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Influence of DRD2 polymorphisms on the clinical outcomes of patients with schizophrenia

Zahari Z, Teh LK, Ismail R, Razali SM

Psychiatr Genet, 2011 Aug;21(4):183-9.
PMID: 21206399 DOI: 10.1097/YPG.0b013e3283437250

Variations in the gene for dopamine D2 receptor (DRD2) might have an influence on the outcome of antipsychotic treatment in schizophrenia. The objective of this study was to investigate the influence of DRD2 polymorphisms on treatment outcomes in patients with schizophrenia.

Matched MeSH terms: Schizophrenia/drug therapy*
Weight gain and first-generation antipsychotics: experience from a developing country

Yoon CK

J Clin Psychopharmacol, 2008 Oct;28(5):574-6.
PMID: 18794660 DOI: 10.1097/JCP.0b013e3181855cbc
Matched MeSH terms: Schizophrenia/drug therapy*
Brexpiprazole for the treatment of schizophrenia

Yee A

Expert Rev Neurother, 2016;16(2):109-22.
PMID: 26650624 DOI: 10.1586/14737175.2016.1129901

Brexpiprazole (OPC-34712) is a novel serotonin-dopamine activity modulator, which has recently been approved by the U.S Food and Drug Administration for the treatment of schizophrenia. The aim of this paper is to systematically synthesize all data of the efficacy, safety and tolerability of Brexpiprazole in treating schizophrenia. The terms 'Brexpiprazole', 'OPC-34712' and 'schizophrenia' were searched. A total of 12 clinical trials with 7 available data records were found. The pooled effect size of Brexpiprazole 1 mg, 2 mg and 4 mg were all superior to placebo in terms of the change from baseline in positive and negative syndrome scale (PANSS) total score at week 6 (weighted mean difference = -3.74, p = 0.044; weighted mean difference = -5.76, p schizophrenia. Brexpiprazole displays a good safety and tolerability profile. The incidence of akathisia, headache, insomnia, sedation, agitation, diarrhea, weight gained, nausea, and dyspepsia are comparable to placebo.

Matched MeSH terms: Schizophrenia/drug therapy*
Prescribing patterns of low doses of antipsychotic medications in older Asian patients with schizophrenia, 2001-2009

Xiang YT, Dickerson F, Kreyenbuhl J, Ungvari GS, Wang CY, Si TM, et al.

Int Psychogeriatr, 2012 Jun;24(6):1002-8.
PMID: 22300452 DOI: 10.1017/S1041610211002791

This study examined the use of low doses of antipsychotic medications (300 mg/day CPZeq or less) in older Asian patients with schizophrenia and its demographic and clinical correlates.

Matched MeSH terms: Schizophrenia/drug therapy*
Use of first- and second-generation antipsychotic medications in older patients with schizophrenia in Asia (2001-2009)

Xiang YT, Kreyenbuhl J, Dickerson FB, Ungvari GS, Wang CY, Si TM, et al.

Aust N Z J Psychiatry, 2012 Dec;46(12):1159-64.
PMID: 22790175 DOI: 10.1177/0004867412453625

This study examined the prescribing patterns of several first- (FGAs) and second-generation antipsychotic (SGAs) medications administered to older Asian patients with schizophrenia during the period between 2001 and 2009.

Matched MeSH terms: Schizophrenia/drug therapy*
Antipsychotic treatment in older schizophrenia patients with extrapyramidal side effects in Asia (2001 - 2009)

Xiang YT, Kreyenbuhl J, Dickerson FB, Ungvari GS, Wang CY, Si TM, et al.

Int J Clin Pharmacol Ther, 2012 Jul;50(7):500-4.
PMID: 22541750 DOI: 10.5414/CP201683

This study surveyed the prescribing patterns of antipsychotic medications in Asian older schizophrenia patients with extrapyramidal side effects (EPS) during the period between 2001 and 2009.

