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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the introduction of chlorpromazine in the 1950s, antipsychotics have been used for the treatment of schizophrenia. The phenothiazines were followed by the butyrophenones, particularly haloperidol. With all the movement disorder side effects of these medications (extrapyramidal syndrome, akathisia, tardive dyskinesia), the pharmaceutical industry has gradually released atypical antipsychotics. This class includes clozapine (released in the USA in 1990), risperidone (1994), olanzapine (1996), quetiapine (1998) and ziprasidone (2001). However, the rate of diabetes mellitus in patients with schizophrenia appeared to increase with the availability of this class of medications. In reviewing rate and degree of changes in weight, glucose control and lipid levels induced by typical and atypical antipsychotics, it was found that in contrast to case reports, there is a dearth of retrospective, open and controlled studies. However, in studies as early as 1964, significant weight increases were found to be associated with use of chlorpromazine. While the phenothiazines may have some effect on patients with chemical diabetes, there is little evidence of the typical antipsychotics producing diabetes mellitus de novo, or worsening diabetes that is already been discovered. Ziprasidone appears to be the antipsychotic with the most beneficial combination of effects: no weight gain, no change in glucose utilisation and reductions in cholesterol and serum triglycerides (TGs).
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PMID:Antipsychotic medication: effects on regulation of glucose and lipids. 1182

Psychopharmacology research aims to expand the therapeutic ratio between efficacy, on the one hand, and adverse events and safety, on the other. The novel antipsychotics are now the antipsychotics of choice in the treatment of bipolar disorders. They have the advantages of potential antidepressant properties and low risks of extrapyramidal side effects and, especially, of tardive dyskinesia. However, novel antipsychotics may also have varying propensities to cause side effects, such as somnolence, hyperprolactinemia, weight gain (sometimes significant), and possibly diabetes mellitus. The increasing use of these novel agents requires careful assessment and monitoring of emergent side effects and diligent consideration of associated medical complications. Two new anticonvulsants, lamotrigine and topiramate, have recently shown promise in the treatment of bipolar disorders. Most of their adverse effects can be avoided by slow titration toward the recommended doses. In contrast to carbamazepine and valproic acid, topiramate may be associated with weight loss.
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PMID:Psychotropic drugs and adverse events in the treatment of bipolar disorders revisited. 1190 17

Issues to consider when evaluating maintenance drug therapy for patients with schizophrenia are discussed; these include potential adverse effects of antipsychotic therapy, such as weight gain, diabetes mellitus, extrapyramidal symptoms, sexual dysfunction, cognitive dysfunction, and cardiac effects, as well as quality of life. Patients with schizophrenia are more likely to be overweight than the general population. Olanzapine and clozapine have been associated with the greatest weight gain of the newer antipsychotics. While patients with schizophrenia are at increased risk of developing diabetes mellitus independent of antipsychotic therapy, diabetes may be more prevalent in patients taking the newer agents. Acute extrapyramidal symptoms occur in 75-90% of patients receiving first-generation antipsychotics like thioridazine and haloperidol. The probability of tardive dyskinesia (TD) occurring with second- and third-generation agents is less than 1% per year, compared with about 5% per year for the traditional antipsychotics. When patients are switched from a traditional antipsychotic to clozapine or olanzapine, TDs usually abate somewhat. Thioridazine causes a pronounced prolongation of the QTc interval, which can lead to ventricular arrhythmias. The slight increase in QTc interval caused by ziprasidone most likely will not be a problem in healthy individuals. Newer antipsychotics are associated with improved neurocognitive functioning and most cause less prolactin elevation, compared with traditional agents. The newer antipsychotic agents are not devoid of adverse effects, but those that do occur can be managed. Once issues related to adherence are resolved, rehabilitation of patients with schizophrenia will be a high priority.
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PMID:Clinical issues associated with maintenance treatment of patients with schizophrenia. 1222 83

Although olanzapine therapy has been associated with fewer extrapyramidal side effects than the traditional antipsychotic medications, reported side effects include dystonia, tardive dyskinesia, hypotension, diabetes mellitus, seizures and neuroleptic malignant syndrome. There are no previous published reports of hyperventilation associated with olanzapine therapy, but we present the case of a male patient who developed dyspnea and hyperventilation while taking olanzapine.
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PMID:Olanzapine-induced hyperventilation: case report. 1227 91

The aim of this observational study was to compare the prevalence of tardive dyskinesia (TD) in diabetic and non diabetic patients. We compared 34 diabetic patients with 34 non diabetic controls, matched by sex, age and time of admission, who had received a complete neuropsychiatric evaluation and who had been exposed to antidopaminergic treatment for at least 3 months. Among them, 8 of 24 diabetic (33.3%) and 6 of 15 (40.0%) non diabetic patients presented TD. The prevalence of TD in the diabetic group is numerically lower than in the controls but the difference is not statistically significant (chi(2) = 0.006; fd = 1; p = 0.937). These results suggest that diabetes is unlikely to play a major role in the pathogenesis of TD.
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PMID:Diabetes is not a risk factor for tardive dyskinesia: a retrospective observational study. 1240 8

The pharmacoeconomic implications of adverse effects caused by antipsychotic drugs during the treatment of schizophrenia are discussed. When new treatment options are considered by a health system, a comprehensive assessment is required that includes not only the cost of treating the disease but also the ancillary costs of treating adverse effects and comorbidities associated with treatment. Atypical antipsychotic drugs constitute a significant advance over conventional antipsychotics in terms of broader efficacy and lower rates of extrapyramidal symptoms and tardive dyskinesia. However, these agents appear to be associated with certain adverse medical conditions that can increase overall treatment costs. These adverse effects include serious weight gain, dyslipidemia, diabetes, and changes in cardiac conduction. The available data suggest that the risk of these events is not uniform among the drugs. A comprehensive evaluation of risk factors, outcomes, and costs should be include in economic evaluations of antipsychotic drugs so that realistic strategies for reducing costs and improving health can be identified.
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PMID:Pharmacoeconomic implications of adverse effects during antipsychotic drug therapy. 1245 95

