Receptor Profiles Should Drive Sleep Intervention Choices: Video Transcript

June 19, 2014

Karl Doghramji, MD, Professor at the Sleep Disorders Center at Jefferson University in Philadelpha, Pennsylvania, joined Rakesh Jain, MD, MPH, to talk about how clinicians can benefit from considering the mechanistic receptor profiles of interventions for sleep disorders. The transcript of their conversation is below. Click here to view the video.

Dr. Jain: We have Dr. Karl Doghramji with us, and therefore I want to take advantage of every minute I have with you. Sleep, as we know, is a tremendous challenge for us in psychiatry and primary care, and we are learning, aren’t we, that gabaergic interventions, while useful, there are some challenges with that. So, do this for me. Would you tell us a little bit more about how we clinicians should think about interventions—that are either here or that are coming—from a mechanistic receptor profile standpoint.

Dr. Doghramji: This is a very critical question, because we’re beginning to understand that the mechanism of depression is not uniform across depressive states. So, for example, we know that insomnia is a big feature of depression, but that insomnia might be mediated through melatonin receptor issues, serotonergic issues, or other receptor profile abnormalities. 

I think one of our first jobs as clinicians is to be able to identify the nature of the sleep disturbance to be able to treat it more directly. 

As an example, we know that a number of people with depression feature circadian or psychoabnormalities—delayed sleep phase is one example where people fall asleep late and then wake up late. Now, that sort of delayed sleep phase is eminently treatable even with agents that we have available to us currently, such as melatonin. 

Melatonin given for a few hours before bedtime, in conjunction with bright light therapy in the morning, can gradually produce a phase advance (an earlier sleep-wake time) in people who are either depressed or not depressed, who have delayed sleep phase syndrome. 

Dr. Jain: So you are advocating for the appropriate use of melatonin for that, but what if it doesn’t work? What are some options that I have? What should I be thinking mechanistically? 

Dr. Doghramji: Mechanistically, in people like this, it may be a good idea to think more about the melatonin system. For example, agents that are being developed in this area, tasimelteon is one of them, which may be soon available for the treatment of what we call non-24-hour sleep wake syndrome. (Note: In January 2014, The FDA approved tasimelteon for non-24 hour sleep-wake disorder in totally blind people only). These are individuals who sometimes are blind, who develop a gradual phase delay. Their sleep-wake cycle begins to become later and later and later in the day. And they really have no control. They stumble, if you will, to a later and later time. And agents such as that may be very useful for them. 

Dr. Jain: What about non-pharmacologic? What can I do from a non-medication, behavioral standpoint. 

Dr. Doghramji: So, let’s take light as an example. The timing of light can be so critical in when we wake up and when we go to sleep. When we wake up in the morning, exposure to bright artificial lights, or bright regular lights, is very helpful in terms of correcting our circadian rhythm. 

And the converse is true as well. When we go to bed, there should be minimum light exposure. Interestingly, data have shown that light as bright as some of the PDAs could influence sleep in a negative way if people use them close to bedtime. 

So, darkness for about an hour or two before bedtime, as much as possible, and bright light in the morning, can be very helpful in terms of shifting things in the correct direction. 

Dr. Jain: I’ve got it. Thanks, I’ve really enjoyed this one-on-one consultation regarding a problem I face all the time in my clinical practice.