Severity Of Extrapyramidal Side Effects Research Articles

Histone deacetylase 1 regulates haloperidol-induced motor side effects in aged mice

BackgroundAntipsychotic drugs prescribed to elderly patients with neuropsychiatric disorders often experience severe extrapyramidal side effects. Previous studies from our group suggest that changes in histone modifications during aging increase the risk for antipsychotic drug side effects, because co-administration of antipsychotics with class 1 histone deacetylase (HDAC) inhibitors could mitigate the severity of motor side effects in aged mice. However, which HDAC subtype contributes to the age-related sensitivity to antipsychotic drug side effects is unknown. MethodsIn this study, we overexpressed histone deacetylase type 1(HDAC1) in the striatum of 3-month-old mice and knocked down HDAC 1 in the striatum of 21-month-old mice by microinjection of AAV9-HDAC1-GFP or AAV9-CRISPR/Cas9-HDAC1-GFP vectors. Four weeks after the viral-vector delivery, the typical antipsychotic drug haloperidol was administered daily for 14 days, followed by motor function assessments through the open field, rotarod, and catalepsy behavioral tests. ResultsYoung mice with overexpressed HDAC1 showed increased cataleptic behavior induced by haloperidol administration, which is associated with the increased HDAC1 level in the striatum. In contrast, aged mice with HDAC1 knocked down rescued locomotor activity, motor coordination, and decreased cataleptic behavior induced by haloperidol administration, which is associated with decreased HDAC1 level in the striatum. ConclusionsOur results suggest that HDAC1 is a critical regulator in haloperidol-induced severe motor side effects in aged mice. Repression of HDAC1 expression in the striatum of aged mice could mitigate typical antipsychotic drug-induced motor side effects.

The ANKK1/DRD2 gene TaqIA polymorphism (rs1800497) is associated with the severity of extrapyramidal side effects of haloperidol treatment in CYP2D6 extensive metabolizers with schizophrenia spectrum disorders.

Extrapyramidal symptoms (EPS) are one of the most prominent side effects of haloperidol. Variability of EPS severity may be associated with the genetic factors, affecting both haloperidol pharmacokinetics (e.g., CYP2D6) and pharmacodynamics (e.g., DRD2, ANKK1). We conducted a 3-week prospective study to investigate the associations of ANKK1/DRD2 TaqIA (rs1800497), DRD2-141C Ins/Del (rs1799732) polymorphisms and CYP2D6 metabolic phenotype on the efficacy of haloperidol treatment and severity of EPS in patients with schizophrenia spectrum disorders. In total, 57 inpatients with schizophrenia spectrum disorders (24 (42.1%)) females; age-46.7 (11.8) years (M(SD)) of European ancestry were enrolled. BARS and SAS scales were used to assess EPS. PANSS and CGI scales- to assess the efficacy of haloperidol treatment. Genotyping was performed by real-time PCR. CYP2D6 metabolic phenotype was predicted by the CYP2D6 *3, *4, *5, *6, *9, *10, *41 and xN genotypes. Minor C allele of TaqIA was associated with higher scores of BARS (p=0.029) and SAS (p=0.024) on day 21 and minor Del allele of-141C Ins/Del- with more prominent clinical improvement by CGI scale (p=0.007) but not by PANSS. These differences were observed only in extensive CYP2D6 metabolizers, although no associations with the metabolic type itself were found. General linear model showed that the combination of TaqIA genotype and metabolic type was significantly associated with BARS score on day 21 (p=0.013). Our results highlight the importance of using both pharmacokinetic and pharmacodynamic genetic markers for predicting haloperidol treatment response to personalize schizophrenia spectrum disorders treatment.

Methylenetetrahydrofolate dehydrogenase-1 (MTHFD1) 1958 G>A genetic polymorphism (rs2236225) is associated with lower schizophrenia risk: Preliminary study

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the methylenetetrahydrofolate dehydrogenase-1 (MTHFD1) 1958 G>A polymorphism in this disorder is still poorly understood. The aim of this study was to assess the distribution of MTHFD1 1958 G>A allele and genotype frequencies in patients with schizophrenia and healthy controls. Also, we aimed to study the association of allele/genotype carriage of this single nucleotide polymorphism (SNP) with biochemical markers of the one-carbon metabolism (OCM) and with the severity of schizophrenia symptoms. Methods: The carriage of MTHFD1 1958 G>A alleles/genotypes were evaluated in 116 patients with schizophrenia and 62 healthy volunteers. Biochemical markers of OCM were studied in 89 patients and 59 volunteers. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG/AA: χ2 = 5.34; p = 0.021). A higher level of cobalamin in carriers of the wild GG genotype may indicate competitive inhibition of methylation processes in carriers of this genotype, which requires further study.

