Risk Of Extrapyramidal Side Effects Research Articles

<b>３．分子イメージングによる向精神薬の評価</b>

Positron emission tomography (PET) allows the evaluation of target molecules of various psychotropic drugs in the living human brain. PET studies have demonstrated that conventional antipsychotics induce high (70-90%) dopamine D2 receptor occupancy in the striatum. The risk of extrapyramidal side effects increases when the striatal D2 receptor occupancy exceeds 80%. Thus, D2 receptor occupancy between 70 and 80% appears to represent the optimal therapeutic window, at which antipsychotic effect can be expected with a minimal risk of extrapyramidal side effects. The clinical dose of the second-generation antipsychotics nicely fit this range of D2 receptor occupancy. Serotonin transporter occupancy has been the main biomarker for the evaluation of antidepressants, and has been used in the assessment of selective serotonin reuptake inhibitors. Recently, we have successfully measured norepinephrine transporter occupancy of antidepressants. These occupancy markers are useful for setting optimal doses of antipsychotics or antidepressants.

Synthesis and Pharmacological Evaluation of 3-Amino-1-(5-indanyloxy)-2-propanol Derivatives as Potent Sodium Channel Blockers for the Treatment of Stroke

In investigating potent sodium (Na(+)) channel blockers for the treatment of ischemic stroke, we synthesized a novel series of 3-amino-1-(5-indanyloxy)-2-propanol derivatives and evaluated their inhibitory effects on neuronal Na(+) channels. The 3-amino-1-(5-indanyloxy)-2-propanol derivatives exhibited potent blocking activity for Na(+) channels and a significantly low affinity for dopamine D(2) receptors, which demonstrates a minimal clinical risk for extrapyramidal side effects. In particular, compound 4b, a 3-amino-1-(5-indanyloxy)-2-propanol derivative bearing a benzimidazole moiety, showed desirable neuroprotective activity in a rat transient middle cerebral artery occlusion model. Furthermore, compound 4b displayed a high binding affinity for neurotoxin receptor site 2 of the Na(+) channels, which suggests that 4b would act as a use-dependent Na(+) channel blocker in sustained depolarization during ischemic stroke.

Antipsychotics in the Treatment of Schizophrenia

Schizophrenia is characterized by positive, negative, cognitive, disorganization, and mood symptoms. Antipsychotics are the mainstay in the pharmacologic treatment of schizophrenia. Findings concerning efficacy for positive symptoms and disorganization suggest no consistent differences among available antipsychotics, with the exception of clozapine's superior efficacy for treatment-resistant schizophrenia. Efficacy for negative, depressive, and cognitive symptoms appears to be determined by (1) the extent to which reduction in positive symptoms brings about improvement in these other domains and (2) the extent to which extrapyramidal side effects (EPS) and anticholinergic effects (of the antipsychotic and of agents used to treat EPS) exacerbate them. Thus, the ability of antipsychotics to produce a potent antipsychotic effect without EPS and need for concomitant anticholinergic therapy yields multiple therapeutic benefits. In contrast to their broadly similar efficacy, antipsychotics differ markedly in their propensity to cause various adverse effects. Although second-generation antipsychotics (SGAs) have generally been believed to be associated with a lower risk of EPS but a higher risk of metabolic adverse effects than first-generation agents (FGAs), the substantial variation in these and other side effects among agents within both classes indicates that it is not clinically useful to make a categorical distinction between FGAs and SGAs. Choice of antipsychotic medication should be based on individual preference, prior treatment response and side effect experience, medical history and risk factors, and adherence history, with side effect profile a major determinant of antipsychotic choice.

