My husband has bipolar disorder. In the past year he has developed epilepsy, which we have been told "overlaps with bipolar" in the frontal lobes and hypothalamus area. His seizures keep getting worse and more frequent even though he is on 400 mg. of lamictal everyday. He really wants the vagus nerve stimulator. He has researched that it will help with long term chronic depression (which is the worst on him) , seizures and memory. This seems to be a new hope for him. I know its a new technology, but is it safe long term? Effective? Costly?  If you can help shed some light we would greatly appreciate it!     

                         

Dear Ms. R' --

You and your husband have learned correctly that the vagus nerve stimulator (VNS) can treat epilepsy and may also have some value in the treatment of depression. The data on its effectiveness for depression are rather weak, unfortunately. It did not perform well enough in a randomized trial against a placebo condition to get a routine approval from the FDA, for example. However, there is a lot of suggestive evidence in support of at least some affect on depression.

Therefore it is not unreasonable to think that there might be a "two birds with one stone" benefit from VNS. As you're probably aware, the same rationale applies to the use of lamotrigine (Lamictal), but as you know, 400 mg is generally presumed to be the maximum dose in the treatment of mood problems. I understand that some physicians have used significantly higher doses, although in my experience the likelihood of side effects increases substantially at 400 mg and higher. These are relatively mild side effects (nausea, dizziness, difficulty finding words and names, not thinking sharply) and easily reversed by reducing the dose. You probably have already had the discussion with his doctor about the pros and cons of simply turning up the Lamictal dose. A bipolar specialist at Stanford, Dr. Terry Ketter, has described getting a blood level of lamotrigine to see if it is already a relatively high (he described using a level of seven for this purpose). If it is, he presumes that there is little additional benefit to be had from pushing the dose higher. If it is not, then he pushes the dose regardless of the absolute number of milligrams in use at time. Mind you, this is a specialist maneuver and should only be done in close consultation with your psychiatrist, shooting the agree with the plan, and if he did not, it would be entirely reasonable to point out that this is just too experimental, too far outside the domain of conventional treatment.

There may be other stones with which you might hit two birds without turning to VNS. If the depressions are very recurrent, coming and going, then any medication that can treat mood cycling might prevent them. This opens the option of numerous mood stabilizers, including good old lithium as perhaps the most routine for this purpose. Unfortunately, lithium can make seizures more likely even at therapeutic doses (reference, e.g. Bellesi), so this might be a relatively low on the list. The new generation of antipsychotic medications has also been used to treat mania, and many of them are thought to have "mood stabilizer" properties in terms of preventing recurrence of episodes. Unfortunately, these also have a statistical association with increased seizure frequency and so weren't the same caution as would lithium. 

That leaves the mood stabilizers which are anti-seizure medications originally, such as Depakote, carbamazepine, and a few others less well established for use in bipolar disorder. Of these, Depakote is thought to combine particularly well with lamotrigine in terms of effectiveness by a least a few mood specialists; however, there is a known medication interaction between Depakote and lamotrigine that must be handled with care (it does not make the use of the two together impossible, in fact heading Depakote when lamotrigine is in place is relatively straightforward but maintaining adequate anti-seizure control while in a transition phase would require careful attention).

After all that, then one might consider VNS. I think it deserves to be low on the list in part because it has induced hypomania in several patients being treated for depression and so is not as reliable in bipolar disorder in terms of not making the bipolar disorder worse -- at least in theory. We really don't have enough experience with it yet in this dual role of epilepsy and bipolar treatment. Otherwise, from a safety point of view, initially it is relatively safe as a procedure, but you're asking the right question: what about long term? And the answer there: we don't know, as the procedure has not been around for very long nor have very many people had it yet. 

Finally, yes it is extremely costly, about $50,000, and many insurances either do not cover it or require extensive prior authorization arrangements. In my limited experience so far, it is probably easier to pursue it as a treatment for epilepsy than for mood.

Dr. Phelps



Published November, 2007