Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loxapine is a dibenzoxazepine, tricyclic compound recommended for the treatment of acute and chronic schizophrenia. In its therapeutic effectiveness and profile and incidence of side-effects, loxapine closely resembles the traditional antipsychotic agents. Although loxapine has tended to be less effective than some standard antipsychotic drugs in a few short-term (3 to 4 weeks) studies, it has been superior to a placebo and about as effective as chlorpromazine, haloperidol, trifluoperazine or thiothixene when evaluated after 4 to 12 weeks. Like the phenothiazine (e.g. chlorpromazine) and butyrophenone (e.g. haloperidol) antipsychotic agents, loxapine causes a high incidence of extrapyramidal reactions. Sedation occurs frequently, especially during early stages of treatment. Other, less common side-effects such as anticholinergic effects (dry mouth, blurred vision, etc.), hypotension, tachycardia and precipitation of epileptic seizures, which occur with the older antipsychotic drugs, have also been reported with loxapine.
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PMID:Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent. 2 67

The selective serotonin reuptake inhibitors (SSRIs) are a tribute to the ingenuity of pharmacologists and designers of molecules. Not only do these drugs have remarkable selectivity for the reuptake of serotonin compared with other monoamines, but also they have a commendable lack of affinity for receptors including the serotonin receptor. In contrast, the classical tricyclic antidepressants (TCAs) are less specific in their pharmacological action. In addition to inhibiting the reuptake of serotonin, TCAs inhibit the uptake of noradrenaline, dopamine and tyramine, and antagonize cholinergic (muscarinic), adrenergic and histaminergic receptors. Moreover, TCAs have quinidine-like anti-arrhythmic activity and lower the seizure threshold. Clinical investigations have shown that the SSRIs have equivalent therapeutic efficacy compared with the TCAs in the treatment of depression. However, the pharmacological specificity of the SSRIs is a clinical advantage since they lack the propensity to cause dry mouth, blurred vision, urinary hesitancy, constipation, hypotension and arrhythmia. Furthermore, the SSRIs are relatively safe in overdosage. The similarities between the SSRIs are more obvious than their differences: all are highly potent and selective inhibitors of serotonin reuptake with efficacy in the treatment of depression. Nevertheless, each has a distinctive pharmacological profile. In this review the characteristics desired in an "ideal" antidepressant are examined, and the ways in which the TCAs and SSRIs fit this ideal are compared.
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PMID:Clinical implications of the pharmacology of serotonin reuptake inhibitors. 148 74

Citalopram is an antidepressant belonging to a new class of drugs which enhance serotoninergic neurotransmission through potent and selective inhibition of serotonin reuptake. Preliminary trials suggest that its short term therapeutic efficacy is significantly greater than that of placebo and mianserin, and comparable to that of amitriptyline, maprotiline and imipramine. It appears to be a weaker antidepressant agent than clomipramine, but better tolerated. Its elimination half-life of 33 hours permits once daily oral administration. Symptomatic improvement obtained with short term treatment has been maintained when therapy has been extended for up to 1 year; in the few patients studied for this extended period, the relapse rate was lower than with fluvoxamine, fluoxetine or imipramine. Compared to standard antidepressant agents, citalopram is well tolerated. It does not appear to be cardiotoxic, has not been associated with seizures in humans, and is relatively nonsedating. Unlike the tricyclic antidepressants, citalopram has minimal anticholinergic effects. Mild and transient nausea, with or without vomiting, is the most frequent adverse effect--occurring in 20% of patients--and increased perspiration, headache, dry mouth, tremor and insomnia are experienced by 15 to 18% of patients. Citalopram thus offers similar therapeutic efficacy and a more favourable tolerability profile than the tricyclic antidepressants. Preliminary data suggest that it may be particularly useful in patients who cannot tolerate the anticholinergic or cardiovascular side effects of tricyclic antidepressants and in those for whom sedation is not indicated.
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PMID:Citalopram. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. 171 47

Bupropion is a new antidepressant medicine that is chemically distinct from previous agents. Clinical studies have shown it to be as effective as the standard antidepressant drugs currently used in the treatment of major depression. It is useful in patients resistant to other agents as well as in patients with atypical depression. Bupropion is 10 to 100 times less likely to induce cardiac conduction problems than the tricyclic drugs, and orthostatic hypotension is rare. Minimal anticholinergic effects account for its being generally well tolerated. The most common side effect is dry mouth. An epileptogenic potential is prominently reported. Because it may lower the convulsive threshold, bupropion is not recommended for individuals who may be predisposed to seizures. In people without an increased ictal risk factor, and when dosage is maintained at 450 mg/day or less in a divided schedule, the seizure rate is comparable to that of other antidepressant drugs.
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PMID:Bupropion: overview and prescribing guidelines in depression. 189 94

