TCPR: Dr. Baldassano, it’s great for generalist psychiatrists to talk to an expert in bipolar disorder because, let’s face it, it can be a tough and confusing diagnosis, and deciding on treatment isn’t always easy either. How much of your time is spent treating patients with bipolar disorder?

Dr. Baldassano: Quite a bit of it. At UPenn, I’m the director of the bipolar outpatient clinic and co-director of our mood disorder consultation service. I see patients with bipolar disorder and educate residents through hands-on teaching. We follow over 500 patients with bipolar disorder, often seeing patients who are relatively refractory to treatment.

 

TCPR: I’m guessing that many of the patients you see come into the clinic with a diagnosis of bipolar disorder already?

Dr. Baldassano: Often that’s true, but even when patients come in with the diagnosis, an important part of my job is to review their history and not make the assumption that they have the disorder. Just because they’ve carried the diagnosis in the past doesn’t mean they actually have it.

 

TCPR: So how does one go about doing a world-class evaluation for bipolar disorder?

Dr. Baldassano: You have to be as systematic as possible. Before we talk to patients, we have them fill out some forms that are useful. These include a diagnostic screening form, the Mood Disorder Questionnaire (MDQ), three symptom scales—the Beck Depression Inventory, the Beck Anxiety Inventory, and the Quick Inventory of Depressive Symptomatology—and finally, and very importantly, we’ve created a medication history form that allows them to quickly circle all the meds they’ve been on in the past [Editor’s note: This form is available at http://bit.ly/1rTgHyu]. It may sound like a lot, but patients can fill these out in the waiting room and it takes them less than 10 minutes.

 

TCPR: What sorts of questions do you begin with in order to ascertain patients’ diagnoses?

Dr. Baldassano: I start with the usual things, “Why are you here? Are you coming here for ongoing care, or consultation?” and then I always ask, “What diagnosis have previous physicians given you?” and if they say bipolar, my first question is often, “Well why did they diagnose you with bipolar?” Because the answer to that question can really help with the rest of your interview. They might say, “I was in the hospital after a manic episode,” and then you would go right to that episode and ask about that, which helps very quickly to identify if the patient has bipolar. But if they’re not sure—which is more common than you’d think—they’ll often come in and say, “Well I don’t know, someone diagnosed me with this, but I don’t know why.”

 

TCPR: Where do you go from there?

Dr. Baldassano: At that point I will start by focusing on previous depressive episodes. I’ll go through a structured clinical interview, starting with, “Have you ever had an episode where you felt sad or down for most of the day for nearly two weeks?” Then we’ll go through all the DSM-5 symptoms and ascertain that they’ve had a depressive episode. Then I want to know how many episodes of depression they’ve had, and a lot of times patients will say, “I’ve been depressed my whole life,” and I say, “Really? Let’s talk more about that. Have you ever had a period of two months or so when you felt better than that?” And you’ll often find that although patients perceive these as one long episode, if you persist, you discover that there were actually periods of inter-episode recovery. Another way I’ll put it is: “Over the past two years what’s the longest period your mood has been well or normal?” My goal here is to avoid the “snap shot” and attempt to put together an entire photo album. I want to understand their longitudinal course. I’m trying to figure out how many depressive episodes they’ve had, and what percent of time they’ve suffered from depression. Now it’s possible that they’ve in fact had a two-year depression, but that is unusual. After I ask about depression, I’ll go through a similar string of questions for mania, and in this case I try to focus on whether their periods of mania really interfered with their functioning (which would qualify them for bipolar type 1) or whether they were milder hypomanic episodes, which would imply bipolar type 2.

 

TCPR: Does it really matter what kind of bipolar you diagnose?

Dr. Baldassano: For research it does, but even clinically it can have an impact. For example, if the mood elevations are milder and had little impact, I would be more likely to prescribe lamotrigine (Lamictal) as monotherapy—as it has more evidence for preventing depression than preventing manic episodes, and its side effect profile is good.

 

TCPR: Does a bipolar 2 diagnosis also make you more comfortable prescribing antidepressants, because you might be less concerned about the consequences of triggering a hypomanic episode?

Dr. Baldassano: Not really. My main qualm about using antidepressants in type 2 is a lack of efficacy rather than a manic switch. That being said, I don’t often use antidepressants in either type 1 or type 2.

 

TCPR: What about patients with other syndromes, like anxiety or substance abuse. How do you disentangle these kinds of symptoms from bipolar disorder?

