Alprazolam in panic disorder

Ballenger JC, Post RM Therapeutic effects of carbamazepine in affective illness preliminary report. Communications in Psychopharmacology 2 159-175, 1978 Ballenger JC, Burrows GD, Dupont R, et al Alprazolam in panic disorder and agoraphobia results from a multicenter trial, I efficacy in short term treatment. Arch Gen Psychiatry 45 413-422, 1988... 

Marks IM, De Albuquerque A, Cottraux J, et al. The efficacy of alprazolam in panic disorder and agoraphobia a critique of recent reports. Arch Gen Psychiatry 1989 46 668670. 

Noyes R, DuPont RL, Pecknold JC, et al. Alprazolam in panic disorder and agoraphobia results of a multicenter trial. II. Patient acceptance, side effects, and safety. Arch Gen Psychiatry 1988 45 423-428. 

Speigel DA. Efficacy studies of alprazolam in panic disorder. Psychopharmacol Bull 1998 34 191-5. 

In two studies in which benzodia2epines were gradually tapered, concurrent cognitive-behavioral therapy (CBT) did not increase the proportion of patients who were able to successfully discontinue their use of these agents (Oude Voshaar et al. 2003 Vorma et al. 2003). On the other hand, other studies of patients with panic disorder found that CBT facilitated the discontinuation of benzodiazepine use (Otto et al. 1993). Similarly, CBT may be superior to supportive medical management in preventing the reoccurrence of panic attacks in panic disorder patients in whom alprazolam has been tapered (Bruce etal. 1999). 

Boyer W (1995) Serotonin uptake inhibitors are superior to imipramine and alprazolam in alleviating panic attacks a metaanalysis. Int Clin Psychopharmacol 10 45-49 Bradwejn J, Koszycki D (1994) Imipramine antagonism of the paniogenic effects of chole-cystokinin tetrapeptide in panic disorder patients. Am J Psychiatry 151 261-263 Bradwejn J, Koszycki D, Paradis M, Reece P, Hinton J, Sedman A (1995) Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers. Biol Psychiatry 38 742-746... 

Curtis, G.C., Abelson, J.L., and Gold, P.W. (1997) Adrenocorticotropic and hormone and cortisol responses to corticotropinreleasing hormone changes in panic disorder and effects of alprazolam treatment. Biol Psychiatry 41 76-85. 

Ravaris, C.L., Friedman, M.J., Hauri, P.J., and McHugo, G.J. (1991) A controlled study of alprazolam and propranolol in panic-disordered and agoraphobic outpatients. / Clin Psychopharmacol 11 344-350. 

A larger set of placebo-controlled studies show conclusively that imipramine is also effective for the treatment of panic disorders. Other agents shown to be effective in panic disorders include the SSRIs paroxetine, sertraline, fluvoxamine, fluoxetine and citalopram. Generally, initial treatment of moderate to severe panic disorders may require the initiation of a short course of benzodiazepines e.g. clonazepam (0.5 1 mg twice daily), and an SSRI. The patient will obtain immediate relief from panic attacks with the benzodiazepine whereas the SSRI may take 1 6 weeks to become effective. Once a patient is relieved of initial panic attacks, clonazepam should be tapered and discontinued over several weeks and SSRI therapy continued thereafter. There are no pharmacological treatments available for specific phobias, however controlled trials have shown efficacy for several agents, e.g. phenelzine, moclobemide. clonazepam, alprazolam, fluvoxamine. sertraline and paroxetine in the treatment of social phobia (Roy-Byrne and Cowlev, 2002). 

Lydiard RB, Laraia MT, Ballenger JC, et al. Emergence of depressive symptoms in patients receiving alprazolam for panic disorder. Am J Psychiatry 1987 144 664-665. 

DuPont RL, Pecknold JC. Alprazolam withdrawal in panic disorder patients. Presented at the Annual Meeting of the American Psychiatric Association, Dallas, Texas, May 1985. 

Nagy LM, Krystal JH, Woods SW, et al. Clinical and medication outcome after short-term alprazolam and behavioral group treatment in panic disorder. Arch Gen Psychiatry 1989 46 993-999. 

Ballenger JC, Lydiard RB, Lesser IM, et al. Acute fixed dose alprazolam study in panic disorder patients. Presented at the Pharmacology/Pharmacokinetic Studies Workshop at the Panic Disorder Biological Research Workshop, Washington, DC, April 1986. 

Bond AJ, Curran HV, Bruce MS, et al. Behavioural aggression in panic disorder after 8 weeks treatment with alprazolam. J Affect Disord 1995 35 117-123. 