TPC2 targeting evolution: Leveraging therapeutic opportunities for cancer

Growing evidence implicates a vital role for TPC2/Ca2+ signaling in pathophysiological processes attributed to cancer, raising questions regarding the utility of TPC2 as a cancer therapeutic target. In this issue of Cell Chemical Biology, Müller etal. (2021) develop TPC2 inhibitors, SG005 and SG-094, exhibiting anti-tumor effects with potential translational relevance.

The DRD2/ANKK1 Taq1A polymorphism in CYP2D6 extensive metabolizers is associated with the severity of extrapyramidal side effects of haloperidol treatment in schizophrenia spectrum disorders patients

IntroductionSchizophrenia is one of the most severe mental disorders. Haloperidol and other first-generation antipsychotics are widely used for schizophrenia treatment, but have prominent side effects, primarily extrapyramidal symptoms (EPS). The EPS severity is highly variable and may be underlied by genetic factors.ObjectivesWe performed a prospective study to test the association of DRD2/ANKK1 Taq1A polymorphism (rs18000497) and CYP2D6 phenotype, predicted from genotypes using 8 CYP2D6 alleles (*3, *4, *5, *6,*9, *10,*41, xN) with EPS severity during haloperidol treatment in schizophrenia spectrum disorders patients.Methods57 inpatients with schizophrenia spectrum disorders (42,1% females; mean age - 46,7±11,8 y.o (M±SD) of European ancestry were enrolled in the study. Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Simpson-Angus Scale (SAS) were used to assess EPS on two timepoints: day 1 and day 21 of haloperidol treatment.ResultsTaqIA T-allele carriers in contrast to wild-type allele homozygous patients had higher scores of BARS (p=0.029) and SAS (p=0.024) on day 21. After stratification by CYP2D6 phenotype, these differences were observed only in extensive metabolizers (p=0.006 and p=0.001 respectively), although the CYP2D6 phenotype itself was not associated with EPS severity. The combined effect of TaqIA T allele with CYP2D6 extensive phenotype on BARS score on day 21 was confirmed by General Linear Model (p=0.013).ConclusionsOur results show that minor TaqIA T-allele is associated with the severity of EPS after 3 weeks of haloperidol treatment only in CYP2D6 extensive metabolizers. That highlights the importance of using both pharmacokinetic and pharmacodynamic genetic markers in pharmacogenetic EPS risk assessment.DisclosureNo significant relationships.

The interaction of folate cycle enzyme genes and the risk of extrapyramidal side effects of antipsychotics

Personalized medicine means the selection of therapy for patients, taking into account the assessment of genetic risk factors for side effects. A number of studies show that folate metabolism disorders, including single nucleotide polymorphisms (SNPs) in the genes of folate-metabolizing enzymes, are more frequently detected in schizophrenic patients than in the general population. The role of SNPs of the key folate cycle enzymes in developing the extrapyramidal side effects of antipsychotics has not yet been studied, although there is evidence of their association with other movement disorders.Objective: to analyze the association between the carriage of SNP alleles of MTHFR 677C>T, MTR 2756A>G, and MTRR 66A>G and the severity of extrapyramidal side effects of antipsychotics in patients with schizophrenia.Patients and methods. The investigation included 61 patients with schizophrenia (according to the criteria for ICD-10 Code F20). All the patients took antipsychotics for at least 7 hospital days were examined using real-time polymerase chain reaction (PCR) with allele-specific primers, followed by detection for the carriage of SNP alleles of MTHFR 677C>T, MTR 2756A>G, and MTRR 66A>G. The standardized Simpson–Angus scale (SAS) was used to evaluate the severity of extrapyramidal symptoms; the PCR test results were unknown during their examination.Results and discussion. In the patients carrying a low-functional 677 T allele in the gene of the key folate cycle enzyme MTHFR, the severity of extrapyramidal side effects of antipsychotics was statistically significantly higher than in the carriers of the wild-type genotype: 13.27±5.10 versus 9.84±6.03 SAS scores, respectively (t=-2.40; p=0.020). In addition, the carriage of the wild allele A of SNP in the MTRR 66A>G gene (F=3.83; p=0.0283; pcorr.=0.043) is associated with the severity of extrapyramidal symptoms. There was a direct moderate correlation of the number of risk alleles at two loci with the total SAS score (r=0.51; p=0.00017).Conclusion. The polymorphic allele of MTHFR 677T and the wild allele of MTRR 66A can be regarded as risk alleles for the development of extrapyramidal side effects of antipsychotics.

