Transcript: Concerns for Patients with Major Depressive Disorder and Insomnia Symptoms

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Dr. McCall:  Hi. I'm Vaughn McCall. I am the Case‑Distinguished Chair of Psychiatry for the Medical College of Georgia and the Executive Vice‑Dean for MCG. My clinical and research interests revolve around the intersection between sleep problems and mood disorders.

Q:  What were the key takeaways from your recent session at the APA conference?

A:  I recently had the opportunity to present some information about the relationship between sleep problems, specifically insomnia and suicide, at the recent American Psychiatric Association annual meeting. Some of the key takeaways are that it's quite clear that insomnia is a risk factor for suicidal ideation, suicidal behavior, and suicide death.

This has been replicated at least 80 times. It's been shown to be true in children, adolescents, young adults, and the elderly. It's true in North America, South America, Europe, Asia, and Australia. It's definitely true, true, and true. We're still working out the reasons why this might be true.

One of the key takeaways in my opinion for the clinician is that, since insomnia is often a signal of increase in suicide risk, I view it as the canary in the coal mine. In the event that a patient presents for their first visit with serious insomnia, that's a signal that it's worth digging a little bit into the details about any present suicide risk or prior suicidal behavior.

By the same token, if an established patient who has been sleeping well now presents with new complaints of emerging severe insomnia, then the same thing is true. It'd be worth segueing and asking questions about suicidal ideation and behavior. An important question, of course, is what to do about it besides asking about the presence of absence of insomnia.

Should we treat insomnia as a way of reducing suicide risk? The very preliminary answer is it seems to be the case. Now how we go about treating insomnia is more complicated than it should be. The American College of Physicians and the American Academy of Sleep Medicine both recommend non‑pharmacologic treatments for insomnia first.

The formalized approach to this, of course, would be cognitive behavior therapy for insomnia. For the psychiatrists who are listening, I want to assure you that we all have simple things we can do to help our patients sleep better without using medications without necessarily being experts in the details of cognitive behavior therapy for insomnia.

Simple things like paying attention to when patients go to bed, when they get up, do they take naps, and so on and so forth can be useful. In many cases, we will decide to prescribe. Another key takeaway from our presentation was trying to understand the real risk of hypnotic medications, FDA‑approved hypnotics, Schedule IV drugs in particular, for suicide risk.

What we know is that it's absolutely true that hypnotics are often part of a suicidal behavior or a suicide attempt. What's not clear, if that is actually hypnotic that is making someone suicidal. Instead, in the vast majority of cases, the hypnotic is simply a vehicle or a means which is used for the suicidal act. It is not clear that it causes people to become suicidal, at least not very often.

That's not the primary concern. The final takeaway from our presentation was a medium‑sized clinical trial showing that targeted treatment in insomnia, in this case with extended‑release Zolpidem, compared with placebo produced better results in mitigating suicidal ideation in depressed outpatients who were already taking an SSRI.

Q: What are the implications for clinicians in the field treating insomnia?

A: A interesting question is, if hypnotics have a role in reducing suicidal ideation or suicide risk via the treatment of insomnia, then how should the hypnotics be handled? I can just reflect upon changes in my own practice over the last 10 to 20 years. 20 years ago, I would sometimes have the initial prescription for hypnotics be a 30‑day supply. In retrospect, that would seem now to be a mistake.

In treating patients that are in particular those who have major depressive disorder, who have severe insomnia, and have some degree of suicidal ideation, my practice is now only to give a one‑week supply.

Then to check back with the patient at the end of a week to see if the treatment is having the desired effect and hopefully the avoidance of unwanted side effects such as daytime sedation or bizarre nighttime behavior such as parasomnias. At the end of a week, if things are going well, I might refill it for another week.

Then, when we all are comfortable with the situation, perhaps a two‑week supply.

A final comment based upon our work and then the work of others is interestingly in the specific instance of depressed folk who have insomnia and who are getting an SSRI, for example, as their mainstay antidepressant treatment, it's not at all clear that we really have to continue the hypnotic, if you add it on, for more than a month.