Antipsychotic drugs and extrapyramidal side effects in first episode psychosis: a systematic review of head–head comparisons

This systematic review aimed to determine whether the risk of extrapyramidal side effects (EPS) differed between antipsychotic drugs used in first episode psychosis (FEP). We identified 11 RCTs comparing two or more antipsychotics in FEP and reporting on EPS. All trials assessed one or more second generation antipsychotics (SGAs), one assessed chlorpromazine, one zuclopenthixol and seven trials assessed haloperidol. Assessment and reporting of EPS varied. Compared with one or more SGA comparators, haloperidol was associated with significantly higher rates/severity of parkinsonism (seven trials) and akathisia (six trials) and greater use of anticholinergics (five trials) and beta-blockers (two trials). Two trials with low-dose haloperidol (≤ 4 mg) showed significantly worse EPS outcomes versus a SGA. Two of four long-term haloperidol trials (≥ 1 year) found a higher dyskinesia-risk with haloperidol versus olanzapine and risperidone respectively; the remaining two trials found no difference (various SGA comparators). There was an EPS advantage for clozapine versus chlorpromazine (one trial) and risperidone versus zuclopenthixol (one trial). There was little evidence of EPS-differences between SGAs, possibly reflecting use of low doses. We conclude that SGAs offer an EPS advantage over FGAs in FEP though the evidence largely relates to comparisons with haloperidol. Standardized assessment and reporting of EPS would assist future research.

A REVIEW ON PHARMACOLOGICAL AND ADJUVANT THERAPIES FOR SCHIZOPHRENIA

Schizophrenia is a psychological disorder, diagnosed by observed behavior and patient reported experiences. Antipsychotic medication mainly works by suppressing dopamine activity. Neuroleptics are also called as antipsychotic drugs. There is a increased risk of extrapyramidal side effects with typical antipsychotics. Atypical antipsychotics refers to newer antipsychotics that confer to less risk of extrapyramidal side effects. Along with these Neuroleptic treatment other adjuvant treatments like Insulin shock, Electroconvulsive, Oestrogen, Glycine, Cox 2 and Antioxidant therapies are also used for Schizophrenia. Insulin is a hormone that maintain blood sugar level. Repeated injections with large doses of insulin causes daily comas over several weeks during which the patient lost psychotic thoughts. In electroconvulsive therapy controlled electric currents pass through the brain, altering brain chemistry and reducing depression and schizophrenic symptoms. Repeated applications of electric current alter the neurotransmitter level in central nervous system. In oestrogen therapy epidemiological, clinical and animal studies exploring the protective effect of oestrogen against schizophrenic symptoms. Psychoprotective action of oestrogen appears to be mediated by central dopaminergic and serotonergic mechanisms. Glycine(amino acid), antioxidants and vitamins are potential treatments for the negative symptoms of Schizophrenia. There is an imbalance between the type 1 and type 2 immune systems in patients with psychosis, this imbalance can be restored by Cox 2 inhibitors.

Improvement of Oral Dyskinesia After Switching From Aripiprazole to Paliperidone: A Case Report

