Are African American patients at a higher risk for olanzapine-induced glucose intolerance?
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Biomedical subjects
Publications and source records attributed to J Ananth.
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Understanding the action of atypical antipsychotics is useful in exploring the pathophysiology of schizophrenia and in synthesizing drugs that improve various domains of psychopathology without unwanted side effects. In animal models, atypical antipsychotic drugs appear to have a preferential action in the limbic dopaminergic system. Regionally specific action has been studied by measuring the amount of Fos protein produced in a particular brain region as a consequence of a drug's effects on the c-fos gene. Evidence suggests that the atypical and typical antipsychotic drug-induced increases in Fos levels in the nucleus accumbens are related to improvements in positive symptoms, whereas Fos increases in the prefrontal cortex, with the atypical antipsychotics only, correlate with negative symptom improvement. The extrapyramidal effects seen with typical antipsychotics are thought to be related to Fos increases in the striatonigral pathway. However, studies of Fos levels in specific brain regions reveal only the site of action, not the mode of action. The finding that atypicality is related to surmountable D2 dopamine receptor blocking provides another venue to define and explore atypical antipsychotic drug action.
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BACKGROUND: How to best treat psychotic patients who have had past clozapine-induced agranulocytosis or granulocytopenia remains a problem. CASE REPORTS: We report 3 patients with chronic schizophrenia who had previously stopped clozapine due to hematologic side effects. The patients evidenced improvement with olanzapine that equated to 16- to 31-point decreases in rating scale scores during 1-year follow-up without any hematologic abnormalities. CONCLUSION: The results suggest that olanzapine may be useful in treating patients with clozapine-induced granulocytopenia without the risk of recurrence of hematologic side effects.
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Our ability to treat depression has improved with the availability of receptor-specific and chemically diverse groups of antidepressants. Even now, most of the short-term studies indicate that about 20% of depressed patients remain resistant to treatment. Therefore, it is important to properly assess the treatment-resistant depressed (TRD) patients and to separate the truly refractory patients from those inadequately treated. Undiagnosed medical conditions should be eliminated. TRD is neither a clinically nor a biologically identifiable entity. As there are no established methods for the treatment of TRD, all options should be considered. The clinician can be enriched by the knowledge of the treatment modalities available, and yet, in treating an individual patient, clinical skills, intuitive judgment, family history of response to drugs and side effects, all play a vital role. Several of the approaches described in the paper indicate available methods and their merits in general but there is no way of ascertaining by which particular method a patient should be treated. The three common methods of treatment are substitution of one antidepressant drug for another, combination therapies and augmentation techniques. These are based on clinical experiences and not research findings. Therefore the treatment of TRD patients is more an art than a science. The physician should assess all the psychopathological, phenomenological and psychosocial variables to appropriately treat an individual patient.
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Tardive dyskinesia (TD) is a side effect of long-term neuroleptic administration. The wide variation of 2 to 51% in its reported prevalence can be attributed to the varied definitions of TD, the use of different methods of assessment, and the lack of control of independent variables. Why only certain patients develop this side effect is an intriguing question. The occurrence of TD in family members and in those persons with a family history of Parkinson's disease (PD) is suggestive of genetic vulnerability. Further support for a genetic predisposition comes from the fact that only certain strains of monkeys, such as the Cebus apella strain, have a higher propensity to develop TD than others, such as the Macaca sepciosa strain. If genetic factors play a significant role in the development of TD, then, genetically diverse ethnic groups may have a different propensity for the development of TD. One method of evaluating such a possibility is to compare its prevalence in different countries. The current literature on ethnic differences in the prevalence rates of TD is reviewed. This area of study needs further rigorous investigation.
We previously reported increased regional cerebral cortical uptake and decreased caudate nucleus uptake of 99mTc-HMPAO in patients with obsessive-compulsive disorder(OCD) before treatment compared to matched normal controls. In the present study, we determined whether or not these changes persisted during treatment. Single-photon emission computed tomography was used to measure regional cerebral blood flow (rCBF) by 133Xe inhalation and cerebral uptake of 99mTc-HMPAO in eight adult male OCD patients before and during treatment with chlomipramine, and in eight age-matched normal male controls. With 133Xe, there were no significant differences in rCBF between patients with OCD and their matched controls, and no significant differences in rCBF in the patients before and during treatment. Significantly increased HMPAO uptake in the orbital frontal cortex, posterofrontal cortex, and high dorsal parietal cortex bilaterally occurred in the OCD patients before treatment compared to their matched controls, and there were significant reductions of HMPAO uptake, into the normal range, in all these areas in the patients during treatment. Significantly reduced HMPAO uptake in the caudate nucleus bilaterally occurred in the patients before treatment compared to their matched controls, and these reductions persisted during treatment. This study provides additional support for the involvement of both the orbital frontal cortex and the caudate nuclei in the pathophysiology of OCD.
