Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a postoperative delirium expressed by a 49-year-old female patient during recovery from anaesthesia. Prominent features of the delirium, which lasted for nearly 2 days, included agitation, confusion, uncontrolled limb movements, abnormal ocular function, hypertension, pyrexia, brisk reflexes, ankle clonus and raised creatine kinase. The delirium did not respond to naloxone, diazepam or flumazenil. The patient had not been prescribed neuroleptics but, before surgery, she had been taking the selective serotonin reuptake inhibitor, paroxetine, to relieve her depression. During surgery, she was given morphine, which increases release of the neurotransmitter, serotonin, and ondansetron, which blunts neuronal release of dopamine. Although there is no clear explanation for the delirium, it had many features in common with problems associated with paroxetine withdrawal, the serotonin syndrome and the malignant neuroleptic syndrome. We offer several alternative explanations for this event, all of which rest on disruption of serotonergic and/or dopaminergic transmission and which could also involve inhibition by paroxetine of the P450 enzyme, CYP2D6, which metabolizes ondansetron.
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PMID:Postoperative delirium indicating an adverse drug interaction involving the selective serotonin reuptake inhibitor, paroxetine? 1089 Mar 14

It is now possible to develop a dynamic neuronal network model for generalized convulsive seizures because of in vivo data recently obtained in a naturally occurring epilepsy model--the genetically epilepsy-prone rats (GEPR-9s). GEPR-9s exhibit audiogenic seizures (AGS) that consist of a sequence of discrete behavioral phases (i.e., wild running, clonus-tonus, and post-ictal depression). The neuronal firing changes in most nuclei implicated in the network during each phase of AGS in behaving GEPR-9s have been examined. The inferior colliculus is critical in AGS initiation, because extensive firing increases in inferior colliculus are observed preceding seizure initiation. The deep layers of superior colliculus (DLSC) are crucial to wild running, based on the emergence of tonic firing of DLSC neurons just preceding this phase. The pontine reticular nucleus (PRF) and periaqueductal gray (PAG) are critical to the clonic-tonic phase, because tonic firing patterns appear in these neurons just prior to this phase. During post-ictal depression all areas except the PRF are quiescent. These temporal relationships suggest that each nucleus plays a specific hierarchic role in each discrete convulsive behavior. Generalized tonic-clonic seizure behavior observed in human epilepsy, in GEPR-9s, and in other seizure models is likely to involve similar neuronal network components. The neurotransmitter mechanisms subserving the abnormal neuronal responses in the GEPR-9 neuronal network involve an increased availability of glutamate and a decrease in the effectiveness of gamma-aminobutyric acid (GABA) in many brain regions. Focal modification of the effects of GABA, glutamate, norepinephrine, or serotonin also modulates the nuclei of the network differentially. Together, these data reveal the anatomic, neurotransmitter, and neurophysiologic mechanisms of the neuronal network hierarchy in GEPR-9s, which is currently the most completely developed of any generalized convulsive model. Differential effects of anticonvulsants on the AGS phases and concomitant differential modifications of neuronal firing are observed on neurons in these network nuclei. With nearly complete identification of the network nuclei, the differential effects of these anticonvulsant drugs on different aspects of neuronal firing in different brain sites indicate that this experimental approach can likely identify the most sensitive therapeutic target for these agents. This concept is potentially vital to developing the most selective treatment of different convulsive behaviors occurring in human epilepsy. The neuronal network for AGS does not require brain structures rostral to the midbrain for seizure expression. However, the forebrain is recruited into an expanded seizure network through AGS repetition ("kindling"), resulting in prolonged AGS, post-tonic clonus, and epileptiform electrographic cortical abnormalities. AGS kindling produces network expansion into medial geniculate body (MGB) and amygdala and involves neuronal firing increases in MGB.
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PMID:Neuronal networks in the genetically epilepsy-prone rat. 1051 23

Running and tonic convulsions induced by sound stimulation (audiogenic seizures, AS) are known to be brainstem-dependent, but their repeated induction leads to the recruiting forebrain structures into AS expression manifested by the development of clonic convulsions and cortical epileptic activity (audiogenic kindling). Behavioral and electrophysiological manifestations of audiogenic kindling were studied in AS-prone WAG/Rij rats exhibiting two types of genetically determined generalized seizures: convulsive audiogenic and nonconvulsive absence (spontaneous spike-wave discharges generated by thalamocortical circuits). Twenty three repeated (with 2 days intervals) sound stimulations inducing a short running episode led to a progressive increase in AS duration from 6.2 +/- 0.4 s to 24.7 +/- 2.9 s mainly due to the appearance of additional postrunning facial-forelimb clonic convulsions of increasing duration and severity. Fully kindled (Racine's stage 5) seizures were accompanied by a bilateral slow-potential wave of cortical spreading depression (SD) nonsynaptically propagating to both striata and by a long-term postictal suppression of spontaneous absence seizures. Neither corticostriatal SD, nor the spike-wave discharges suppression were observed after running induced by sound in non-kindled rats or by attenuated (subthreshold for clonus) sound in kindled rats. Subthreshold stimulation of kindled rats provoked postictal high-amplitude spiking in the cortex. It is concluded that the recruitment of the cortex into a kindled AS network triggers a corticostriatal SD which may underlie the postictal inhibition of non-convulsive seizures, which follow the kindled AS.
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PMID:[Audiogenic kindling in WAG/Rij rats: change in behavioral and electrophysiological responses to repetitive short acoustic stimulation]. 1557 1