Matched MeSH terms: Schizophrenia/drug therapy*
Use of electroconvulsive therapy for Asian patients with schizophrenia (2001-2009): Trends and correlates

Xiang YT, Ungvari GS, Correll CU, Chiu HF, Lai KY, Wang CY, et al.

Psychiatry Clin Neurosci, 2015 Aug;69(8):489-96.
PMID: 25708964 DOI: 10.1111/pcn.12283

Little is known about electroconvulsive therapy (ECT) use in Asian inpatients with schizophrenia. This study examined trends of ECT use for schizophrenia patients in Asia between 2001 and 2009 and its independent demographic and clinical correlates.

Matched MeSH terms: Schizophrenia/drug therapy
Cost analysis of risperidone long-acting injection in the treatment of schizophrenia and schizoaffective disorders in Hong Kong: an approach using generalised estimating equations

Wu DB, Lee EH, Chung WS, Chow DP, Lee VW, Wong MC, et al.

Psychiatry Res, 2013 Dec 30;210(3):745-50.
PMID: 24012164 DOI: 10.1016/j.psychres.2013.07.012

Schizophrenia is one of the most expensive psychiatric illnesses. This study compared retrospectively health-care resources consumed 12 months before and 24 months after risperidone long-acting injection (RLAI) treatment in Hong Kong. A mirror-image analysis was conducted using data (N=191) from three public hospitals in Hong Kong from 2003 to 2007. The main outcome measure was hospitalisation cost. Other secondary outcomes such as hospitalisation episodes, outpatient visits and adverse events were also compared. A predictive model was established using linear regression based on generalised estimating equations. Analysis showed that RLAI was associated with a reduction in hospitalisation cost by HK$10,001,390 (24.7%) (HK$40,418,694 vs. HK$30,417,303; P-value <0.05). Days of hospitalisation were reduced by 1538 days (10.1%) (15,271 vs. 13,733; P-value <0.05). The predictive model estimated that the hospitalisation cost of patients using RLAI was only 11.1% (3.1-3.93%, 95% confidence interval (CI)) compared to those receiving conventional antipsychotics combined with oral risperidone. Cost of hospitalisation was significantly reduced after RLAI therapy. However, results should be considered as indicative or suggestive only, due to potential channelling bias where certain drug regimens are preferentially prescribed to patients with particular conditions. The findings from our study may be useful in health-care decision making considering treatment options for schizophrenia in resource-limited settings.

Matched MeSH terms: Schizophrenia/drug therapy*
Olanzapine-induced and Risperidone-induced Leukopenia: A Case of Synergistic Adverse Reaction?

Woon LS, Tee CK, Gan LLY, Deang KT, Chan LF

J Psychiatr Pract, 2018 Mar;24(2):121-124.
PMID: 29509183 DOI: 10.1097/PRA.0000000000000292

Leukopenia is a known hematological side effect of atypical antipsychotics. We report a case of an antipsychotic-naive patient with schizophrenia who developed leukopenia after a single dose of olanzapine, which worsened during subsequent treatment with risperidone. Normalization of the white blood cell counts occurred within 24 hours of risperidone discontinuation. Possible synergistic mechanisms underlying olanzapine-induced and risperidone-induced leukopenia are discussed. This case highlights the challenges in identifying and managing nonclozapine antipsychotic-induced leukopenia in a susceptible patient.

Matched MeSH terms: Schizophrenia/drug therapy*
The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness

Velligan DI, Weiden PJ, Sajatovic M, Scott J, Carpenter D, Ross R, et al.

