The
treatment approach is focused primarily on the utilization of Tegretol,
which has been shown to be extremely effective in preventing many of the
major symptoms of Xanax withdrawal, as well as attenuating significantly
most of the minor symptoms. The Tegretol is utilized along with Klonopin
as a cross-over benzodiazepine to stabilize and to create control of
withdrawal until adequate Tegretol blood levels have been achieved, then
allowing one to discontinue the Klonopin. The total length of treatment
will span somewhere between 10 to 30 days which, relative to the natural
course of this withdrawal syndrome, actually represents a short period of
time.
The
first step is to estimate the total daily dose of Xanax and start the
patient on an equivalent amount of Klonopin, which relates to Xanax on a
ration of 2mg Klonopin to 1mg of Xanax. Thus, a patient with a daily dose
of 4 mg of Xanax would be given a single bed time dose of Klonopin at 8mg,
which will quickly and effectively stabilize them and prevent further
symptoms of withdrawal. Additionally, the patient is started on Tegretol
at 50mg three times a day and is increased by 50mg increments until a
total daily dose of 400mg daily, in divided doses qid, is achieved, at
which the first Tegretol blood level will be ascertained. It will
generally take four to seven days to reach therapeutic blood levels.
Since
Klonopin has an extremely long half life of 40 to 60 hours, the patient is
well covered with a single bed time dosaging, and this benzodiazepine has
shown little abuse potential for drug seeking behavior and provides
smooth, steady serum levels during the course of treatment. Generally,
beginning on day 2 or 5, the dose of Klonopin is decreased as the dose of
Tegretol is increased. Since therapeutic levels of Tegretol can often be
achieved while the patient is being titrated to a therapeutic blood level
of Tegretol, the Klonopin is reduced at a rate of approximately 1 mg per
day. generally, with doses in excess of 6 to 8mg per day of Klonopin,
there is enough time with this rate of withdrawal to slowly establish a
Tegretol level without neurotoxicity during the cross-over, and there is
little probability of any breakthrough major symptoms of withdrawal due to
Klonopin's very long half life. Since both Klonopin and Tegretol are very
potent anti-convulsants, the incidence of seizure has been essentially 0
in over 300 cases that we have treated so far. The Klonopin is thus being
decreased at 1mg daily until one reaches 1mg, at which point decreases are
then done by 0.25mg increments anywhere from once a day, on average, once
a week.
It
is important to understand that Tegretol has a significant impact on
auto-induction of liver enzymes, and initially, for the first exposure to
Tegretol, a dose as low as 200mg may produce a blood level in the
therapeutic range of somewhere between 4 to 10 mcg/L necessary for control
of seizure and withdrawal; but as liver enzymes are induced, increasing
doses will be necessary over the necessary weeks to maintain an adequate
blood level. The average dose eventually that is achieved in steady state
with induction of liver enzymes is somewhere between 400mg and 800mg
daily, with an average of approximately 600mg. Additionally, the half life
of Tegretol will be essentially 20 to 26 hours when initially used, but
will progressively shorten as liver enzyme induction takes place,
approaching a half life as short as six to eight hours and requiring
multiple daily dosaging at that time.
The
major complications with Tegretol are neurotoxic effects when blood level
will be generally too high, or above the level of 10 mcg/L, or due to an
accumulation of its first order epoxide metabolite. These complications of
neurotoxicity present themselves as nauseousness and vomiting, significant
sedation, dizziness and disco-ordination. Also frequently reported is a
sense of significant gastric retention with delayed gastric emptying.
Although the side effects of Tegretol can be successfully treated with
Reglan, Tigan and/or Antivert, it is far better to titrate the dose slowly
and avoid developing these side effects. The presence of them can be
ascertained to represent blood levels that are unacceptably high and to
slow the rate of increasing the Tegretol dosage. There is a small
percentage of the population of people who simply do not tolerate Tegretol
because of the GI side effects.
