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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenytoin (PT) and carbamazepine (CBZ) are the two most prescribed anticonvulsants in Finland. Their effect on the cognitive functions of 43 newly diagnosed epileptic patients was examined. The medication was randomly assigned. The patients were tested before the medication was started, and after half a year's therapy. In order to estimate the practice effect in repeated testing a control group of 21 volunteers was similarly tested and retested. Both anticonvulsants, PT in particular, decrease the normal practice effect observed in neuropsychological testing. Compared to the CBZ group, patients with PT became somewhat slower, and their visual memory decreased. Within the PT group the motor slowing was more marked in female patients, and in patients having higher PT serum levels. In PT and CBZ groups there was an equal decrease in negative mood i.e. tension, depression, bewilderment and irritability.
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PMID:Effects of phenytoin and carbamazepine on cognitive functions in newly diagnosed epileptic patients. 819 81

The effect of pretreatment with phenytoin (diphenylhydantoin), lidocaine, and, for comparison, quinidine, on the doses of ouabain which produce a maximal inotropic effect, onset of arrhythmias and cardiac arrest, was explored in the cat heart-lung preparation. Ouabain was administered as an infusion (0.5 micrograms/min) either alone or after treatment with phenytoin (0.095 +/- 0.012 mM), lidocaine (0.090 +/- 0.004 mM) or quinidine (0.028 +/- 0.006 mM) and the cardiodynamic and electrophysiological changes monitored. Phenytoin, lidocaine and quinidine were administered in doses which were maximally tolerated by the preparations to ensure full effect, as evidenced by early cardiac depression. Ouabain alone produced a maximal increase in contractility prior to the development of arrhythmias at a blood concentration of 0.212 +/- 0.014 microM, onset of arrythmias at 0.227 +/- 0.015 microM, stable ventricular tachycardia at 0.269 +/- 0.010 microM and cardiac arrest at 0.342 +/- 0.014 microM. Pretreatment with phenytoin or lidocaine did neither modify these values nor change the pattern of the arrhythmias or the terminal cardiac event. Pretreatment with quinidine prevented the development of ventricular extrasystoles and aberrant ventricular conduction, which were the earliest arrhythmias in all other series. It also made the preparations develop stable ventricular tachycardia at an ouabain blood concentration of 0.246 +/- 0.007 microM, which was not significantly different from the concentration at which early arrhythmias were noted in the other series. In addition, quinidine decreased the dose of ouabain producing cardiac arrest by 13% but did not modify the terminal event. Pretreatment with phenytoin, lidocaine and quinidine did not affect the electrocardiographic pattern, but at the maximal increase in contractility with ouabain prior to the development of arrhythmias, the PR interval increased to comparable limits with ouabain alone and ouabain after quinidine and lidocaine. However, with ouabain after phenytoin, this increase was 61% less than that with ouabain alone and 31% less than that with ouabain after quinidine. Ouabain given alone or after phenytoin, lidocaine or quinidine produced comparable maximal effects on dp/dt, -dp/dt and left atrial pressure. It may be concluded that pretreatment with phenytoin and lidocaine does not modify the maximal inotropic dose of ouabain prior to the development of arrhythmias, the arrhythmogenic dose or the dose producing cardiac arrest, and that phenytoin partly counters the ouabain-induced depression of AV conduction. Quinidine has an additive effect on the ouabain-induced depression of AV conduction, prevents the ouabain-induced increase in idioventricular rhythm responsible for extrasystoles but not that responsible for ventricular tachycardia, and reduces the dose of ouabain producing cardiac arrest.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of pretreatment with phenytoin, lidocaine and quinidine on the cardiodynamic and electrophysiological effects of ouabain in the cat heart-lung preparation. 829 85