Back to table of contents Previous article Next article LettersFull AccessImprovement of Oral Dyskinesia After Switching From Aripiprazole to Paliperidone: A Case ReportChien-Han Lai, M.D., M.Sc.Chien-Han LaiSearch for more papers by this author, M.D., M.Sc.Published Online:1 Jul 2011AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Paliperidone is associated with fewer extrapyramidal side effects (EPS) than typical antipsychotics. Here, we reported a case of schizophrenia with oral and tongue dyskinesia after aripiprazole treatment. The patient had improvement of dyskinesia after switching to paliperidone.Case Report“Miss B” had her first episode of schizophrenia 1 year ago. The symptoms included delusion of persecution toward her colleagues, delusion of reference toward her boss, auditory hallucinations, and visual hallucinations. Her psychotic symptoms improved after the first 3 months of therapy with aripiprazole 15 mg/day. However, she had irregular, involuntary, persistent, and repetitive movements of mouth and tongue after aripiprazole treatment for 1 month. These movements were very irregular, either in intensity or direction. The intensity of movements varied over time and ranged from mild to moderate. The direction of tongue movements was random, in any possible direction, either within the oral cavity or outside the mouth. Her oral dyskinesia was not relieved after the aripiprazole was tapered to 10 mg/day in the 6th month and 5 mg/day in the 9th month. After 3 months of 5 mg/day aripiprazole therapy, her oral dyskinesia had still not responded to biperidin 2 mg/day. Because of the possibility of aripiprazole-related oral dyskinesia, the antipsychotic was switched to paliperidone. The irregular movements improved, with gradual decline in intensity, frequency, and duration within 1 month. No significant cholinergic rebound symptoms or side effects were noted after the abrupt switch. Her psychotic symptoms still remained stable. The remission of dyskinesia remained after therapy of paliperidone for the next 3 months.DiscussionThis patient had improvement of dyskinesia after switching to paliperidone. The dose (3 mg/day) is relatively low for schizophrenia but equal to her previous aripiprazole dose of 5 mg/day. This patient had dramatic relief of dyskinesia side effects, which might be related to different binding patterns for neurotransmitter receptors of these two kinds of atypical antipsychotics. In a positron emission tomography study, 6–9 mg/day of paliperidone showed equal dopamine-binding at D2 receptors (around 70%–80%) over striatum and temporal cortex.1 This patient just received 3 mg/day of paliperidone and had complete remission of dyskinesia. Lower binding of D2 receptors over striatum at the dose of 3 mg/day might be the reason. Aripiprazole has a well-known low risk of EPS, with incidence comparable to placebo, and it could modulate dopamine release over prefrontal cortex through the action on serotonin 5-HT1A receptors.2 The dopamine release is not observed over sriatum areas, and, with D2 occupancy over 90%, still did not produce EPS.3 Its tardive dyskinesia incidence is also comparable to placebo group without significant risk. However, this patient had dyskinesia side effects even using aripiprazole at a lower dose. The relatively higher antagonism over 5-HT2A receptor of paliperidone than aripiprazole4 might provide another reason why this patient had remission of dyskinesia after the antipsychotic switch. 5-HT2A antagonism also suppressed the abnormal involuntary movements and dyskinesia of dopamine-depleted rats after receiving dopamine agonists.5 These findings might help explain clinical phenomenon in this patient.Dept. of Psychiatry, Buddhist Tzu-Chi General Hospital, Taipei Branch, Taipei, Taiwan;Institute of Brain Science, National Yang Ming University, Taipei City, Taiwan e-mail: [email protected]com.tw1. Arakawa R , Ito H , Takano A , et al.: Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology (Berl) 2008; 197:229–235Crossref, Medline, Google Scholar2. Bortolozzi A , Diaz-Mataix L , Toth M , et al.: In-vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain. Psychopharmacology (Berl) 2007; 191:745–758Crossref, Medline, Google Scholar3. Yokoi F , Grunder G , Biziere K , et al.: Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C]raclopride. Neuropsychopharmacology 2002; 27:248–259Crossref, Medline, Google Scholar4. Pae CU , Serretti A , Patkar AA , et al.: Aripiprazole in the treatment of depressive and anxiety disorders: a review of current evidence. CNS Drugs 2008; 22:367–388Crossref, Medline, Google Scholar5. Taylor JL , Bishop C , Ullrich T , et al.: Serotonin 2A receptor antagonist treatment reduces dopamine D1 receptor-mediated rotational behavior but not L-dopa-induced abnormal involuntary movements in the unilateral dopamine-depleted rat. Neuropharmacology 2006; 50:761–768Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 23Issue 3 Summer 2011Pages E18-E18 Metrics PDF download History Published online 1 July 2011 Published in print 1 July 2011

Risperidone long-acting injectable (Risperdal Consta®) for maintenance treatment in patients with bipolar disorder