High-potency benzodiazepines (alprazolam, clonazepam) generally are more effective in panic disorder than low-potency benzodiazepines (diazepam, lorazepam, etc.). Although less research has been done on the low-potency benzodiazepines, it is generally accepted that they frequently result in sedation prior to adequately relieving panic attacks. The reader is referred to the discussion of benzodiazepines in Chapter 8 for a detailed overview of mechanism of action. A critique of the issues of benzodiazepine dependence and appropriate use is given in Chapter 13-... 

Alprazolam has been researched more extensively than any other benzodiazepine in panic disorder, and is very effective. Because of its short duration of action, it generally must be administered in three to five daily doses. Clonazepam, which has a longer duration of action than alprazolam, has also been investigated in panic disorder. It can generally be administered twice a day. Clonazepam is reported to have less abuse potential than alprazolam and to be easier to taper during discontinuation owing to its longer half-life. 

Alprazolam, a triazolobenzodiazepine, has been marketed as an anxiolytic with additional antidepressant properties an analogue, adinazolam, also has partial antidepressant activity (1) and is useful in panic disorder. Like other benzodiazepines, alprazolam is effective in acute and generalized anxiety its efficacy in panic disorder (2,3), premenstrual syndrome (4), and chronic pain (5) is complicated by high rates of adverse effects (6). On the other hand, low-dose alprazolam (1.4 mg/day) is useful and well tolerated in the treatment of anxiety associated with schizophrenia (SEDA-19, 34). 

Treatment. The choice lies between a fast-acting benzodiazepine such as alprazolam (1-3 mg/day p.o.) and a drug with delayed efficacy but fewer problems of withdrawal such as a TCA, e.g. clomipramine (100-250 mg/day p.o.) or an SSRI, e.g. paroxetine (20-50 mg/day p.o.). The different time course of these two classes of agent in panic disorder is depicted in Fig. 19.5 (see also Tables 19.5 and 19.6). 

Of the three possible triazole isomers that maintain a nitrogen at position 1 of the benzodiazepine ring, only the 4H-[l,2,4]-tria-zolo[4,3-a]-l,4-benzodiazepine analogs, exemplified by alprazolam (5), appear to have useful activity (285). Alprazolam is clinically effective in GAD and is approved for use in panic disorder. Other members of this class in clinical use include the hypnotics estazolam... 

Fyer AJ, Liebowitz MR, Gorman JM, et al Effects of clonidine on alprazolam discontinuation in panic patients a pilot study. J Clin Psychopharmacol 8 270—274,1988 Garvey MJ, Tollefson GD Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. Am J Psychiatry 143 1601-1603, 1986... 

Benzodiazepines. The introduction of the benzodiazepines represented a significant advance in the treatment of panic disorder. In contrast to MAOIs and TCAs, the benzodiazepines begin to provide relief the very first day of treatment, and many patients experience a complete response by the end of the second week of therapy. All benzodiazepines should theoretically alleviate the symptoms of a panic attack at comparable doses, but the benzodiazepines of choice are alprazolam (Xanax, Xanax XR) and clonazepam (Klonopin). It likely is not coincidental that these two are among the highest potency benzodiazepines. However, they differ considerably from a pharmacokinetic standpoint. If clonazepam is the tortoise of benzodiazepines, then alprazolam is the hare. 

We do not use benzodiazepines as readily when treating GAD as we do when treating panic disorder. In comparison to those with panic disorder, most patients with GAD can more easily tolerate the delay in treatment response and even any transient exacerbation of anxiety associated with antidepressant therapy. Benzodiazepines are reserved for those who present with especially severe anxiety that necessitates more rapid relief than an antidepressant can afford and for those who do not achieve a satisfactory response to antidepressant or buspirone therapy. Due to the persistent nature of the anxiety experienced by patients with GAD, shortacting benzodiazepines such as alprazolam are not especially helpful unless dosed 3-4 times per day. Instead, we prefer long-acting agents such as clonazepam. When used to treat GAD, clonazepam should be started at a low dose (0.25-0.5 mg/day) and titrated to higher doses (1-4 mg/day) if clinically necessary. 

Alprazolam is short-lasting tranquilizer used in conditions of anxiety, panic disorders, and depressive syndrome. The most conunon synonym for this drug is xanax. 

Greenblatt, D.J., Harmatz, J.S., and Shader, R.I. (1993) Plasma alprazolam concentrations relation to efficacy and side effects in the treatment of panic disorder. Arch Gen Psychiatry 50 715-722. 

A multitude of studies show that benzodiazepine is effective in the treatment of panic disorder, sometimes freeing patients from panic attacks after six to eight weeks of use. Benzodiazepines tend to work quickly, with a reduction in panic being observed as little as one week after the start of treatment. However, benzodiazepines have the risks of tolerance and dependency. Common benzodiazepines used to treat panic disorder include alprazolam (Xanax) and clonazepam (Klonopin). 

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