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 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clozapine is the only antipsychotic agent that is effective in treatment-resistant schizophrenia. Despite its superior efficacy to chlorpromazine and the fact that it has fewer extrapyramidal side effects than conventional antipsychotics do, clozapine is relatively underused. This may be due in part to a lack of appreciation of clozapine's favorable risk-benefit ratio in many patients. In addition, clozapine is only indicated for use in patients who fail to respond adequately to standard antipsychotic treatment. Treatment with clozapine considerably improves psychiatric well-being and reduces readmission to the hospital and reduces family burden in many severely ill patients. However, clozapine is associated with severe side effects, including weight gain, tachycardia, sedation, seizures, and agranulocytosis. These risks must be weighed against the risks associated with schizophrenia (e.g., suicide). The death rate attributed to clozapine-induced agranulocytosis has been low, a fact that is largely attributable to safety measures such as the Clozaril National Registry. Determining the optimal dosage for each patient will maximize the benefits of treatment while reducing side effects. In some patients, monitoring plasma levels of drug may aid in optimizing treatment. The optimal plasma level of clozapine is 200 to 350 ng/mL. This usually corresponds to a daily dose of 200 to 400 mg, although dosage must be individualized. If patients improve significantly during treatment with clozapine, they should continue to be treated with clozapine and should be withdrawn from this treatment only when medically warranted. Psychotic relapse rates may be as high as 80% among patients switched from clozapine to other novel antipsychotic agents.
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PMID:Optimizing treatment with clozapine. 954 38

Clozapine has been found to be superior to traditional neuroleptics in the treatment of refractory schizophrenia and is increasingly being used to treat schizophrenia, affective disorders, some neurological disorders, and aggression. For many patients, clozapine offers new hope for the successful pharmacological management of a disabling mental disorder. However, up to 17 percent of patients must discontinue treatment with clozapine because of adverse effects, which also limit the rate at which the dose can be increased and the maximum dose that can be tolerated. This article reviews strategies for minimizing and managing the adverse effects of clozapine, including agranulocytosis, seizures, sedation, delirium, obsessive-compulsive symptoms, hypotension, tachycardia, weight gain, sialorrhea, elevated liver enzymes, constipation, nausea, enuresis, fever, and neuromuscular effects. Incidence and morbidity are presented first. Then, the known or hypothesized pathophysiology of the adverse effects are described. Finally, nonpharmacological and pharmacological interventions are reviewed. Under-standing the incidence, pathophysiology, and treatments of adverse effects is essential for a positive therapeutic outcome when prescribing clozapine.
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PMID:Management of the adverse effects of clozapine. 971 30

Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.
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PMID:Adverse effects of the atypical antipsychotics. Collaborative Working Group on Clinical Trial Evaluations. 976 15

Clozapine is a drug with many side effects, some of them with potentially hazardous outcome (e.g. seizures, agranulocytosis), if not carefully monitored. It has been shown that the metabolism of clozapine may be affected by concomitant treatment with selective serotonin reuptake inhibitors (SSRIs), while there have been reports of improved efficacy on negative symptomatology of clozapine in combination with SSRIs. Therefore, this prospective open clinical trial was performed to investigate the safety and tolerability of the coadministration of clozapine and paroxetine under control of serum concentrations of clozapine and its metabolites and the effect of this combination treatment on psychopathological outcome was evaluated. A total of 14 patients suffering from schizophrenia or schizodepressive disorder with predominant negative symptomatology were included. The duration of the study was at least 6 weeks for each patient. Initial treatment was a monotherapy with clozapine at a daily dose of 2.5 mg/kg weight. After two measurements of serum concentrations of clozapine and metabolites during steady state conditions, an add-on therapy with 20 mg paroxetine was initiated. No concomitant medication was allowed. The main finding of our prospective study was that addition of paroxetine to a monotherapy with clozapine was a well tolerated medication that did not give rise to new clinically relevant side effects. After addition of paroxetine the serum concentrations of clozapine and its major metabolites remained virtually constant. The results of the psychopathological measurements indicated a further clinical improvement, although the small open study could not test for efficacy.
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PMID:Combination treatment with clozapine and paroxetine in schizophrenia: safety and tolerability data from a prospective open clinical trial. 992 23