Poor adherence to pharmacotherapy during maintenance-phase treatment of bipolar disorder is a common occurrence, exposing patients to a high risk of illness relapses, rehospitalization and other negative outcomes. In view of this, there has been a reawakening of interest in the potential of long-acting injectable antipsychotic medications to improve treatment outcome during bipolar maintenance therapy. Indeed, long-acting injectable medications have practical advantages of assuring delivery of medication at a prescribed dose, and perhaps also making it easier to monitor adherence, at least to the long-acting drug. However, there are important limitations to the long-term use of depot typical neuroleptics in patients with bipolar disorder, including risk of extrapyramidal side effects and tardive dyskinesia, which may exceed that of patients with schizophrenia, and the potential for treatment-emergent exacerbation of depressive symptoms. Long-acting injectable risperidone (RLAI) has recently been approved for maintenance treatment in patients with bipolar I disorder. Evidence supporting the use of RLAI for this indication consists of several nonrandomized, open-label studies; one randomized, open-label trial; and two adequately powered randomized, double-blind trials. In general, these studies have shown RLAI to be effective for the prevention of relapse or hospitalization during bipolar maintenance treatment. In the double-blind studies, RLAI was associated with reduced relapse rates, increased time to relapse and greater control of clinical symptoms during maintenance treatment following initial stabilization, compared with oral medication treatment or placebo injection. RLAI appeared to be more effective for preventing manic/mixed episodes than depressive episodes. RLAI showed good tolerability across studies; however, dose-related extrapyramidal effects, sedation, weight gain and prolactin elevation may occur during long-term treatment. Responder-enriched designs and exclusion of important clinical subgroups in the double-blind trials may limit translation of these results to routine care settings.

Atypical antipsychotic tolerability and switching strategies in bipolar disorder

Importance to the field: Atypical antipsychotics have unequivocally advanced the pharmacotherapy of bipolar disorders. These broad-spectrum treatments offer efficacy against core symptoms of acute mania, mixed state, depressed and maintenance phases of the disorder. Atypical antipsychotics are not, however, a panacea and are associated with several problematic tolerability and safety concerns. For example, emerging evidence militates against the original notion that atypical agents are without risk for extrapyramidal side effects and possibly tardive dyskinesia when compared to their therapeutic predecessors, the conventional antipsychotics. Although classified together, atypical antipsychotics are heterogeneous in their tolerability and safety profile, an issue relevant to individualizing treatment selection and switching antipsychotics for optimal clinical management.Areas covered in this review: This article reviews relevant adverse events attributable to the use of atypical antipsychotics and strategies for switching these agents, with particular attention to the bipolar disorder population.What the reader will gain: The reader will gain both a perspective of treatment-emergent adverse events associated with atypical agents in the treatment of bipolar disorder and a precise analysis of common adverse events that frequently lead to treatment discontinuation and/or switching to a separate agent.Take home message: Atypical antipsychotics provide for a different array of treatment-emergent adverse events than conventional agents. The therapeutic index of treatment is a ratio of the relative benefit divided by the probability of harm (i.e., side effects). Taken together, the atypical antipsychotics offer an improved therapeutic index when compared to conventional agents in bipolar disorder. Nevertheless, atypicals fall short of the ideal, necessitating frequent discontinuation and switching.

Second-generation antipsychotic drugs and extrapyramidal side effects: a systematic review and meta-analysis of head-to-head comparisons.