Diphenylhydantoin (D; Dilantin) is widely used in neurologic and psychiatric practice for treating convulsive disorders. D overdosage and poisoning may cause behavioral disturbances, such as schizophreniform and delusional states. To the best of our knowledge, D has been linked with mood disorders in just 1 documented case. We report a 70-year-old woman who developed major depression as a complication of D intoxication. Treatment with folic acid led to complete recovery. We believe that D causes depression by lowering folic acid blood levels by a biochemical mechanism. We suggest that levels of D and folic acid be monitored continually all patients treated with the drug.
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PMID:[Dilantin toxicity as a possible cause of major depression]. 837 70

To determine whether the anti-inflammatory effects of phenytoin might reduce cardiopulmonary dysfunction we studied the effects of phenytoin treatment on acute lung injury induced by smoke inhalation. Twenty-one chronically instrumented sheep were observed for 24 h after smoke inhalation injury. Myocardial contractility was evaluated by left ventricular end-systolic pressure-diameter relationship (LVESPDR) with a pair of ultrasonic transducers and strain-gauge transducer. In the control group (n = 6), uninjured sheep were given a bolus of phenytoin (12.5 mg/kg). Smoke-insufflated sheep were divided into nontreatment (n = 7) and phenytoin (n = 8) groups. Phenytoin alone had no effects in uninjured sheep except an early rise in heart rate and LVESPDR. In the group given smoke without treatment, there was a significant increase in pulmonary artery pressure and pulmonary vascular resistance index and a decrease in cardiac index. Pulmonary vascular changes were attenuated by treatment with phenytoin. Pulmonary transvascular fluid flux was evaluated by using a lung lymph fistula. LVESPDR fell in the smoke group but not in the group given phenytoin. There was a marked increase in lung lymph flow with smoke inhalation but this phenomenon was not affected by phenytoin treatment. In conclusion, phenytoin treatment reduced early hemodynamic depression.
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PMID:Effect of phenytoin on smoke inhalation injury in sheep. 857 57

Drugs administered to patients undergoing anaesthesia may complicate the use of the neuromuscular blockers that are given to provide good surgical conditions. The various sites of interaction include actions on motor nerve conduction and spinal reflexes, acetylcholine (ACh) synthesis, mobilisation and release, sensitivity of the motor end plate to ACh and the ease of propagation of the motor action potential. In addition, many drugs affect the pharmacokinetics of neuromuscular blockers, especially as most drugs depend to a greater or lesser extent upon renal excretion. The clinically significant interaction between nondepolarisers and depolarisers may be due to blockade of the pre-synaptic nicotinic receptors by the depolarisers, leading to decreased ACh mobilisation and release. Synergism between nondepolarisers probably results from post-synaptic receptor mechanisms. Volatile anaesthetic agents affect the sensitivity of the motor end-plate (post-synaptic receptor blockade) in addition to having effects on pre-synaptic nicotinic function. The effects of nondepolarisers are likely to be potentiated and their action prolonged by large doses of local anaesthetics due to depression of nerve conduction, depression of ACh formation, mobilisation and release, decreases in post-synaptic receptor channel opening times and reductions in muscular contraction. Most antibacterials have effects on pre-synaptic mechanisms. Procainamide and quinidine principally block nicotinic receptor channels. Magnesium has a marked inhibitory effect on ACh release. Calcium antagonists could theoretically interfere with neurotransmitter release and muscle contractility. Phenytoin and lithium decrease ACh release, whilst corticosteroids and furosemide (frusemide) tend to increase the release of the transmitter. Ecothiopate, tacrine, organophosphates, propanidid, metoclopramide and bambuterol depress cholinesterase activity and prolong the duration of the neuromuscular block. The probability of clinically significant interactions increases in patients receiving several drugs with possible effects on neuromuscular transmission and muscle contraction.
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PMID:Drug interactions with neuromuscular blockers. 890 51