Dr. Baldassano: Let’s start with anxiety, because anxiety is the single most common comorbid condition in bipolar patients. It certainly adds a layer of complexity. I get referrals from anxiety disorder clinics and find that patients who were diagnosed with anxiety actually have bipolar, but it goes the other way too—patients come to me with a bipolar diagnosis and it’s actually anxiety.

 

TCPR: Which comorbid anxiety disorder muddies the diagnosis the most?

Dr. Baldassano: Probably generalized anxiety disorder (GAD). These patients will describe racing thoughts and feeling restless, and many clinicians will not probe deeply enough when they hear about “racing thoughts.” They’ll jump right to manic symptoms. But patients with GAD may have racing thoughts that sound more like anxious ruminations. To clarify, I’ll ask about symptoms such as irritability, sleeplessness, and feeling hyper. One of my favorite go-to questions is, “Do you feel like the Energizer bunny but you have nowhere to go?” If a patient acknowledges that, I’m more likely to suspect bipolar.

 

TCPR: Any tips on diagnosing bipolar disorder in substance abusers?

Dr. Baldassano: My rule of thumb is to refrain from making the diagnosis until there is a period of sobriety. For example, I recently saw a patient with a history of cocaine abuse. He had been off drugs for several months and when I evaluated him he had clear cut hypomania, was sleeping less, and feeling good; his thoughts were racing, he was more likely to want to spend money. I saw him two weeks later when his mood dropped into a depression, and he said he was more likely to want to use cocaine during depression. In that case I felt pretty certain that the primary disorder was bipolar disorder, and the secondary diagnosis was cocaine abuse—but it can be challenging to make these distinctions.

 

TCPR: I’d like to shift to a topic that psychiatrists probably don’t think about as much as we should, which is how we discuss our diagnostic impressions with our patients. How do you approach this in your work with bipolar disorder?

Dr. Baldassano: I do think it’s important in your diagnostic interview to save enough time for psychoeducation. If we did that, we would be more likely to have compliant patients, because they would understand the need for treatment. I will typically spend 15 to 20 minutes explaining to my new patients what I believe their diagnosis to be. I’ll come right out and say, “I think you have bipolar disorder.” You look at their reaction. Sometimes they are obviously uncomfortable with the diagnosis, and sometimes they might disagree. I’ll say, “This is why I think you have it,” and go through my thought process. If I sense it’s a difficult diagnosis for them to accept, I’ll soften the blow by saying something such as, “There are two major types of depression—unipolar depression and bipolar depression. You suffer from bipolar depression.”

 

TCPR: Are there other things you discuss with patients?’

Dr. Baldassano: I also talk to patients about the prognosis and treatment course, saying something such as: “Bipolar disorder is lifelong, we don’t cure it, but we have medications that can help treat it and our goal is to extend your period of wellness as long as we can.” I’ll often use the analogy of diabetes, and it’s an analogy that works well, because bipolar disorder, like diabetes, is lifelong. You probably have to stay on medication, but it’s not enough to just take meds—you have to eat right, get exercise, check your blood glucose. In both illnesses, you have to be an active participant in your care by adhering to a routine and structure. For bipolar, I talk about the importance of mood charting, being aware of what triggers your mood episodes, knowing that early identification of episodes tends to help treatment. And I give them handouts and recommend two books in particular, one is Take Charge of Bipolar Disorder (Fast JA, Preston J. New York: Warner Wellness; 2006), and the other is a cognitive therapy workbook titled Managing Bipolar Disorder: A Cognitive Behavior Treatment Program Workbook (Otto MW, Reilly-Harrington NA, Kogan JN, Henin A, Knauz RO, Sachs GS. New York: Oxford University Press; 2009).

 

TCPR: I thought we might wrap up by talking about ways that we non-specialists can improve. What are one or two of the biggest improvements you'd like to see in the way referring clinicians practice?

Dr. Baldassano: One of the things I see is that patients often come to me on very complex regimens of too many medications. We tend to be good at adding medications, but not good at taking away meds. We as a field need to get better at evaluating how a patient is responding to a course of medications, and if they are not responding, we need to be willing to discontinue some of them. And related to that, we need to do a better job of ascertaining whether patients are taking their medications at all. In my interviews, I usually ask patients if they are taking their medication, because unless you ask it, they won’t tell you. The other major thing I’ve seen is a reluctance to prescribe lithium, which can be very effective for patients in all phases of bipolar disorder. So often, I’ll do a four hour consultation for someone with treatment-resistant bipolar disorder only to find that they’ve never had a lithium trial, and are not doing well on the more modern and more expensive medications.

