TCR: Dr. Posternak, thank you for agreeing to speak with us and I also want to thank you for having collaborated on a series of research articles that have been extremely useful to clinicians. I’d like to start with your article about factors that we use when we are selecting antidepressants (Zimmerman, Posternak, et. al., Am J Psychiatry 161:1285-1289, July 2004). How did that study come about?
Dr. Posternak: Most psychiatrists pretty much agree that all antidepressants are more or less equally effective. So if you start with that premise and you have 10-15 antidepressants out there, why are you picking one versus another? And what algorithm are we all using? Dr. Zimmerman developed a questionnaire for psychiatrists to fill out immediately after they wrote antidepressant prescriptions. We asked, “What influenced you to choose that medication?”
TCR: And what were your findings?
Dr. Posternak: We found that there were three compelling factors: The first was avoiding specific side effects, the second was the presence of comorbid psychiatric disorders, and the third was the presence of specific clinical symptoms. For example, many people wanted to avoid sexual side effects or weight gain and would choose meds based on this. And if a patient had depression plus panic disorder, for example, we would lean toward the SSRIs. And if someone’s clinical profile included both insomnia and poor appetite, we might choose Remeron (mirtazapine). As you can see, there was nothing terribly earth shattering about any of these findings, but they give us insight into what factors people are actually considering when they prescribe an antidepressant.
TCR: Do you find that there is much research support for the validity of these factors?
Dr. Posternak: No, because there isn’t much research to begin with. For example, if you look for papers on antidepressant efficacy for patients with comorbidity (and comorbidity is the norm rather than the exception) there is almost nothing out there. Most treatment trials assessing depression exclude patients with comorbid disorders or do not assess for them. A prototypical example would be the common practice of avoiding bupropion in patients with depression and significant anxiety. And yet John Rush and colleagues have published three papers showing no difference between Wellbutrin and sertaline in efficacy for anxiety in depressed patients (see, for example, J Clin Psychiatry 2001; 62:776-781).
TCR: You and Dr. Zimmerman have also written about the concept of “remission,” which has become the gold standard for antidepressant trials lately. How do you suggest we decide when a patient has responded well enough to an antidepressant?
Dr. Posternak: I think that is a terrific question. Even from a research standpoint, there is something problematic about using “remission” as the endpoint of a study. The problem is that, both in clinical trials and in our practices, patients start off with different degrees of depression. So let’s say you define your endpoint as a HAM-D score of 7 or less. A patient who starts at a HAM-D of 26 and has a 50% improvement will not meet criteria for remission, but will nonetheless feel much better than when they started the medication. Many patients may not reach the formally-defined point of remission, and may have residual symptoms and yet you and your patient may decide that you are satisfied with that response and you don’t want to keep pushing the dose or switching medications.
TCR: What research instruments would you suggest for use in our practices?
Dr. Posternak: Over the years, I have come to conclude that the CGI (Clinical Global Impression) is a pretty good judge. I ask patients, “Do you think your depression is partially improved or much improved since starting medication?” Usually if they are “much improved,” this corresponds with a greater than 50 percent improvement on the HAM-D, and most of us are not going to switch medications at that point. You might still try to tweak the regimen to help them sleep or improve their energy, but generally we would say that we have found something that seems to be worth sticking to.
TCR: And what are your favorite medication manipulations for tweaking the regiment to enhance response?
Dr. Posternak: The two that I use the most, and that I think are the simplest and most effective are: 1) Ensuring that patients get adequate sleep, and 2) Enhancing energy.
TCR: Tell me a bit about sleep. Why is this so important in resolving depression?
Dr. Posternak: When people don’t sleep it affects many other things like energy, concentration and mood, often leading to irritability. So one of the simplest interventions that I can do for my patients is to help them get a good night’s sleep. Some people are reluctant to take a sleep medicine and if so, I say to them, “This is important for your depressive illness, because if you don’t sleep well the research studies have demonstrated that you are going to be at higher risk for relapse.”
TCR: What are your “go-to” agents for insomnia?
