Psychiatric side effects associated with the ten most commonly dispensed prescription drugs: a review

Journal of Family Practice, August, 1991 by John R. Hubbard, James L. Levenson, Graham A. Patrick

Xanax

GENERIC-ALPRAZOLAM

General Information. Alprazolam is commonly prescribed in doses of 0.25 to 0.5 mg orally, three times daily (up to 4 mg each day).[11] This drug is primarily used as an antianxiety agent, though antidepressant effects have also been claimed.[2,11] Although many mechanisms for its CNS depressant action have been proposed, it appears likely that it increases the effect of GABA as an inhibitory neurotransmitter.[3]

POTENTIAL PSYCHIATRIC SIDE EFFECTS

(******) Depression

****** Anxiety, delirium and paranoid reaction

with drug withdrawal

(******) Aggressive behavior

*** Libido changes

Discussion. It is perhaps not too surprising that a drug such as alprazolam that is used for psychiatric purposes also appears to have numerous potential adverse neuropsychiatric side effects. This is because such a drug must be effective in reaching and altering the central nervous system (CNS) for its therapeutic (and therefore adverse) effects. Naturally, in these and the other reports of psychiatric side effects of alprazolam, observations are complicated by previous psychiatric illnesses in addition to the difficulty in statistical approaches. However, it is clear from the many studies cited herein that adverse psychiatric side effects of alprazolam must be considered in the differential diagnosis of behavioral changes that occur m patients recently put on or taken off the medication.

In 1987, in a placebo-controlled study of 46 patients with panic disorder receiving 3 to 10 mg of alprazolam per day, as many as 33% developed DSM-III criteria for major depression.[26] However, because many patients with panic disorder have comorbid major depression, it is problematic in this study as to whether the depression was a true "side effect" or whether treatment with alprazolam unmasked an underlying depressive disorder. In fact, the incidence of depression appears to be much lower, as indicated in a much larger (n = 263) 1988 multicenter placebo-controlled study in which only one patient was found with apparent depressive side effects at comparable dosage.[27] Aggressive or manic behavior in three patients was also noted in the multicenter study cited above.27 Numerous independent case reports also indicate that alprazolam can cause manic and aggressive behavior in both men and women.[28-33] In one case report, alprazolam at 0.5 mg three times daily had little effect on aggressive behavior, as did alcohol alone, but a combination of the two produced aggressive dyscontrol.[29] In most reports, however, there is no mention of alcohol use. Manic symptoms did not occur until dosage was increased to 2 mg, diminished considerably when reduced to 0.75 mg, and then reappeared when a 1.5 mg dose was given.30

Changes in libido may also occur with alprazolam use.[26,34-36] In a retrospective study of 32 patients treated with alprazolam, 15 had decreased libido while four reported increased sexual desire.[37] Other cases of decreased libido have also been reported.[35,36] Decreased sexual desire and orgasm appear to be dose-dependent and to recover with dose reduction.[35] Case reports and placebo-controlled studies indicate that rebound anxiety can occur upon withdrawal of alprazolam.[37-39] While it is difficult to distinguish withdrawal symptoms from reemergence of an original disorder, withdrawal anxiety occurs even in patients who receive alprazolam for reasons other than anxiety disorder. In one placebo-controlled study of 126 patients, 27% of patients treated for panic disorder reported rebound panic attacks and 13% had rebound anxiety when their dosage of alprazolam was reduced by 2 to 10 mg. Several case reports have also suggested that delirium[40] and paranoid reactions[41] can occur with alprazolam withdrawal, even when tapering is gradual.[42]