PROTOCOL FOR TREATMENT OF XANAX WITHDRAWAL
By: Ronald A. Gershman, M.D.
Xanax is a triazolobenzodiazepine that is very similar to other benzodiazepines in most of its properties, but does have some properties that distinguish it from the group in general, which are specifically its anti-panic an anti-depressant properties. As an anxiolytic or anti-anxiety agent, it functions more or less indistinguishably from other benzodiazepines. In that capacity, it is a relatively short-acting anti-anxiety agent
with a half life of somewhere between 8 and 12 hours.
Xanax, when administered on a regular basis, will produce physiological dependence with a severe withdrawal syndrome that relates to both dose and duration of usage, with duration being more important than actual dosage. Higher doses will produce more rapid physiologic addiction than lower doses, but severe levels of physical addiction can occur in even the low therapeutic range of dosaging at 1 mg. or 2 mg. per day. Average length of time necessary to occur to the extent that the patient will clinically experience clearly noticeable symptoms of withdrawal is approximately four to six months at dosages between 2 mg. to 4 mg. If there is a history of addiction to benzodiazepines, an addiction can occur much more rapidly over a shorter period of time, with a more intense withdrawal.
Since Xanax is a relatively short-acting agent, the symptoms of withdrawal have a relatively rapid onset and rapidly accelerate, producing severe dysphoria and symptoms of withdrawal in the patient beginning at approximately six hours from the last dose and generally peaking at approximately 24 to 72 hours after discontinuation. What has become clinically apparent with Xanax which appears to be somewhat different than the other benzodiazepines is that the patients ability to self-detox or be able to be gradually tapered off of the medication is markedly more difficult. Thusly, once the physiologic dependence has occurred with Xanax, the ability of the patient to discontinue use successfully on their own is quite low, and medical assistance becomes of significant necessity in the majority of cases. THE WITHDRAWAL SYNDROME
The withdrawal syndrome from Xanax and other benzodiazepines are quite similar, with the exception that Xanax has a much higher incidence of panic attack and a bereavement type of emotional lability that is singularly more severe. Since the symptoms are almost all internal, with a few physical or objective manifestations, the diagnosis of it can be very difficult. Patients have a difficult time verbally describing what is occurring, and much of the descriptions often take on a quality or character reminiscent of the emotional or psychiatric problem for which they originally began taking Xanax, and is not understood or elucidated as withdrawal symptomology.
The withdrawal syndrome, though, is quite clearly different and can be easily diagnosed with a clear understanding of some of the more defining features. In the early stage of withdrawal, there is a presentation of a sense of anxiety and apprehension associated with increasing subjective sense of tremor and mild bifrontal headache. This rapidly progresses to feelings of panic-like anxiety with tachycardia and palpitations, as well as a rapidly progressing feeling of de-realization, which is an altered sense of reality, additionally associated with marked startle response and a general amplification of most sensory input. As the withdrawal syndrome progresses, there is a marked disturbance of proprioception, with difficulty in ambulation relative to feeling "dizzy" and "unsteady," needing to use reference and physical objects to steady oneself. With the proprioceptive problem increasing in severity simple acts such as swallowing, signing one's name, talking or even buttoning a shirt can become extremely difficult. many patients at this stage describe hot/cold sensations and generalized myalgia.
There is also a progession of extreme emotional lability with sudden outbursts of crying or near panic levels of anxiety and fearfulness which will have sudden onset without clear connection to external events. Associated with this are frequent hypochodriacal fears of morbid consequence from the sensations they are feeling, such as fear of heart attack or stroke. patients will also experience a type of emotional dysphoria which is very difficult for them to verbalize, but which come very close by cumulative description to a bereavement type of feeling that is very painful emotionally. Additionally, the amplification of almost all sensory information coming into the brain, other than that of taste, can produce many bizarre misinterpretation of sensory stimulation ranging from feeling one's teeth rotating in their sockets to parts of their bodies disassociating or "falling off".
As the withdrawal symptom further progresses, illusionary and hallucinatory phenomena, predominately of a visual nature, will begin to manifest themselves, initially with patterens and geometric shapes, and then into full-formed complex visual hallucinations. These also often will become associated with delusions of bodily dysfunction or discorporation. It is very frequent and common for the patient to conclude that he is having a nervous breakdown, or "going crazy" as an attempt to try to understand the process at hand, not understanding it as withdrawal phenomena. With further progression, disorientation to person and place will occur with full delirium, and eventually withdrawal will finalize with tonic-clonic major motor seizure activity, generally singular in nature, although several cases of status have been reported.
The last triad of symptoms--of hallucinosis, delirium and seizure--are classified as major symptoms of Xanax withdrawal, with the others classified as minor symptoms. The withdrawal syndrome can take from six months to two years to fully resolve and is well-documented in literature regarding this. Not all patients will experience withdrawal symptomology for that length of time, but most will have withdrawal for at least several months.
The treatment approach is focused primarily on the utilization of Tegretol, which has been shown to be extremely effective in preventing and 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 2 mg. Klonopin to 1 mg. of Xanax. Thusly, a patient with a daily dose of 4 mg. of Xanax would be given a single bed time dose of Klonopin at 8 mg., which will quickly and effectively stabilize them and prevent further symptoms of withdrawal. Additionally, the patient is started on Tegretol at 50 mg. three times a day and is increased by 50 mg. increments until a total daily dose of 400 mg. daily, in divided doses q.i.d., 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 day 2 or 5, the dose of Klonopin is decreased as the dose of Tegretol being 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 8 mg. 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 Klonopins 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 thusly being decreased at 1 mg. daily until one reaches 1 mg., at which point decreases are then done by 0.25 mg. 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 200 mg. 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 400 mg. and 800 mg. daily, with an average of approximately 600 mg. 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 dyscoordination. 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 slowly titrate the dose and avoid developing these side effects. The presense of them can be ascertained to represent blood levels that are unacceptably high and to slow the rate of increasing of 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 very 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 0.25 mg 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. There often 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.
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 60 mg. 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 situatioons 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 inadvertant 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 offwithin 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 sich as Atenolol at 50 mg. q. day is highly effective in stopping this and generally does not need to be continued for more than 4 to 6 weeks.