Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin enhancing drugs, including L-tryptophan and, more recently, fluoxetine and paroxetine, have been tested as pharmacologic treatments for sleep apnea syndrome. Although some patients have demonstrated reduced apnea expression after treatment with these compounds, this improvement has been restricted to nonrapid eye movement (NREM) sleep, with some patients showing no improvement. This study reports the effects of mirtazapine, an antidepressant with 5-HT(1) agonist as well as 5-HT(2) and 5-HT(3) antagonist effects, on sleep and respiration in an established animal model of central apnea. We studied nine adult male Sprague-Dawley rats chronically instrumented for sleep staging. In random order on separate days, rats were recorded after intraperitoneal injection of: (1) saline, (2) 0.1 mg/kg +/- mirtazapine (labeled as Remeron), (3) 1 mg/kg mirtazapine, or (4) 5 mg/ kg mirtazapine. With respect to saline injections, mirtazapine at all three doses reduced apnea index during NREM sleep by more than 50% (p < 0.0001) and during REM sleep by 60% (p < 0.0001) for at least 6 h. In association with this apnea suppression normalized inspiratory minute ventilation increased during all wake/sleep states (p < 0.001 for each state). The duration of NREM sleep was unaffected by any dose of mirtazapine (p = 0.42), but NREM EEG delta power was increased by more than 30% at all doses (p = 0.04), indicating improved NREM sleep consolidation after mirtazapine injection. We conclude that mirtazapine, over a 50-fold dose range, significantly reduces central apnea expression during NREM and REM sleep in the rat. The efficacy of this compound to suppress apnea in all sleep stages most probably arises from its mixed agonist/antagonist profile at serotonin receptors. The implications of these findings for the management of sleep apnea syndrome must be verified by appropriate clinical trials.
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PMID:Mirtazapine, a mixed-profile serotonin agonist/antagonist, suppresses sleep apnea in the rat. 1058 92

More than two thirds of stroke patients suffer from sleep apnea. A recent study showed that mirtazapine reduced the respiratory disturbance index (RDI) of a stroke patient by 80%. These promising results prompted us to offer mirtazapine to non-depressed stroke patients who suffered from sleep apnea and refused treatment with a continuous positive airway pressure (CPAP) device. Polysomnography was performed between 2200 and 0600 hours. We examined ten inpatients [nine male, one female; mean age of 68.7 +/- 1.5 years +/- SE; body mass index of 26.1 +/- 1.2 kg/m(2), basal ganglia bleeding (n = 3), middle cerebral artery ischemia (n = 4), basal ganglia ischemia (n = 1), cerebellar bleeding (n = 2)] in the Neurologic Clinic's sleep laboratory. The mean duration of illness before the first polysomnography was 52.6 +/- 11.4 days. Mirtazapine effectively consolidated sleep in all patients, i.e., sleep efficiency significantly increased from 63.1 +/- 4.8% to 75.7 +/- 5.0%. A moderate increase in RDI (137.4 +/- 15.3% of baseline) occurred during initial mirtazapine administration (intake duration 15.8 +/- 5.5 days). After 51.9 +/- 8.4 days, the RDI was either reduced (51.9% in "responders" who were identified arbitrarily by a reduction in RDI >or= 25% at any time point of the investigation) or increased (154.4% in "non-responders"). Mirtazapine administration was stopped in the four patients with increased RDI. Mirtazapine may be a probably effective treatment in stroke survivors with obstructive sleep apnea who refuse nasal CPAP treatment. As it may worsen central and mixed sleep apnea, patients who receive mirtazapine to alleviate sleep apnea or to control post-stroke depression with sleep disturbances should be monitored for changes in breathing parameters during sleep.
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PMID:Success and failure of mirtazapine as alternative treatment in elderly stroke patients with sleep apnea-a preliminary open trial. 1836 72