Reboxetine, a Selective Norepinephrine Reuptake Inhibitor, Is an Effective and Well-Tolerated Treatment for Panic Disorder

Versiani, Márcio; Cassano, Giovanni B.; Perugi, Giulio; Benedetti, Alessandra; Mastalli, L.; Nardi, Antônio Egídio; Savino, Mario

doi:10.4088/jcp.v63n0107

Cited by 124 publications

(60 citation statements)

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“…In clinical studies, reboxetine and atomoxetine were effective in the treatment of panic disorder and comorbid anxiety disorder, respectively (Versiani et al, 2002;Geller et al, 2007), suggesting their anxiolytic properties. Although their therapeutic effects are generally thought to be primarily attributable to inhibition of norepinephrine reuptake in the brain (Hajós et al, 2004;Simpson and Plosker, 2004), inhibition of GIRK channels may also contribute to improvement of anxiety symptoms.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

Kobayashi

Washiyama

Ikeda

2010

Neuropsychopharmacol

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Atomoxetine and reboxetine are commonly used as selective norepinephrine reuptake inhibitors (NRIs) for the treatment of attentiondeficit/hyperactivity disorder and depression, respectively. Furthermore, recent studies have suggested that NRIs may be useful for the treatment of several other psychiatric disorders. However, the molecular mechanisms underlying the various effects of NRIs have not yet been sufficiently clarified. G-protein-activated inwardly rectifying K + (GIRK or Kir3) channels have an important function in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to be a potential treatment for several neuropsychiatric disorders and cardiac arrhythmias. In this study, we investigated the effects of atomoxetine and reboxetine on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2, GIRK2, or GIRK1/GIRK4 subunits, extracellular application of atomoxetine or reboxetine reversibly reduced GIRK currents. The inhibitory effects were concentrationdependent, but voltage-independent, and time-independent during each voltage pulse. However, Kir1.1 and Kir2.1 channels were insensitive to atomoxetine and reboxetine. Atomoxetine and reboxetine also inhibited GIRK currents induced by activation of cloned A 1 adenosine receptors or by intracellularly applied GTPgS, a nonhydrolyzable GTP analogue. Furthermore, the GIRK currents induced by ethanol were concentration-dependently inhibited by extracellularly applied atomoxetine but not by intracellularly applied atomoxetine. The present results suggest that atomoxetine and reboxetine inhibit brain-and cardiac-type GIRK channels, revealing a novel characteristic of clinically used NRIs. GIRK channel inhibition may contribute to some of the therapeutic effects of NRIs and adverse side effects related to nervous system and heart function.

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Section: Discussionmentioning

confidence: 99%

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

Kobayashi

Washiyama

Ikeda

2010

Neuropsychopharmacol

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“…Nevertheless, electrical stimulation of human locus coeruleus (LC) which caused a 4 to 9 fold increase in NE plasma metabolites produced only alertness (Libet & Gleason, 1994). Although the latter data makes unlikely the LC contribution to aversiveness, NE may play roles either modulatory or permissive in panic attacks as suggested by several reports of successful treatments of PD with selective or preferential inhibitors of NE reuptake (Bertani et al, 2004;Dannon, Iancu, & Grunhaus, 2002;Kalus et al, 1991;Lydiard, 1987, Lydiard et al, 1993Nardi et al, 2003;Sasson et al, 1999;Seedat et al, 2003;Versiani et al, 2002;). More important, whereas the α 2 -adrenergic antagonist yohimbine is an established panicogen (Bremner, Krystal, Southwick, & Charney, 1996;Charney, Woods, Goodman, & Heninger, 1987;Charney, Woods, Krystal, Nagy, & Heninger, 1992), appropriate doses of the α 2 -adrenergic agonist clonidine promote a rapid but transient improvement of PD patients (Liebowitz, Fyer, McGrath, & Klein, 1981).…”

Section: Challenging the Modelmentioning

confidence: 99%

Towards a translational model of panic attack.

Schenberg

2010

Psychology & Neuroscience

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About 20 years ago, Deakin and Graeff proposed that whereas generalized anxiety disorder is produced by the overactivity of 5-HT excitatory projections from dorsal raphe nucleus to the areas of prefrontal cortex and amygdala which process distal threat, panic attacks are a dysfunction of 5-HT inhibitory projections from dorsal raphe nucleus to the dorsal periaqueductal gray matter, thereby releasing the responses to proximal threat, innate fear or anoxia. Besides, they suggested that the decrease in 5-HT1A neurotransmission in the hippocampus results in learned helplessness and depression. Accordingly, the Deakin Graeff hypothesis provided a unified frame to the widespread use of 5-HT selective reuptake inhibitors in generalized anxiety, panic disorder and depression. Competitor hypotheses implicate panic attacks with the abnormal functioning of locus coeruleus, basolateral amygdala, dorsomedial hypothalamus or an as-yet-unknown suffocation alarm system. Conversely, cognitive psychologists suggest that panic attacks result from the catastrophic (cortical) interpretation of bodily symptoms. In any event, translational models of panic attack are expected to reproduce the main features of clinical panic, namely, the patient's higher sensitivity to both lactate and CO2, the drug specific sensitivity, the lack of stress hormone responses during panic attacks, the higher vulnerability of women and the high comorbidity with agoraphobia, major depression and childhood separation anxiety. Therefore, here we review the main steps in the experimental approach to anxiety disorders which are paving the route towards a translational model of panic attack.

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“…To avoid overstimulation and insomnia, doses should be given in the morning and mid-day (D). Á The efficacy of the norepinephrine (noradrenaline) reuptake inhibitor (NaRI) reboxetine was shown in a DBPC study (Versiani et al 2002).…”

Section: Monoamine Oxidase Inhibitors (Maoi)mentioning

confidence: 99%

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

Bandelow

Zohar

Hollander

et al. 2008

The World Journal of Biological Psychiatry

712

410

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In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo-or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/ SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

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Reboxetine, a Selective Norepinephrine Reuptake Inhibitor, Is an Effective and Well-Tolerated Treatment for Panic Disorder

Cited by 124 publications

References 0 publications

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

Inhibition of G-Protein-Activated Inwardly Rectifying K+ Channels by the Selective Norepinephrine Reuptake Inhibitors Atomoxetine and Reboxetine

Towards a translational model of panic attack.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

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