There are now two studies. One is ours and another with the hypnotic, Eszopiclone, which showed, after eight weeks of combined treatment with an SSRI, the hypnotic can be stopped without fear of a rebound insomnia. The patients continue to do very well, probably because the antidepressant medication's doing its job.

Just to recap a couple of points. The initial prescriptions in people at risk for suicide should now, of course, be only a handful of days, maybe a week or so with rapid follow‑up, and then refills of prescriptions as indicated. Then hopefully, after a period of a couple of months, withdraw one of the hypnotics altogether.

Q: What are the concerns in patients with MDD who are also experiencing symptoms of insomnia?

A: The vast majority of outpatients, and especially in patients who have major depressive disorder, are going to complain of insomnia. In the outpatient setting, it's at least 60 percent. In the inpatient setting, it's close to 90 percent.

One of the concerns about trying to address this particular scenario is that SSRIs by themselves don't necessarily seem to be reliable treatments for insomnia. We now know that one of the most common residual symptoms of major depression after initiation of SSRI monotherapy is residual insomnia. We need to be alert to the fact that insomnia may, in fact, require its own targeted treatment.

The second thing that I would mention is that, while most insomniac persons do not have obstructive sleep apnea and while obstructive sleep apnea most often presents, I think, with hypersomnia or falling asleep during the daytime, it's certainly possible that a person with depression who only complains of relentless insomnia may, in fact, have obstructive sleep apnea.

In our series we found on a couple of occasions that about one in seven major depressive disorder patients with insomnia actually had obstructive sleep apnea. We need to be alert to that possibility.

Q: You mentioned that there is no firm evidence that any one hypnotic is more likely to lead to suicide. What do clinicians need to know about strategic prescription of hypnotics?

A: When providers are thinking about selecting a specific FDA‑approved hypnotic to address insomnia complaints in patients with depression, or even in patients that don't have depression, we have a lot of choices.

There is at least a dozen or more FDA‑approved hypnotics on the market, which include Benzodiazepines, non‑Benzodiazepine/Benzodiazepine receptor agonists, melatonin one receptor agonists, orexin receptor blockers, and low‑dose Doxepin among others.

There really is no evidence that any one of these classes of medications is more likely to induce the very rare event of suicidal ideation. What we do know, based upon adverse reports which had been sent to the FDA, is that very, very rarely we do see what appears to be a specific parasomnia behavior with Zolpidem.

There are case reports of people with no prior history of suicidal ideation or suicidal behavior who, within a span of one or two nights, committed suicide after their first few doses of Zolpidem. It's as if they had a paradoxical reaction, a somnambulistic response when they were intoxicated with the medication.

The medication had produced an adverse central‑nervous‑system effect. Yet the patient was still able to get up and walk around under those conditions. Under that particular set of conditions, terrible things happened. I want to re‑emphasize this is extremely rare. Probably no more than one in every million doses of hypnotic medication, if that. Perhaps fewer.

It's still such a terrible event that, when we prescribe hypnotic for the first time, as we're collecting adverse events from our patients who have just started the prescription, it's always worth asking, "Have they had any weird behavior occur during the first couple of nights?"

As we wrap up, I'd like to just reiterate and speak to several misconceptions in the area of treating insomnia.

The first is that doing simple behavioral interventions from a psychiatrist's point of view is out of reach for us. We've perhaps not been specifically trained in how to do cognitive behavior therapy.

I will agree. Cognitive behavior therapy for insomnia is a specific undertaking, requires skill and training. There are elements of it which are so simple that I mentioned earlier, such as asking the patient direct questions about when they go to bed and when they get up. It will reveal easy opportunities for correction.

The second misconception would be that hypnotics frequently induce suicidal ideation or behavior. While this can happen, it's exceptionally rare and should not be an impediment for the occasional prescription of short doses of hypnotic medications when we feel like it's in the patient's best interest.

The third misconception is that hypnotics necessarily have to be prescribed for very, very long periods of time. Once you open the genie's box, the genie comes out, and you can't put it back in. That's not necessarily true.

At the initiation of hypnotic prescription, if we're very clear to the patient that our hope is this is for a timed limited period of maybe four to eight weeks, there's a reasonable chance that the hypnotic, in fact, could be stopped after four to eight weeks without rebound or without the need to reintroduce the hypnotic.