breast cancer recurrence, compared with women with extensive CYP2D6 metabolism.
SSRIs can varyingly inhibit CYP2D6. In a prospective trial of 158 breast cancer patients receiving tamoxifen, paroxetine and fluoxetine were found to be strong inhibitors of CYP2D6 and led to low levels of endoxifen.31 In contrast, weaker inhibitors, including sertraline and citalopram, led to intermediate levels of endoxifen. In a retrospective cohort study, Kelly et al32 demonstrated that women treated with paroxetine, in combination with tamoxifen, had an increased risk of death compared with women treated with other SSRIs or venlafaxine and tamoxifen. They estimated that paroxetine use in women treated with tamoxifen would lead to 1 additional breast cancer death per 20 women within 5 years of discontinuing tamoxifen.
According to American Psychiatric Association practice guidelines for treatment of MDD, depressed breast cancer patients who receive tamoxifen generally should be treated with an antidepressant that has minimal effect on CYP2D6 metabolism, such as citalopram, escitalopram, venlafaxine, or desvenlafaxine.33
Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used to treat depressive disorders. In addition, venlafaxine may be helpful in treating post-mastectomy pain syndrome. Approximately one-half of patients who undergo mastectomy or breast reconstruction may experience a postoperative pain syndrome.34 The most common symptom is a burning, stabbing pain in the axilla, arm, and chest wall of the affected side. This pain is worsened by movement and is poorly responsive to opioids.35
In a 10-week RCT of 13 patients with neuropathic pain after breast cancer treatment, venlafaxine significantly improved pain relief compared with placebo, although the drug did not affect depression or anxiety.36 In a study of 100 patients given venlafaxine or placebo for 2 weeks starting the night before undergoing partial or radical mastectomy with axillary dissection, those receiving venlafaxine had a significantly lower incidence of pain in the chest wall, arm, and axillary region, and scores of pain with movement were decreased.37 There was no difference in opioid usage between groups.