J Clin Psychiatry, 2009;70 Suppl 4:1-46; quiz 47-8.
PMID: 19686636

OBJECTIVES: Poor adherence to medication treatment can have devastating consequences for patients with mental illness. The goal of this project was to develop recommendations for addressing adherence problems to improve patient outcomes.
METHODS: The editors identified important topics and questions concerning medication adherence problems in serious mental illness that are not fully addressed in the literature. A survey was developed containing 39 questions (521 options) asking about defining nonadherence, extent of adherence problems in schizophrenia and bipolar disorder, risk factors for nonadherence, assessment methods, and interventions for specific types of adherence problems. The survey was completed by 41 (85%) of the 48 experts to whom it was sent. Results of the literature review and survey were used to develop recommendations for assessing and improving adherence in patients with serious mental illness.
RESULTS: ASSESSING ADHERENCE: The experts endorsed percentage of medication not taken as the preferred method of defining adherence, with 80% or more of medication taken endorsed as an appropriate cut-off for adherence in bipolar disorder and schizophrenia. Although self- and physician report are the most common methods used to assess adherence in clinical settings, they are often inaccurate and may underestimate nonadherence. The experts recommend that, if possible, clinicians also use more objective measures (e.g., pill counts, pharmacy records, and, when appropriate, serum levels such as are used for lithium). Use of a validated self-report scale may help improve accuracy.
SCOPE OF THE PROBLEM: The majority of the experts believed the average patient with schizophrenia or bipolar disorder in their practices takes only 51%-70% of prescribed medication. FACTORS ASSOCIATED WITH NONADHERENCE: The experts endorsed poor insight and lack of illness awareness, distress associated with specific side effects or a general fear of side effects, inadequate efficacy with persistent symptoms, and believing medications are no longer needed as the most important factors leading to adherence problems in schizophrenia and bipolar disorder. The experts considered weight gain a side effect that is very likely to lead to adherence problems in patients with schizophrenia and bipolar disorder; sedation was considered a more important contributor to adherence problems in bipolar disorder than schizophrenia. The experts rated persistent positive or negative symptoms in schizophrenia and persistent grandiosity and manic symptoms in bipolar disorder as the most important symptomatic contributors to adherence problems in these illnesses.
INTERVENTIONS: It is important to identify the specific factors that may be contributing to a patient's adherence problems in order to customize interventions to target those problems. Multiple problems may be involved, requiring a combination of interventions.
CONCLUSIONS: Adherence problems are complex and multidetermined. The experts recommended customized interventions focused on the underlying causes.

Matched MeSH terms: Schizophrenia/drug therapy
New admissions to Woodbridge Hospital 1975 with special reference to schizophrenia

Tsoi WF, Chen AJ

Ann Acad Med Singap, 1979 Jul;8(3):275-9.
PMID: 547870

Woodbrige Hospital had 2,257 patients in 1975. Of these 75 percent were suffering from Schizophrenia. This pattern was similar to that of developing countries like Padistan and Malaya. A study was carried out on all new admissions in 1975. There were 1,068 patients whose age ranged from 10 to 89. Schizophrenia which constituted 62% of the cases was analysed in detail. They were mainly in the age range 10-29 (64%). The sex ratio was 3 males to 2 females. Their distribution by their type of housing was similar to that of the general populations. They were better educated. The most common presentation were reports of aggressive, violent, disturbed, abnormal or withdrawn behaviour. The 10 most common symptoms were paranoid ideas, hearing of voices, talking to oneself, insomnia, aggression, abnormal behaviour, laughing to oneself, disturbed behaviour, crying to oneself and withdrawn behaviour. The most common drugs used were trifluoperazine (47%) and chlorpromazine (45%). Electroconvulsive therapy was given to 25% of the patients. Most of the patients (63%) stayed less than 20 days.

Matched MeSH terms: Schizophrenia/drug therapy
Schizophrenia and Nicotine Dependence: What Psychopharmacological Treatment Options are Available for the Duo Perturbationes?

