The relative effectiveness of the available treatments for panic disorder may best be understood in the context of the longitudinal course of the disorder. This study examines a number of clinically relevant issues, including long-term outcome after acute treatment, the proportion of patients remaining on single-agent treatment or requiring multiple medications or nonpharmacologic interventions over time, evidence for dose escalation during maintenance high-potency benzodiazepine therapy, and predictors of acute and long-term response to treatment. Fifty-nine panic disorder patients originally randomized to treatment in a controlled trial comparing alprazolam, clonazepam, and placebo were reevaluated in a follow-up study. At a mean follow-up of 1.5 years, 78% of patients remained on medication and the mean dosage of alprazolam and clonazepam did not increase. Our data suggest that most patients maintain benefit with long-term pharmacotherapy but that residual symptomatology may require more intensive or additional treatment strategies. Response at the endpoint of the acute trial was significantly associated with pretrial baseline Clinical Global Impression Scale score and the presence of dysthymia. Poor outcome at follow-up was associated with total duration of the disorder, agoraphobic subtype, and the presence of comorbid social phobia. We underscore the potential importance of comorbid affective and anxiety disorders as well as phobic patterns in determining long-term response to treatment.

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.

Back to table of contents Previous article Next article ArticleNo AccessPilot Outreach Services to Homebound Agoraphobic PatientsMark H. Pollack, Gary S. Sachs, George E. Tesar, Julie Shushtari, John B. Herman, Michael W. Otto, and Jerrold F. RosenbaumMark H. PollackSearch for more papers by this author, Gary S. SachsSearch for more papers by this author, George E. TesarSearch for more papers by this author, Julie ShushtariSearch for more papers by this author, John B. HermanSearch for more papers by this author, Michael W. OttoSearch for more papers by this author, and Jerrold F. RosenbaumSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ps.42.3.315AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail PDFThis content is only available as a PDF. Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - Psychiatric Services $35.00 Add to cart PPV Articles - Psychiatric Services Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited bySanté mentale au Québec, Vol. 34, No. 1 Volume 42Issue 3 March 1991Pages 315-317 Metrics PDF download History Published online 1 April 2006 Published in print 1 March 1991

L'article synthetise les donnees obtenues par differentes etudes evaluant l'efficacite des anticonvulsivants ― en particulier du clonazapam ― dans le traitement des troubles de l'anxiete et de la panique

Interest in benzodiazepines for treatment of panic attacks followed a report of the success of alprazolam, used for generalized anxiety, in blocking such attacks. Twelve controlled trials and several open studies have substantiated the antipanic and antiphobic activity of alprazolam and concluded it is comparable to but more rapid than antidepressants in its effects and better tolerated. In a controlled trial of clonazepam, alprazolam, and placebo, the two active agents had similar positive effects. Diazepam and lorazepam have been effective in other studies. Clonazepam, with its relatively long half-life, permits less frequent dosing than possible with benzodiazepines with shorter half-lives and more continuous control of anxiety, although around 20% of patients experience unacceptable sedative effects or no reduction in anxiety. In general, benzodiazepines are safe and well tolerated. The most common adverse effects are intoxication, dependence, rebound, withdrawal, hostility, and affective disturbances. Discontinuation of alprazolam is particularly difficult and is sometimes associated with serious rebound and withdrawal symptoms. The morbidity and mortality associated with panic disorder suggest that the benefits of benzodiazepine treatment outweigh its risks.

We hypothesized that the dehydroepiandrosterone-sulfate (DHEA-S)/cortisol ratio, which has been used as an index of adrenocortical function, would be altered in panic disorder patients and would change after treatment. We evaluated 10 male and 14 female outpatients meeting DSM-III-R criteria for panic disorder. Of these 24 subjects, 13 were treated with clonazepam, 8 were treated with alprazolam, and 3 were treated with placebo as part of a double-blind study. The DHEA-S/cortisol ratio values in the 24 patients with panic disorder (mean = 20.5, SD = 11.6) were significantly higher than those of a group of 60 normal controls (mean = 11.5, SD = 6.01) and were also significantly higher than those of a group of 22 depressed patients (mean = 10.6, SD = 6.33). Although there was no significant difference in the pretreatment DHEA-S/cortisol ratio values between male (mean = 23.6, SD = 11.8) and female (mean = 18.2, SD = 11.3) panic disorder patients, the effects of treatment on this ratio differed between the two sexes. In fact, in the female patients there was a significant decrease in the DHEA-S/cortisol ratio at the end of the study (mean = 15.1, SD = 7.9), while in the male patients there was no significant change in this ratio at the end of the study (mean = 30.2, SD = 21.4). No significant differences were noted between pretreatment and posttreatment DHEA-S/cortisol ratio values in patients treated with alprazolam (n = 8), in patients treated with clonazepam (n = 13), or in patients treated with placebo (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

The authors present interim results of a prospective, random assignment, double-blind, placebo-controlled trial conducted to determine whether clonazepam is as effective as alprazolam in reducing the frequency of panic attacks and whether both agents are superior to placebo. Analysis on 44 of 60 randomized subjects showed no statistically significant differences between the clonazepam and alprazolam groups on the following clinically meaningful outcome measures: total number of panic attacks and percent of time subjects experienced anticipatory anxiety, extent of phobic avoidance, and fear. Statistically significant differences did exist among the drug and placebo groups on these measures. The authors conclude that this interim analysis of the data supports the inclusion of clonazepam in the treatment of panic disorder.

Fifty patients with panic disorder or agoraphobia with panic attacks with treated with clonazepam, a high potency benzodiazepine. The authors report on the outcome of these patients after an average follow-up interval of 1 year, suggesting that clonazepam is a safe, effective, and easy to administer medication in a relatively treatment-refractory population of nondepressed patients with panic disorder and agoraphobia.

Ten cases are presented--two in detail--in which clonazepam was used successfully in patients with treatment-resistant panic disorder with or without agoraphobia. Seven of 10 patients who had been resistant to standard pharmacological treatments of panic attacks and agoraphobia achieved cessation of their attacks while three had mild to moderate symptom persistence. These data underscore other reports of clonazepam's usefulness in the treatment of panic disorder. Clinical use of clonazepam is discussed.