While all second-generation antipsychotics (SGAs) are promoted for having a low risk of extrapyramidal side effects (EPS), clinical observations suggest differences between the various agents. Nevertheless, this question has never been examined in a systematic review and meta-analysis of head-to-head comparisons. We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE (last search July 2009) for randomized, blinded studies comparing the following SGAs in the treatment of schizophrenia or related disorders: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, and zotepine. At least 3 reviewers extracted the data independently. The primary outcome was "use of antiparkinson medication." The results were combined in a meta-analysis. We included 54 studies with 116 arms. Risperidone was associated with more use of antiparkinson medication than clozapine, olanzapine, quetiapine, and ziprasidone. Ziprasidone showed more use of antiparkinson medication than olanzapine and quetiapine and zotepine more than clozapine. There was no significant difference between amisulpride and its comparators (olanzapine, risperidone, or ziprasidone). Quetiapine showed significantly less use of antiparkinson medication than the 3 other SGAs it was compared with (olanzapine, risperidone, and ziprasidone). Scale-derived data (Barnes Akathisia Scale and Simpson Angus Scale) were limited. Our meta-analysis demonstrates that there are differences between the SGAs in their ability to induce EPS that clinicians consider warrant treatment with antimuscarinic drugs. Even though the differences were relatively small, they might be important for individual patients and should be taken into account in drug choice.

Sigma-1 receptor agonist fluvoxamine for delirium in patients with Alzheimer's disease

BackgroundDelirium in older adults is a common and serious acute neuropsychiatric syndrome, with core features of inattention and global cognitive impairment. Although antipsychotic drugs are the medications most frequently used to treat this syndrome, these drugs are associated with a variety of adverse events, including sedation, extrapyramidal side effects, and cardiac arrhythmias.MethodsWe report on two cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the delirium of patients with Alzheimer's disease.ResultsDelirium Rating Scale (DRS) scores in the two patients with Alzheimer's disease decreased after fluvoxamine monotherapy.ConclusionDoctors should consider that fluvoxamine could be an alternative approach in treating delirium in patients with Alzheimer's disease because of the risk of extrapyramidal side effects by antipsychotic drugs.

Fluvoxamine monotherapy for psychotic depression: the potential role of sigma-1 receptors

BackgroundPsychotic depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI)) and an atypical antipsychotic or electroconvulsive therapy in treating psychotic depression. In some cases, the clinician or patient may prefer to avoid antipsychotic drugs altogether because of the risk of extrapyramidal side effects (EPS) in patients with psychotic depression treated with these drugs.MethodsWe report five cases where fluvoxamine monotherapy was effective in the patients with psychotic depression.ResultsThe scores on the Hamilton Depression (HAM-D) scale and the Brief Psychiatric Rating Scale (BPRS) in the five patients with psychotic depression were reduced after fluvoxamine monotherapy.ConclusionDoctors should consider fluvoxamine monotherapy as an alternative approach in treating psychotic depression because it avoids the risk of EPS from antipsychotic drugs.

Quetiapine XR efficacy and tolerability as monotherapy and as adjunctive treatment to conventional antidepressants in the acute and maintenance treatment of major depressive disorder: a review of registration trials

Results from pivotal registration trials in major depressive disorder cohere with outcomes from effectiveness studies indicating that the majority of individuals receiving single-agent pharmacotherapy fail to achieve and sustain symptomatic remission. Several factors provided the impetus for this review: suboptimal efficacy with existing pharmacotherapy for major depressive disorder, quetiapine XR efficacy in the acute and maintenance treatment of bipolar depression, emerging pharmacodynamic evidence that quetiapine XR (and/or its metabolites) uniquely engages monoaminergic systems salient to symptom relief in depressive syndromes, the increasing use of second-generation antipsychotics in the treatment of major depressive disorder and the recent FDA review of quetiapine XR in major depressive disorder. Studies reviewed herein are pivotal registration trials that evaluated the acute and maintenance efficacy and tolerability of quetiapine XR (as monotherapy and as adjunctive treatment) in major depressive disorder. In addition, we also review recent investigations characterizing the pharmacodynamic effect of quetiapine's principal active metabolite, norquetiapine. All studies were obtained from AstraZeneca (Wilmington, DE, USA) and have been presented at national/international scientific meetings. Taken together, extant studies demonstrated that quetiapine XR (50 – 300 mg) provides rapid and sustained symptomatic improvement in the acute and maintenance treatment of major depressive disorder. Quetiapine XR may also offer advantages relative to duloxetine in time to onset of antidepressant action. The major limitations of quetiapine XR use in major depressive disorder relate to weight gain and disrupted glucose/lipid homeostasis as well as sedation/somnolence. Quetiapine XR has tolerability advantages compared with duloxetine on measures of sexual dysfunction. The data from the studies reviewed herein also indicate that quetiapine XR poses a low risk for extrapyramidal side effects in middle-aged and elderly individuals with major depressive disorder.

