The Incidence of Seizures during Tricyclic Antidepressant Drug Treatment in a Brain-Injured Population

Wroblewski, Bruno; McColgan, Karen; Smith, Kathleen M.; Whyte, John; Singer, William

doi:10.1097/00004714-199004000-00009

Cited by 60 publications

(4 citation statements)

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“…No impedance on cognitive recovery was noted. One review of patients with TBI on various tricyclic antidepressants revealed an increase in seizure rate of 19 percent [134].…”

Section: Antidepressantsmentioning

confidence: 99%

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Chew

Zafonte²

2009

JRRD

161

103

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Abstract-Pharmacological management of neurobehavioral disorders following traumatic brain injury (TBI) is common practice. However, the evidence available to guide this practice remains sparse. This review summarizes, in brief, the state of knowledge, organized via a time continuum from injury as well as by symptom complex. The areas of neuroprotection, hypoarousal, attention and memory deficits, aggression, agitation, depression, and mania are reviewed. The literature was searched with PubMed on the terms "traumatic brain injury" or "brain injury" with "pharmacology" (and the symptoms according to which this review is arranged). Additional searches were conducted with the specific symptoms as search terms, crossed with the therapeutic agents or drug classes discussed. Where a paucity of prospective data exists, case reports and retrospective studies are included. Studies to date have yielded minimal positive evidence for enhancing function, memory, and behavior after TBI. No single agent likely will become sentinel in the recovery process, and combination therapy in the acute and postacute settings are required. A need exists to further define the role of psychopharmacology in postacute TBI medicine and the specific characteristics of subpopulations who might benefit.

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“…No impedance on cognitive recovery was noted. One review of patients with TBI on various tricyclic antidepressants revealed an increase in seizure rate of 19 percent [134].…”

Section: Antidepressantsmentioning

confidence: 99%

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Chew

Zafonte²

2009

JRRD

161

103

View full text Add to dashboard Cite

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“…Thus, some of our animals could still have had epileptiform activity when the clomipramine treatment was initiated. Because tricyclic antidepressants, including clomipramine, are known to reduce the seizure threshold in animal models and humans [66,67,68], worsening of post-TBI epileptiform activity and its influence on the evolution of secondary pathologies must be taken into account in future studies. The effect appeared to be test-dependent, however, as no impairment was observed in the beam-walking test performed on the same day as the neuroscore test.…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Pipeline for Validation of Disease-Modifying Effects of Systems Biology-Derived Network Treatments for Traumatic Brain Injury—Lessons Learned

Lipponen

Natunen

Hujo

et al. 2019

IJMS

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We developed a pipeline for the discovery of transcriptomics-derived disease-modifying therapies and used it to validate treatments in vitro and in vivo that could be repurposed for TBI treatment. Desmethylclomipramine, ionomycin, sirolimus and trimipramine, identified by in silico LINCS analysis as candidate treatments modulating the TBI-induced transcriptomics networks, were tested in neuron-BV2 microglial co-cultures, using tumour necrosis factor α as a monitoring biomarker for neuroinflammation, nitrite for nitric oxide-mediated neurotoxicity and microtubule associated protein 2-based immunostaining for neuronal survival. Based on (a) therapeutic time window in silico, (b) blood-brain barrier penetration and water solubility, (c) anti-inflammatory and neuroprotective effects in vitro (p < 0.05) and (d) target engagement of Nrf2 target genes (p < 0.05), desmethylclomipramine was validated in a lateral fluid-percussion model of TBI in rats. Despite the favourable in silico and in vitro outcomes, in vivo assessment of clomipramine, which metabolizes to desmethylclomipramine, failed to demonstrate favourable effects on motor and memory tests. In fact, clomipramine treatment worsened the composite neuroscore (p < 0.05). Weight loss (p < 0.05) and prolonged upregulation of plasma cytokines (p < 0.05) may have contributed to the worsened somatomotor outcome. Our pipeline provides a rational stepwise procedure for evaluating favourable and unfavourable effects of systems-biology discovered compounds that modulate post-TBI transcriptomics.

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“…Desipramine has been shown to improve depression in severe TBI [ 50 ]. However, tricyclic antidepressants (TCAs) are probably less effective than SSRIs in the treatment of post-TBI depression [ 51 , 52 ], and are associated with more complications [ 53 ].…”

Section: Established Pharmacologic Therapies For Tbimentioning

confidence: 99%

Current and Potential Pharmacologic Therapies for Traumatic Brain Injury

Tani

Wen

et al. 2022

Pharmaceuticals

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The present article reviewed the pharmacologic therapies of traumatic brain injury (TBI), including current and potential treatments. Pharmacologic therapies are an essential part of TBI care, and several agents have well-established effects in TBI care. In the acute phase, tranexamic acid, antiepileptics, hyperosmolar agents, and anesthetics are the mainstay of pharmacotherapy, which have proven efficacies. In the post-acute phase, SSRIs, SNRIs, antipsychotics, zolpidem and amantadine, as well as other drugs, have been used to manage neuropsychological problems, while muscle relaxants and botulinum toxin have been used to manage spasticity. In addition, increasing numbers of pre-clinical and clinical studies of pharmaceutical agents, including potential neuroprotective nutrients and natural therapies, are being carried out. In the present article, we classify the treatments into established and potential agents based on the level of clinical evidence and standard of practice. It is expected that many of the potential medicines under investigation will eventually be accepted as standard practice in the care of TBI patients.

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The Incidence of Seizures during Tricyclic Antidepressant Drug Treatment in a Brain-Injured Population

Cited by 60 publications

References 0 publications

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

In Vitro and In Vivo Pipeline for Validation of Disease-Modifying Effects of Systems Biology-Derived Network Treatments for Traumatic Brain Injury—Lessons Learned

Current and Potential Pharmacologic Therapies for Traumatic Brain Injury

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