Clomipramine is a newly marketed tricyclic antidepressant drug prescribed for obsessive-compulsive disorder (OCD). It selectively blocks neuronal uptake of serotonin. Clomipramine has been prescribed in Europe and Canada for 20 years in management of depression. Studies have now shown clomipramine to be effective in treating OCD. Dry mouth, visual disturbances, constipation, sexual dysfunction, somnolence, tremors, and dizziness are among the commonly reported side effects. Like other tricyclics, clomipramine exhibits a potential for cardiotoxicity, especially by impairing conduction and/or orthostasis. It also has the effect of lowering seizure threshold. Overdose risk is considerable. Careful medical supervision and adherence to prescribing guidelines are presumed to reduce medication risk factors. The outstanding benefit of this drug is its proved efficacy in the management of obsessive-compulsive disorder, as the first pharmacotherapy approved for this previously rather treatment-resistant condition.
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PMID:Clomipramine for obsessive-compulsive disorder: prescribing guidelines. 192 26

Sixty-five cases of mental depression were treated with maprotiline (Ludiomil), including 46 cases of endogenous depression, 18 cases of neurotic depression and 1 case of depression in association with hypertension and cerebral arteriosclerosis. Ludiomil of 50-200 mg/d was given for 4 weeks and clinical pictures evaluated weekly. Clinical results showed complete recovery in 33 cases (50%), improvement in 22 cases (34%), fair in 7 cases (11%) and poor in 3 cases (5%). Dry mouth, constipation and faintness were the commonest side effects. Seizure occurred in 1 case and skin rash in 3 cases. The authors suggest that Ludiomil at a maximal dosage of 150 mg/d can be considered a relatively safe and effective antidepressant.
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PMID:Maprotiline (Ludiomil) treatment of mental depression--a clinical report of 65 cases. 259 36

Twelve parallel, open, uncontrolled therapeutic studies on 3-fluoro-6-(4-methyl-piperazinyl)- 11H -dibenz[b,e]azepine ( fluperlapine , NB-106 689) were performed as a multicenter trial using standardized protocol/case report forms and inclusion and global assessment criteria. 66% of 104 medium to severe acute or relapsed schizophrenic patients showed a very good or good overall benefit (responder rate 80%) with 200-400 mg fluperlapine daily, median 300; 20-1200 mg; 6 weeks. Ratings ( FSCL -NL = (Fischer Symptom Check List Neuroleptics, BPRS = Brief Psychiatric Rating Scale, FSUCL = Fischer Somatic Symptoms and Untoward Effects Check List) showed a quick onset of action (25% improvement in 5 days) and a very good improvement of all important and secondary single symptoms or symptom groups. FSCL -NL and BPRS were highly correlated (R = 0.87). Tolerability was very good or good in 88% of patients (very good in 65%, poor or bad in 12%), mild to moderate fatigue being the most prominent untoward effect (means 25% of patients, max. 31 per control) followed by dizziness, tremor, dry mouth (10%). No drug-induced Parkinsonism was seen. No recurrent or relevant abnormalities in relation to fluperlapine were observed in safety data (circulation, blood, kidney or liver function). Several times paroxysmal dysrhythmias/sharp waves were seen in the EEG, and in our studies 2 patients experienced epileptiform seizures of short duration after overdosage. In one patient showing a granulocytopenia before starting fluperlapine , an agranulocytosis was seen, which normalized quickly after stopping fluperlapine .
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PMID:Fluperlapine in 104 schizophrenic patients. Open multicenter trial. 614 28

