Gabapentin and Pregabalin for the Treatment of Anxiety Disorders

Greenblatt, H. Karl; Greenblatt, David J.

doi:10.1002/cpdd.446

Cited by 48 publications

(25 citation statements)

References 56 publications

(88 reference statements)

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“…Thrombospondins are matrix proteins involved in synaptogenesis [ 45 ], bind to α2δ-1, are upregulated after peripheral nerve injury, and disrupt intracellular Ca2 + signaling due to the interaction with this auxiliary subunit of the calcium channel [ 46 ]. A better understanding of these phenomena is of the utmost importance to clarify the mechanism of action of α2δ-1 ligands such as gabapentin, pregabalin, and the newest mirogabalin [ 47 , 48 ], which is reportedly endowed with neuropsychiatric activities during chronic pain states [ 49 , 50 , 51 ], clinical conditions in which, for instance, these drugs are often inappropriately used in non-communicative patients [ 52 , 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Scuteri

Rombolà

Natoli

et al. 2021

Life

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Background: DYT1 dystonia is the most common form of early-onset inherited dystonia, which is caused by mutation of torsin A (TA) belonging to the “ATPases associated with a variety of cellular activities” (AAA + ATPase). Dystonia is often accompanied by pain, and neuropathic pain can be associated to peripherally induced movement disorder and dystonia. However, no evidence exists on the effect of gabapentin in mice subjected to neuropathic pain model overexpressing human normal or mutated TA. Methods: Mice subjected to L5 spinal nerve ligation (SNL) develop mechanical allodynia and upregulation of the α2δ-1 L-type calcium channel subunit, forming a validated experimental model of neuropathic pain. Under these experimental conditions, TA is expressed in dorsal horn neurons and astrocytes and colocalizes with α2δ-1. Similar to this subunit, TA is overexpressed in dorsal horn 7 days after SNL. This model has been used to investigate (1) basal mechanical sensitivity; (2) neuropathic pain phases; and (3) the effect of gabapentin, an α2δ-1 ligand used against neuropathic pain, in non-transgenic (NT) C57BL/6 mice and in mice overexpressing human wild-type (hWT) or mutant (hMT) TA. Results: In comparison to non-transgenic mice, the threshold for mechanical sensitivity in hWT or hMT does not differ (Kruskal–Wallis test = 1.478; p = 0.4777, although, in the latter animals, neuropathic pain recovery phase is delayed. Interestingly, gabapentin (100 mg/Kg) reduces allodynia at its peak (occurring between post-operative day 7 and day 10) but not in the phase of recovery. Conclusions: These data lend support to the investigation on the role of TA in the molecular machinery engaged during neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Scuteri

Rombolà

Natoli

et al. 2021

Life

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“…Pregabalin is approved in the European Union for use as an anxiolytic agent in the management of generalised anxiety disorder (GAD) and is commonly used-off label in the US [ 78 ]. With a mechanism of action distinct from other anxiolytic agents, it also offers broad-spectrum treatment for the characteristic psychosomatic symptoms of GAD including excessive generalised worry, hypervigilance and persistent nonspecific anxiety [ 5 ].…”

Section: Methodsmentioning

confidence: 99%

Pregabalin in the Management of Painful Diabetic Neuropathy: A Narrative Review

et al. 2018

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Pregabalin is a first-line treatment in all major international guidelines on the management of painful diabetic neuropathy (pDPN). Treatment with pregabalin leads to a clinically meaningful improvement in pain scores, offers consistent relief of pain and has an acceptable tolerance level. Despite its efficacy in relieving neuropathic pain, more robust methods and comprehensive studies are required to evaluate its effects in relation to co-morbid anxiety and sleep interference in pDPN. The sustained benefits of modulating pain have prompted further exploration of other potential target sites and the development of alternative GABAergic agents such as mirogabalin. This review evaluates the role of pregabalin in the management of pDPN as well as its potential adverse effects, such as somnolence and dizziness, which can lead to withdrawal in ~ 30% of long-term use. Recent concern about misuse and an increase in deaths linked to its use has led to demands for reclassification of pregabalin as a class C controlled substance in the UK. We believe these demands need to be tempered in relation to the difficulties it would create for repeat prescriptions for the many millions of patients with pDPN for whom pregabalin provides benefit.Plain Language Summary: Plain language summary available for this article.

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“…Although both compounds are structurally related to GABA, neither has affinity for GABA receptors: instead, they exert their action through binding to the a2-δsubunit of voltage-gated calcium channels in the central nervous system and the resulting inhibition of neuronal signaling. 84 In an 8-week, double-blind clinical trial, 133 PD patients received either gabapentin (600-3600 mg/ day) or placebo. 73 Overall, no significant difference between active treatment and placebo was observed.…”

Section: Anticonvulsants In Patients With a Primary Diagnosis Of Pd mentioning

confidence: 99%

Anticonvulsant and antipsychotic medications in the pharmacotherapy of panic disorder: a structured review

Masdrakis

Baldwin

2021

Therapeutic Advances in Psychopharmacology

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Background: As the remission rate of panic disorder (PD) achieved with conventional pharmacotherapy ranges between 20% and 50%, alternative psychopharmacological strategies are needed. We aimed to firstly review data regarding use of antipsychotic and non-benzodiazepine anticonvulsant medication in PD patients with or without comorbidities; secondly, to review data concerning reduction of panic symptoms during treatment of another psychiatric disorder with the same medications; and thirdly, to examine reports of anticonvulsant- or antipsychotic-induced new-onset panic symptomatology. Methods: We performed a PubMed search (last day: 28 April 2020) of English-language studies only, combining psychopathological terms (e.g. ‘panic disorder’) and terms referring either to categories of psychotropic medications (e.g. ‘anticonvulsants’) or to specific drugs (e.g. ‘carbamazepine’). All duplications were eliminated. All studies included in the review met certain inclusion/exclusion criteria. The level of evidence for the efficacy of each drug was defined according to widely accepted criteria. Results: In treatment-resistant PD, beneficial effects have been reported after treatment (mostly augmentation therapy) with a range of anticonvulsant (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbamazepine, valproate, vigabatrin, tiagabine) and antipsychotic (aripiprazole, olanzapine, risperidone, sulpiride) medications: overall, most medications appear generally well tolerated. Additionally, bipolar patients receiving valproate or quetiapine-XR (but not risperidone or ziprasidone) demonstrated reductions of comorbid panic-related symptoms. There are case reports of new-onset panic symptoms associated with clozapine, haloperidol, olanzapine and topiramate, in patients with conditions other than PD. The small-to-modest sample size, the lack of control groups and the open-label and short-term nature of most of the reviewed studies hinder definitive conclusions regarding either the short-term and long-term efficacy of antipsychotic and anticonvulsant medications or their potential long-term side effects. Conclusion: Some atypical antipsychotic and anticonvulsant medications may have a role in the treatment of some PD patients, mostly when more conventional approaches have not been successful, but the quality of supporting evidence is limited.

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Gabapentin and Pregabalin for the Treatment of Anxiety Disorders

Cited by 48 publications

References 56 publications

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Pregabalin in the Management of Painful Diabetic Neuropathy: A Narrative Review

Anticonvulsant and antipsychotic medications in the pharmacotherapy of panic disorder: a structured review

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