Association of MTHFR 677C > T genetic polymorphism with extrapyramidal side effects of antipsychotic treatment

Several studies have revealed a positive association between methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphism 677C > T and schizophrenia. In T-allele carriers the functional activity of MTHFR is reduced contributing to hyperhomocysteinemia development, methionine deficiency and as a consequence - redox dysregulation and the alteration of dopamine synthesis. The aim of this study was to investigate the association of MTHFR677C > T with the severity of extrapyramidal side effects of antipsychotics in schizophrenia. The average score on the Simpson-Angus scale (SAS) in a group of patients with MTHFR 677 T-allele (n = 30; 13.27 ± 5.10, M ± SD) was statistically significantly higher (t = −2.40; p = 0.02) than in the comparison group of wild genotype MTHFR 677 CC carriers (n = 31; 9.84 ± 6.03, M ± SD), confirming the working hypothesis about a possible association of the MTHFR677 T-allele carriage with the development of extrapyramidal side effects of antipsychotics.

Psychopathology and extrapyramidal side effects in smoking and non-smoking patients with schizophrenia: Systematic review and meta-analysis of comparative studies

The association between smoking and psychopathology and extrapyramidal side effects (EPSE) in schizophrenia has been controversial. This systematic review and meta-analysis compared psychopathology and EPSE between smoking and non-smoking schizophrenia patients. The PubMed, EMBASE, PsycINFO, Cochrane Library, and Web of Science databases were independently and systematically searched by two researchers to identify relevant articles. Standardized mean differences (SMDs) and their 95% confidence intervals (CI) were calculated with random effect models. Subgroup and meta-regression analyses were performed to explore sources of heterogeneity. The systematic review and meta-analysis included 29 studies that compared psychotic, depressive and anxiety symptoms and EPSE between smoking (n = 3591) and non-smoking schizophrenia patients (n = 2980). Smoking patients had significantly more severe positive symptoms (24 studies; SMD = 0.33, 95% CI: 0.16 to 0.50, P < 0.001), but less severe EPSE (7 studies; SMD = −0.20, 95% CI: −0.38 to −0.02, P = 0. 03). No significant group differences in negative, depressive and anxiety symptoms were found. In conclusion, this systematic review and meta-analysis found that smoking schizophrenia patients had more severe positive symptoms but less severe EPSE than non-smoking patients.

Extended-release of chlorpromazine intercalated into montmorillonite clays

Drugs are rarely defined by a single act in a disease treatment but often elicit a cure with few side effects. In this respect, recent clinical analyses of treatment with antipsychotic drugs such as chlorpromazine (CPZ) show that high dose of CPZ leads to severe extrapyramidal side effects. To address the incidence of these side effects, CPZ was incorporated into montmorillonite (MMt) clay in order to gradually release it over a prolonged period. As a consequence of a lamellar structure and biocompatibility, MMt is mainly used as nanocarrier for the controlled release of several chemical drugs. XRD, FT-IR, DSC-TGA and SEM techniques were used to characterize the structure of the prepared formulation, all confirming the successful intercalation of CPZ into MMt interlayer spaces. The potential application was verified through release of CPZ from CPZ/MMt formulation. The drug release profile indicated that the release of the intercalated CPZ was slower than the release of the CPZ lonely (pure). The presence of the MMt clay in CPZ/MMt capsule beads reduced the release rate and upheld the sustained release of the model drug for a longer period. To elucidate the release mechanism of CPZ from CPZ/MMt formulation, the release data were subjected to release kinetic. Thus, the results suggested the feasibility of the use of MMt clay materials for controlled manner of drugs, and thereby, a sustained release is favorable and side effects reduced.