Can Metformin or Rosiglitazone Reduce Metabolic Side Effects Associated with Atypical Antipsychotics?

When treating schizophrenia, the newer atypical antipsychotic medications (AAPs) are generally preferred for their minimal risk of extrapyramidal side effects and sedation as compared to typical an...

Antipsychotic-induced extrapyramidal side effects in bipolar disorder and schizophrenia: a systematic review.

Newer atypical antipsychotics have been reported to cause a lower incidence of extrapyramidal side effects (EPS) than conventional agents. This review is to compare antipsychotic-induced EPS relative to placebo in bipolar disorder (BPD) and schizophrenia. English-language literature cited in Medline was searched with terms antipsychotics, placebo-controlled trial, and bipolar disorder or schizophrenia and then with antipsychotic (generic/brand name), safety, akathisia, EPS, or anticholinergic use, bipolar mania/depression, BPD, or schizophrenia, and randomized clinical trial. Randomized, double-blind, placebo-controlled, monotherapy studies with comparable doses in both BPD and schizophrenia were included. Absolute risk increase and number needed to treat to harm (NNTH) for akathisia, overall EPS, and anticholinergic use relative to placebo were estimated. Eleven trials in mania, 4 in bipolar depression, and 8 in schizophrenia were included. Haloperidol significantly increased the risk for akathisia, overall EPS, and anticholinergic use in both mania and schizophrenia, with a larger magnitude in mania, an NNTH for akathisia of 4 versus 7, EPS of 3 versus 5, and anticholinergic use of 2 versus 4, respectively Among atypical antipsychotics, only ziprasidone significantly increased the risk for overall EPS and anticholinergic use in both mania and schizophrenia, again with larger differences in mania, an NNTH for overall EPS of 11 versus 19, and anticholinergic use of 5 versus 9. In addition, risks were significantly increased for overall EPS (NNTH = 5) and anticholinergic use (NNTH = 5) in risperidone-treated mania, akathisia in aripiprazole-treated mania (NNTH = 9) and bipolar depression (NNTH = 5), and overall EPS (NNTH = 19) in quetiapine-treated bipolar depression. Bipolar patients, especially in depression, were more vulnerable to having acute antipsychotic-induced movement disorders than those with schizophrenia.

Long-term Effects of JL 13, a Potential Atypical Antipsychotic, on Ionotropic Glutamate Receptors

Changes in ionotropic glutamate (Glu) N-methyl-d-aspartic acid (NMDA), and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in rat forebrain regions were autoradiographically quantified after continuous infusion of JL 13 [(5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine fumarate] for 28 days using osmotic minipumps, and compared to the effects of representative typical (haloperidol) and atypical (clozapine, olanzapine, and risperidone) antipsychotic drugs from previous studies. Similar to other atypical and not typical antipsychotics, JL 13 decreased labeling of NMDA receptors in medial and lateral caudate-putamen (CPu; by 40%). These findings indicate that down-regulation of NMDA receptors by JL 13 and other atypical antipsychotic agents in CPu may contribute to their low risk of extrapyramidal side effects. In addition, and similar to olanzapine and risperidone, JL 13 increased AMPA receptor binding in CPu (by 42%). Changes in AMPA receptors may contribute to psychopharmacological properties of JL 13 and other atypical agents. Similar to clozapine, JL 13 did not alter levels of NMDA and AMPA receptors in hippocampus and entorhinal cortex. Long-term effects of JL 13 on ionotropic Glu receptors, as well as on other dopamine and serotonin receptors, support the atypical antipsychotic profile of this novel agent.