Atypical antipsychotic agents offer significant advantages over older conventional antipsychotic agents. The reduction in antipsychotic drug-associated extrapyramidal symptoms and the potential reduced risk for tardive dyskinesia, compared to conventional drugs, are major advances in the treatment of psychotic patients. However, recent reports of hyperglycemia, new-onset diabetes mellitus, diabetic ketoacidosis, weight gain, and lipid abnormalities associated with atypical antipsychotic agents have emerged. A review of the recent literature and an approach to the evaluation of risk factors to aide in the safe use of atypical antipsychotic agents in presented.
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PMID:Diabetes mellitus and other metabolic disturbances induced by atypical antipsychotic agents. 1264 33

Depression can occur either with or without alternation with periods of mania. Depression that alternates with mania (bipolar depression) is a particularly difficult problem in clinical practice. The evidence base of the treatment for this condition is not strong and the choices at best are limited. Furthermore, although there are a number of effective antidepressants for the non-cycling variety ('unipolar' major depression), > 50% of patients experience incomplete response to any given drug. Given the proportion of the population involved, these represent fairly sizeable markets. Studies over the last several years indicate that the combination of the novel antipsychotic olanzapine and the serotonin-selective re-uptake inhibitor (SSRI), fluoxetine, may be effective for both conditions. One trial in 28 patients showed that this combination was an effective treatment, compared to the individual components with unipolar depressed patients who had not responded to two antidepressants of different chemical classes. Two subsequent large-scale attempts at replication have resulted in failed trials. Patients randomly assigned to antidepressant monotherapies showed a good response, indicating that the populations being studied were not actually treatment-resistant; therefore, more research is needed. Alternatively, a recent study showed that monotherapy with olanzapine produced a greater effect than placebo in bipolar depression and the combination of olanzapine and fluoxetine yielded an even more robust response. However, important questions remain, e.g., the issue of comparative effectiveness, that is to say, whether the same result could occur with combinations of other novel antipsychotics and SSRIs. In addition, there remain significant concerns regarding the safety and tolerability of olanzapine in these populations. Essential questions about the potential for substantial weight gain, Type II diabetes and for the development of tardive dyskinesia (a syndrome of permanent, disfiguring abnormal involuntary movements) remain. These problems will have to be vigorously addressed in order to achieve a substantial market penetration for these conditions.
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PMID:The combination of olanzapine and fluoxetine in mood disorders. 1283 42

Atypical antipsychotics are associated with fewer movement disorders and a lower risk of tardive dyskinesia than conventional antipsychotics, but are not without side-effects. Metabolic side-effects associated with some of the atypical antipsychotics are a concern for both clinicians and patients. Adverse events related to central nervous system effects, weight gain, and alterations in glucose, lipid, and prolactin levels in patients with depression, bipolar, and anxiety disorders have been reported. Balancing the significant benefits of treatment with these agents against the potential risks of metabolic disturbances and other adverse effects is crucial. Emerging data are making it possible to determine the risk-benefit analysis for specific atypical antipsychotics in individual patients and allow for targeted selection of treatment. A new concept of effectiveness is emerging that attempts to balance adverse effects of treatment with patient quality of life. Patients treated with atypical antipsychotics should have their weight, waist circumference, glucose, and lipids monitored on a regular basis. Monitoring of prolactin levels is not suggested; however, a baseline measurement before initiating treatment can be useful, with subsequent assessment only if a patient demonstrates symptoms. Prevention of weight gain is important. Diet and exercise should be considered for prevention and management, with the use of pharmacologic strategies approached with caution in patients with mood disorders. If a patient is at high risk of developing diabetes, certain pharmacologic agents have been shown to delay the onset of overt diabetes. Once diabetes or dyslipidemia are diagnosed, management should proceed in accordance with approved guidelines for these conditions.
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PMID:Safety and tolerability of atypical antipsychotics in patients with bipolar disorder: prevalence, monitoring and management. 1470 15

The pharmacotherapy of schizophrenia remains an ongoing challenge for researchers and clinicians alike. Current medications remain suboptimal to effectively treat this illness despite the recent surge of what are considered to be better antipsychotics: the atypicals. The atypicals cause fewer extrapyramidal symptoms and tardive dyskinesia, but there is growing concern regarding the significant long-term metabolic and cardiac adverse effects of these novel antipsychotics. There are differences among the atypicals in their propensity to produce these adverse effects, and clinicians should weigh the risk-benefit ratio for each drug with each individual patient. Diabetes, heart disease, obesity, and unhealthy lifestyle choices are on the rise in the general population, and individuals with chronic schizophrenia are even more at risk. The dilemma clinicians face in trying to avoid the neurological morbidity of the typicals (extrapyramidal side effects and tardive dyskinesia) is the risk of consequently exposing patients to both the morbidity and potential mortality of the atypicals (cardiovascular, endocrine, and metabolic adverse effects). The importance of baseline investigations and monitoring at regular intervals as well as identification of patients at risk for obesity, diabetes, and cardiovascular morbidity has become crucial. Informed decision making is essential for successful antipsychotic pharmacotherapy. For a condition, which often necessitates long-term pharmacotherapy, the importance of prevention and (or) minimization of morbidity and mortality related to adverse effects of such pharmacotherapy cannot be understated.
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PMID:From chlorpromazine to clozapine--antipsychotic adverse effects and the clinician's dilemma. 1563 57


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