Alzheimer's disease (AD) is the most common CNS disorder occurring worldwide. There is neither proven effective prevention for AD nor a cure for patients with this disorder. Hence, there is an urgent need to develop safer and more efficacious drugs to help combat the tremendous increase in disease progression. The present review is an attempt at discussing the treatment strategies and drugs under clinical trials governing the modulation of neurotransmitter. Therefore, looking at neurotransmitter abnormalities, there is an urge for developing the pharmacological approaches aimed at correcting those abnormalities and dysfunctioning. In addition, this review also discusses the drugs that are in Phase III trials for the treatment of AD. Despite advances in treatment strategies aimed at correcting neurotransmitter abnormalities, there exists a need for the development of drug therapies focusing on the attempts to remove the pathogenomic protein deposits, thus combating the disease progression.
Schizophrenia is a chronic psychiatric disorder and pharmacotherapy plays a major role in its management. The 1950s and early 1960s saw milestones in the introduction of psychotropic drugs in clinical practice. A review of drug prescriptions in different settings provides an insight into the pattern of drug use, identifies drug-related problems and may be used to compare recommended guidelines with actual practice. This effort led to the evaluation of the drug prescribing pattern of antipsychotics in patients attending the psychiatric clinic at a government hospital. The data from 371 antipsychotic medication prescriptions that included 200 prescriptions for schizophrenia were collected during one month (1rst-31rst August 2008) at the outpatient pharmacy department. The mean age of patients was 35.0 years (SD = 1.131), with a male to female ratio of 2:1. The most widely used oral antipsychotic was haloperidol (16.3%) while the most common depot preparation prescribed was zuclopenthixol decanoate (8.8%). The daily dose of the average antipsychotic prescribed in this clinic was 342.06 mg equivalent of chlorpromazine. There was no relation between the doses received and ethnicity of the patient (Malay, Chinese or Indian). However, there was a significant relationship between the prescribed dose and patient age (P < 0.042). Nearly 32% of the schizophrenia patients were prescribed with atypical antipsychotics such as olanzapine (10.8%), risperidone (10.0%), quetiapine (7.6%) and clozapine (3.2%). Monotherapy was given to 73.0% of the schizophrenia patients. The majority of patients also received antidepressants. To conclude, this study gave evidence that physicians had a strong preference for monotherapy with conventional antipsychotic drugs while the use of atypical drugs was less prevalent.
Haloperidol is an antipsychotic drug that exerts its' antipsychotic effects by inhibiting dopaminergic neurons. Although the exact pathophysiology of haloperidol extrapyramidal symptoms are not known, the role of reactive oxygen species in inducing oxidative stress has been proposed as one of the mechanisms of prolonged haloperidol-induced neurotoxicity. In the present study, we evaluate the protective effect of alpha lipoic acid against haloperidol-induced oxidative stress in the rat brain. Sprague Dawley rats were divided into control, alpha lipoic acid alone (100 mg/kg p.o for 21 days), haloperidol alone (2 mg/kg i.p for 21 days), and haloperidol with alpha lipoic acid groups (for 21 days). Haloperidol treatment significantly decreased levels of the brain antioxidant enzymes super oxide dismutase and glutathione peroxidase and concurrent treatment with alpha lipoic acid significantly reversed the oxidative effects of haloperidol. Histopathological changes revealed significant haloperidol-induced damage in the cerebral cortex, internal capsule, and substantia nigra. Alpha lipoic acid significantly reduced this damage and there were very little neuronal atrophy. Areas of angiogenesis were also seen in the alpha lipoic acid-treated group. In conclusion, the study proves that alpha lipoic acid treatment significantly reduces haloperidol-induced neuronal damage.
The REAP-AP study recruited 3,746 patients with schizophrenia, in March and April 2016, from 71 centers in 15 Asian countries/territories namely Bangladesh, China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, Thailand and Vietnam. Our findings reveal a trend according to which high dose antipsychotic prescription is more prevalent in Eastern Asia (especially, Japan and Korea) than in other regions of Asia. This historical factor may be associated with our finding of an Eastern Asian preponderance of high dose antipsychotic prescription.
