Development Of Extrapyramidal Symptoms Research Articles

Manganese and copper levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis

The liver and the biliary tree form the main excretory route of manganese (Mn) and copper (Cu). Cholestasis, can lead to the accumulation of these trace elements in the organism, resulting in toxicity to the basal ganglia of the central nervous system. The aim of our study was to reveal the influence of long-term cholestasis on the Mn and Cu levels in the blood of patients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). We recruited patients with PBC (n = 20) and PSC (n = 32). A control group (n = 40) was also set up. We also examined serum bile acid concentrations and liver enzyme activities. We did not observe any significant differences in any of these parameters between the PBC and PSC groups. The Mn and Cu levels in the PBC and PSC patients differed significantly from the that in the control group (p < 0.0001 and p < .021, respectively). Patients in whom the laboratory cholestasis markers normalized during ursodeoxycholic acid treatment (18/52;35%) presented with significantly lower levels of Mn and Cu (p = .015 and p = .012, respectively). Ten PSC patients showed normal levels of Mn and Cu six months after liver transplantation. Fine tremors, rigidity, dysarthria, and hypomimia were reported in nine (23%), eight (20%), four (10%), and eight (20%) patients, respectively. In addition to monitoring the cholestasis levels, liver function, and Mn and Cu levels during the long-term treatment of PBC and PSC patients, it is important to also regularly monitor the occurrence and development of extrapyramidal symptoms of Parkinson’s-like syndromes.

Toxic encephalopathy in a clinicl case of polycythemia vera

The article deals with a clinical case description of a female patient with toxic encephalopathy against the background of Ph-negative myeloproliferative diseases. The article discusses symptoms and neuroimaging of hepatic encephalopathy developed as a result of a shunt placed after portal vein thrombosis. The issues of etiology and pathogenesis of hepatic encephalopathy, principles of therapy, as well as the unique clinical picture of nervous system damage in this condition are also discussed. Data on the role of manganese in development of toxic encephalopathy, accumulation of paramagnetic substance in the basal ganglia of the brain and development of extrapyramidal symptoms are presented. The pathogenesis of toxic damage to neurons, increase in their sensitivity to hypoxia, and the relationship with the risk of cerebrovascular disorders and development of chronic cerebral ischemia, contributing to reduction of cognitive functions, are described.

Antidepressants and extrapyramidal symptoms

The newer non‐tricyclic antidepressants have occasionally been associated with development of extrapyramidal symptoms (EPSs). However, no large‐scale epidemiological or observational studies have examined this reported association. Recognizing the need to evaluate further the association between antidepressant use and extrapyramidal reactions in clinical practice settings, investigators conducted a pharmacoepidemiological study in a large cohort.

Call to Caution with the Use of Atypical Antipsychotics for Treatment of Depression in Older Adults.

Atypical antipsychotics are increasingly being used to manage depression in older adults where these symptoms can often be refractory to first-line treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). Unfortunately, atypical antipsychotics can be associated with the development of extrapyramidal symptoms (EPS), with drug-induced parkinsonism (DIP) being the most common movement disorder induced by this class of medication. The management of treatment-resistant depression in older adults is of particular concern as depression is a common feature of idiopathic Parkinson’s disease (IPD) and can manifest prior to the development of motor symptoms. Herein, we discuss the use of atypical antipsychotics for the management of depression in older adults including the risk of DIP and propose that antipsychotics may potentially unmask IPD.

Pharmacogenetic-based risk assessment of antipsychotic-induced extrapyramidal symptoms

