Abnormal Ventilatory Response to Carbon Dioxide: a Potential Biomarker for Seizure Induced Respiratory Depression & Modification by SSRI
| Status: | Recruiting |
|---|---|
| Conditions: | Depression, Neurology, Pulmonary, Epilepsy |
| Therapuetic Areas: | Neurology, Psychiatry / Psychology, Pulmonary / Respiratory Diseases, Other |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 9/16/2018 |
| Start Date: | February 16, 2017 |
| End Date: | April 2019 |
Sudden unexpected death in epilepsy patients (SUDEP) is devastating outcome for some patients
with epilepsy. It ranks second only to stroke among neurological diseases in years of
potential life lost. Patho-mechanisms of SUDEP remain not well understood, however peri-ictal
respiratory dysfunction likely plays an important role in many cases.
Literature supports a critical role for the serotonergic system in central control of
ventilation. Serotonin neurons in the raphe nuclei of the brainstem sense rising carbon
dioxide and low pH, thereby stimulating breathing and arousal. These responses may serve as
mechanisms that protect against asphyxia, particularly during sleep or the post-ictal state.
In mouse models of seizure-induced sudden death, pre-treatment with selective serotonin
reuptake inhibitor (SSRI) agents prevents death following seizures. Hence, the investigators
hypothesize that a subset of drug resistant epilepsy patients who have impaired central
chemo-responsiveness have a greater degree of peri-ictal respiratory depression, therefore a
higher risk of SUDEP. The investigators further hypothesize that fluoxetine will improve
central chemo-responsiveness and therefore will reduce peri-ictal respiratory depression.
with epilepsy. It ranks second only to stroke among neurological diseases in years of
potential life lost. Patho-mechanisms of SUDEP remain not well understood, however peri-ictal
respiratory dysfunction likely plays an important role in many cases.
Literature supports a critical role for the serotonergic system in central control of
ventilation. Serotonin neurons in the raphe nuclei of the brainstem sense rising carbon
dioxide and low pH, thereby stimulating breathing and arousal. These responses may serve as
mechanisms that protect against asphyxia, particularly during sleep or the post-ictal state.
In mouse models of seizure-induced sudden death, pre-treatment with selective serotonin
reuptake inhibitor (SSRI) agents prevents death following seizures. Hence, the investigators
hypothesize that a subset of drug resistant epilepsy patients who have impaired central
chemo-responsiveness have a greater degree of peri-ictal respiratory depression, therefore a
higher risk of SUDEP. The investigators further hypothesize that fluoxetine will improve
central chemo-responsiveness and therefore will reduce peri-ictal respiratory depression.
Inclusion Criteria:
1. Adult patients aged 18 or older
2. Patients with epilepsy
3. Native English speaker or adequate fluency in English to provide informed consent.
4. Female patients of child-bearing potential must be using an acceptable method of
contraception, and willing to refrain from sexual intercourse during the study.
Exclusion Criteria:
1. Progressive neurological disease.
2. Clinical diagnosis of bipolar disease, panic disorder, psychosis or severe depression,
or PHQ-9 score > 20
3. Patients with prior hospitalization related to depression or Electroconvulsive
therapy.
4. History of suicidal ideation or intent in past or present
5. Clinical history or laboratory evidence of hepatic or renal insufficiency.
6. Pregnant or lactating women.
7. Current heavy alcohol use (>14 drinks per week for men or >7 drinks per week for
women) or) known medical disorder related to alcohol use or current illicit drug use,
other than marijuana and its derivatives.
8. Patients with recent use (<1 month) or already taking fluoxetine or other selective
serotonin reuptake inhibitors (SSRIs).
9. Concurrent use of monoamine oxidase inhibitors, antipsychotic agents, antidepressant
agents other than SSRIs or frequent use of triptan agents (>2/week).
10. History of a previous allergic reaction or adverse effects with fluoxetine,
hypersensitive reaction-anaphylaxis; laryngeal edema; hives
11. History of serotonin syndrome.
12. History of uncontrolled pulmonary or cardiac illness.
13. Patients with hypercapnic ventilatory response (HCVR) slope of > 2.0
14. Patients with known prolong QT interval
15. Patients with family history of prolong QT interval
16. Patients with family history of sudden cardiac death under the age of 40 in a first
degree relative.
We found this trial at
1
site
200 Hawkins Drive
Iowa City, Iowa 52242
Iowa City, Iowa 52242
Principal Investigator: Rup K Sainju, MBBS
Phone: 319-356-4337
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