Theng YM, Wahab S, Wahab NAA, Sidi H, Das S

Curr Drug Targets, 2019;20(2):173-181.
PMID: 29046149 DOI: 10.2174/1389450118666171017163741

Nicotine dependence has progressively become a foremost community health interest in both the developed and developing nations due to the economic burden and health-related problems. Smoking was significantly higher among patients with schizophrenia in comparison to the general population. Nicotine dependence is not only associated with public stress, but among patients with schizophrenia, smoking brings major challenges to the management. Nicotine may diminish the therapeutic efficacy of the bioavailability of the psychopharmacological agents in-vivo. These duo perturbations, i.e. two clinical conditions co-existed may prevent psychotic symptoms remission among patients suffering from schizophrenia who smoke at the same time. The aim of this review was to highlight the role of pharmacological treatment options and strategies for patients with nicotine dependence in schizophrenia with emphasis on the underlying neurobiological process. The role of nicotine replacement therapy, i.e. norepinephrine-dopamine reuptake inhibition (NDRI) e.g. bupropion and selective partial agonist of α4β2 and full α7-nicotinic acetylcholine receptor e.g. varenicline was deliberated. An ideal choice of drug targets for patients with schizophrenia with nicotine dependence is pivotal to foster a better therapeutic alliance.

Matched MeSH terms: Schizophrenia/drug therapy*
Patterns of long acting injectable antipsychotic use and associated clinical factors in schizophrenia among 15 Asian countries and region

Tang CT, Chua EC, Chew QH, He YL, Si TM, Chiu HF, et al.

Asia Pac Psychiatry, 2020 Dec;12(4):e12393.
PMID: 32468725 DOI: 10.1111/appy.12393

INTRODUCTION: Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established.
METHODS: Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region.
RESULTS: Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications.
DISCUSSION: These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.

Matched MeSH terms: Schizophrenia/drug therapy*
Fulltext When all else fails: supervised treatment in outpatient for schizophrenia (STOPS)

Tan HJR

BMJ Case Rep, 2017 Sep 23;2017.
PMID: 28942410 DOI: 10.1136/bcr-2017-221518

This was about a case of a patient requiring admission to psychiatry ward twice a year for relapse schizophrenia due to medication non-compliance. Medication adherence was previously monitored by her husband. However, following the death of her husband, she stopped treatment. The lack of insight and poor family support further contributed to her relapse. She presented with positive and negative symptoms of schizophrenia during her relapse, neglecting her hygiene and oral intake. She was also found to have anaemia as a result of poor diet when she was in relapse. Community psychiatry services had attempted to ensure compliance with postdischarge plan but failed as patient was not present every home visits. Supervised treatment in outpatient for schizophrenia (STOPS) provided an alternative method to ensure compliance in this patient. Patient has remained in remission for 1 year since the use of STOPS.

Matched MeSH terms: Schizophrenia/drug therapy
Oculogyric spasm in Asian psychiatric in-patients on maintenance medication

Tan CH, Chiang PC, Ng LL, Chee KT

Br J Psychiatry, 1994 Sep;165(3):381-3.
PMID: 7994510

BACKGROUND: The objective was to investigate the occurrence and characteristics of oculogyric spasm (OGS) in an Asian country.
METHOD: All 2035 Asian (88% Chinese, 7% Malays and 5% Indonesians) psychiatric in-patients in the state psychiatric hospital in Singapore were surveyed for occurrence of oculogyric spasm (OGS) over a two-month period.
RESULTS: Thirty-four patients (1.7%) developed OGS (53% male and 47% female). All the 34 patients had been on maintenance antipsychotic drugs for more than five months. Eighteen patients had recurrent attacks. The mean chlorpromazine equivalent daily dose for those patients with recurrent OGS was 511 mg. This was significantly higher (P < 0.05) than the 277 mg daily dose received by those without recurrent OGS. Most (68%) of the attacks occurred between 1400-2000 h suggesting that OGS may have a diurnal variation.
CONCLUSIONS: OGS presenting as tardive dystonia may be due to a relative increase in cholinergic activity.

