Researchers want to know whether a sleeping pill reduces suicidal thoughts in depressed patients with insomnia.

"The more we look at it, the more it looks like insomnia by itself is a predictor of suicide so the next question becomes: Why not treat insomnia strategically as a focus of care and see if that reduces suicidal thinking," said Dr. W. Vaughn McCall, Chair of the Medical College of Georgia Department of Psychiatry and Health Behavior at Georgia Regents University.

McCall is principal investigator on a $1.2 million National Institute of Mental Health grant to objectively assess patient response to this strategy. The study at GRU, Duke University and the University of Wisconsin is enrolling 138 adults over four years. To help ensure their safety, all participants will receive the anti-depressant fluoxetine for the eight-week trial while half will also get the sedative-hypnotic zolpidem.

It's a complex treatment conundrum that the study hopes to unravel. Some physicians are understandably concerned about giving sleeping pills to people with suicidal thoughts. "We are faced very commonly with a patient who is not sleeping, is depressed, is suicidal and the treating physician is understandably concerned about giving that patient sleeping pills," McCall said.

In fact, some sleep experts routinely condemn sleeping pills, saying the pills are potentially deadly, independent of suicide. Other people with chronic insomnia never seek professional help, trying home or natural remedies while their negative thoughts about sleep escalate. If they do seek medical care as problems mount, they may find themselves with a doctor hesitant or even adamant about hypnotics, McCall said.

If researchers can show a direct link between insomnia treatment and reduced suicidal thinking, it could help mainstream targeted drug therapy as well as non-drug approaches such as cognitive behavior therapy, a structured talk therapy that targets faulty thinking such as, 'I will never sleep again,' said McCall, who also uses this approach.  

Researchers have evidence that the intensity of insomnia correlates with the intensity of suicidal thoughts as well as a pilot study linking proactive hypnotic treatment to reduced suicidal thoughts. In fact, 31 studies have linked insomnia to suicidal thoughts, behavior or death. Still suicide risk factors and prevention often overlook insomnia, McCall said.

Acknowledging the very vulnerable population they study, there are numerous safeguards built into the research protocol such as participants only getting one week's supply of sleeping pills for the first two weeks, then getting a two-week supply if their suicidal thoughts stabilize. Additionally, they will be asked to take the drug shortly before going to bed and to allow eight hours for sleep.

Sleeping pills such as zolpidem accentuate the body's normal mechanism for sleep by targeting GABA, a neurotransmitter that essentially turns the brain's metabolism down, McCall said. Existing antidepressants don't affect GABA.  Many over-the-counter sleep aids are essentially anti-histamines; histamine is another neurotransmitter that helps keep you awake. In insomniacs, GABA tends to be underactive while histamine works overtime.

Insomnia is a symptom and about half of all cases are related to a mental disorder such as depression. About 90 percent of patients hospitalized for depression and 60 percent of those treated as outpatients also have insomnia, McCall said.  Not sleeping also can also be tied to personality, specifically hypervigilant individuals who are always "on." "They just can't relax," said McCall, who admits to at least a small case of that himself. Others have life-issues, such as divorce or illness, that can cause transient insomnia. In others, it's a long-standing problem with no obvious basis.

Patients with insomnia that persists over a year have a 30-fold increased risk of developing depression compared to the insomniac who gets treatment. "That is like the risk of cigarette smoking for cancer: it's huge," McCall said. This begs more questions about how insomnia causes depression and, if you're already depressed, how insomnia aggravates suicide risk, he said.

He notes there is a subset of depressed people, particularly young people, who sleep too much, and that older people generally have a harder time falling and staying asleep.

Wake Forest University will assist in statistical analysis for the study. Individuals with sleep apnea as severe suicidal thoughts will be excluded. Participants will be referred for outpatient management at the end of the study.