Carbamazepine is a commonly prescribed anticonvulsant medication that affects various levels of the nervous system. We report a case of temporary sensorineural hearing loss in a patient after overdosing with 36 g of carbamazepine. Six days after the overdose, the patient complained of bilateral hearing loss and tinnitus. Audiograms revealed a 30- to 40-dB sensorineural hearing loss bilaterally. Another audiogram 2 weeks later showed a complete recovery in both ears accompanied by a clinical resolution in audiovestibular symptoms. Carbamazepine is used to treat partial and generalized seizures, trigeminal neuralgia, and bipolar illness. Adverse effects are not common but most frequently include dizziness, drowziness, nausea, and skin rashes; rare complications are agranulocytosis, bradycardia, and heart block. Documented hearing loss as a side effect of carbamazepine has not been reported, to our knowledge.
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PMID:Carbamazepine-induced sensorineural hearing loss. 1003 90

1. The aim of the study was to determine if a more rational therapeutic approach could be devised for neuroleptic resistant psychotic patients treated for months and years with clozapine. Clozapine is an atypical antipsychotic medication, but its therapeutic benefit has been limited by a high incidence of agranulocytosis and seizures. 2. The study has been performed in an open setting and included 12 patients. Some of them developed a secondary depression and were treated with fluoxetine. 3. Pharmacokinetic analysis were conducted at the same time as clinical evaluations, grading using the BPRS, the PDS, and QLS, and determinations of plasma and red blood cell clozapine and desmethylclozapine, plasma and RBC fluoxetine and norfluoxetine, whole blood serotonin and tryptophan. 4. A positive linear correlation was found only between RBC concentration and the evolution of the QLS. 5. Clozapine is efficacious both on positive and negative symptoms but its mechanism of action remains unclear. Positive symptoms disappear more quickly, sometimes followed by a post psychotic depression. Negative symptoms improve more slowly but regularly. They seem to be correlated with serotoninergic mechanisms. For whole blood 5HT, an important increase was seen about 4 weeks after Cloza administration, and then a decrease. 6. Therapeutic drug monitoring (on the same sample drawn for haematological monitoring providing) could play a useful role in the management of patients treated by clozapine: compliance, lowest dose, possible toxicity, drug interaction, lack of efficacy, relapse predictivity.
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PMID:Pharmacoclinical strategy in neuroleptic resistant schizophrenic patients treated by clozapine: clinical evolution, concentration of plasma and red blood cell clozapine and desmethylclozapine, whole blood serotonin and tryptophan. 1036 54

Typical antipsychotics often combine efficacy in treating antipsychotic illnesses with a side effect profile that can affect every system of the body and range from the annoying-photosensitivity and jaundice, for example-to the disabling-seizures and blindness, among others-to the potentially fatal-agranulocytosis and neuroleptic malignant syndrome. The side effects of conventional antipsychotics are associated with effects at CNS transmission and receptor sites and appear in relation to dose levels and potency of the drug. Characteristics of patients-including gender, age, and comorbid medical illness-can make them more or less susceptible to particular antipsychotic side effects. Side effects influence patient quality of life and affect patient compliance with medications. This article will consider the physiologic systems affected by conventional neuroleptics, the sexual and reproductive side effects of typical antipsychotics, and the central nervous side effects of the conventional neuroleptics in the light of these concerns.
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PMID:An overview of side effects caused by typical antipsychotics. 1081 Dec 37