Neuroleptic malignant syndrome: a case responding to electroconvulsive therapy plus bupropion.

Neuroleptic malignant syndrome (NMS) is a severe motor syndrome occurring as a consequence of neuroleptic treatment. We present a case of a 67-year-old Caucasian woman with a history of a major depressive disorder with psychotic features. During her third hospital admission, symptoms of autonomic instability, hyperpyrexia, severe extrapyramidal side effects, and delirium appeared, suggesting NMS due to concomitant treatment with risperidone and quetiapine, among other drugs. Despite several consecutive pharmacological treatments (lorazepam, bromocriptine and amantadine) and prompt initiation of electroconvulsive therapy (ECT), clinical improvement was observed only after combining bupropion with ECT. The symptoms that had motivated the admission gradually remitted and the patient was discharged home. Bupropion increases dopaminergic activity in both the nucleus accumbens and the prefrontal cortex. Therefore, from a physiopathological standpoint, bupropion has a potential role in treating NMS. However, there is scarce evidence supporting this approach and therefore future cases should be carefully considered.

Experimental treatment of antipsychotic-induced movement disorders.

Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs.

Clozapine prescription and quality of life in Chinese patients with schizophrenia treated in primary care.

Clozapine is frequently used to treat schizophrenia in China. Maintenance treatment for clinically stable patients with schizophrenia is usually provided by Chinese primary care physicians, but no study has investigated the frequency of its use prescribed by primary care physicians. This study described the frequency, demographic and clinical characteristics of clozapine treatment and its impact on insight and quality of life (QOL) of patients with schizophrenia treated in primary care in China. A total of 623 patients with schizophrenia treated in 22 primary care services in Guangzhou, China in 2013 formed the study sample. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects and QOL were recorded using a standardized protocol and data collection. The frequency of clozapine prescription was 35.6% with a mean daily dose of 127.7±88.2 mg. There were no significant differences between the patients with and without clozapine in either of the QOL domains after controlling the confounding factors. Multiple logistic regression analyses revealed that patients on clozapine had younger age of onset, more hospitalizations, more severe extrapyramidal side effects, but better insight and fewer prescriptions of first generation antipsychotics. Clozapine use was found to be common and associated with better insight in patients with schizophrenia treated in primary care in China. Further examination of the rationale and appropriateness of clozapine in primary care in China is warranted.

A Case of Acute Disseminated Encephalomyelitis Disguised as Mania in a Woman With Known Bipolar Disorder