Dr. Posternak: Well I often start with trazodone, because it is safe, it generally doesn’t lead to tolerance, and people like the fact that it has no addictive potential. I usually start at 25 mg because I don’t want them to get turned off from being groggy in the morning. If it doesn’t work at that dose, I will titrate the dose fairly aggressively until they are either sleeping well or they have limiting side effects. You can safely go up to 600 mg, which is an antidepressant dosage.
TCR: What do you do if trazodone doesn’t work?
Dr. Posternak: I like Remeron, but very often this is not an option because people are concerned about weight gain, so then I will move to benzodiazepines.
TCR: What about the non-benzo’s, like Ambien or Sonata?
Dr. Posternak: I rarely go to these next for a very simple reason, which is cost. I generally stick with the generics. I think that they are at least as effective and they are a fraction of the cost. My sense is that the non-benzos are marketed based on their lower risk of dependence or addiction, and yet I find in my clinical practice that people do not get addicted to sleeping pills. It just doesn’t happen, so why should we spend so much money on these other medications? I explain that to patients.
TCR: What benzos do you usually use?
Dr. Posternak: I simply use Valium (diazepam), 5-10 mg.
TCR: Why Valium and not Ativan (lorazepam) or Restoril (temazepam), or the others?
Dr. Posternak: Lorazepam is short-acting, so I find it less effective. Xanax (alprazolam) is the same thing; it is a very short-acting medication. It may help them fall asleep. It may even help the first few nights, but I find if I am treating more long-term insomnia that tolerance builds up. Restoril should be as effective as Valium in theory based on half-life, but in clinical practice I haven’t found that to be the case.
TCR: What about Klonopin?
Dr. Posternak: Klonopin I find is less sedating, which is useful for a daytime anxiolytic but I find that it is just not as effective as a hypnotic.
TCR: You also mentioned enhancing energy?
Dr. Posternak: Yes, and what I use for this, and what I feel is underutilized, is psychostimulants. A lot of times people are depressed, are not as happy as they would like, because they are not as focused or their energy isn’t as good. Like sleeping pills, stimulants have an immediate effect, which is nice and it is quite dramatic.
TCR: And then which specific medication do you like to use?
Dr. Posternak: Well, being boring and simple, I start with plain old generic Ritalin (methylphenidate) and I dose it 5 to 10 mg twice a day, early morning and early afternoon.
TCR: And what do you tell patients when you give it to them about potential side effects?
Dr. Posternak: I tell them that it is very well-tolerated, that its purpose is to increase their energy and help their concentration, and that we can increase the dose if it doesn’t work. As far as side effects, I’ll say, “You might get a tremor, it could increase your anxiety, it could cause insomnia, it could increase your heart rate, but in general people tolerate it very well.”
TCR: Do you see problems with stimulant abuse?
Dr. Posternak: A small minority of my patients report that they tended to get euphoric on stimulants and then crash afterwards. But this is rare.
TCR: How do you deal with prescribing stimulants long term?
Dr. Posternak: Once they are stable and I want to see them every three months I give them two post-dated prescriptions.
TCR: Is there anything else that you have been doing lately for antidepressant augmentation?
Dr. Posternak: Yes, we just completed a randomized trial of T3 (triidothyronine, trade name “Cytomel”) augmentation, and we found that it accelerated antidepressant response in comparison to placebo augmentation.
TCR: What dose did you use?
Dr. Posternak: 25 mcg QD.
TCR: Many psychiatrists are tempted to use Cytomel but are concerned about causing medical problems by adding thyroid hormone to our patients’ systems. What are your thoughts about that?
Dr. Posternak: I don’t think that they have to be concerned about that. If someone has an arrhythmia, I wouldn’t use it, but otherwise 25 mcg. is a very low dose; it is quite safe and you really don’t have to be concerned about that from a clinical standpoint.
TCR: And before you start, do you recommend that we get any particular labs?
Dr. Posternak: No, it is not necessary. If you use T3 and it works, then you will want to get a TSH at some point just to make sure you are not affecting the thyroid gland. But if it doesn’t work, you’ll just stop the medication and you’ll save your patient a blood draw.