Clozapine has demonstrated superior efficacy in relieving positive and negative symptoms in treatment-resistant schizophrenic patients; unlike other antipsychotics, it causes minimal extrapyramidal side effects (EPS) and has little effect on serum prolactin. Despite these benefits, the use of clozapine has been limited because of infrequent but serious side effects, the most notable being agranulocytosis. In recent years, however, mandatory blood monitoring has significantly reduced both the incidence of agranulocytosis and its associated mortality. The occurrence of seizures appears to be dose-related and can generally be managed by reduction in clozapine dosage. Less serious and more common side effects of clozapine including sedation, hypersalivation, tachycardia, hypotension, hypertension, weight gain, constipation, urinary incontinence, and fever can often be managed medically and are generally tolerated by the patient. Appropriate management of clozapine side effects facilitates a maximization of the benefits of clozapine treatment, and physicians and patients alike should be aware that there is a range of benefits to clozapine use that is wider than its risks.
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PMID:Review and management of clozapine side effects. 1081 Dec 38

Clozapine is a dibenzodiazepine derivative with established antipsychotic efficacy in adult patients with schizophrenic psychoses. There are more than 15 studies that have also demonstrated the antipsychotic efficacy of clozapine in childhood and adolescent schizophrenia. The main advantages of clozapine treatment in this age group in comparison with typical antipsychotics are: (i) high antipsychotic efficacy during an acute schizophrenic episode; (ii) better improvement in chronic cases with a high load of negative symptoms; and (iii) markedly fewer extrapyramidal adverse effects and, therefore, fairly good tolerability. However, because of its possible adverse effects on the haemopoetic system (granulocytopenia, agranulocytosis), clozapine should not be used as first-line antipsychotic medication. Other adverse effects are related to the cardiovascular system (hypotonia, tachycardia or arrhythmia), the central nervous system (epileptic seizures, fever) and liver function (transient increases in levels of hepatic transaminases). Two other frequent adverse effects are hypersalivation and body-weight gain, which may present a particular problem in adolescents and young adults. Careful monitoring of haematological parameters and other adverse effects are preconditions for a successful treatment programme.
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PMID:Management of schizophrenia in children and adolescents. The role of clozapine. 1094 14

Antipsychotics are frequently used in the treatment of a variety of neuropsychiatric conditions in children and adolescents. Atypical antipsychotics have come to the forefront in child psychiatry due largely to their tolerability profiles as well as their efficacy. Potential treatment options include clozapine, risperidone, olanzapine, quetiapine and ziprasidone. A number of studies investigating the use of clozapine have been published in children; however, owing to the frequent monitoring required for agranulocytosis, the use of clozapine may be restricted to patients with treatment-refractory disease. With accumulating data on the development of glucose intolerance in adults receiving clozapine, closer monitoring of bodyweight and fasting blood glucose is imperative. Clozapine also has an increased seizure risk, therefore a baseline electroencephalogram should be performed, as well as continued vigilance for this adverse effect. Risperidone is an atypical antipsychotic that is generally well tolerated and numerous studies have been published investigating this drug in children. Unlike clozapine, its receptor interaction profile lends itself toward increased risk of extrapyramidal symptoms (EPS) and hyperprolactinaemia. Bodyweight gain is a common adverse effect, although somewhat less than that reported with olanzapine. Baseline liver function studies prior to initiation of this medication are recommended. Risperidone-induced mania has been reported in adults and, therefore, increased caution should be used when deciding to treat children and adolescents with risperidone, particularly in those with a predisposition toward mania. Olanzapine, like risperidone, has also been associated with onset of mania in adults. Olanzapine has a receptor profile that results in significant risk for bodyweight gain and sedation. Furthermore, this drug has been linked to the development of glucose intolerance; thus, it is important to monitor bodyweight and fasting blood glucose on a frequent basis. Less information is known about quetiapine in children and adolescents. Reports about its efficacy and tolerability vary. Quetiapine appears to have increased risk for sedation and bodyweight gain, albeit less than that of olanzapine. The compound appears to be less likely to induce EPS. Finally, ziprasidone has recently been approved for use in the adult population. This compound, in terms of its receptor profile, has more in common with risperidone. This suggests a potential for increased risk of EPS and hyperprolactinaemia. It also has an increased risk of QTc prolongation; thus, a baseline electrocardiogram is suggested, particularly in those patients with a history of cardiovascular illness. Lack of evidence for bodyweight gain with ziprasidone is a considerable advantage.
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PMID:Tolerability profile of atypical antipsychotics in children and adolescents. 1177 53


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