"Typical" antipsychotics remain the wide-prescribed drugs in modern psychiatry. But these drugs are associated with development of extrapyramidal symptoms (EPS). Preventive methods of EPS are actively developed and they concentrate on personalized approach. The method of taking into account genetic characteristics of patient for prescribing of treatment was proven as effective in cardiology, oncology, HIV-medicine. In this review the modern state of pharmacogenetic research of antipsychotic-induced EPS are considered. There are pharmacokinetic and pharmacodynamic factors which impact on adverse effects. Pharmacokinetic factors are the most well-studied to date, these include genetic polymorphisms of genes of cytochrome P450. However, evidence base while does not allow to do the significant prognosis of development of EPS based on genetic testing of CYP2D6 and CYP7A2 polymorphisms. Genes of pharmacodynamics factors, which realize the EPS during antipsychotic treatment, are the wide field for research. In separate part of review research of such systems as dopaminergic, serotonergic, adrenergic, glutamatergic, GABAergic, BDNF were analyzed. The role of oxidative stress factors in the pathogenesis of antipsychotic-induced EPS was enough detailed considered. The system of those factors may be used for personalized risk assessment of antipsychotics' safety in the future. Although there were numerous studies, the pharmacogenetic-based prevention of EPS before prescribing of antipsychotics was not introduced. However, it is possible to distinguish the most perspectives markers for further research. Furthermore, brief review of new candidate genes provides here, but only preliminary results were published. The main problem of the field is the lack of high- quality studies. Moreover, the several results were not replicated in repeat studies. The pharmacogenetic-based research must be standardized by ethnicity of patients. But there is the ethnical misbalance in world literature. These facts explain why the introduction of pharmacogenetic testing for risk assessment of antipsychotic-induced EPS is so difficult to achieve.

Dopamine D2 Occupancy as a Biomarker for Antipsychotics: Quantifying the Relationship with Efficacy and Extrapyramidal Symptoms

For currently available antipsychotic drugs, blockade of dopamine D(2) receptors is a critical component for achieving antipsychotic efficacy, but it is also a driving factor in the development of extrapyramidal symptoms (EPS). To inform the clinical development of asenapine, generic mathematical models have been developed for predicting antipsychotic efficacy and EPS tolerability based on D(2) receptor occupancy. Clinical data on pharmacokinetics, D(2) receptor occupancy, efficacy, and EPS for several antipsychotics were collected from the public domain. Asenapine data were obtained from in-house trials. D(2) receptor occupancy data were restricted to published positron emission tomography studies that included blood sampling for pharmacokinetics. Clinical efficacy data were restricted to group mean endpoint data from short-term placebo-controlled trials, whereas EPS evaluation also included some non-placebo-controlled trials. A generally applicable model connecting antipsychotic dose, pharmacokinetics, D(2) receptor occupancy, Positive and Negative Syndrome Scale (PANSS) response, and effect on Simpson-Angus Scale (SAS) was then developed. The empirical models describing the D(2)-PANSS and D(2)-SAS relationships were used successfully to aid dose selection for asenapine phase II and III trials. A broader use can be envisaged as a dose selection tool for new antipsychotics with D(2) antagonist properties in the treatment of schizophrenia.

Basal ganglia involvement in a child with herpes simplex encephalitis

Herpes simplex encephalitis (HSE) is a leading cause of sporadic, nonepidemic viral encephalitis in children and adults. We report a very rare case of HSE with involvement of bilateral thalamus, putamen, upper pons and midbrain, with development of extrapyramidal symptoms which responded to corticosteroid therapy. A 15-mth-old female baby admitted with complaint of fever for 5 days and generalised tonic clonic seizure 10 hours before admission. On clinical examination patient was drowsy, temperature was 39.4 degrees C and vitals were stable with signs of increased intracranial tension. There were no signs of meningeal irritation. Patient gradually become unconscious in the next few hours and pupils were constricted bilaterally with development of atonia in all four limbs and neck muscles. Doll's eye phenomenon was absent.

Persistent dystonia induced by fluoxetine

Serotonin-selective re-uptake inhibitors are prescribed widely because they are regarded as having less severe side-effects compared with tricyclics and monoamine oxidase inhibitors. With this popularity, increasing attention has been drawn to their adverse effects. Development of extrapyramidal symptoms has been reported in some patients while taking fluoxetine, a commonly used serotonin-selective re-uptake inhibitor. Here, we report a case of persistent dystonia, thought to be associated with short-term fluoxetine use, which required treatment with botulinum toxin type A.

