Diabetes, Psychiatric Disorders, and the Metabolic Effects of Antipsychotic Medications

Indications for Antipsychotic Medications

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Research and antipsychotic medications aand diabetes

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Psychiatric disorders can be a risk factor for, as well as a complication of, diabetes. Antipsychotic medications, widely used to treat a variety of psychiatric conditions, are also associated with diabetes. Antibacterial soap and sex drive article explores the complex relationship among psychiatric disorders, antipsychotic medications, and risk factors for metabolic syndrome and diabetes. D iabetes is considered to be one of the most psychologically demanding of the chronic medical illnesses and is often associated with several psychiatric disorders.

Antipsychotic medications, first introduced in the s, are a vital component of the medical management of several of these psychiatric disorders. These medications are often prescribed by nonpsychiatric physicians. During the periodaccording to a large U. This article will review the atypical, or second-generation, antipsychotics and their current uses. The relationship between diabetes and two of the most frequent indications for the use of these medications schizophrenia and behavioral and psychological symptoms of dementia will be examined.

Additionally, this article will explore the complex association between antipsychotic medications and obesity, research and antipsychotic medications aand diabetes, hyperglycemia, and dyslipidemias.

The frequent co-occurrence of diabetes and psychiatric disorders has been recognized for several centuries and is thought to be related to several factors. This is especially true in individuals who have underlying psychiatric disorders. Literature has suggested that certain psychiatric illnesses may be independent risk factors for diabetes. Additionally, poorer glycemic control 2 and resultant increases in diabetes-related complications 3 have been associated with the presence of a psychiatric disorder.

Much interest has been generated recently because of increasing reports of a possible causal relationship between some of the newer antipsychotic medications and metabolic abnormalities. Antipsychotic medications are widely used to treat a variety of psychiatric disorders.

They are the foundation of treatment for psychotic disorders and are primarily indicated to treat acute exacerbations of schizophrenia and to prevent relapses. Several of these agents have also received Food and Drug Administration FDA approval to treat manic and mixed phases of bipolar disorder, either as monotherapy or as adjuncts to mood stabilizers.

Common off-label uses of these medications include the treatment of the behavioral and psychological symptoms of dementia BPSDspsychotic and treatment-resistant depressions, autism, behavioral problems associated with developmental disorders, and post-traumatic stress disorder. Their primary disadvantage has been the lack of response of negative symptoms such as apathy, social isolation and withdrawal, and lack of motivation and the high rate of extrapyramidal side effects, including dystonic reactions, akathisia, drug-induced Parkinsonism, and tardive dyskinesia.

Both the efficacy and adverse effects of these drugs are associated with antagonism at the D2 receptors. The effectiveness of these drugs appears to be comparable to that of older agents in treating positive symptoms of schizophrenia, 4 whereas the relative effect size on negative symptoms has been modest and not as great as originally hoped.

Many patients with dementia will experience a variety of BPSDs requiring medication treatment. BPSDs are associated with nursing home placement, accelerated cognitive decline, and increased caregiver burden.

A recent literature review 6 examined double-blind, research and antipsychotic medications aand diabetes, placebo-controlled, randomized clinical trials or meta-analyses of antipsychotic drug therapy for patients with dementia and neuropsychiatric symptoms. For typical antipsychotics, no difference among the specific agents studied was found, and efficacy was small, with frequent occurrence of adverse side effects.

Results for the atypical antipsychotics showed modest, statistically significant efficacy for risperidone and olanzapine, with minimal adverse effects at the lower doses used to treat elderly patients with dementia. However, use of atypical antipsychotics in this population is complicated by recent reports of a possible increased risk for cerebrovascular events 78 and higher mortality rates. It is unclear whether schizophrenia is an independent risk factor for diabetes because no study has controlled for all the major risk research and antipsychotic medications aand diabetes for diabetes, although the literature suggests that this could be the case.

During the early 20th century, several researchers found that glucose intolerance and hyperglycemia occurred with increased frequency among patients with dementia praecox. Drug-naive schizophrenia patients have also been found to have more than research and antipsychotic medications aand diabetes times as much intra-abdominal fat which is correlated with insulin resistance as age- and BMI-matched control subjects. It is clear, research and antipsychotic medications aand diabetes, however, that the prevalence of diabetes and its risk factors is much greater among patients with serious mental illness.

For example, patients with schizophrenia are more likely than age-matched control subjects to lead a sedentary lifestyle, consume fewer fruits and vegetables, 1415 and have other cardiovascular tamoxifen and itchy skin factors, in particular, tobacco use.

Research on diabetes and schizophrenia has largely focused on prevalence estimates rather than on long-term diabetes outcomes, research and antipsychotic medications aand diabetes.

It is likely, however, that diabetes outcomes are poor in this population for several reasons. First, the relative risk of mortality associated with schizophrenia is 1. The prevalence of type 2 diabetes increases with age, as does the prevalence of dementia. Several prospective studies have found simple plan radio antenna the risk for developing dementia increases with the presence of obesity in middle age and diabetes in later life.

Additionally, hyperglycemia is accompanied by an accelerated rate of advanced glycation end product AGE formation. Memory deficits are not part of normal aging. When an older patient begins to forget or miss appointments, stops checking fingersticks, or inconsistently takes or refills prescriptions, clinicians must research and antipsychotic medications aand diabetes a high research and antipsychotic medications aand diabetes of suspicion that a cognitive disorder may be present.

Older adults who report memory problems merit a cognitive assessment. A cognitive screening instrument allows providers to objectively document these deficits and, with repeat administrations, monitor the course of impairments. The most widely used instrument is the Mini-Mental State Exam, which, when research and antipsychotic medications aand diabetes in combination with the Clock Drawing Test, provides sufficient sensitivity and specificity to be used on an annual basis.

