Personalized medicine in panic disorder: where are we now? A meta-regression analysis

Caldirola, Daniela; Grassi, Massimiliano; Alciati, Alessandra; Riva, Alice; Sangiorgio, Erika; Daccò, Silvia; Perna, Giampaolo

doi:10.1016/j.pmip.2016.12.003

Cited by 6 publications

(6 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results reinforce the idea that behavior during CAS exposure is qualitatively different from behavior after CAS exposure. We also show that behavior in both contexts are differentially sensitive to clonazepam, a high‐potency benzodiazepine commonly used in the clinical management of panic disorder (Caldirola et al, ). Increasing serotonin levels by treating zebrafish with acute fluoxetine blocked the effects of CAS during and after exposure, but blocking serotonin receptors with metergoline, or blocking serotonin synthesis with para ‐chlorophenylalanine ( p CPA), produced an effect only after exposure.…”

Section: Introductionmentioning

confidence: 54%

“…The increased erratic swimming observed during CAS exposure suggests escape and/or avoidance attempts, while the increased freezing observed after CAS exposure suggests a role in risk assessment. The effects of clonazepam also suggest different neurobehavioral states: this drug usually decreases panic attacks, but has small effects on generalized anxiety in human clinical settings (Caldirola et al, ; Cloos, ). These results imply good predictive validity, suggesting that behavior during and after CAS can be used to study fear‐ versus anxiety‐like effects.…”

Section: Discussionmentioning

confidence: 99%

“…Clonazepam (CLZ; CAS #1622‐61‐3) was bought from Roche in 2018, and dissolved in Cortland's salt solution (NaCl 124.1 mM, KCl 5.1 mM, Na 2 HPO 4 2.9 mM, MgSO 4 1.9 mM, CaCl 2 1.4 mM, NaHCO 3 11.9 mM, polyvinylpyrrolidone 4%, 1,000 USP units heparin; Wolf, ). Clonazepam, as a high‐potency benzodiazepine widely used in treating panic disorder (Caldirola et al, ; Cloos, ), is expected to decrease fear‐like responses to CAS, and therefore used as a positive control. Fluoxetine (FLX) is expected to acutely increase serotonin levels in the synapse (Figure b).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Phasic and tonic serotonin modulate alarm reactions and post‐exposure behavior in zebrafish

Lima-Maximino

Pyterson

Silva

et al. 2020

Journal of Neurochemistry

View full text Add to dashboard Cite

Current theories on the role of serotonin (5-HT) in vertebrate defensive behavior suggest that this monoamine increases anxiety but decreases fear, by acting at different levels of the neuroaxis. This paradoxical, dual role of 5-HT suggests that a serotonergic tone inhibits fear responses, while an acute increase in 5-HT would produce anxiety-like behavior. However, so far no evidence for a serotonergic tone has been found. Using zebrafish alarm responses, we investigate the participation of phasic and tonic 5-HT levels in fear-like behavior, as well as in behavior after stimulation.Conspecific alarm substance (CAS) increased bottom-dwelling and erratic swimming, and animals transferred to a novel environment after CAS exposure (post-exposure behavior) showed increased bottom-dwelling and freezing. Clonazepam blocked CAS effects during and after exposure. Acute fluoxetine dose-dependently decreased fear-like behavior, but increased post-exposure freezing. Metergoline had no effect on fear-like behavior, but blocked the effects of CAS on post-exposure behavior; similar effects were observed with para-chlorophenylalanine. Finally, CAS was shown to decrease the activity of monoamine oxidase in the zebrafish brain after exposure.These results suggest that phasic and tonic serotonin encode an aversive expectation value, switching behavior toward cautious exploration/risk assessment/anxiety when the aversive stimulus is no longer present. K E Y W O R D Salarm substance, fear, panic, serotonin, zebrafish | INTRODUC TI ONThe neurocircuitry of defensive reactions involves regulation by a plethora of neuromodulators, including monoamines and peptides (Maximino, 2012). In vertebrates, the monoamine serotonin (5-HT) is produced in specific brain nuclei, including the raphe, and is thought to inhibit fear/escape responses to proximate threat by acting on more caudal structures of the aversive brain system (Deakin & Graeff, 1991; S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Lima-Maximino M, Pyterson MP, do Carmo Silva RX, et al. Phasic and tonic serotonin modulate alarm reactions and post-exposure behavior in zebrafish. J. Neurochem. 2020;153:495-509.https://doi.

show abstract

Section: Introductionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Phasic and tonic serotonin modulate alarm reactions and post‐exposure behavior in zebrafish

