Could Benzodiazepines Worsen Hypomania or Depression?
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Q:  Could Benzodiazepines Worsen Hypomania or Depression?

Hello Dr. Phelps, I have been diagnosed and am being treated for bipolar II depression.  I was wondering a few things.  For one, do you have any experience/have you ever seen the effects of benzodiazepines on bipolar II patients?  I was wondering if they could have the effect of worsening either hypomania or depression.  Also, I find that  anxiety is often a key player in setting off my depression and I wanted to know if you could recommend a mood stabilizer targeted toward that.      

Dear Mr. C' --

1. As you know, benzodiazepines (Valium, lorazepam/Ativan, clonazapam/Klonopin, alprazolam/Xanax, others) are "anti-anxiety" medications, formally referred to as "minor tranquilizers". They are often used in bipolar disorder as anti-manic agents, primarily to help people sleep and decrease agitation. Concerns have been raised about worsening depression by using such medications, although in practice this seems to be a very minor problem if it indeed is an issue at all. If so, it might be through lowering energy levels so that people don't get up and do the things they need to do -- but in my experience, this has not been a major problem. Indeed, I have stopped these medications on a few occasions to see if mood might improve, and offhand I can think of only one or two cases that might have improved thereby, and even then it was equivocal.

As for worsening hypomania, I'm not sure I have ever seen that concern raised. We often use them to damp down energy levels when only a minor adjustment is required (they do not have the clout to act as a "mood stabilizer" by themselves, although some mood experts think that clonazapam comes pretty close in this role).

Occasionally one sees a "disinhibition" in people who are already not inhibiting their impulses very well, e.g. in hypomania or mania, when a benzodiazepine is added. 10 years ago this was such a concern that we avoided using Valium in favor of lorazepam, which was taught not to be as "disinhibiting". Since we hardly ever use Valium anymore this issue has largely disappeared.

In your circumstances, I would keep clonazapam on the list as a possible "mood stabilizer" in the hopes that by addressing anxiety one might be able to prevent depression, as you describe.

2. Which mood stabilizers have anti-anxiety affects? Well, that depends on where the anxiety is coming from. As you have probably learned, there are several different kinds of anxiety which have been characterized: social anxiety, restricted largely to interactions with others or anticipation thereof; generalized anxiety, characterized by excessive worry; obsessive-compulsive disorder, in which the anxiety is focused on particular excessive concerns; and most common of all, most problematic in terms of its overlap with bipolar disorder, "posttraumatic stress disorder" (PTSD). 

PTSD causes a general overactivation of the "sympathetic nervous system", an automatic portion of our nervous system which is designed to monitor for threats and prepare to react to them. There is a complex interaction between PTSD and bipolar disorder: they can be mistaken for one another diagnostically, that commonly occur together, and each seems to be capable of making the other worse when they do co-occur. In this context, clonazapam/Klonopin is very commonly used. What about other official "mood stabilizers"?

As you probably know, there is really no official list of "mood stabilizers". Lately everybody wants to be one. Here's my working list of
mood stabilizer options. From this list, which ones have the most anti-anxiety affect? Certainly I think most psychiatrists would put Zyprexa and Seroquel very high on that list. Zyprexa is very fast and can reduce anxiety from completely out-of-control to manageable within 45-60 minutes; but it can be quite sedating, and it is one of our worst medications for causing weight gain. Seroquel is much slower, has to be ramped up to full dose, and causes a significant morning slowness even after you get used to it. It helps a great deal with sleep at night but is also associated with a potential for substantial weight gain.

Because of the concern about weight gain, it would be nice to find a candidate or two which is not associated with that problem. Lamotrigine, one of the few such candidates, is one of my favorite medications for Bipolar II, but it is not famous for anti-manic effects. To my knowledge, it has never been studied in terms of potential anti-anxiety affects. It does not generally have a reputation for this, although occasionally it seems to do very well (I think perhaps most particularly so when the anxiety is "cyclic", where the lamotrigine can prevent anxiety by preventing cycling).

By contrast, carbamazepine is much more complex to use than lamotrigine and carries a similar risk of a serious rash. It interacts with other medications, changing their levels. It can bother one's liver and, more rarely, blood cell production. But it does not cause weight gain (with some rare exceptions) and often has quite substantial anti-anxiety affects, in my experience.

Good luck finding your way along.

Dr. Phelps

Published March, 2008

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