Matched MeSH terms: Schizophrenia/drug therapy*
Clinical evaluation and serum concentration of zuclopenthixol acetate in psychotic Asian patients: a single-dose preliminary study

Tan CH, Low BL, Ng LL, Khoo YM, Lee HS

Ther Drug Monit, 1993 Apr;15(2):108-12.
PMID: 8099240

Nineteen acutely disturbed psychotic Asian patients were treated with a single intramuscular injection of 50 mg of zuclopenthixol acetate in Viscoleo. Patients were assessed clinically before and after treatment using the Brief Psychiatric Rating Scale (BPRS). Serum zuclopenthixol and the inactive geometric isomer trans(E)-clopenthixol were determined by high-performance liquid chromatography after intramuscular injection. All patients improved, with the BPRS being significantly reduced (p < 0.001) at 72 h after injection. Adverse effects were generally few. The mean +/- SEM serum zuclopenthixol concentrations at 24, 48, and 72 h were 19.9 +/- 2.8, 31.5 +/- 4.5, and 17.8 +/- 2.9 micrograms/L, respectively. trans(E)-Clopenthixol concentrations ranged from negligible to 39.5 micrograms/L. This study confirms that a single intramuscular injection of 50 mg is adequate for managing severely disturbed psychotic patients for the first 3 days. The serum zuclopenthixol concentrations attained in the Asian patients were higher than those reported in Caucasian psychiatric patients. In some patients, a considerable amount of zuclopenthixol had been transformed to trans(E)-clopenthixol.

Matched MeSH terms: Schizophrenia/drug therapy
Adjunctive mood stabilizer treatment for hospitalized schizophrenia patients: Asia psychotropic prescription study (2001-2008)

Sim K, Yong KH, Chan YH, Tor PC, Xiang YT, Wang CY, et al.

Int. J. Neuropsychopharmacol., 2011 Oct;14(9):1157-64.
PMID: 21557883 DOI: 10.1017/S1461145711000563

Recent studies indicate relatively high international rates of adjunctive psychotropic medication, including mood stabilizers, for patients with schizophrenia. Since such treatments are little studied in Asia, we examined the frequency of mood-stabilizer use and its clinical correlates among hospitalized Asian patients diagnosed with schizophrenia in 2001-2008. We evaluated usage rates of mood stabilizers with antipsychotic drugs, and associated factors, for in-patients diagnosed with DSM-IV schizophrenia in 2001, 2004 and 2008 in nine Asian regions: China, Hong Kong, India, Korea, Japan, Malaysia, Taiwan, Thailand, and Singapore. Overall, mood stabilizers were given to 20.4% (n=1377/6761) of hospitalized schizophrenia patients, with increased usage over time. Mood-stabilizer use was significantly and independently associated in multivariate logistic modeling with: aggressive behaviour, disorganized speech, year sampled (2008 vs. earlier), multiple hospitalizations, less negative symptoms, younger age, with regional variation (Japan, Hong Kong, Singapore>Taiwan or China). Co-prescription of adjunctive mood stabilizers with antipsychotics for hospitalized Asian schizophrenia patients increased over the past decade, and was associated with specific clinical characteristics. This practice parallels findings in other countries and illustrates ongoing tension between evidence-based practice vs. individualized, empirical treatment of psychotic disorders.

Matched MeSH terms: Schizophrenia/drug therapy*
Metabolic syndrome and antipsychotic monotherapy treatment among schizophrenia patients in Malaysia

Said MA, Hatim A, Habil MH, Zafidah W, Haslina MY, Badiah Y, et al.