Acute intermittent porphyria mimics a variety of commonly occurring disorders and thus poses a diagnostic quagmire. Psychiatric manifestations include hysteria, anxiety, depression, phobias, psychosis, organic disorders, agitation, delirium, and altered consciousness ranging from somnolence to coma. Some patients develop psychosis similar to schizophrenia. Psychiatric hospitals have a disproportionate number of patients with this disorder as only difficult and resistant patients accumulate there. Presence of photosensitive porphyrins in the urine is diagnostic. When porphyrins are absent, excess of alpha aminolevulinic acid and porphobilinogen are present in the urine. The definitive test is to measure monopyrrole porphobilinogen deaminase in RBCs. This diagnosis should be entertained in the following situations: (a) unexplained leukocytosis; (b) unexplained neuropathy; (c) etiologically obscure neurosis or psychosis; (d) 'idiopathic' seizure disorder; (e) unexplained abdominal pain; (f) conversion hysteria, and (g) susceptibility to stress. Porphyria is important in psychiatry as it may present with only psychiatric symptoms; it may masquerade as a psychosis and the patient may be treated as a schizophrenic person for years; the only manifestation may be histrionic personality disorder which may not receive much attention. Diagnosis is based on a high index of suspicion and appropriate investigation. Various psychotropic drugs exacerbate acute attacks. While it is important not to use the unsafe drugs in porphyric patients, it is also imperative to look for this diagnosis in cases where these drugs produce unprecedented drug reactions.
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A relationship between hepatic diseases and psychiatric symptoms has long been speculated. While liver detoxication makes the exogenous substances harmless for the body, there are occasions where the liver may convert a harmless substance into a more toxic substance. With such an important role, the liver protects all the organs of the body. When liver is malfunctioning, toxic metabolites injurious to the brain may be produced. As the brain receives a high blood supply, a large amount of metabolites reach this organ. Hence, the metabolic function of the liver keeps a delicate reciprocal relationship between the two organs. In addition, a number of psychiatric medications affect liver functions. Another perplexing clinical problem is the difficulty in treating psychiatric symptoms in patients with liver disease. For example, benzodiazepines which do not affect the liver function in physically healthy psychiatric patients, may induce hepatic coma in patients with liver disease. Benzodiazepine antagonists produce dramatic and temporary improvement in patients with hepatic coma. Clinically, many psychoactive drugs produce hepatic complications. The very same drugs which produce hepatic side effects are required for the treatment of psychiatric symptoms in patients with hepatic disorders. To appropriately handle these situations, a thorough knowledge of the side effects of these drugs is necessary.
This paper describes a previously sufficiently functioning 57 year old man who presented with a recent onset of frontal behaviour. Partial agenesis of corpus callosum was an incidental finding on a computerized tomography scan. The EEG was within normal limits and neuropsychological testing did not reveal any interhemispheric disconnection. A SPECT-Scan revealed bilateral hypoperfusion, consistent with Alzheimer's dementia. Normal functioning up to 50 years of age and a later manifestation of Alzheimer's disease along with agenesis of carpus callosum is of clinical interest as such an association has not been published.
The concept of rapid cycling is confusing in terms of its definition, clinical features, course of illness and the outcome. To complicate the matter further, rapid cycling has been reported to be drug resistant. Currently this condition has been reported to be secondary to lithium, tricyclic antidepressants and other agents such as cyproheptadine, a serotonin antagonist, piribedil, propranolol and levodopa. The increase in rapid cycling has coincided with the rapid increase in cocaine use in the society even though such an association cannot prove a causal relationship. Clinical or subclinical hypothyroidism as well as hyperthyroidism have been implicated in rapid cycling. In addition to the lack of specific knowledge on the etiology, a number of heterogeneous disorders has been grouped under this entity. It is useful to attempt a classification to ascertain whether clinically distinguishable subgroups have a common or different pathophysiology and to tailor the treatment that is most desirable for each subgroup.
Three cases of rapid cycling bipolar patients manifesting episodic parkinsonism are described. Moderate to severe parkinsonism and tardive dyskinesia appeared in all three of these patients before the onset of depression, then worsened during depression and disappeared during mania. A possible mechanism for this phenomenon is hypothesized.
Thirty-four psychiatric patients, assessed for a physical illness that was missed during diagnosis, underwent a CT scan. After investigation, the diagnosis of 14 patients changed from a functional to an organic illness. In nine patients, the CT scan was reported to be abnormal, and yet only two were diagnosed as having an organic syndrome. In seven patients, the CT scan was normal but the patients had an undisputed organic brain syndrome. These findings indicate that the use of CT scans should be restricted to cases in which the diagnosis is seriously in question. The clinical findings should dictate the use of CT scans either to clarify or to complement them.
We measured regional cerebral blood flow (rCBF) with the xenon 133 (133Xe) inhalation method and with regional cerebral uptake of technetium 99m d,l-hexamethyl propyleneamine oxime (99mTc-HMPAO) by single-photon emission computed tomography in 10 adult male patients with obsessive-compulsive disorder (OCD) and in 10 age-matched adult male normal controls. With the 133Xe method, there were no significant differences in cortical or basal ganglia blood flow between the patients with OCD and their matched controls. In the patients, there was a positive relationship between rCBF and the severity of both obsessive and compulsive symptoms (average r = .48). These rCBF findings were consistent with those of earlier reports of increased rCBF in patients with OCD who were undergoing imaginal flooding and who had exacerbation of symptoms following m-CPP administration. 99mTc-HMPAO is a lipophilic molecule that crosses the blood-brain barrier and is converted to a hydrophilic form that is trapped in the brain. The amount that is trapped is determined primarily by blood flow, but also by membrane permeability and kinetics of conversion of the 99mTc-HMPAO to the hydrophilic form. Compared with their matched controls, the patients with OCD had significantly increased 99mTc-HMPAO uptake in the high dorsal parietal cortex bilaterally, in the left posterofrontal cortex, and in the orbital frontal cortex bilaterally. Possible explanations include (1) increased rCBF that was not detected with 133Xe, (2) increased permeability of the blood-brain barrier and/or cell membranes, and (3) increased conversion and trapping of the lipophilic, injected form of 99mTc-HMPAO in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)