Luteolin, a flavonoid widely distributed in the plant kingdom, contains two benzene rings and hydroxyl groups, and this structural specificity contributes to its diverse biological activities. However, no previous studies have simultaneously investigated the therapeutic potency of luteolin isolated from a plant as an antipsychotic and antidepressant. Here, luteolin exhibited selective inhibition of hMAO-A (IC50 = 8.57 ± 0.47 μM) over hMAO-B (IC50 > 100 μM). In silico proteochemometric modeling predicted promising targets of luteolin, and verification via cell-based G protein-coupled receptor functional assays showed that luteolin is a selective antagonist of the vasopressin receptor V1AR (IC50 = 19.49 ± 6.32 μM) and the dopamine D4 receptor (IC50 = 39.59 ± 1.46 μM). Molecular docking showed the tight binding of luteolin with a low binding score and the high stability of the luteolin-receptor complex, corroborating its functional effect. Thus, hMAO-A, hD4R, and hV1AR are prime targets of luteolin and potential alternatives for the management of neurodegenerative diseases.
The purpose of this study was to investigate whether there were gender-specific depressive symptom profiles or gender-specific patterns of psychotropic agent usage in Asian patients with depression.
Matched MeSH terms: Antipsychotic Agents/therapeutic use
OBJECTIVE: To evaluate the effect of curcumin on olanzapine-induced obesity in rats.
MATERIALS AND METHODS: Sprague-Dawley (SD) rats were used for experiments. The animals were divided into six groups, namely, normal control, olanzapine control, betahistine (10 mg/kg), and curcumin 50, 100, and 200 mg/kg treated groups. Except the normal control group, all other animals were administered with olanzapine 4 mg/kg intraperitoneally to induce obesity. The drugs were administered once daily, per oral for 28 days. During the experiment, body weight changes and behavior alterations were monitored at regular intervals. At the end of the experiment, blood sample was collected from all the experimental animals for biochemical analysis. Part of the liver and kidney tissues was harvested from the sacrificed animals and preserved in neutral formalin for histopathological studies.
RESULTS: Curcumin showed a significant reduction in olanzapine-induced body weight gain on the rats and improved the locomotor effects. The effect of curcumin on olanzapine-induced body weight gain is not comparable with that of betahistine.
CONCLUSION: This study has shown metabolic alteration effect of curcumin on olanzapine, an antipsychotic drug, treated SD rats.
SUMMARY: Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia and bipolar disorder. Obesity is an adverse effect of olanzapine, and the present study was made an attempt to study the effect of curcumin on olanzapine-induced obesity in rats. In this present study, curcumin significantly reduced olanzapine-induced body weight gain in rats. Abbreviations Used: 5HT: 5-hydroxytryptamine, ALP: Alkaline phosphatase, ALT: Alanine transaminase, ANOVA: Analysis of variance, AST: Aspartate transaminase, CMC: Carboxymethyl cellulose, D: Dopamine, H and E: Hematoxylin and Eosin stain, H: Histamine, HDL-C: Highdensity lipoprotein cholesterol, IP: Intraperitoneal, MAO: Monoamine oxidase, NaOH: Sodium hydroxide, SD rats: Sprague Dawley rats, TCs: Total cholesterols, TG: Triglyceride.
A young male presented with many years of delusions and hallucinations, with concurrent heroin use and subsequent amphetamine uses. There were no depressive or manic symptoms and psychotic symptoms prior to the amphetamine use. After the trials of two atypical antipsychotics and later clozapine due to treatment resistance, adherence and functionality were poor and there was still persistent drug use. As a result, a long acting injectable adjunct was commenced, but only minimal effects were observed. However after initiation of directly observed treatment of clozapine with methadone, there has been functional and clinical response and drug use has ceased.