Back to table of contents Previous article Next article LettersFull AccessA Case of Acute Disseminated Encephalomyelitis Disguised as Mania in a Woman With Known Bipolar DisorderDenise Cupina, and Brooke ShortDenise CupinaSearch for more papers by this author, and Brooke ShortSearch for more papers by this authorPublished Online:1 Apr 2012https://doi.org/10.1176/appi.neuropsych.11060118AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Acute disseminated encephalomyelitis (ADEM) is a rare acute widespread demyelinating condition affecting brain and spinal cord.1 It is characterized by multiple white matter lesions present on neuroimaging studies.1 The clinical manifestations vary widely and usually include a combination of neurological and psychiatric symptoms, however a predominantly psychiatric presentation is possible.2, 3Bipolar disorder is an affective disorder (BPAD) characterized by distinctive episodes of depression and mania with or without psychotic symptoms and full interepisode recovery.4We report a case of a woman with history of bipolar disorder who developed ADEM which presented clinically very similarly to a manic episode initially indistinguishable from her pre-existing psychiatric condition.A 31 year old woman with bipolar disorder was admitted with a relapse of manic symptoms. On admission, her physical examination, baseline blood tests and urine drug screen were unremarkable. She was recommenced on lithium and quetiapine but continued to present as elevated, highly labile and irritable despite restarting her usual treatment. After five weeks she achieved only partial resolution of symptoms, in contrast to her previous manic episodes that had resolved within a few weeks. Her medication was gradually changed to sodium valproate and risperidone, to which she developed severe extrapyramidal side effects. Risperidone was thus changed to olanzapine. Her mental state continued to fluctuate with evidence of disorientation, confusion and fluctuating attentiveness. A full neurological exam found no specific abnormalities other than parkinsonian signs. Neuroleptic malignant syndrome was considered but excluded due to normal serum creatine kinase, absence of pyrexia and autonomic instability. Her white cell count was mildly elevated with neutrophilia, but no infective focus was detected. Electroencephalogram was normal. Upon further questioning of family members history of an observed seizure prior to initial admission was obtained. An urgent magnetic resonance image (MRI) of her brain was arranged showing multiple areas of increased signal intensity on T2/FLAIR images in periventricular, subcortical, and brainstem regions bilaterally with no enhancement post-gadolinium.The patient was transferred urgently to the neurology ward. A lumbar puncture was conducted which found no abnormalities. Oligoclonal bands were positive in cerebrospinal fluid only. Serology testing and autoimmune markers were negative. A diagnosis of ADEM was made. The patient was commenced on IV Ceftriaxone and Methylprednisolone. Her delirium resolved but she continued to have residual mood and psychotic symptoms that took several weeks to improve. Her follow up brain MRI scan performed two months after the symptoms onset was unchanged. She was discharged home with a scheduled follow up appointment in the neurology outpatient clinic.Our patient developed ADEM that was initially diagnosed and treated as a relapse of bipolar disorder. ADEM can mimic various psychiatric disorders3 making its diagnosis in psychiatric patients extremely difficult. This case highlights the importance of taking a detailed neurological and medical history in every patient presenting with psychiatric symptoms. It additionally emphasizes the significance of recognizing atypical clinical features, such as poor response to usual treatment, increased sensitivity to medication side effects, changeable presentation and onset of delirium indicating organic rather than purely psychiatric aetiology.References1 Garg RK: Acute disseminated encephalomyelitis. Postgrad Med J 2003; 79:11–17Crossref, Medline, Google Scholar2 Patel SP, Friedman RS: Neuropsychiatric features of acute disseminated encephalomyelitis: a review. J Neuropsychiatry Clin Neurosci 1997; 9:534–540Link, Google Scholar3 Habek M, Brinar M, Brinar VV, et al.: Psychiatric manifestations of multiple sclerosis and acute disseminated encephalomyelitis. Clin Neurol Neurosurg 2006; 108:290–294Crossref, Medline, Google Scholar4. Kaplan HI, sadock BJ: Mood disorders. Kaplan and Sadock’s Synopsys of Psychiatry, 10th Edition, Sydney, Lippincott Williams & Wilkins 2077:527–578Google Scholar FiguresReferencesCited byDetailsCited ByAcute demyelinating encephalomyelitis presenting with psychiatric symptoms5 November 2013 | International Journal of Geriatric Psychiatry, Vol. 28, No. 12 Volume 24Issue 2 Spring 2012Pages E18-E18 Metrics PDF download History Published online 1 April 2012 Published in print 1 April 2012

