Alprazolam in Panic Disorder and Agoraphobia: Results From a Multicenter Trial

Pecknold, John C.; Swinson, Richard P.; Kuch, Klaus; Lewis, Carl P.

doi:10.1001/archpsyc.1988.01800290043006

Cited by 194 publications

(51 citation statements)

References 63 publications

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“…For anxiety disorders such as generalized anxiety, panic disorder, or social phobia, placebo effects in clinical trials have been reported ranging between 10% and 60% (Loebel et al, 1986;Mavissakalian, 1988;Mellergard and Rosenberg, 1990;Piercy et al, 1996;Huppert et al, 2004;Khan et al, 2005;Stein et al, 2006). Moreover, in RCTs investigating the anxiolytic effect of the benzodiazepine alprazolam, improvement in the placebo arm remained stable after the pill intake was discontinued, whereas patients in the drug arm suffered relapses to baseline levels (Ballenger et al, 1988;Pecknold et al, 1988), indicating that placebo responses in anxiety disorders can indeed be long lasting and clinically relevant. The substantial and robust placebo responses observed in clinical studies of anxiety disorders motivated experimental investigations in their neurobiological underpinnings and inspired the search for an individual's predictors of placebo responses, although the results so far have been vague (Dager et al, 1990;Woodman et al, 1994;Feltner et al, 2009).…”

Section: Neuropsychiatric Diseases and Behavioral Disordersmentioning

confidence: 99%

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

Schedlowski¹,

Enck²,

Rief³

et al. 2015

Pharmacol Rev

262

257

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Section: Neuropsychiatric Diseases and Behavioral Disordersmentioning

confidence: 99%

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

Schedlowski¹,

Enck²,

Rief³

et al. 2015

Pharmacol Rev

262

257

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“…Many of the trials that report the efficacy of alprazolam in the treatment of panic disorder do not indicate the proportion of patients who became free from panic attacks at endpoint. Nevertheless, placebo-controlled trials have reported panic-free rates in 46-75% of patients treated with alprazolam compared with 14-50% of the placebo group Pecknold et al, 1988;Tesar et al, 1991;Munjack et al, 1989;Lydiard et al, 1992;Noyes et al, 1996]. Associated symptomatology.…”

Section: Treatment Options In Panic Disordermentioning

confidence: 99%

“…Alprazolam [Lydiard et al, 1992;Noyes et al, 1996;Pecknold et al, 1988;Keller et al, 1993] and diazepam [Noyes et al, 1996] reduced phobic symptoms to a greater extent than placebo, in double-blind, controlled studies in panic disorder patients.…”

Section: Treatment Options In Panic Disordermentioning

confidence: 99%

Management of anxiety disorders: The added challenge of comorbidity

Dünner

2001

Depress. Anxiety

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Patients with anxiety present with a wide variety of disorders that cause significant impairment to their everyday lives. To complicate matters, patients seldom present with just one anxiety disorder. Such comorbidity, particularly where depression is also present, has important implications for both the patient and the physician. The patient typically suffers from a greater degree of everyday impairment, is more reliant on healthcare services, in particular mental health services, and may be at a greater risk of attempting suicide. For the physician, comorbidity in anxiety disorders presents a challenge as the patient's symptoms are often more severe, present earlier in life, and are frequently prolonged which makes their management more complex. This review will focus on the anxiety disorders: panic disorder, obsessive-compulsive disorder, social anxiety disorder, and post-traumatic stress disorder. The impact of co-existing multiple anxiety disorders, depression, or a history of substance abuse will be discussed with a view to choosing the appropriate management strategy. Treatment options will be reviewed.

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“…An anxiolytic treatment for panic attacks unfortunately increased panic attacks during medication withdrawal when compared to a placebo which had no withdrawal effects (Ballenger et al, 1988;Brown et al, 2016;Johnson, Federici, & Shekhar, 2014;Pecknold, Swinson, Kuch, & Lewis, 1988;Salzman & Shader, 2015).…”

Section: Cautionary Talesmentioning

confidence: 99%

The fallacy of the placebo-controlled clinical trials: Are positive outcomes the result of ‘indirect’ treatment effects?

Peper

Harvey

2017

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This paper argues that placebo effects have a larger influence on clinical trial outcomes than purported treatment effects, raising questions about the size of effects currently attributed to clinical treatments. Placebo-controlled clinical trials usually do not include an "active" placebo and thus the clinical outcome could be due to the placebo responses to nontherapeutic side effects of the treatment. For this paper, an active placebo includes substances or procedures that permit attribution of a physiological effect such as a B-vitamin that safely causes flushing, or a very low, subtherapeutic dose of a medication, as well as a biofeedback training procedure that safely trains physiological responses other than the target response. The paper also discusses the positive outcome of a sham treatment procedure (e.g., not actually doing the proposed treatment) in contrast to the nocebo effect (e.g., a worse or negative outcome associated with unintended effects of the treatment procedure). This paper emphasizes exercising caution when interpreting results from clinical trials using pharmaceutical or surgical treatments. The paper discusses possible mechanisms underlying the acceptance of treatment procedures which later have been shown to be ineffective or harmful, and highlights the importance of incorporating active placebo procedures to address any covert treatment side effects induced by placebo response. Finally, the authors suggest that clinical trials of bio/neurofeedback treatments carefully consider the important and consequential influences of placebos when designing studies or interpreting the results of trial outcomes.

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Alprazolam in Panic Disorder and Agoraphobia: Results From a Multicenter Trial

Cited by 194 publications

References 63 publications

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

Management of anxiety disorders: The added challenge of comorbidity

The fallacy of the placebo-controlled clinical trials: Are positive outcomes the result of ‘indirect’ treatment effects?

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