Extrapyramidal Side Effects with Atypical Antipsychotics

Atypical antipsychotics are believed to have a substantially lower risk of extrapyramidal side effects (EPS) than neuroleptics, making atypicals more

Brain imaging research: Does the science serve clinical practice?

Brain imaging represents a potent tool to characterize biomarkers, biological traits that are pathognomonic for specific neurological and neuropsychiatric disorders. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are imaging techniques used to identify alterations in the density and distribution of neurotransmitters, neuroreceptors, and transporters in specific regions of the brains of people with these disorders. Brain imaging research currently facilitates the elucidation of dysfunction of dopamine, serotonin, acetylcholine, and other substances in people with Alzheimer's and Parkinson's diseases, schizophrenia, alcoholism and other substance abuse disorders, attention deficit/hyperactivity disorder, and the syndromes of restless legs, Lesch-Nyhan, Rett, and Tourette. Thus, brain imaging research offers great potential for the diagnosis, treatment, prevention, and cure of neurological and neuropsychiatric disorders. Brain imaging research also facilitates new drug development and helps establish therapeutic doses of novel drugs. In particular, studies of specific receptors, such as the dopamine D2 receptor, before and after the administration of doses of drugs that occupy these D2 receptors, provide the means to determine receptor occupancy. For example, an optimal dose of D2 antagonist antipsychotics produces occupancy of 65% to 80% of D2 receptors, while a greater dose carries a risk of extrapyramidal side effects.

Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients

Perphenazine, a classical antipsychotic drug, has the potential to induce extrapyramidal side effects (EPS). Dopaminergic and serotonergic pathways are involved in the therapeutic and adverse effects of the drug. To evaluate the impact of polymorphisms in the dopamine D(2) and D(3) and serotonin 2A and 2C receptor genes (DRD2, DRD3, HTR2A, and HTR2C) on short-term effects of perphenazine monotherapy in schizophrenic patients. Forty-seven Estonian inpatients were evaluated before and after 4-6 weeks of treatment by Simpson-Angus rating scale, Barnes scale, and Positive and Negative Symptom Scale. Genotyping was performed for common DRD2, DRD3, HTR2A, and HTR2C gene polymorphisms, previously reported to influence receptor expression and/or function. Most of the patients (n = 37) responded to the treatment and no significant association was observed between the polymorphisms and antipsychotic response. The 102C allele of HTR2A and the -697C and 23Ser alleles of HTR2C were more frequent among patients with EPS (n = 25) compared to patients without EPS (n = 22) (p = 0.02, 0.01, and 0.02, respectively). The difference between patients with and without EPS in variant allele frequencies remained significant after multiple model analyses including age, gender, and duration of antipsychotic treatment as covariants. There was no significant association between EPS occurrence and polymorphisms in the DRD2 and DRD3 genes. An association was observed between polymorphisms in HTR2A and HTR2C genes and occurrence of acute EPS in schizophrenic patients treated with perphenazine monotherapy. Larger study populations are needed to confirm our findings.

Tardive Dyskinesia Circa 2006

Tardive Dyskinesia Circa 2006

Quetiapine-induced neuroleptic malignant syndrome in dementia with Lewy bodies: A case report

Patients with dementia with Lewy bodies (DLB) are particularly vulnerable to adverse effects of neuroleptics; this sensitivity is included among the clinical diagnostic criteria for DLB. Recently atypical neuroleptics, which carry less risk of extrapyramidal side effects than typical agents, have come into increasing use in treating psychotic symptoms and behavioral disturbances related to DLB. The present report is the first to describe a DLB patient who developed neuroleptic malignant syndrome (NMS) induced by quetiapine, an atypical neuroleptic known to have relatively infrequent extrapyramidal side effects in DLB patients. Physicians should be aware of the possibility of the occurrence of NMS in DLB even when atypical neuroleptics are administered.