Prev Med, 2013;57 Suppl:S50-3.
PMID: 23337566 DOI: 10.1016/j.ypmed.2013.01.005

OBJECTIVE: The objective of this study is to determine the prevalence of metabolic syndrome among schizophrenia patients receiving antipsychotic monotherapy in Malaysia.
METHOD: A cross-sectional study was conducted at multiple centres between June 2008 and September 2011. Two hundred and five patients who fulfilled the DSM IV-TR diagnostic criteria for schizophrenia and who had been on antipsychotic medication for at least one year, were screened for metabolic syndrome. Patients receiving a mood stabilizer were excluded from the study. Metabolic syndrome was defined by using the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Treatment Panel III (ATP III) modified for Asian waist circumference.
RESULTS: In the first-generation antipsychotic (FGA) group, the highest prevalence of metabolic syndrome was among patients treated with trifluoperazine and flupenthixol decanoate (66.7% each). For the second-generation antipsychotic (SGA) group, the highest prevalence of metabolic syndrome was among patients treated with clozapine (66.7%). The component with the highest prevalence in metabolic syndrome was waist circumference in both FGA and SGA groups except for aripiprazole in SGA.
CONCLUSION: The prevalence of metabolic syndrome in schizophrenia patients receiving antipsychotic monotherapy in Malaysia was very high. Intervention measures are urgently needed to combat these problems.
KEYWORDS: Antipsychotics; Metabolic syndrome; Monotherapy; Prevalence; Schizophrenia

Matched MeSH terms: Schizophrenia/drug therapy*
Fulltext Metabolic syndrome and cardiovascular risk among patients with schizophrenia receiving antipsychotics in Malaysia

Said MA, Sulaiman AH, Habil MH, Das S, Bakar AK, Yusoff RM, et al.

Singapore Med J, 2012 Dec;53(12):801-7.
PMID: 23268153

INTRODUCTION:This study aimed to determine the prevalence of metabolic syndrome and risk of coronary heart disease (CHD) in patients with schizophrenia receiving antipsychotics in Malaysia.
METHODS:This cross-sectional study, conducted at multiple centres, involved 270 patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR diagnostic criteria for schizophrenia, were on antipsychotic medications for at least one year, and were screened for metabolic syndrome. Patients receiving mood stabilisers were excluded. Metabolic syndrome was defined according to the National Cholesterol Education Program ATP III criteria modified for Asian waist circumference. Risk for cardiovascular disease was assessed by using Framingham function (all ten-year CHD events).
RESULTS:The prevalence of metabolic syndrome was 46.7% (126/270). Among all the antipsychotics used, atypical antipsychotics (monotherapy) were most commonly used in both the metabolic and non-metabolic syndrome groups (50.8% vs. 58.3%). The ten-year risk for CHD was significantly higher in patients with metabolic syndrome. The proportion of patients with high/very high risk for CHD (Framingham ≥ 10%) was greater in patients with metabolic syndrome than in those with non-metabolic syndrome (31.5% vs. 11.0%, odds ratio 3.9, 95% confidence interval 2.0-7.6; p < 0.001). The mean body mass index was higher in patients with metabolic syndrome than in those without (29.4 ± 5.1 kg/m2 vs. 25.0 ± 5.6 kg/m2; p < 0.001).
CONCLUSION:Patients with schizophrenia receiving antipsychotics in Malaysia have a very high incidence of metabolic syndrome and increased cardiovascular risk. Urgent interventions are needed to combat these problems in patients.

Matched MeSH terms: Schizophrenia/drug therapy*
Fulltext The association between dyslipidaemia and types of antipsychotic medications among patients with chronic schizophrenia

Ruzanna ZZ, Ong LY, Cheah YC, Fairuz A, Midin M

Med J Malaysia, 2012 Feb;67(1):39-44.
PMID: 22582547 MyJurnal

This cross sectional study aimed to explore the association between dyslipidaemia and types of antipsychotics in 100 patients with chronic schizophrenia. Lipid profile, weight, height and waist circumference together with other relevant factors were measured. We found there was a high rate of dyslipidaemia among patients with chronic schizophrenia treated with antipsychotics (66%), however there was no significant difference found between typical or atypical antipsychotics (OR=1). All sociodemographic and clinical factors were not significantly associated with dyslipidaemia. Only non-Malays were found to have significant dyslipidaemia (p<0.1). Effective management is needed to deal with the dyslipidaemia in this group.

Matched MeSH terms: Schizophrenia/drug therapy*

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