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The Growing Evidence for Antidepressants as Anticancer Agents

Prostaglandins are infinitesimal, ephemeral lipid signalers in every cell in the body, and regulating every activity that takes place within a cell. As regulators of cellular activity, prostaglandins influence how cells are formed and what part of the body the cell will become. Prostaglandins are vital for cellular growth, health, and replication. Prostaglandins regulate the normal life cycle of a cell, knowing when each cell must be repaired and when each one is beyond repair and has reached the end of its cycle.

Laboratory animal experiments in the 1960s demonstrated a powerful influence of prostaglandins on the brains of the animals and birds. Subsequent experiments showed that lithium and every antidepressant tested inhibit prostaglandins. Excessive synthesis of prostaglandins activates a number of mechanisms that result in cancer. Cancer cells grow too fast and multiply too rapidly. They aren’t repaired and don’t die at the end of their cycle. Excessive synthesis of prostaglandins disrupts the signaling mechanisms in which cells communicate with each other. It hinders optimum performance of the immune system, weakening it and turning it against itself. The weakened immune system allows cancer cells to thrive. About 20% of cancers are caused by pathogenic, or disease-causing, microbes. By inhibiting prostaglandins, lithium and antidepressants stimulate immune function and defeat microbes.

A study of people aged 70 and older, conducted in 1998, demonstrated that the chronically depressed were 88% more likely to develop cancer than their robust counterparts, the inference that antidepressants may be effective in treating or preventing cancer. There are more than forty laboratory studies showing that antidepressants destroy cancer cells, inhibit their multiplication, convert multidrug resistant cells to sensitive, protect nonmalignant cells from ionizing radiation and chemotherapy toxicity and enhance chemotherapy.

And there is even more good news. A mitochondrion is a tiny organelle that supplies cellular energy and is involved in signaling, cellular differentiation, control of the cell cycle, growth and programmed cell death. The cells of malignant gliomas of the brain, and small and non-small cell cancers of the lung, tend to repair DNA-breaks caused by radiation and chemotherapy. In an effort to accomplish cell death by an alternative method, investigators are targeting mitochondria. Small molecule agents known as “mitocans” are able to enter tumor cell mitochondria, reduce oxygen consumption and activate mechanisms leading to cell death. Agents that can destroy cancer cells in this manner, while leaving normal cells intact, notably include antidepressants. Laboratory experiments using this approach on various cancer cells, including those of gliomas, are very encouraging. It almost goes without saying that prostaglandins are intermediaries between antidepressants and mitochondria.

The mucus that lines the colon contains a high concentration of the enzyme that breaks down prostaglandins. The enzyme,15- hydroxyprostaglandin dehydrogenase, is absent when colon cancer is present. The absence of the enzyme promotes the growth of both benign and malignant tumors in the colon. Twenty years ago researchers showed, that of numerous drug tested, only two were capable of stimulating this enzyme-the antidepressants amitriptyline and imipramine, which increased enzyme production by more than a thousand fold.

Hot flashes are an unpleasant side effect of chemotherapy, but antidepressants have been shown to reduce their number and severity. Antidepressants can prevent or stop the nausea and vomiting that chemotherapy often causes. They can reduce pain and boost the effects of narcotics. They can promote sleep, stimulate appetite, and invigorate. When taking antidepressants, a patient is more likely to comply with treatment. Antidepressants increase the body’s ability to fight off infections caused by radiation or chemotherapy.

It is not known if antidepressants alone can be used effectively to treat cancer, or when and if they should be used in conjunction with traditional methods of treatment such as radiation and chemotherapy. There are no known biological markers that can match antidepressant to patient, and multiple trials may be needed. By elevating a patient’s mood - minimizing feelings of remorse, soothing anxiety, and softening the fear of death - antidepressants can have a favorable impact on the emotional aspects of cancer.

Clinical evidence supporting anticancer properties of antidepressants has not as yet accumulated, largely because drug companies seldom fund studies with generics. Moreover, as David Horrobin pointed out, large scale clinical trials in rapidly lethal diseases may well be unethical. It should be for patients and their physicians to decide whether the epidemiological and laboratory evidence supports a role for antidepressants in cancer therapeutics. Innovation is direly needed in many branches of medicine, but there are powerful forces arrayed against it.

Source: PubMed

Posted by: Julian Lieb, MD 

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