This study records noise-free intracerebral EEG of the genetically epilepsy prone rat (GEPR-9), along with behavioral correlates, during a seizure on unanesthetized freely behaving unrestrained animals. The GEPR-9 exhibits acoustically triggered generalized tonic-clonic seizures, and often times the EEG, recorded with conventional techniques, has resulted in data with imbedded movement artifact. For noise-free video-EEG recordings, we used a previously developed system that consists of a head connector with a FET preamplifier and battery, signal conditioning device (5000x gain, 1 Hz-100 Hz filters), A/D converter and video/PC-PC/video computer boards for recording image data. Each animal was implanted with three monopolar/referential electrodes chosen among the following areas: cortex, inferior colliculus, reticular formation and caudal medulla. The video-EEG data were quite similar for all recorded animals: (1) basal desynchronized EEG before sound stimulus; (2) increase in EEG frequency after stimulus and before seizure onset; (3) high-amplitude polyspikes during massive myoclonic thrusts with or without a very fast running episode; (4) an electrodecremental response during tonic extension; (5) wave and spike complex during forelimb and hindlimb tonic rigidity and posttonic clonus; (6) low-amplitude EEG during postictal depression. Time sequenced spectral analysis also highlights the epileptiform EEG pattern during seizure with high reproducibility between animals. While testing seizure naive GEPR-9s, there was a clear evolution from modest epileptiform EEG activity on the first acoustic stimulation to progressively higher amplitude, duration and frequency epileptiform EEG activity throughout seizure repetition.
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PMID:A comprehensive electrographic and behavioral analysis of generalized tonic-clonic seizures of GEPR-9s. 1568 Mar 33

Comorbidity of epilepsy and depression is not rare. Stress can affect both depression and seizures. Therefore, it is important to know whether an antidepressant drug has pro- or anticonvulsant properties and whether these properties will be modified by stress. We tested the effects of the antidepressant drug fluoxetine on the seizure threshold for picrotoxin in unstressed and swim-stressed mice. The mice were, prior to exposure to swim stress and the intravenous infusion of picrotoxin (a non-competitive GABA(A) receptor antagonist), pretreated with fluoxetine (a selective serotonin reuptake inhibitor), either acutely or repeatedly (5 days), and the latency to the onset of two convulsant signs and death was registered. The convulsant signs were running/bouncing clonus and tonic hindlimb extension. As expected, swim stress enhanced the seizure threshold for picrotoxin. Fluoxetine (20 mg/kg ip) given acutely increased in unstressed and swim-stressed mice the dose of picrotoxin producing tonic hindlimb extension and in unstressed mice the dose of picrotoxin producing death. Neither 10 nor 20 mg/kg of fluoxetine affected doses of picrotoxin needed to produce running bouncing/clonus. Repeated treatment with fluoxetine (20 mg/kg ip) enhanced significantly in unstressed and swim-stressed mice doses of picrotoxin needed to produce tonic hindlimb extension and death, and in stressed mice also the dose of picrotoxin producing running/bouncing clonus. The results demonstrate that the antidepressant drug fluoxetine, given acutely or repeatedly, shows anticonvulsant properties against convulsions induced in unstressed and swim-stressed mice by antagonist of GABA(A) receptors, picrotoxin. Swim stress failed to modify the anticonvulsant properties of fluoxetine.
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PMID:Anticonvulsant effects of acute and repeated fluoxetine treatment in unstressed and stressed mice. 1568 Mar 43

A 65-year-old female patient with major depressive disorder suffered from clonus, shivering and impaired visual acuity after 20 mg/day of paroxetine administration. The symptoms were initially regarded as further manifestations of her somatic symptoms of depression, and paroxetine was increased to 30 mg/day resulting in frequent clonus, increased shivering, serious dysarthria, ongoing impairment in visual acuity and agitation. These symptoms subsided upon paroxetine discontinuation. Ten mg/day of paroxetine rechallenge provoked dysarthria, tremor and headache, but these symptoms improved again upon paroxetine discontinuation. These findings indicate that the patient's symptoms were not somatic in origin but were in fact the symptoms of serotonin syndrome. In conclusion, the present case suggests the difficulty in diagnosing serotonin syndrome in a patient with somatic symptoms.
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PMID:Serotonin syndrome in a case of depression with various somatic symptoms: the difficulty in differential diagnosis. 1691 68

Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is due to an overstimulation of central and peripheral serotonin receptors that lead to neuromuscular, mental and autonomic changes. Moclobemide is a reversible inhibitor of monoamine oxidase (MAO)-A, selegiline is an irreversible selective inhibitor of MAO-B, and paroxetine is a selective serotonin reuptake inhibitor. Combined use of these agents is known to cause serotonin toxicity. A 53-year-old woman had been treated with paroxetine and selegiline. After moclobemide was prescribed in place of paroxetine without a washout period, she quickly developed confusion, agitation, ataxia, diaphoresis, tremor, mydriasis, ocular clonus, hyperreflexia, tachycardia, moderately elevated blood pressure and high fever, symptoms that were consistent with serotonin toxicity. Discontinuation of the drugs, hydration and supportive care were followed by remarkable improvement of baseline status within 3 days. This case demonstrates that serotonin toxicity may occur even with small doses of paroxetine, selegiline and moclobemide in combination. Physicians managing patients with depression must be aware of the potential for serotonin toxicity and should be able to recognize and treat or, ideally, anticipate and avoid this pharmacodynamically-mediated interaction that may occur between prescribed drugs.
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PMID:Serotonin toxicity caused by moclobemide too soon after paroxetine-selegiline. 1968 3

The serotonin syndrome is a toxic state largely attributable to changes in sensitivity of serotonin receptor system in the brainstem and spinal cord resulting from increased serotonergic activity in central neurologic system, due to use of serotonergic agents either in overdose or in combination. Serotonin syndrome may present with neuromuscular (clonus, myoclonus, tremor, hyperreflexia) and autonomic (fever, mydriasis, tachycardia, tachypnea) symptoms and mental status changes (confusion, agitation) and may result in death in severe cases. The risk for the development of serotonin syndrome is increased with the combined use of agents from different groups such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). The growing use of SSRIs for depression and the introduction of pharmacological agents newly developed for the treatment of various medical disorders increases the risk of drug-drug interactions and toxic states like serotonin syndrome. In the presented case clinical presentation and outcome of the serotonin syndrome which has developed as a consequence of concomitant linezolid use in a young patient who was already on an SSRI antidepressant is discussed. Linezolid is an oxazolidinone antibiotic which has MAOI-like properties. This case is presented to inform psychiatrists especially working in consultation-liaison settings about the risk of drug-drug interactions and possible prevention of these.
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PMID:[Serotonin syndrome associated with linezolid use: a case report]. 2001 32

The aim of this study was to establish the modulation pattern of the reciprocal inhibition exerted from tibialis anterior (TA) group I afferents onto soleus motoneurons during body weight support (BWS) assisted stepping in people with spinal cord injury (SCI). During assisted stepping, the soleus H-reflex was conditioned by percutaneous stimulation of the ipsilateral common peroneal nerve at one fold TA M-wave motor threshold with a single pulse delivered at a short conditioning-test interval. To counteract movement of recording and stimulating electrodes, a supramaximal stimulus at 80-100 ms after the test H-reflex was delivered. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. The conditioned soleus H-reflex was significantly facilitated throughout the stance phase, while during swing no significant changes on the conditioned H-reflex were observed when compared to the unconditioned soleus H-reflex recorded during stepping. Spontaneous clonic activity in triceps surae muscle occurred in multiple phases of the step cycle at a mean frequency of 7 Hz for steps with and without stimulation. This suggests that electrical excitation of TA and soleus group Ia afferents did not contribute to manifestation of ankle clonus. Absent reciprocal inhibition is likely responsible for lack of soleus H-reflex depression in swing phase observed in these patients. The pronounced reduced reciprocal inhibition in stance phase may contribute to impaired levels of co-contraction of antagonistic ankle muscles. Based on these findings, we suggest that rehabilitation should selectively target to transform reciprocal facilitation to inhibition through computer controlled reflex conditioning protocols.
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PMID:Reduced reciprocal inhibition during assisted stepping in human spinal cord injury. 2168 74

Lithium salts have been used in treatment of depression and bipolar disorder for more than 50 years. Neurotoxic side-effects such as nystagmus, ataxia, tremor, fasciculation, clonus, seizure and even coma have been well described in the literature. We present a case of generalised peripheral neuropathy following lithium intoxication. It is a rare presentation with delayed onset and characterised by a rapid downhill course. Diagnosis was confirmed by nerve conduction tests, which showed axonal neuropathy. Despite the profound neurological effects of this toxicity, it is readily reversible with supportive care and the prognosis is good.
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PMID:A rare neurological complication due to lithium poisoning. 2286 82


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