In this double-blind, two-period, crossover trial with randomized treatment assignment, progabide (+/- 30 mg/kg/day) and placebo were compared as add-on to standard therapy in 20 "therapy-resistant" epileptic patients (11 males, nine females; age range, 7-47 years). The duration of each treatment period was 6 weeks. Crossover was performed gradually over 3-4 days. Twenty-four patients entered the study: three dropped out for reasons unrelated to progabide effects; one dropped out during the placebo period because of increased seizure frequency. Of the 20 patients who completed the study, 14 had partial, two partial plus secondary generalized, and four generalized seizures. Preexisting antiepileptic treatment consisted of one antiepileptic drug (AED) in three, two AEDs in eight, three AEDs in five, and four AEDs in four patients (mean, 2.5 AEDs/patient). The following parameters were recorded at biweekly intervals: (a) efficacy parameters--total seizure count, counts of each seizure type, and global clinical judgment; (b) safety parameters--adverse drug effects, brief clinical and neurological examinations, and laboratory tests; and (c) plasma concentrations of progabide and of the associated AEDs. Twelve patients were considered to be improved (p less than 0.01) with progabide by global clinical judgment compared with two patients improved with placebo. Nine patients of 20 had a 48-100% reduction of total seizure count in the verum period, leading to a significant reduction of total seizure number and of complex partial seizures in the verum period as compared with the placebo period (p less than 0.05). Adverse effects were reported or observed in 10 patients during the progabide period and in five patients in the placebo period. The side effects were generally mild and consisted of somnolence in four cases and of tremors, dry mouth, troubles of equilibrium, anorexia, euphoria, depression, and anxiety in individual patients; a 15-20% reduction of the progabide dose was required in two cases only. No treatment-related alterations in results of laboratory tests were observed.
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PMID:Double-blind crossover trial of progabide versus placebo in severe epilepsies. 635 72

A total of 221 cases of deliberate acute overdose with fluvoxamine reported to the Paris Poison Centre, and 78 cases collected by the International Drug Safety Department of Duphar BV were analysed. Other agents, mainly benzodiazepines, neuroleptics, other antidepressants and alcohol, were also taken in 77% of the cases. The acute toxicity that could be attributed to fluvoxamine alone was rarely severe. The symptoms observed were always benign when the dose of fluvoxamine was below 1000 mg and included drowsiness, tremor, nausea, vomiting, abdominal pain, bradycardia and/or anticholinergic effects (dry mouth, mydriasis, sinus tachycardia, urinary retention). Seizures occurred in a few cases after high doses (generally > 1500 mg). Cardiotoxicity was not a serious problem; sinus bradycardia was noted with doses of less than 1000 mg, but was always moderate and required no treatment. Conduction abnormalities were rare.
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PMID:Acute fluvoxamine poisoning. 790 58

Major depression is a common and disabling disorder with far-reaching social and economic implications. Nonetheless, major depression is treatable by one of the many currently available antidepressants with response rates of approximately 65-70%. Treatment of depression has improved in recent years because of the availability of effective and well-tolerated antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). The currently available antidepressants are generally equally effective and are distinguished primarily by side-effect profiles. The side effects of tricyclic antidepressants (TCAs) are attributed to their nonspecific interaction with cholinergic, histaminergic, serotonergic, and dopaminergic receptors in the central nervous system. The secondary amine TCAs, nortriptyline and desipramine, are preferred among the TCAs because of a more favorable side-effect profile. The TCAs are cardiotoxic, and overdoses are frequently fatal. Adverse effects, including potentially fatal drug and food interactions, limit the use of the monoamine oxidase inhibitors (MAOIs); however, these agents have a role in the treatment of depression with comorbid anxiety, refractory depression, atypical depression, and bulimia. The SSRIs possess a class side-effect profile of headache, nausea, and sexual dysfunction. Individual differences in side effects may distinguish fluoxetine (nervousness, restlessness), sertraline (diarrhea, loose stools), and paroxetine (dry mouth). The SSRIs all inhibit certain cytochrome P450 isoenzymes involved in the metabolism of drugs, such as the TCAs, and each SSRI has been reported to increase plasma concentrations of concomitantly administered TCAs. Bupropion therapy is associated with a risk of seizure development, which can be minimized by multiple daily doses. Trazodone is sedating and can rarely cause priapism. The related compound, nefazodone, does not cause sexual dysfunction or priapism, but is associated with sedation. Venlafaxine, a recently available antidepressant that appears to have efficacy in treatment-refractory depression, may cause nausea that requires gradual upward dosage titration. Higher doses of venlafaxine may also cause elevations in blood pressure, heart rate, and serum cholesterol. As more is learned about the pathophysiology of depression, even more specific and well-tolerated antidepressants will be developed.
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PMID:Contemporary management of depression. 799 23


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