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Side Effects of alprazolam (Xanax)
By Stuart Shipko, M.D.

This article summarizes the most common side effects of alprazolam (Xanax). Required reading prior to starting this medication.

While alprazolam (Xanax) seems to be the most effective agent in stopping clusters of panic attacks (see article above), people should be aware of the potential problems and side effects of this medication. This applies to other benzodiazepines (BDZ's) as well. Above all, one must make sure that the diagnosis as correct before starting alprazolam. It is most useful in the "classic" generational PNE with childhood onset; gastroesophageal reflux or irritable bowel syndrome, with panic attacks not phobic anxiety. Panic attacks and phobic anxiety are often confused. Panic attacks occur "from nowhere" often waking the person up from sleep or while the person is relaxing after work. As the untreated condition progressive anticipatory or phobic reactive attacks frequently develop and may overshadow the original true panic attacks. The DSM-IV diagnostic criterion is too broad and would include people with toxic based panic attacks and phobic syndromes as well as posttraumatic stress disorder (PTSD). The prescribing doctor needs to do a careful diagnostic examination to insure proper diagnosis. It takes at least an hour. Beware of physicians that pronounce your diagnosis as panic disorder after just a few minutes of discussion. If you do not feel that you have the more rigorous criterion for panic disorder as described above and in the rest of this site, then you might want to deal with your anxiety problem through cognitive behavioral therapy (CBT).

The major concern about alprazolam has been the so-called "idiosyncratic reaction". People taking alprazolam can become disinhibited, violent or have marked personality changes. As I understand it, this is why Halcion and alprazolam are prohibited in the UK. In my experience this does not occur in people with panic disorder, but does occur in people with anxiety due to personality disorder or other psychiatric conditions. I have not seen documentation of this reaction in PNE. When alprazolam first came out it was considered "another Valium" and was often prescribed as a general tranquilizer in many different diagnostic categories.

Dependency is an issue. Some people will find that they cannot discontinue alprazolam. It is highly variable and dependency will be most pronounced in people who take higher dosages, are older and have taken it for a long period of time. It is estimated that as many as 1/3 of people who take alprazolam for a year will experience inability to discontinue alprazolam or prolonged, uncomfortable discontinuation symptoms. Unless a person is willing to risk the possibility of long-term use of alprazolam, they should not start it at all. While dependency is a concern, when used for generational PNE the same dosage has been shown to be effective over long periods of time (a good long term study I have read was by Lessor et al at UCLA in which 20 year follow-up was done and the patients did not find that alprazolam lost effectiveness and that dosage tended to decrease slightly over time. The average patient was taking between 3 mg and 5 mg daily). Tolerance to the therapeutic effect of alprazolam is quite rare, and if it occurs then the drug should be stopped. People often ask about whether alprazolam can cause "permanent brain damage." Some uncontrolled anecdotal reports have shown enlargement of the ventricles in people who have used BDZ's for long periods of time, but to date, there is not clinical or research evidence that long term use of the BDZ's causes brain damage. Long-term use of BDZ's is not associated with cancer and may be negatively associated with pancreatic cancer. Since PNE is associated with increased morbidity and mortality from cardiovascular causes it is possible (but never studied) that long term BDZ use may reduce this risk. Certainly many people with hypertension and PNE find that alprazolam lowers blood pressure.

Memory impairment is a common side effect. This seems to be mild but fairly common. Many people on alprazolam notice memory loss, but others will have memory loss but will not notice it. Studies have shown that verbal recall seems to be most affected by alprazolam. Short-term memory is much more prone to problems than long-term memory. Memory problems are very common with panic anxiety, but I have not seen a controlled study, which compares memory problems with alprazolam to memory problems in PNE. Some people actually find memory improved on alprazolam since the "blanking out" of memory with anxiety is improved. Still, people who take alprazolam often note problems with memory.

Sedation is another very common side effect. Sedation may occur with dosages administered at certain times of day but not others. It may occur at irregular intervals and may not occur at all. Alprazolam tends to be sedating on initial administration, this is to be expected -- especially if the person has not slept for a long period of time. Initial sedation should wear off after about 3 to 4 days. Anxious fatigue is a common symptom in PNE. Some people feel clearly more energetic once the anxious fatigue is treated. A recent study showed that people who take alprazolam have more car accidents, however this was not compared to the number of car accidents in people with untreated PNE and I am unsure whether PNE patients properly treated with alprazolam really do have a higher incidence of car accidents. Coordination can sometimes be impaired. This is uncommon and I consider it a definite reason to discontinue alprazolam.

The single most important effect of alprazolam is to reduce or eliminate panic attacks. Alprazolam helps somewhat with interattack anxiety, but this aspect of the illness is often best dealt with through cognitive behavioral therapy. Pushing up the dosage to eliminate interattack anxiety usually does not work.

Other side effects of alprazolam are much less common, and can be found in exhaustive lists in the Physicians Desk Reference. This FAQ is intended to outline the major concerns people have addressed the most significant concerns relating to the side effects of alprazolam use, but does not describe all of the side effects that have been reported.

If possible, short-term use of alprazolam for panic disorder is most desirable. Often, after a cluster of attacks has been successfully treated alprazolam can be tapered to a lower dosage and stopped within a 6-week period of time. Use of alprazolam on an "as needed basis" is not advised when first starting. First, alprazolam works best to prevent attacks and regular dosing prior to an attack is more helpful. Second, often it is very difficult for a person to distinguish significant phobic and anticipatory anxiety from true panic attacks and it is confusing as to when it is "needed." After having experience with taking alprazolam on a regular basis a person may be in a better position to determine when an extra dosage is needed.

The most important concern is that a correct diagnosis of panic disorder be made prior to starting alprazolam. It should not be used in place of a sleeping pill or a general tranquilizer. I consider it a medication specific for panic attacks, and best reserved for generational PNE with early onset, GERD with frequent panic attacks. The literature is clear that people who are not on any medication have a better long term prognosis, however it is difficult to say whether this is a medication effect or whether or not the people who were not on medication had a less severe syndrome to begin with.

Read the transcripts of Psychiatrist and Neurologist, Stuart Shipko, M.D.