Clinical impact of selective serotonin reuptake inhibitors therapy with bleeding risks

The selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of multiple psychiatric conditions. In vitro and ex vivo data with these agents indicate they may have varying degrees of antiplatelet activity via multiple receptors. Reports of bleeding in patients receiving SSRIs appeared soon after their introduction. A review of the literature suggests SSRI therapy may increase the risk of bleeding especially with concomitant aspirin or nonsteroidal anti-inflammatory agents. Clinicians should exercise caution when prescribing these agents in high risk patients and maintain awareness of the potential contribution of SSRIs to unexplained bleeding episodes.

Early events in the life cycle of JC virus as potential therapeutic targets for the treatment of progressive multifocal leukoencephalopathy.

The human polyomavirus, JC virus (JCV), is the etiological agent of progressive multifocal leukoencephalopathy (PML). PML occurs almost exclusively in the setting of severe and prolonged immunosuppression and it remains an important and life-threatening complication in the acquired immunodeficiency syndrome (AIDS) population. Several drugs that target DNA replication have shown efficacy at inhibiting JCV replication in vitro but none to date have shown in vivo efficacy. The authors' laboratory has been studying early events that contribute to infection of susceptible cells by JCV. They previously demonstrated that infection of glial cells by JCV requires clathrin-dependent endocytosis and that this early step in the viral life cycle can be blocked by the antipsychotic drug, chlorpromazine. As chlorpromazine is associated with the development of extrapyramidal symptoms that may be heightened in AIDS patients, the authors sought to test the atypical antipsychotic, clozapine, for antiviral activity against JCV. In this report, the authors show that clozapine is as effective as chlorpromazine at inhibiting infection. They further demonstrate that low-dose combinations of both drugs synergistically inhibit infection.

How much do novel antipsychotics benefit the patients?

Although great advances have been made in the pharmacotherapy of schizophrenia, many patients are still not taking full advantage of the beneficial effects of antipsychotic drugs. This is largely a result of the low levels of compliance. Conventional antipsychotics have little efficacy against negative symptoms, and so many patients with schizophrenia are refractory to treatment with these drugs. Additionally, clinically effective doses of conventional antipsychotics can actually aggravate negative symptoms through the development of extrapyramidal symptoms (EPS). Patients taking these drugs, therefore, often felt that the treatment was making them worse instead of better, and were reluctant to continue with it. The novel antipsychotics offer great potential for improving compliance. Clinical trials have shown that atypical drugs such as sertindole do not induce EPS, are effective against negative as well as positive symptoms and do not affect cognition. These observations have been reflected in postmarketing clinical experience, leading to recommendations that novel antipsychotics, such as sertindole, should be prescribed to first-episode patients. These patients would then not experience EPS and would be more likely to continue with their medication in the long term and thus avoid relapse. The major problems affecting compliance with pharmacotherapy for schizophrenia are outlined here showing, by means of case histories, how sertindole has benefited schizophrenic patients.

Latest atypical antipsychotic agents move closer to approval

The benefits of using conventional antipsychotic agents to treat schizophrenia are countered by the agents’ lack of efficacy in treating negative symptoms and their association with the development of extrapyramidal symptoms (EPS). The introduction of the atypical antipsychotic clozapine, and later risperidone, marked a significant advance in the therapeutic options for schizophrenia. Now, another generation of atypical antipsychotic drugs looks set to reach the market. This will provide clinicians with a much greater range of options for treating schizophrenia by the end of the decade. Data on the newer antipsychotic drugs, and future prospects in schizophrenia treatment, were discussed at the 20th Collegium Internationale Neuro-Psychopharmacologicum (CINP) meeting [Melbourne, Australia; July 1996].

Use of psychotropic drugs in patients with HIV infection.