Successful Use of Quetiapine in Two Successive Pregnancies

Back to table of contents Previous article Next article LettersFull AccessSuccessful Use of Quetiapine in Two Successive PregnanciesSandeep Grover, M.D., and Rohit Madan, M.D.Sandeep GroverSearch for more papers by this author, M.D., and Rohit MadanSearch for more papers by this author, M.D.Published Online:1 Jan 2012https://doi.org/10.1176/appi.neuropsych.11020053AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Ethically, it is not possible to conduct randomized, controlled trials in pregnant women; hence, most of the data with respect to use of quetiapine in pregnancy is in the form of case reports, case series, and only few studies have reported its effect on pregnancy.1 However, there are no data with respect to use of quetiapine in successive pregnancies. We report on a patient who received quetiapine throughout two successive pregnancies.Case ReportsA 24-year-old woman who was premorbidly well-adjusted presented with an insidious-onset illness of 3 months' duration, with symptoms of catatonic schizophrenia. Her blood count, blood biochemistry, serum electrolytes, liver function tests, renal function test, chest X-ray (PA view), computerized tomography of the brain, and ECG did not reveal any abnormality. She was initially treated with ECT and tablet risperidone. She developed severe extrapyramidal side effects with risperidone and had to be shifted to quetiapine, which was gradually increased to 250 mg/day. With quetiapine and ECT, she showed significant improvement in symptoms. We explained to the patient and her husband about the contraceptive measures to be taken while she was on quetiapine. When on quetiapine for about 6 months, the patient conceived for the first time. Throughout the pregnancy, patient received quetiapine 250 mg/day, along with folic acid and iron supplementation. She was monitored closely and underwent regular ultrasonography. At full term, she gave birth to a healthy female child weighing 2.5 kg. The patient nursed the child during the postpartum period without any complications. She conceived again after about a year and again continued taking quetiapine 250 mg/day throughout the pregnancy. As in the previous pregnancy, the patient was closely monitored and she again delivered a healthy female child, weighing 2.4 kg, and continued breast-feeding for 6 months. Both the daughters were healthy, the first one about 2 years old and the second one about 9 months at the last assessment.DiscussionMost of data available with respect to exposure of quetiapine during pregnancy does not suggest major malformation or neonatal problems. Data maintained by the manufacturer and as reported by McKenna et al.2 as of March 2005, 446 pregnancies were exposed to quetiapine, and outcome was available for 151, of which congenital malformations were seen in 8 pregnancies, all of which were different from one another. In 7 out of the 8 cases of congenital anomaly, the women were also receiving other medications during pregnancy. McKenna et al.2 also reported the outcome of 36 pregnancies exposed to quetiapine and concluded that, compared with a control group of women exposed to non-teratogenic agents, quetiapine was not associated with an increase in teratogenic risk. There are limited data with respect to use of atypical antipsychotics in successive pregnancies. We could only find two case reports, one of which described exposure to clozapine,3 and another, to risperidone.4 Until now, no study or case report has reported successful use of quetiapine in two successive pregnancies. Our case suggests that quetiapine in low dose can be used safely in pregnancy.Dept. of PsychiatryPostgraduate Institute of Medical Education & ResearchChandigarh, IndiaCorrespondence: Dr. Sandeep Grover; e-mail: [email protected]com1. Gentile S : Antipsychotic therapy during early and late pregnancy: a systematic review. Schizophr Bull 2010; 36:518–544Crossref, Medline, Google Scholar2. McKenna K , Koren G , Tetelbaum M : Pregnancy outcome of women using atypical antipsychotic drugs: a prospective, comparative study. J Clin Psychiatry 2005; 66:444–449Crossref, Medline, Google Scholar3. Gupta N , Grover S : Safety of clozapine in two successive pregnancies. Can J Psychiatry 2004; 49:863Crossref, Medline, Google Scholar4. Mendhekar D , Lohia D : Risperidone therapy in two successive pregnancies. J Neuropsychiatry Clin Neurosci 2008; 20:485–486Link, Google Scholar FiguresReferencesCited byDetailsCited ByCNS Spectrums, Vol. 22, No. 3Basic & Clinical Pharmacology & Toxicology, Vol. 116, No. 4Journal of Obstetrics and Gynaecology, Vol. 35, No. 6Mood stabilizers in pregnancy and lactationIndian Journal of Psychiatry, Vol. 57, No. 6Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology, Vol. 24, No. 4Treatment Considerations for the Pregnant Adolescent with Bipolar DisorderChild and Adolescent Psychopharmacology News, Vol. 18, No. 4 Volume 24Issue 1 Winter 2012Pages E38-E38 Metrics PDF download History Published online 1 January 2012 Published in print 1 January 2012

Gender Differences in Sociodemographic and Clinical Characteristic and the Quality of Life of Chinese Schizophrenia Patients

The aim of the present study was to determine the sociodemographic and clinical correlates of the gender of Chinese schizophrenia outpatients and their impact on patients quality of life (QOL). Two hundred and fifty-five clinically stable schizophrenia outpatients were randomly selected in Hong Kong. Counterparts matched according to gender, age, age at onset, and length of illness were recruited in Beijing, China. All of the subjects at both sites were interviewed by the same investigator using standardized assessment instruments. The combined Beijing-Hong Kong sample contained 251 male and 254 female patients. On univariate analysis more male patients were employed, they had a significantly higher monthly income, and took higher doses of antipsychotic drugs. No difference was found, however, in any of the QOL domains between the genders. On multivariate analysis being employed, taking a higher dose of antipsychotic drugs, having more severe extrapyramidal side-effects, and a higher score on the physical domain of QOL were independently associated with male gender. Female gender is independently associated with lower scores on the physical aspects of QOL, but there is no difference between the genders in the psychological, social and environmental aspects.