PHARMACOKINETICS PHARMACODYNAMICS: Methadone is metabolized by cytochrome P450 enzymes in the liver microsomes and binds selectively to mu opiate receptors. Drugs metabolized by these enzymes or mu receptor competitors can modify the action of methadone. Genetic polymorphism influences plasma concentrations of the active levo enantiomer and thus clinical efficacy. ANTITUBERCULOSIS DRUGS: Rifampicin lowers methadome plasma levels so dose must be adapted. Rifabutin does not affect methadone kinetics. ANTI-EPILEPSY DRUGS: Phenytoin lowers blood levels of methadone by about 50% in 3 to 4 days. Other anti-epilepsy enzyme inducers (phenobarbital, carbamazepine) increase methadone metabolism. ANTI-VIRAL DRUGS: The area under the curve of plasma concentrations of zidovudine in presence of methadone increase by 43%, increasing the risk of undesirable effects. PSYCHOTROPES: Plasma levels of methadone increase by 20 to 100% in the presence of fluvoxamine. The benzodiazepine-methadone combination can be fatal due to respiratory depression. OTHER DRUGS: Brupenophine is a methadone agonist at the dose of 1 and 2 mg. Chronic alcoholism reduces the area under the curve while acute alcoholism increases it. Pure morphine agonists raise a major risk of respiratory depression while partial agonists favor the development of withdrawal symptoms.
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PMID:[Drug interactions with methadone]. 1050 72

The objective of the present study was to determine whether magnesium sulfate has anticonvulsant actions in the hippocampal-kindled rat model of epilepsy. Fully kindled rats received acute intraperitoneal injections of magnesium sulfate (270 mg/kg), phenytoin (20 mg/kg) or saline in random order. Electrical seizure duration, behavioral seizure stage and duration of postictal EEG depression were examined 15, 30 and 60 min after injection. In an additional group of rats, kindled seizures were measured before and after chronic (2 h) intraperitoneal injections of magnesium sulfate versus saline. There was a significant decrease in electrical seizure duration (p < 0.01) and behavioral seizure stage (p < 0.01) with acute magnesium sulfate injections compared to saline injections. Phenytoin had no statistically significant effects on hippocampal-kindled seizures. Chronic magnesium sulfate treatment significantly reduced behavioral seizure stage at 2, 24, and 48 h postinjection (p < 0.05), but did not affect seizure duration. There was a significant time by treatment effect for magnesium sulfate on postictal EEG depression (p < 0.01). We conclude that in this model of hippocampal epilepsy-induced (kindled) rats, magnesium sulfate has significant anticonvulsant effects. Copyright 1995 S. Karger AG, Basel
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PMID:Anticonvulsant Effects of Magnesium Sulfate in Hippocampal-Kindled Rats. 1172 42

The authors report the unusual case of a 58-year-old woman (MJP) suffering from left temporal throbbing headache, associated with confusion. Magnetic resonance imaging showed a 5 x 3 x 2 cm hematoma at the left posterior temporal--parietal junction (PTPJ). Repeated MRI of MJP's brain performed during a 4-month follow-up period showed decrease in hematoma size (2.3 x 1.5 x 1) with evidence for development of encephalomalacia and resorption of blood products involving the area of hemorrhage. MJP had mild transcortical sensory aphasia characterized by difficulty with reading and processing, with semantic paraphasic errors while speaking and some difficulty with repetition. MJP had remained normotensive and seizure free, on Vasotec therapy and Dilantin prophylaxis. An in vivo proton magnetic resonance spectroscopy (1H-MRS) performed during an 8-month follow-up period showed reduced concentration for N-acetyl aspartate (NAA) by 19.3% (F=4.09, P<0.04), and myo-inositol by 32.0% (F=5.16, P<0.02) in the left orbital frontal cortex (OFC) as compared with 16 healthy subjects (age- and sex-matched). Cognitive tests (the Wechsler abbreviated scale of intelligence (WASI) and the Stroop color--word interference) showed a significant impairment suggesting involvement of higher-order cognitive functioning (memory, learning, and general intelligence) and attentional system. The Spielberger state-trait anxiety inventory (STAI) showed increased anxiety at the moment of the current examination and decreased tendency to be anxious over a long period of time. The Beck Anxiety and Depression Inventory revealed minimal anxiety and mild to moderate levels of depression. It is hypothesized that the PTPJ hematoma triggered long-distance pathways linking PTPJ area and frontal lobe, including OFC, which resulted in abnormal chemical changes in the left OFC and in cognitive tests impairment, and in long-term anxiety state changes.
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PMID:Effect of posterior temporal-parietal hematoma on orbital frontal chemistry in relation to a cognitive and anxiety state: a combined 1H-MRS and neuropsychological study of an unusual case as compared with 16 healthy subjects. 1186 Nov 28

