TCR: Dr. Goldberg, I know you’ve spent a lot of time thinking about and treating bipolar disorder over the years, beginning when you were a researcher at NIMH, then on the faculty of Columbia University, and most recently in your private practice and your managing of Depression Central. I was hoping we could begin by discussing some of the tricky aspects of diagnosing bipolar disorder.
Dr. Goldberg: I think the patients that provide the greatest challenge are those I often refer to as “crypto-bipolars.” These are folks who appear to have unipolar depression, but if you look a little harder and closer you will find a number of hints that, in fact, they may have something in the bipolar spectrum.

TCR: You’ve put together a great screening instrument to help us with the diagnosis (available free at http://www.psycom.net/depression.central.bipolar-screening.html).
Dr. Goldberg: This screening instrument grew out of a depression screening instrument I put together a number of years ago. Some psychiatrists from Denmark then translated it into Danish, and came back to me and said that some of the patients they identified on my scale who they treated with antidepressants went on to develop excited or manic states, and they wondered if I could come up with another scale that would pick up people who might convert to a manic state on antidepressants, and that is what led me to put together the bipolar screening scale.

TCR: And how do you use it in your practice?
Dr. Goldberg: Well, in my practice, before people come to see me, they get about 40 pages of questionnaires to fill out at home to bring in when they come to their first session. Among those 40 pages is the bipolar screening scale, the depression quantification scale, the mania quantification scale, and many other questionnaires.

TCR: And do you typically use scales over the course of treatment as well?
Dr. Goldberg: Yes, I have people fill out some scales both prior to the initiation of treatment and then at each visit subsequently, and find this to be very useful information. There is an old aphorism that says objective change precedes subjective change, and it is not at all unusual for someone to be reporting on the scales that they are able to concentrate better, they are able to make decisions better, they are sleeping better, they are feeling less guilty and so on. Yet, if you simply ask them, “How do you feel?” they might say, “Well, I’m just as depressed as I was two weeks ago.” So it is quite useful for them to see how their scores on these scales have changed from previous visits. This helps to reduce the demoralization that goes along with depression so often, in that the patient can actually see that they are successfully responding to the treatment even before they feel it.

TCR: Let’s shift a bit to a specific treatment issue, which is the use of lamotrigine in mood disorders. I understand that you have been quite impressed with its efficacy.
Dr. Goldberg: I have found lamotrigine to be probably the most interesting treatment that has come along since lithium.

“I think the patients that provide the greatest challenge are those I often refer to as ‘crypto-bipolars.’ These are folks who appear to have unipolar depression, but if you look a little harder and closer you will find a number of hints that, in fact, they may have something in the bipolar spectrum.”
– Ivan Goldberg, M.D.

TCR: That’s quite an endorsement, especially coming from someone who accepts no money from any of the drug companies! Why is lamotrigine so good?
Dr. Goldberg: The treatment of patients with bipolar depression has always been a problem in that a certain number of patients, when treated with conventional antidepressants, will either rapidly cycle, become hypomanic, or develop mixed states. While these complications are all possible with lamotrigine, the percentage of patients who develop them is much lower. So I think it is kind of a quantum leap in our ability to treat patients with bipolar depression and even patients with treatment-resistant unipolar depression.

TCR: So when you diagnose somebody with bipolar disorder, are you typically moving toward lamotrigine as a first-line agent?
Dr. Goldberg: Lamotrigine is frequently my initial drug of choice, but as lamotrigine (to use Calabrese’s terminology) does a much better job of stabilizing from below than from stabilizing from above, frequently my patients end up on a combination of lamotrigine and lithium.

TCR: Is that a combination that you find yourself using more than any other combination for bipolar disorder?
Dr. Goldberg: Definitely.

TCR: Tell me a little bit then how you like to start a patient on lamotrigine, including what you tell them about it before you prescribe it, because I think the issue of Stevens- Johnson Syndrome scares some patients off.
Dr. Goldberg: I tell my patients that lamotrigine is a fairly recently developed drug, that it has been around for eight or nine years now, that very frequently it is effective in controlling depression, and that unlike other antidepressants that could be used, it is much less likely to push people into mania or into rapid-cycling. I tell them that as opposed to most antidepressants, it is fairly easy to take and most people do not to have noticeable side effects, but there is one thing they should look out for and that is a rash. Most rashes that people develop on lamotrigine are benign, but there is a chance that the rash can develop into something quite serious and in fact, there have been some deaths in people taking the drug, but that if you increase the drug very, very slowly and stay alert for the possibility of an allergic reaction, the likelihood of getting into serious trouble is minimal. And patients usually ask me how many people have I treated with the drug, and I say a number of hundred and I then add that none of them has ever had a rash severe enough to require a consultation with a dermatologist.

TCR: When they ask about any other typical side effects, what do you tell them?
Dr. Goldberg: I say occasionally people may become dizzy and may become a little bit unsteady. And on very high doses there can be interference with memory.

TCR: And how do you dose them typically?
Dr. Goldberg: I typically start at 25 mg a day and then go up in 25 mg increments until we get to 200 mg and I will stay at that dose if they are doing well. If they are not doing well, however, I will get a lamotrigine plasma level.

TCR: A lamotrigine plasma level? That’s not something I’ve heard of.
Dr. Goldberg: I started to do plasma levels simply because a lot of people had gotten to 200 mg a day and had absolutely no response, and most of the papers on the use of lamotrigine were suggesting that 200 mg was the effective dose. It turned out that some people had very, very low plasma levels. I gradually identified that the people who seemed to do well often had plasma levels between 4 and 6 mcg/ml and so I began increasing the dose until patients achieved that level.

TCR: And how high will you dose it?
Dr. Goldberg: After reaching 200 mg, I will generally go up in 50 mg increments per week, which of course brings the dose well above the PDR’s recommended maximum of 200 mg QD for the treatment of bipolar disorder. In fact, in one recent case I went up to 400 mg BID before the patient responded.

TCR: Have you noticed any significant problems going up that high?
Dr. Goldberg: The only problem is some people, when they get up over 400 mg a day, may have slowed mentation and memory slippage.

TCR: What time of day should people usually take lamotrigine?
Dr. Goldberg: Most people take it all in the morning, because if they take it late in the day they may have problems sleeping. Other people are able to take it BID without any problem. The blood levels are generally done like lithium levels--exactly 12 hours after the last dose.

TCR: What is your experience in combining lamotrigine with lithium?
Dr. Goldberg: I have never seen any difficulties. What is interesting about the lamotrigine and lithium combination is that, for example, you might start somebody on lamotrigine and if they become a bit hypomanic on it, a relatively small dose of lithium (300 or 600 mg a day) is frequently enough to control the hypomania. You usually don’t have to achieve the same plasma levels as you do when using lithium as monotherapy.

TCR: And what else do you combine lamotrigine with for bipolar? We have certainly all heard about the potential difficulties with Depakote increasing levels.
Dr. Goldberg: Depakote can easily double the lamotrigine blood levels, which means that I’m more careful with lamotrigine dosing when Depakote is on board. You are often stuck with this combination in patients who cannot tolerate lithium.

TCR: Thank you Dr. Goldberg.