Q:  Questions re. BP and Cognitive Deficits

Dear Dr. Phelps,

I am being treated for bipolar with Lexapro, lamictal and recently, risperdal. I recently became aware of the connection between bipolar illness and cognitive deficits. I have been aware of some deficits in the past and am aware that the "blips" seem to be getting worse. Some of them are a delay in processing information, inability to connect certain concepts, and when under alot of stress i have trouble with word retrieval or mix up words and I forget conversations that involved tasks that I am supposed to follow up on.  This happens at work and is a problem.  I wanted to know two things: 

1. Do you think Risperidone may make cognitive deficits worse? and

2. Can you give me an idea what tasks are associated with the problems I  mentioned above, apart from the testing tasks described below.

(I looked up studies on PubMed and am included some of the results here in case it's of interest) I don't understand what tasks are associated with the deficits.  

[J’s list of study results appears just after my reply below – Dr. Phelps]

Thanks for all your work in the area of Bipolar illness!!

J’    
  

Dear J’ --
Your question illustrates a very, very common problem: When people with bipolar disorder are having problems with memory, and intellectual function generally, is the problem coming from the illness, or from the treatment -- or both?

As you can imagine, separating these two potential causes is tricky.  We know that the illness itself can cause very substantial trouble with memory, and other kinds of intellectual processes (often lumped as "cognitive impairment").  On the other hand, as one of my colleagues says, "medications are guilty until proven innocent". Particularly if some worsening of cognitive function seemed to follow quickly after a new medication was introduced, that medication has to be suspected as a culprit.

So far, therefore, we are suspecting the illness itself or medication generally.  In your case, we have to add two more potential causes of cognitive impairment.  First, Lamictal (lamotrigine) has been very clearly associated with difficulty finding words.  This is much more a problem that higher doses, like 400 mg and is relatively uncommon at the typical target dose of 200 mg.  But it is so well recognized, and you mentioned that problem specifically, so Lamictal has to be suspected for playing a role in at least this particular aspect of the problems you describe.  Not that we could be certain it is the culprit, but it must be suspected.

Finally, the fourth potential cause of cognitive impairment which should be considered in trying to sort out what is going on with your intellectual function, is the potential for an antidepressant (Lexapro/escitalopram, in this case) to -- in some degree, from zero to a lot – cause a “mixed state”.  Recall that mixed states are combinations of manic and depressed symptoms occurring at the same time. In the view of most experts, antidepressants can bring on mixed states (although this is not firmly established).

The point here is that mixed states can cause anxiety and agitation, which can interfere with cognitive ability (note study # 4 below, in particular).  In the story you describe, it would be difficult to determine to what degree, if any, Lexapro was contributing to the problem through this mechanism. However, when you first begin to look at potential culprits, lining them up to decide which ones to investigate most thoroughly, and in what order, in my opinion this is one more culprit to place in the line.

Having lined them all up, you then have to decide how much you are willing to go through to identify the role that each of the potential medication culprits might be playing.  As you systematically remove one medication at a time, by tapering it carefully (*further comment below), you are obviously at risk of getting worse if that medication was actually doing something useful.  Ironically, it can be doing something useful and interfering with your cognitive ability at the same time, so this whole evaluation can be tricky.  Meanwhile, you will be aware  all the while that, at the end of your investigations, you may conclude that the primary culprit is the illness itself. 

*Obviously, in determining how to approach all of this, you'll have to discuss your options very carefully and thoroughly with your psychiatrist. I hope it is obvious: you should never take any steps, and figuring out something like this, on your own.

One more thought: study # 5 below correlates antipsychotic treatment with cognitive impairment.  However, in a correlation like this, you can't tell if people with more severe illness, who require ongoing antipsychotic treatment, have more memory and IQ decreases because of the antipsychotic -- or because they have a more severe illness.

Instead, the easiest way to tell when a particular medication might be the basis for decreases in intellectual function is to have noticed dramatic decreases in cognitive ability shortly after the medication was introduced.  In the absence of such an observation, in my experience, it is far more likely to end up concluding that the illness is the problem, not the medication -- even when we try to establish that for sure by tapering off some presumed culprit.

As you can see, this is quite a complex process.  Good luck with that.

Dr. Phelps
 

[The following studies were included in Ms. J’s question.  They illustrate that problems with cognitive function such as memory and decision-making are associated with bipolar illness itself, but medications are implicated as well.]

Study 1: Significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In spatial delayed response tasks, performance suggested deficits in short-term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information-processing tasks.

Study 2:  Psychotic bipolar disorder was associated with differential impairment on tasks requiring frontal/executive processing, suggesting that psychotic symptoms may have correlates partially independent of those in bipolar I disorder generally; deficits in attention, psycho-motor speed, and memory appear to be part of the broader bipolar disorder deficits.

Study 3: Psychosocial functioning was impaired for all groups, but a correlation significantly with neuro-psychological performance occurred in depressed and hypomanic patients.

Study 4: The mixed/manic bipolar patients demonstrated robust deficits in episodic and working memory, spatial attention, and problem solving. In contrast, depressed bipolar and nonbipolar patients had impairments only in episodic memory. 

Study 5: Current antipsychotic meds, duration of illness, and family history of affective disorder were the most significant predictors of IQ and memory function in BD I.

Published April, 2008