Successful Retrial of ECT Two Months After ECT-Induced Takotsubo Cardiomyopathy

heart failure; however, recovery of cardiac function is often complete within the first week following the insult. Cardiac enzymes may be mildly elevated, but on cardiac catheterization there is usually no evidence of coronary artery disease, or only "mild luminal irregularities" may be noted (7). Contraction band necrosis may be seen on biopsy in the more serious cases. The cause of takotsubo cardiomyopathy is unknown, but several mechanisms have been suggested, including ischemia from coronary artery spasm, microvascular spasm, and direct myocyte injury (5).

ORAL MIDAZOLAM FOR DEMENTIA‐RELATED RESPONSE AGITATION

To the Editor: Patients with moderate to severe dementia commonly develop agitation and aggression in response to personal care. Response agitation is a distressing problem that can endanger the patient and caregivers and that often persists despite identification and correction of factors that trigger the agitation. Behavioral and environmental strategies to manage dementia-related response agitation are often ineffective, and medications commonly used to manage dementia-related response agitation are increasingly being found to have specific risks in patients with dementia. Although often effective for short-term management of severe agitation, use of antipsychotic medications in patients with dementia has been associated with risk of serious adverse effects, including stroke,1 pneumonia,2 and death.1 Among other risks, benzodiazepine use in patients with dementia often causes daytime oversedation owing to the half-life of even commonly used short-acting agents (lorazepam, 9–16 hours; oxazepam, 4–14 hours; temazepam, 8–20 hours).3 Regular use of antipsychotic medications or benzodiazepines such as lorazepam for the management of dementia-related response agitation is therefore often unsafe and impractical. The case of a patient suffering from severe dementia with refractory response aggression that remitted with the use of oral midazolam is presented. A 93-year-old woman with a history of dementia of the Alzheimer's type in the severe stages was admitted to a geriatric psychiatry ward for assessment and management of severe aggression and agitation during personal care. The patient presented with extended care needs; she was unable to walk or transfer independently, requiring total assistance for basic activities of daily living, and flexion contractures had developed in her arms and legs. She directed severe agitation and aggression toward nursing staff during toileting, bathing, and transfers but remained calm when unattended during the remainder of the day and slept well most nights. Rigorous nursing care planning and environmental and behavioral management strategies were ineffective. Identification and treatment of potential triggers such as pain failed to extinguish the agitation and aggression. Management of pain included injection of flexion contractures with Botox by a physiatrist and gabapentin titrated up to the maximum tolerated dose (600 mg twice a day) in addition to regular dosing of acetaminophen 1,000 mg every 6 hours. The patient had a disappointing response to pharmacotherapy specifically targeting response agitation. This included quetiapine up to 150 mg daily (ineffective and oversedating), citalopram up to 30 mg daily (ineffective), a low dose of zuclopenthixol (a 72-hour depot-typical antipsychotic; 5 mg intramuscularly) (caused severe extrapyramidal side-effects), pre-care lorazepam use at the minimum effective dose (caused 6–8 hours or more of daytime oversedation), and olanzapine (pre-care use was ineffective and oversedating). Midazolam oral solution was prepared at a concentration of 2 mg/mL. The dosage was started at 2 mg and titrated gradually (over the course of 2 weeks) up to 6 mg given 15 to 30 minutes before personal care or transfers. The patient's response agitation and aggression resolved with no consequent daytime oversedation, and all antipsychotics were discontinued. Midazolam3 is an ultra-brief-acting benzodiazepine with a half-life of 1.5 to 6 hours. It is commonly used for conscious sedation in emergency departments, in minor procedures such as endoscopy,4 and for uncooperative patients such as in pediatric dentistry.5 It has an oral bioavailability of 35% to 40% when given orally and greater than 90% when given parenterally. Parenteral routes are usually limited to emergency department and intensive care settings. Dosage reductions are required with parenteral administration. It undergoes hepatic metabolism and renal excretion. In this patient, the use of oral midazolam was associated with marked improvement in severe dementia-related response agitation. Based on this case study, preparation of a midazolam oral solution with a concentration of 2 to 3 mg/mL is recommended. Nursing staff should be requested to shake the solution to ensure proper constitution before administration. Starting at a dose of 1 to 2 mg given orally 15 to 30 minutes before personal care or transfers is suggested, titrating in increments of 1 to 2 mg as tolerated to induce the required level of sedation. It is anticipated that the usual effective dose would be in the range of 2 to 8 mg. Careful monitoring for respiratory depression is recommended, with a precaution to avoid administration of midazolam to patients with preexisting respiratory compromise, low baseline respiratory rate, or concurrent use of opioid-based medications. Midazolam-related oversedation can be reversed with the benzodiazepine inverse-agonist flumazenil. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this letter. Author Contributions: All the authors made substantial contributions to every aspect of this letter. Sponsor's Role: None.

