A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder

Pollack, Mark H.; Mangano, Richard M.; Entsuah, Richard; Tzanis, Evan; Simon, Naomi M.

doi:10.1007/s00213-007-0821-0

Cited by 60 publications

(15 citation statements)

References 56 publications

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“…OX1R antagonists also have an advantage over SSRIs which become effective 2–3 weeks after daily use (Pollack et al, 2007a,b) and tend to increase anxiety symptoms initially both clinically (Goddard et al, 2001) and preclinically (Ravinder et al, 2013). …”

Section: Resultsmentioning

confidence: 99%

Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation

et al. 2017

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Orexin neurons originating in the perifornical and lateral hypothalamic area are highly reactive to anxiogenic stimuli and have strong projections to anxiety and panic-associated circuitry. Recent studies support a role for the orexin system and in particular the orexin 1 receptor (OX1R) in coordinating an integrative stress response. However, no selective OX1R antagonist has been systematically tested in two preclinical models of using panicogenic stimuli that induce panic attack in the majority of people with panic disorder, namely an acute hypercapnia-panic provocation model and a model involving chronic inhibition of GABA synthesis in the perifornical hypothalamic area followed by intravenous sodium lactate infusion. Here we report on a novel brain penetrant, selective and high affinity OX1R antagonist JNJ-54717793 (1S,2R,4R)-7-([(3-fluoro-2-pyrimidin-2-ylphenyl)carbonyl]-N-[5-(trifluoromethyl)pyrazin-2-yl]-7-azabicyclo[2.2.1]heptan-2-amine). JNJ-54717793 is a high affinity/potent OX1R antagonist and has an excellent selectivity profile including 50 fold versus the OX2R. Ex vivo receptor binding studies demonstrated that after oral administration JNJ-54717793 crossed the blood brain barrier and occupied OX1Rs in the rat brain. While JNJ-54717793 had minimal effect on spontaneous sleep in rats and in wild-type mice, its administration in OX2R knockout mice, selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. JNJ-54717793 attenuated CO2 and sodium lactate induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. These data confirm that selective OX1R antagonism may represent a novel approach of treating anxiety disorders, with no apparent sedative effects.

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Section: Resultsmentioning

confidence: 99%

Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation

et al. 2017

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“…SNRIs: Venlafaxine extended-release (XR) has been shown to be useful in reducing the severity of panic disorder symptoms in RCTs (Level 1) [215,216,227-229]. Two studies found significantly greater rates of panic-free patients compared with placebo [215,216] while two did not [228,229].…”

Section: Panic Disorder and Agoraphobiamentioning

confidence: 99%

“…Two studies found significantly greater rates of panic-free patients compared with placebo [215,216] while two did not [228,229]. …”

Section: Panic Disorder and Agoraphobiamentioning

confidence: 99%

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

et al. 2014

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BackgroundAnxiety and related disorders are among the most common mental disorders, with lifetime prevalence reportedly as high as 31%. Unfortunately, anxiety disorders are under-diagnosed and under-treated.MethodsThese guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Data on the epidemiology, diagnosis, and treatment (psychological and pharmacological) were obtained through MEDLINE, PsycINFO, and manual searches (1980–2012). Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines.ResultsThese guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions.ConclusionsAnxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments.

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“…A maintenance dose of 225 mg of venlafaxine was set as the target for subjects selected to receive active medication. This dose has been shown to have efficacy in clinical trials of several anxiety disorders including general anxiety disorder (Rickels et al, 2000), panic disorder (Pollack et al, 2007), and social anxiety disorder (Liebowitz et al, 2005). In vitro evidence suggests that venlafaxine has greater affinity for the serotonin as opposed to the norepinephrine neuronal transporter (NET) proteins (Roseboom and Kaslin, 2000).…”

Section: Methodsmentioning

confidence: 99%

The effects of venlafaxine and cognitive behavioral therapy alone and combined in the treatment of co-morbid alcohol use-anxiety disorders

Ciraulo

Barlow

Gulliver

et al. 2013

Behaviour Research and Therapy

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The effects of the antidepressant venlafaxine (VEN-225 mg daily) and transdiagnostic cognitive behavioral treatment (CBT) alone and in combination on alcohol intake in subjects with co-morbid alcohol use disorders (AUDs) and anxiety disorders were compared. Drinking outcomes and anxiety were assessed for 81 subjects treated for 11 weeks with one of 4 conditions:1) VEN-CBT, 2)VEN-Progressive Muscle Relaxation therapy (PMR),3) Placebo (PLC)-CBT and 4) a comparison group of PLC-PMR. For subjects who reported taking at least one dose of study medication, the Time × Group interaction was significant for percent days of heavy drinking and drinks consumed per day. For the measure of percent days heavy drinking, the paired comparison of PLC-CBT versus PLC-PMR group indicated that the PLC-CBT group had greater drinking reductions, whereas other groups were not superior to the comparison group. In Week 11, the proportion of subjects in the PLC-CBT group that had a 50% reduction from baseline in percent days heavy drinking was significantly greater than those in the comparison group. Of the 3 “active treatment” groups only the PLC-CBT group had significantly decreased heavy drinking when contrasted to the comparison group. This finding suggests that the transdiagnostic CBT approach of Barlow and colleagues may have value in the management of heavy drinking in individuals with co-morbid alcoholism and anxiety.

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A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder

Abstract: Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder.

Cited by 60 publications

References 56 publications

Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation

Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

The effects of venlafaxine and cognitive behavioral therapy alone and combined in the treatment of co-morbid alcohol use-anxiety disorders

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