Therapy of bipolar disorders is a rapidly evolving field. Lithium has efficacy in classic bipolar disorders whereas divalproex sodium and carbamazepine may have broader spectrum efficacy that includes non-classic bipolar disorder. In the last 10 years, a series of anticonvulsants have been approved for marketing in the United States. Gabapentin has indirect g-aminobuytric acid-ergic actions, is generally well tolerated, and appears to have anxiolytic, analgesic, and hypnotic effects. Lamotrigine has antiglutamatergic actions and is generally well tolerated (aside from rash in 1 in 10, and serious rash in 1 in 1,000 patients). Lamotrigine is indicated for maintenance treatment in bipolar disorder. Emerging evidence suggests lamotrigine may have utility in bipolar disorder patients with depression and treatment-refractory rapid cycling, as well as analgesic effects. Topiramate and zonisamide may allow both weight loss, while topiramate may have specific efficacy in bulimia, binge eating disorder, and alcohol dependence. Two small studies found oxcarbazepine had similar efficacy to lithium and haloperidol in acute mania. Phenytoin, an older anticonvulsant, may have adjunctive acute mania efficacy. Levetiracetam, a newer anticonvulsant, may be worth exploring and has minimal drug-drug interactions. None of these newer agents has been shown effective in a large placebo controlled trial for acute mania. Although the clinical profiles of these newer anticonvulsants do not appear to overlap markedly with divalproex and carbamazepine (except perhaps for oxcarbazepine), these novel agents may still offer important new options in relieving a variety of specific target symptoms in patients with bipolar disorder.
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PMID:New anticonvulsant medication uses in bipolar disorder. 1497 68

Phenytoin, a classical anticonvulsant has been little studied in bipolar disorder. We completed a trial of phenytoin in mania and schizoaffective disorder, manic type. Thirty-nine patients entered a 5-wk double-blind controlled trial of haloperidol+phenytoin vs. haloperidol+placebo; 30 patients completed at least 3 wk; 25 completed 5 wk. Significantly more improvement was observed in those patients receiving phenytoin. Phenytoin has not previously been studied prophylactically in bipolar patients. Bipolar patients were studied who had at least one episode per year in the previous 2 yr despite ongoing prophylaxis. Patients were stable for a mean of 4 months (range 1-13) before entering the study. Phenytoin or placebo was added to their current therapy in a double-blind cross-over design for 6 months in each phase. Thirty observation periods of 6 months each were studied for 23 patients. Three patients had relapse on phenytoin and nine had relapse on placebo. There was a significant prophylactic effect of phenytoin in bipolar disorder [Cox's F test for comparing survival in two groups: F(6, 18)=3.44, p=0.02]. This study suggests prophylactic effects of add-on phenytoin in bipolar illness. However, the number of patients was small and confirmation is necessary. Lamotrigine has recently been reported to have antidepressant effects. In the past, small studies showed antidepressant effects for carbamazepine and valproate. To determine if such effects could be a class property of other voltage-activated sodium channel blockers such as phenytoin, we performed a double-blind controlled trial of phenytoin vs. fluoxetine in unipolar depression. Thirty-three depressed patients entered the study, and 28 completed at least 3 weeks and were included in data analyses. Weekly Hamilton Depression Scales for 6 wk showed no difference between fluoxetine and phenytoin. Clearly pharmaceutical company funding for clinical trials or advertising for phenytoin is minimal and this must be taken into account in evaluating literature on phenytoin vs. other drugs. The present data suggests that effects on affective disorder may be common to many anticonvulsants.
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PMID:Phenytoin: an anti-bipolar anticonvulsant? 1642 79


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