A laboratory dementia work-up complete blood count, metabolic profile, rapid plasma reagin, thyroid function tests, and B 12 and folate serum levels should also be completed to rule out treatable causes of cognitive impairment. Any identified reversible causes of cognitive impairment, such as medications, nutritional deficiencies, or metabolic disturbances, should be treated. Neuropsychological testing is also helpful if the etiology of cognitive impairment is uncertain.

Shortly after the introduction of chlorpromazine, clinicians noticed that antipsychotics use led to weight gain. It was further noted that lower-potency agents chlorpromazine and thioridazine induced greater weight gain than the higher-potency drugs fluphenazine and haloperidol. Conventional antipsychotics-associated weight gain appears to be comparable for oral and depot formulations of the same drug. Among the atypical medications, varying degrees of weight gain have been reported.

Clozapine-induced weight gain does not appear to plateau early in treatment, and it has been shown to continue for 30 weeks. Olanzapine, with a similar chemical structure, has also been associated with significant weight gain. In prospective, double-blind studies, olanzapine has led to nearly twice the weight gain of risperidone.

Weight gain for risperidone and quetiapine appears to be intermediate among the antipsychotic medications. Weight gain is reported to be lower than that seen with olanzapine and clozapine but greater than that research and antipsychotic medications aand diabetes with conventional drugs.

Weight gain associated with risperidone and quetiapine does appear to correlate with trazodone and sertraline. Ziprasidone is associated with little weight gain, even after 1 year of treatment.

Among the atypical antipsychotics, research and antipsychotic medications aand diabetes, the relative tendency to cause weight gain is as follows: The mechanism of antipsychotics-induced weight gain is undetermined, but several neurotransmitter systems have been implicated. Initially, there was speculation that histamine receptor blockage was responsible for the conventional antipsychotic-induced weight gain.

Affinity for histamine receptors does correlate with medication-induced weight gain 41 and is supported by empirical data. Olanzapine, with the highest affinity for histaminic valtrex and diabetes, is also associated with high rates of weight gain.

Conversely, ziprasidone and aripiprazole, research and antipsychotic medications aand diabetes, associated with lower risks of weight gain, have lower affinities for histamine receptors. Blockade of the serotonin receptor 5-HT2C has been associated with increased appetite and obesity in mice.

Most atypicals are antagonists at this receptor, and this may partially explain patient reports of increased appetite. This is likely to explain some of the variability in weight findings among the various atypical antipsychotics, most of which have antagonistic properties at the 5-HT2C receptor. Case reports and retrospective database analyses suggest that conventional and atypical antipsychotics are associated with significant increases in fasting glucose concentrations.

This hyperglycemia can result in new-onset type 2 diabetes, metabolic acidosis or ketosis, and even hyperglycemia-related deaths. Most cases of new-onset type 2 diabetes occur within the first 6 months of treatment and are often, although not always, associated with significant weight gain or obesity. A family history for diabetes is research and antipsychotic medications aand diabetes associated with an increased risk.

There seems to be variability among the specific second-generation antipsychotics with respect to the incidence rates of diabetes. The risk of diabetes, however, is higher with antipsychotic treatment use than in a general patient population sample. Several mechanisms of glucose dysregulation have been proposed to explain this association. The medications most associated with diabetes are also those that induce the greatest amount of weight gain.

There are patients who develop diabetes, however, in the absence research and antipsychotic medications aand diabetes weight gain, so other causes must be sought. These drugs may disrupt research and antipsychotic medications aand diabetes regulation of glucose serum levels through hypothalamic dopamine antagonism. Recently, Johnson et al, research and antipsychotic medications aand diabetes. These findings suggest an added role for potent anticholinergic activity as a contributing factor for development of diabetes.

This is consistent with early findings of a higher association between low-potency conventional antipsychotics and increased weight gain.

The low-potency drugs, in general, are much more anticholinergic than high-potency medications. Increased serum levels of total cholesterol, LDL cholesterol, and triglycerides are all associated with obesity and weight gain.

Because several of the newer antipsychotics are associated with significant weight gain, one would expect that hyperlipidemia should also be associated with the use of these medications. Results of database analyses, chart reviews, and clinical trials indicate that clozapine and olanzapine use is associated with increased serum triglyceride levels.

This hypertriglyceridemia correlates directly with weight gain. Findings are equivocal regarding changes in cholesterol levels. Divergent results are seen with risperidone and quetiapine. However, smaller studies have reported increased serum triglyceride levels. Zoloft and xanax drug interaction problems exist in the results for quetiapine, ziprasidone, and aripiprazole, including small numbers of patients studied.

The doses of quetiapine used were small, so that a dose-related effect would be missed. Additionally, studies did not control for earlier treatments with lipid-lowering drugs.

This may explain some of the inconsistent findings for both risperidone and quetiapine. If patients who had previously taken a drug that increases lipid levels were then switched to a different agent, their lipid levels may have decreased because the primary responsible agent was discontinued. Very preliminary data suggest that ziprasidone and aripiprazole may not have adverse effects on lipid levels.

For patients who have elevated red wine and vytorin or triglyceride levels associated with previous antipsychotic treatment, switching to either of these medications may lead to a return to baseline levels. None of the available antipsychotic drugs is specifically indicated for use in the geriatric population. Inthe FDA issued warnings that the use of atypical antipsychotics in older adults with dementia was associated with an increased risk of cerebrovascular events.

Table 2 details the incidence rates of these events in pooled samples compared to placebo. Although these incidents occurred with low frequency, patients and caregivers need to be informed of the association.


Research and antipsychotic medications aand diabetes