Two classes of antidepressants improve symptoms of depression in cancer patients, according to a comprehensive review of treatments. One single agent, not available in the United States, proved to be superior.
Depression is common in cancer, up to half of all patients facing the disease experience depressive symptoms, ranging from mild to severe. When depression co-exists with cancer, patients may be at an increased risk of death from cancer and from suicide.
Antidepressants are commonly prescribed, but the evidence on their efficacy is mixed. The role of antidepressants in treating cancer-related depression has not been rigorously studied. To identify best practice for the treatment of depression in cancer, Dartmouth researchers in New Hampshire completed a systematic review and meta-analysis of existing research, which was published in General Hospital Psychiatry (2014; doi:10.1016/j.genhosppsych.2014.05.010).
They identified two classes of antidepressants that reduce symptoms of depression. These are the alpha-2-adrenergic receptor antagonist, Mianserin, and two selective serotonin reuptake inhibitors: fluoxetine (Prozac) and paroxetine (Paxil). Available evidence suggests that paroxetine and fluoxetine can improve depressive symptoms but may be less well-tolerated.
Miaserin, which is not approved in the United States, also showed a higher depression response rate compared to placebo, whereas paroxetine and fluoxetine did not. The response rates were low suggesting only modest changes in depressive symptoms.
“All the evidence for alpha-2-andrenergic receptors was based on a single agent, Mianserin,” said lead author Natalie Riblet, MD, MPH, of the Department of Psychiatry, Geisel School of Medicine in Hanover, New Hampshire. “Unfortunately, the most promising agent, Mianserin, is not available in the [United States]. Given that Mirtazapine is a close pharmacological cousin of Mianserin, there may be clinical benefit to further exploring the role of Mirtazapine in the management of cancer-related depression.”
In terms of side effect profiles, Mianserin appeared slightly more tolerable compared to placebo; paroxetine had slightly higher but nonsignificant dropout rate due to side effects compared to placebo; fluoxetine had a significantly higher dropout than placebo, though this finding became nonsignificant after removing a study outlier.
“Adverse drug interactions are possible between chemotherapy agents and antidepressants,” said Riblet. “Specifically tamoxifen, a common chemotherapy agent, may interact with certain antidepressants to increase risk of serious side effects.”
The different classes of antidepressants work on different neurotransmitters. The study reported that the alpha-2-andrenergic receptor antagonists show particular promise in cancer patients possibly due to their pharmacologic profile, which increases norepinephrine and serotonin. Alpha-2-andrenergic receptor antagonists are less likely to cause common serotonin-related side effects such as headache, agitation, jitteriness, or sexual dysfunction, but may contribute to sedation.
The review included nine randomized trials conducted between 1985 and 2011 with 4,700 eligible records from 1,169 patients from various countries. Overall, 83% of subjects were female with a mean age of 54 years.
“There is a scarcity of evidence to address the role of antidepressants in cancer-related depression,” said Riblet. “Our findings suggest there is a need for high-quality randomized clinical trials that explore the role of antidepressants in treating cancer-related depression.”