Psychotropic drugs are frequently employed to treat the wide range of neuropsychiatric syndromes that patients infected with the human immunodeficiency virus (HIV) may develop. In order to administer these agents properly, physicians should take certain factors into account: the central nervous systems of these patients are often impaired, the patients tend to suffer from medical illnesses, and they may be taking various other drugs. The possible interactions between substances taken by these patients may sometimes make it necessary to adjust the dosage of psychotropic agents administered. In addition, some of the antimicrobial, antifungal and antiviral agents used in the management of HIV infection may have adverse effects that include neuropsychiatric symptoms. The use of antipsychotic agents in these patients frequently results in the development of extrapyramidal symptoms. Tricyclic antidepressants are not well tolerated by patients with AIDS, due to the anticholinergic effects of these agents. The new antidepressants, which have fewer and milder adverse effects, are safer and have shown their efficacy in the treatment of the depressive episodes often seen in HIV-infected patients. Benzodiazepines must be prescribed with caution in patients with HIV infection and organic brain syndrome, since they can produce amnesia, confusion, lack of inhibition and paradoxical reactions. The indications for the use of psychostimulants in certain clinical situations, such as HIV-associated dementia and depression, is open to debate. Opiates are indicated in pain treatment, and in methadone maintenance programmes. Lithium and carbamazepine are advisable only in very restricted situations.

Acute Metoclopramide Toxicity in Children

DOI: http://dx.doi.org/10.5915/23-4-15427 Vomiting is a common symptom in children and is usually treated with phenothiazines. A new dopamine antagonist, metoclopramide, considered relatively safe, is widely used as antiemetic. The development of extrapyramida symptoms is a well known manifestation of phenothiazine toxicity. During an epidemic of gastroenteritis, we encountered 18 patients who had received metoclopramide and developed extrapyramidal symptoms. All patients improved with diphenhydramine therapy. Our experience suggests that the development of extrapyramidal symptoms after intake of metoclopramide may not be uncommon.

Clinical efficacy, extrapyramidal symptoms and serum levels: influence of administration schedules and concomitant drugs on serum bromperidol concentrations.

Bromperidol (4 or 12 mg per day) was administered to 18 newly admitted schizophrenics and 29 chronic schizophrenic inpatients once or four times a day and the two dose schedules were compared. The bromperidol levels in the four-times-a-day group were significantly higher than those in the once-a-day group and the daily variation in the serum level of the agent was markedly wider in the latter than in the former patients. The incidence and severity of extrapyramidal symptoms were not significantly different between the two. A clear relationship was not present between the serum levels and the development of extrapyramidal symptoms. The bromperidol serum values were not correlated with the therapeutic response but, at more than 5 ng per ml, there might be a positive correlation between the bromperidol levels and clinical efficacy in the newly admitted schizophrenics. As for concomitant medication, levomepromazine may raise the bromperidol serum level. An anti-parkinson drug failed to depress the bromperidol level.

Serum level of haloperidol and its clinical significance

1. 1. The blood concentration of haloperidol was determined in schizophrenic patients according to the three different schedules by the recently developed radioimmunoassay. 2. 2. There exists a significant positive correlation between the blood concentration and the daily dose per kg of body weight of haloperidol. 3. 3. A certain relationship is present between the blood concentration and the development of extrapyramidal symptoms (EPS). 4. 4. The combined use of antiparkinsonian drugs failed to depress the blood level of haloperidol. 5. 5. The blood concentration of haloperidol varied more widely and required much more time in attaining a steady state after administration in a single dose than after administration in divided doses.

Drug refusal in schizophrenia: causes and prescribing hints.

Many discharged patients diagnosed as schizophrenic do not continue to take their prescribed antipsychotic medication. Reasons for reluctance to take drugs include the development of extrapyramidal symptoms, most notably akathisia and akinesia; a poor doctor-patient relationship; or the patient's preference to continue his schizophrenic existence. To improve drug compliance, the physician should ask the patient about his impressions of side-effects and should let the patient help determine the optimal dosage.

Development of extrapyramidal symptoms in hypertensive patients treated with diazoxide.

Extrapyramidal symptoms developed a variable time after the start of treatment with oral diazoxide in 15% of a series of 100 severely hypertensive patients. Six illustrative cases are described. Treatment with diazoxide could be continued in four of these. The symptoms are usually controllable either by dosage adjustment or by the use of diazepam or procyclidine. There was no evidence of irreversibility of the extrapyramidal syndromes observed.