 

TCPR: Well why don’t we help our readers learn more about lithium. You’ve prescribed it to hundreds of patients. Tell us how you prescribe it.

Dr. Baldassano: First, I prepare patients because many of them are scared of lithium and associate it with the severely mentally ill in state hospitals. I tell them it’s one of the gold standard treatments for bipolar; that it’s been around since 1970 and we have long clinical experience with it. I also say, “It is a natural element. You’ll find it on the periodic chart,” which helps defuse the fear of taking it to some extent. And then I prepare patients for the monitoring required: “This is a medication that requires a level of responsibility because there are certain precautions. For example, we’ll need to get blood levels, because it has a narrow therapeutic index, meaning that if it goes too high it can be dangerous, and if it goes too low it won’t be effective.” I also tell patients right away that they need to stay hydrated while taking it, and by that I don’t mean forcing down eight glasses of water a day. I mean if they are dehydrated for some reason, such as having the flu or running a marathon, they need to be especially aware of the need to drink. Finally, I make sure they tell their other doctors that they are taking it, because there are various drug interactions possible.

 

TCPR: And once you’ve laid this groundwork for your patients, what formulation do you use and how do you dose it?

Dr. Baldassano: I start by prescribing 300 mg immediate-release lithium taken at night. Data shows immediate-release at bedtime is better for kidney function, because the kidney likes having one peak level that goes down, rather than a constant level all day which results from controlled-release formulations. I instruct them to stay at 300 mg for five days, then take 600 mg for five days, then 900 mg. After at least five days on 900 mg, I have them go to the lab for a trough blood level, drawn 12 hours after the last dose. However, in geriatric patients I will have them stay at 600 mg and get that level.

 

TCPR: What baseline labs do you order, and do you make sure to see baseline labs before they take their first dose?

Dr. Baldassano: I order baseline tests to measure thyroid stimulating hormone (TSH), a blood urea nitrogen (BUN) test to see how well the kidney and liver are working, and a creatinine blood test. While textbooks will tell you to get labs before the patient starts taking lithium, in clinical practice this means you end up delaying the first dose, sometimes substantially. Meanwhile, your patient is suffering. So I don’t have patients wait, but I do impress upon them the importance of getting labs soon, within a week of starting the lithium.

 

TCPR: What kinds of issues do you see as patients are titrating their dose up?

Dr. Baldassano: The most common early side effects are gastrointestinal, such as nausea, queasiness, and cramping. I tell patients to stop increasing the dose if they experience these, and to wait until the symptoms go away before resuming the titration. Every once in a while, I will see a patient referred to me who is on an extended-release lithium who is having diarrhea, and an easy fix is to simply switch them to immediate-release once a day—this almost always works.

 

TCPR: How do you interpret lithium levels?

Dr. Baldassano: Before I evaluate the levels, I’ll always ask the patient “was this a 12-hour blood level?” because many times it isn’t a trough level and then the number is not useful. But I’m aiming for a lithium level of 0.8 or above, especially for bipolar depression, which, in my experience, tends to require higher blood levels for efficacy. I try not to go higher than 1.1 because most patients have side effects above that. If they are subtherapeutic, I will increase the dose, using the rule of thumb that every 300 mg addition leads to about a 0.2 increase in blood level in nongeriatric patients. Each time I increase the dose, I ask them to get another level after at least five days have passed. Generally I get patients therapeutic within a month using this procedure.

 

TCPR: What about follow-up labs after the level is therapeutic?

Dr. Baldassano: There are no official, specific guidelines on checking labs. I do another lithium level four to six weeks later, including a BUN, creatinine, and TSH. If they are new to lithium, I might check it one more time in eight weeks, and once I’ve established this person is doing well, and they have a consistent level, I may not check it again for six months. I usually check lithium twice a year, but in some very stable patients only once a year. Meanwhile, I’ll check BUN/creatinine at the same frequency I check lithium levels, and I check TSH less frequently, usually once a year. One important thing to know about the thyroid is that if you see TSH increasing, then you have a discussion with the patient. Because about 3% of patients will develop permanent hypothyroidism, and this is more common in women. It can be reversible, if it’s caught within six to eight months, but the patient has to stop the lithium.

 

TCPR: Thank you, Dr. Baldessano.