Long-Term Use of Mood Stabilizers and Its Impact on the Quality of Life of Chinese Patients With Schizophrenia

To date, no studies have investigated the prescription patterns of mood stabilizers (MSs) in Chinese patients with schizophrenia. This study examined the frequency and sociodemographic and clinical correlates of MS prescription for outpatients with schizophrenia in Hong Kong (HK) and Beijing (BJ), China. Five hundred five clinically stable outpatients with schizophrenia were randomly selected and interviewed in HK and BJ using standardized assessment instruments. Basic sociodemographic and clinical data and psychotropic drug prescriptions were collected at the time of a diagnostic interview. Thirty-four (6.7%) of the patients were prescribed MSs in the whole sample, with 10.2% and 3.2% of the HK and BJ samples, respectively. Use of MSs was associated with a history of violence, number of admissions, and severity of extrapyramidal side effects. In multiple logistic regression analysis, number of admissions, study site, sex, and length of illness were significantly associated with MSs. Although the ethnic and clinical characteristics of the 2 samples were nearly identical, there was a wide variation in the frequency of MS prescriptions between HK and BJ.

Tardive Dyskinesia and the 3-Year Course of Schizophrenia

The objective of this study was to compare the 3-year course of schizophrenia between persons with tardive dyskinesia (TD) and persons without TD on multiple outcome measures. Data were drawn from a large, prospective, naturalistic study of persons treated for schizophrenia-spectrum disorders (DSM-IV criteria) in the United States, conducted between July 1997 and September 2003. Treatment outcomes were assessed at enrollment and at 12, 24, and 36 months postenrollment using measures of symptoms, functioning, productivity, activity, and quality of life. Participants who had TD at enrollment (fulfilling Schooler-Kane criteria, N = 637) were compared with those who did not (N = 1538) on clinical and functional measures at enrollment and across the 3 years of follow-up. Additional analyses examined those with persistent TD compared to those without persistent TD. With adjustment for known correlates of TD, participants with TD compared to those without TD had significantly more severe psychopathology, were less likely to experience symptom remission, had more severe extrapyramidal side effects, and had lower levels of quality of life and functioning, lower productivity, and fewer activities (all p < .001) across the 3-year follow-up. Findings were essentially unchanged when the subgroup of participants with persistent TD (at enrollment and at 1 year) was examined. These results indicate that, in the long-term treatment of schizophrenia, persons with TD have a significantly more severe and more refractory course of illness than those without TD, suggesting poorer prognosis and the need for specialized interventions.

The functionality and economic costs of outpatients with schizophrenia in Taiwan

The aims of this study were to investigate the economic costs of outpatients with schizophrenia in Taiwan, and to survey factors that influence the costs. The direct costs were defined as the costs associated with psychiatric services and other medical treatment. The indirect costs were estimated using the Human Capital Method. Patients' characteristics, including sex, age, duration of education, duration of illness, frequency of hospitalization, type of antipsychotic medication, severity of extrapyramidal side effects caused by antipsychotic medication, and global functions, were used to estimate the costs. The average annual total cost was approximately US$16,576 per patient. The direct and indirect costs were 13% and 87% of the total costs, respectively. Among the direct costs, folk therapy ranked third, just behind prescription drugs and acute ward hospitalization. The productivity loss of both the patients and their caregivers was the major component of the indirect costs. The patient's age and global functions had a significantly negative relationship with the direct costs. The severity of extrapyramidal side effects, type of antipsychotic medication, and the patient's illness duration correlated positively with the indirect costs, while the patient's global function correlated negatively with the indirect costs. Overall, the indirect costs of treating schizophrenia were higher than the direct costs. Improving patients' functionality and decreasing caregivers' burden are essential to reducing costs.