Case 3: Bipolar depression and anxiety

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Dr Steven Pariser: Actually this was a patient who was referred to me by our executive health treatment people, and she had been seen at a prominent medical facility near Columbus. And was told that she had a conversion disorder, because she did have some odd neurologic and anxiety related complaints, and a great deal of fatigue. So she came in to see me, and she was a beautiful woman in her—well she was about 26, actually, and she looked disheveled, unkempt, she was wearing a—one of the running suits. And she was horribly irritable, anxious and pathetically depressed.

It seems that she developed an increased level of symptomatology when she assumed a position with a national retailer where she was called a merchant, and the demands were incredibly horrible. The first few months of her functioning there was just stellar, she impressed everyone. And then she had this rather precipitous decline. She also ended up taking time off from work, which I thought was wise. Historically she'd had multiple episodes of depression and anxiety dating back to her early teens and early adulthood days. But she was also hospitalized for depression in her early 20s, she had no comorbidity. She also was perfectionistic, counting and checking things repeatedly, and had obsessional thoughts.

She denied ever having any symptoms of euphoria or symptoms suggestive of bipolar disorder. But I asked her if she ever felt over stimulated, now for me, if there were one word that would help me define someone ever having been manic. Mental over stimulation allows me to look at everything from mania to agitated depression or dysphoric mania, and people seem to get it then. And she confirmed her tremendous irritability.

This woman was also on venlafaxine, interestingly, because there's some data that it may be a bigger offender than some of the more contemporary antidepressants, Clanazopam and Bupropion SR. So there we have a situation where no treatment for bipolar disorder and no treatment specific for her obsessive compulsive features as well. Her family history was remarkable in that her parents were divorced. She described her father as moody; her mother had depression. And she had a brother who was two years her senior who seemed to be doing quite well. She felt very close to her mother and brother, and in further discussion, it was clear to her that her father probably was—is bipolar. And had no history of the kind of impulsive acting out that one might see with someone who is bipolar. She was, as I mentioned, informally dressed, she was psycho motor retarded, but at the same time, she was obviously irritable and had some angst and agony in her presentation. And she had a very restricted affect, she was at times though became tearful, there was no particular cognitive disability as far as I could tell, but she definitely had complaints about her slowness at work and her difficulty focusing, and also complained about her need to be perfectionistic, and what that imposed in terms of her delays in getting things done.

I worked her up, and she ended up having some macrocytosis, and so you know I also checked her vitamin levels, and she was clearly B12 deficient. So my provisional diagnoses were bipolar mixed disorder, OCD, and B12 deficiency on axis three, lots of stressors, and a functional level that was pretty low. So we tapered her and discontinued the venlafaxine, which by itself can be pretty traumatic for people. We got her off the clonazepam slowly, put her on—started her on quetiapine and then lamotrigine, and then sertraline. And in that order, because I wanted her to have some manic protection before we added the sertraline. And she began to get B12 injections, and the paresthesia she had stopped. So over a period of time, she stabilized, she began to look like her old self, very attractive, very effective in her communications, felt well, had no complaints of mood supplicity. Her OCD symptoms had largely remitted, and by the way, I did a fair amount of therapy, largely sort of CBT based with her in the meantime. She returned to her position, but the conflict she had had earlier with her supervisor was horrific, and at one point, the HR VP called her in and said you know you either need to resign, or you may lose your job, and acknowledged that the supervisor was not very easy to work with.

Dr Henry Nasrallah: I'll start out by commenting that this is an excellent example of a—of a patient—young people who present with a picture of depression and anxiety, and unfortunately get stuck with a label of conversion disorder. Seeing a patient who appears to have a combination of depression and anxiety, and then as you—as you just did so skillfully, eliciting from her symptoms of irritability and being over stimulated, which you know steers the psychiatrist then to the bipolar spectrum with clearly a lot of depression and anxiety and some mixed features.

Dr Joseph Goldberg: So with a working diagnosis of a mixed episode, and an anxiety disorder, I'm wondering if the sertraline is redundant with the Quetiapine. We published some data in STEP last year in the American Journal showing that in a mixed episode, SSRI is worse than the mania symptoms, and don't touch the depression symptoms. And separately, given the Quetiapine data in GAD as well as in reducing anxiety symptoms in the context of depression, whether or not Quetiapine alone might be a safer and as effective probably better remedy both for the depression and the anxiety than the augmentation with the Sertraline.

Dr Steven Pariser: She was on the Quetiapine for quite a while before I added the Sertraline. And it was because the lingering depressive and terribly obsessional features that she had that were really work impairing, tremendously, that I finally did it.

Dr Henry Nasrallah: Well this brings me to the issue of how her initial treatment, her local psychiatrist you know shows Venlafaxine and Clonazepam and Wellbutrin, which does not make sense to me. And he – this is a kind of a rapid combination therapy that is unjustified you know you should try one thing at a time. I'm glad you were able to get her off that, Steve, replace it with Quetiapine, which is not only indicate for bipolar depression, but also has strong anxalytic effects that actually may eventuate in a few months with an FDA indication, because the studies have been done.

But the other comment I have about Wellbutrin is that it's the only antidepressant that is useless in anxiety, because it's purely a norepinephrine reuptake inhibitor rather than a dual action.

Dr Steven Pariser: I would point out that if you go back to Bob Post's work many years ago, over probably 20 years now, and you look at the more recent data, that among bipolars, either agitated depression or mixed bipolar disorders represent a huge number of bipolars in entry into studies. And from the STEP data, we also know that many of those patients, when they entered the trial, were actually suicidal, or had suicidal ideation at the time of entry in the trials. So looking at it a bit differently, I thought the risk of not treating her as though she was bipolar, or having a mixed episode, was huge.

Dr Henry Nasrallah: Yes, I had another question about the conversion disorder diagnosis, presumably that was made on the basis of these paresthesias presented ...

Dr Steven Pariser: And she had headaches and other somatic kinds of complaints as well.

Dr Henry Nasrallah: The point that I was going to make is that when that diagnosis is entertained, it's frequently wrong, and there's usually some organic basis behind the complaint.

Dr Henry Nasrallah: How did you switch her? What was the technique you used to switch her over to Quetiapine?

Dr Steven Pariser: Well first of all—the Quetiapine, she wasn't sleeping, and so it was easy to encourage her to try the Quetiapine, and she gradually began to see how much benefit it offered her, because the sleep disruption itself, which is common in depression and bipolar disorder, may also just keep triggering the illness. So it's not just a symptomatic issue. Venlafaxine in my experience is also worse to taper and eliminate from someone with a discontinuation syndrome than Clonazepam.

Dr David Muzina: I don't know that data would support it, but I've seen the center of this continuation phenomena of Venlafaxine or the new Desvenlafaxine or Duloxatine, so I've treated them equally in terms of tapering when I'm stopping them.

Dr Henry Nasrallah: The stress sensitivity of this patient is obvious. I might even suggest the environmental cues where her illness started can actually have a triggering effect when you return the patient to that environment, even after you stabilize them with treatment. Very good, this has been a very good case to discuss the various complications of presentations like this.