As
noted, Tegretol is almost 100% effective in controlling major symptoms of
Xanax withdrawal, but will vary in its effectiveness in attenuating the
minor symptoms, thus requiring sometimes slower titration down off the
Klonopin. It is infrequent that one needs to go slower than once a week in
the 0.25mg decreases, and often one can be decreased on a daily basis
without symptoms of withdrawal, but at times the decrease may have to be
as slow as once a month. Once the patient is off the Klonopin and on the
Tegretol in a steady state basis, the patient is maintained on Tegretol
for approximately one to two months after achieving this state, and then
tapered off of the Tegretol over a four to five day period of time. Should
there be a recurrence of withdrawal symptomology, then the Tegretol is
reinstated for an additional month, and then the process repeated.
CBC
and checks of white blood count should be done periodically while the
patient is on Tegretol. Often there will be mild leukopenia with white
count at 3000 to 4000 found with Tegretol, which is benign. The incidence
of agranulocytosis is extremely rare with Tegretol, and there is support
in the literature for the lack of need for rigorous routine white count
testing while on this medication. Prudence, though, would require some
periodic evaluation of white count while the patient is being maintained
on the Tegretol.
POST
WITHDRAWAL TREATMENT
Once
the patient has been successfully detoxed off Xanax and/or the Tegretol,
the issues of underlying conditions, such as Agoraphobia, Panic Disorder,
Generalized Anxiety Disorder, or Major Depressive Disorder, often must
still be dealt with. Whereas Buspar is of no utility in managing Xanax
withdrawal or Xanax-generated anxiety, it can be quite helpful for anxiety
that is non-benzodiazepine withdrawal related, and patients, after
completion of withdrawal, can be, and often have been, successfully
maintained on Buspar at 40 to 60mg daily as a final dose with good control
of underlying anxiety. Treatment of Panic Disorder and/or Agoraphobia will
often require a tricyclic anti-depressant in conjunction with Buspar, with
essentially good success. The introduction of the anti-depressant can be
begun at the time withdrawal is started, or can be deferred to a later
date, depending on the intensity and frequency of panic attacks that the
patient may be having.
It
should be kept in mind that a patient with underlying Agoraphobia or Panic
Disorder will have a marked exacerbation of his/her pre-existing illness
during the course of withdrawal. It is often then of necessity to start an
anti-depressant to stop panic attacks in order to get the patient through
the withdrawal process successfully. The presence of a tricyclic will not
interfere materially in any way with the medications for withdrawal.
Patients
having gone through this process will generally need a significant degree
of emotional support and constant re-assurance during the withdrawal stage
that they are indeed in withdrawal and are not suffering some morbid
physical or psychiatric disorder other than the withdrawal process. Weekly
visits with medication management, plus frequent phone consultation
generally is what is required and generally produces a successful outcome
on an outpatient basis. In more severe cases, and in situations where time
or efficiency is paramount, then inpatient treatment is the most effective
route to be travelled, and the detoxification can be accomplished much
more rapidly in that modality.
It
is critically important during the course of this that the patient refrain
from use of all psychoactive drugs, particularly alcohol and stimulants,
as well as over the counter preparations that contain pseudoephedrine and
phenylpropanolamine. Lastly, caffeine must be avoided by the patient for a
period of approximately six months to one year. Caffeine is a
benzodiazepine antagonist and will occupy the receptor site, blocking
Klonopin or other agents and intensify withdrawal markedly. Innocuous or
inadvertent ingestion of high doses of caffeine is often a major
complication to the withdrawal process, and patient education in this area
is very important, as well as reassurance should it happen that it will
wear off within a relatively short period of time.
Lastly,
for patients who have severe symptoms of tachycardia or palpitations as an
attendant withdrawal symptom, the addition of a beta blocker such as
Atenolol at 50mg q day is highly effective in stopping this and generally
does not need to be continued for more than 4 to 6 weeks.