Lima-Maximino

Pyterson

Silva

et al. 2020

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Our results reinforce the idea that behavior during CAS exposure is qualitatively different from behavior after CAS exposure. We also show that behavior in both contexts are differentially sensitive to clonazepam, a triazolobenzodizepine commonly used in the clinical management of panic disorder (Caldirola et al 2016). Increasing serotonin levels by treating zebrafish with acute fluoxetine blocked the effects of CAS during and after exposure, but blocking serotonin receptors with metergoline, or blocking serotonin synthesis with pCPA, produced an effect only after exposure.…”

Section: Introductionmentioning

confidence: 77%

“…The increased erratic swimming observed during CAS exposure suggest escape and/or avoidance attempts, while the increased freezing observed after CAS exposure suggest a role in risk assessment. The effects of clonazepam also suggest different neurobehavioral states: this drug usually decreases panic attacks, but has small effects on generalized anxiety in human clinical settings (Caldirola et al 2016). These results imply good predictive validity, suggesting that behavior during and after CAS can be used to study fear-vs. anxiety-like effects.…”

Section: Behavior During and After Cas Exposurementioning

confidence: 87%

Phasic and tonic serotonin modulate alarm reactions and post-exposure behavior in zebrafish

Lima-Maximino

Pyterson

Silva

et al. 2019

Preprint

View full text Add to dashboard Cite

Current theories on the role of serotonin (5-HT) in vertebrate defensive behavior suggest that this monoamine increases anxiety but decreases fear, by acting at different levels of the neuroaxis. This paradoxical, dual role of 5-HT suggests that a serotonergic tone inhibits fear responses, while an acute increase in 5-HT would produce anxiety-like behavior. However, so far no evidence for a serotonergic tone has been found. Using zebrafish alarm responses, we investigate the participation of phasic and tonic 5-HT levels in fear-like behavior, as well as in behavior after stimulation.Conspecific alarm substance (CAS) increased bottom-dwelling and erratic swimming, and animals transferred to a novel environment after CAS exposure (post-exposure behavior) showed increased bottom-dwelling and freezing. Clonazepam blocked CAS effects during and after exposure. Acute fluoxetine dose-dependently decreased fear-like behavior, but increased post-exposure freezing.Metergoline had no effect on fear-like behavior, but blocked the effects of CAS on post-exposure behavior; similar effects were observed with pCPA. Finally, CAS was shown to decrease the activity of monoamine oxidase in the zebrafish brain after exposure. These results suggest that phasic and tonic serotonin encode an aversive expectation value, switching behavior towards cautious exploration/risk assessment/anxiety when the aversive stimulus is no longer present. zebrafish, 5-HT 1A and 5-HT 1B receptor antagonists decrease anxiety-like behavior (Maximino et al. ,635 was not able to alter anxiety-like behavior after exposure, the drug blocked the increased geotaxis during CAS exposure, both in the first minutes of exposure and in the last minutes (Nathan et al. 2015). Blocking 5-HT 2 -type receptors with methysergide did not affect these responses,

show abstract

Management of Treatment-Resistant Panic Disorder

Perna

Caldirola²

2017

Curr Treat Options Psych

Self Cite

View full text Add to dashboard Cite

Purpose of Review Purpose of Review Management of treatment-resistant (TR) panic disorder (PD) is an unresolved issue. In this paper, we provide a brief summary of previous findings, an updated (2015–2017) systematic review of pharmacological/non-pharmacological studies, and our personal perspective on this topic.Recent Findings Recent Findings We found a very limited number of recent findings. Quetiapine extended-release augmentation has not been found to be beneficial, in comparison to placebo, in non-responders to previously recommended pharmacotherapy. In non-responders to cognitive behavioral therapy (CBT), switching to paroxetine/citalopram has been found to be more effective than continuing CBT. Acceptance and commitment therapy (ACT) has shown some improvement in patients’ resistance to previous psychological/pharmacological interventions compared with a waiting-list condition.Summary Summary Previous and recent findings regarding the treatment of TR PD suffer from several methodological limitations. Available studies provide insufficient evidence to support the use of medications alternative to the recommended medications; the efficacy of ACT needs confirmation with more rigorous methodology. Prolonged pharmacotherapy may produce significant improvement in patients with unsatisfactory response to short-term pharmacotherapy, while switching to pharmacotherapy may help non-responders to CBT. We discuss our personal perspective on the definition of “treatment resistance” as it relates to PD and provide personalized intervention strategies to increase favorable clinical outcomes based on our clinical expertise and review of experimental studies on the pathophysiology of PD.

show abstract

Personalized medicine in panic disorder: where are we now? A meta-regression analysis

Cited by 6 publications

References 89 publications

Phasic and tonic serotonin modulate alarm reactions and post‐exposure behavior in zebrafish

Phasic and tonic serotonin modulate alarm reactions and post‐exposure behavior in zebrafish

Phasic and tonic serotonin modulate alarm reactions and post-exposure behavior in zebrafish

Management of Treatment-Resistant Panic Disorder

Contact Info

Product

Resources

About