New research on Bipolar Disorders

by Dr. R. M. Post
as presented to the NAMI 1997 Convention

New info about Bipolar Genetics

A change on chromosome 18 appears to be involved when the disorder is
passed down from the father.  A change on chromosome 21 may account
for some of the disorder when it is passed down from the mother.

There is increasing evidence that the incidence of bipolar is increasing in
successive generations since WW1   There are also studies that show
that children of those w/bipolar get affected 10 years earlier than their
parents were.

New info about Bipolar Neurobiology.

Lots of (too technical for me, but nonetheless interesting) information
was presented showing that the cerebralspinal fluid of people with
bipolar is different than that of other folks. The same is true of cerebral
spinal fluid of those with depression.  In addition, the chemical makeup of
the cerebralspinal fluid seems to vary depending on whether the person
is experiencing, mania, depression, or some other mood states.  Dr. Post
also showed that hypercortisolemia is associated with depression and
dysphoric mania.  He also pointed out that bipolar patients have
increased intracellular calcium in platelets.

New info about bipolar from brain imaging

Frontal hypometabolism (how the front of the brain uses chemicals) is
slowed down depending on the severity of depression.  Structural
alterations in the brain, such as larger pituitary and adrenal, and
amygdala, hippocampus, and subgenual preforontal coretex have been
confirmed in depressed patients.  Some people with bipolar have
hypermetabolism in specific parts of the brain that are associated with
their response to carbamazepine.  In addition, different patterns of of
how chemicals flow and are metabolised in the brain have been
associated with how people respond to different meds.

New info about how meds work in bipolar.

This part of the presentation was probably most of interest to the
scientists in the room.  For the rest of us, the important thing to know is
that we do know meds (and ECT) work, but we're not sure how.  Post and
his group have made advances that may help us understand this.  The
other significant finding is that some of the new atypical neuroleptics
(clozapine/olanzapine) are increasingly being used in refractory
mania/recyling instead of traditional neuroleptics.

New info about cycling, recurrence, and remission of bipolar disorders

New evidence continues to suggest htat the greater numbers of prior
episodes incresases the risk for further episodes and treatment that
doesn't work.

Stopping lithium carries a susbstantial risk of relapse (50% in 1st 5
months off drug).

More and more people w/bipolar are being found to have ultra-fast
frequencies of mood cycling.   In fact some have fluctuations within a
single day.  These may be responsive to a combo of mood stabilizer and
dihydropyridine calcium channel blockers such as nimodipine, isradipine,
and amlodipine.

More and more evidence is showing the importance of early intervention
in preventing bipolar episodes, the risk of relapse, and perhaps, lithium
refractoriness.

New medical approaches to treating bipolar

Carbamazepine and valproate have emerged as anticonvulsant and mood
stabilizing alternatives and adjuncts to lithium.  But new evidence
suggests that multiple meds be used instead of a single meds.  More and
more people are being discharged from hospitals on multiple mood
stabilizers in combo w/thyroid augmentation and (more rarely)
antidepressant and neuroleptic augmentation.

Verapamil may be useful in mania, but recent studies indicate it does not
work as well as lithium in acute mania and does not work as a
preventative.  About one third of people with treatment refractory
bipolar were helped by nimodipine/isradapine.  But often, these had to be
used with other meds like carbamazepine.  This was usually very
effective.

Some studies have reported lamotrigine (Lamictal) is very useful as an
"add on" therapy.  A smaller group had a good responce when gabapentin
(Neurontin) was used, but it worked well for them.

Dr. Mark Frye noted a 50% response rate in depression and 58%
response rate in mania was possible with lamotrigine (Lamictal).  He
found a 40% response rate with gabepentin (Neurontin).  There is also
mounting evidence that atypical neuroleptics may play a useful role in
treating some people with bipolar.

New research on alternatives to electroconvulsive therapy (ECT)

ECT Is an effective treatment for some people with depression and/or
bipolar.  But researchers have come up with a way to stimulate the brain
with magnetic fields rather than electricity.  It is called Repeated
Transcranial Magnetic Stimulation (rTMS).  Ongoing studies are trying to
determine how useful this can be. Results are promising, but premature.

New Research in predicting response to meds and stability

A lot of Stanley funded research is going towards trying to figure out
who responds to what treatments and why.  Once this is discovered,
individuals can be given the most efficacious treatment early on, rather
than going through the current trial and error approach.