Unlike clozapine, and despite its structural similarities, olanzapine is not usually associated with haematological suppression. Nonetheless this case report highlights an incident of olanzapine-induced thrombocytopenia and neutropenia in a first-contact patient. We report on a 50-year-old male who presented with 7 years of delusions and hallucinations. A diagnosis of schizophrenia was made in the absence of any suggestive features of mood disorders, substance abuse or organicity, and olanzapine as second-line treatment. Within a week of starting treatment he developed biochemical neutropenia and thrombocytopenia without any clinical symptoms that resolved after cessation of the offending drug. An organic workup for infective, inflammatory, and neoplastic causes was unremarkable. Comparison with other case reports and 3 postulated mechanisms are discussed. Despite its comparative rarity, the addition of this case report to a growing corpus suggests that clinicians should maintain heightened surveillance of patients prescribed olanzapine, to identify any untoward iatrogenic haematological abnormalities or immunosuppression.
Noni fruit is widely consumed in tropical regions of Indonesia to the Hawaiian Islands. The noni plant has a long history of use as a medicinal plant to treat a wide variety of ailments including CNS disorders. The present investigation was designed to evaluate the antipsychotic effect of noni fruits (Morinda citrifolia Linn.) using mouse models of apomorphine-induced climbing behaviour and methamphetamine-induced stereotypy (licking, biting, gnawing and sniffing).
In an earlier report, we demonstrated an antipsychotic-like activity of a methanolic extract of Morinda citrifolia Linn fruit in mouse models and postulated the contribution of its bioactive principles, scopoletin and rutin. Moreover, the antidopaminergic activities of scopoletin and rutin were reported in isolated vas deferens preparations. In the present study, scopoletin and rutin were assessed for antipsychotic-like activity using apomorphine-induced climbing behavior and methamphetamine-induced stereotypy in mice. The results of this study revealed that scopoletin and rutin (0.05, 0.1, 0.5, and 1 mg/kg, p.o.) had a "U-shaped" dose-dependent effect on climbing and stereotyped behaviors induced by apomorphine and methamphetamine, respectively, in mice. A significant reduction in climbing and stereotyped behaviors caused by scopoletin and rutin was observed only at a dose 0.1 mg/kg. This study suggests that scopoletin and rutin can alleviate positive symptoms of schizophrenia only at a specific dose. Further studies evaluating the effects of scopoletin and rutin on animal models for negative symptoms of schizophrenia are required for a novel drug discovery in the treatment of neuropsychiatric diseases.
Drug interactions can cause iatrogenic disease. If concurrent medications are taken, the potential exists for a drug interaction to occur. Renewed interest in the topic interactions has been generated by the fatal interactions involving non-sedating histamine H-1 antagonists and the recent intriduction of two therapeutic agents, the selective serotonin reuptake inhibitors (SSRIs) and HIV protease inhibitors, for the treatment of depression and AIDS, respectively. These three therapeutic agents have been implicated in clinically significant drug interactions. The consequences of these interactions vary in clinical significance, extent, and effect. Some interactions are theoretical whereas others may lead to severe iatrogenic adverse experiences including lethal consequences.The purpose of this review is to alert the medical practioner to potential drug interactions that may occur when these drugs are prescribed to patients. The pharmacological basis and clinical signficance of these interactions are reviewed. The pharmacological mechanisms underlying these interactions are illustrative of those that may be involved for many other medications. Doctors should be aware of the potential pitfall that may occur when certain groups of drugs are prescribed with concurrent medications.
Atraumatic trismus can be one of the presentations of medication-induced acute dystonia, particularly by antipsychotics and less commonly antidepressants. A case of an unusual emergency presentation of atraumatic trismus on initiation of duloxetine is reported. The patient was a 40-year-old woman experiencing sudden difficulty in mouth opening and speaking due to a stiffened jaw after taking 5 days of duloxetine prescribed for her fibromyalgia-related chest pain. Assessment of vital signs is prudent to ensure there is no laryngeal involvement. Other physical examinations and her recent investigations were unremarkable. She was treated for acute dystonia and intravenous procyclidine was given together with oral diazepam. Her symptoms improved immediately and her duloxetine was suggested to be stopped. To our knowledge, this is the first case of isolated trismus induced by duloxetine. Clinicians should be aware of this risk, especially considering the limitation of important physiological functions (such as swallowing, eating, etc) associated with this condition.
The dopamine hypothesis has earlier dominated the theories for the
development of schizophrenia based on the early pharmacologic evidence. The
antipsychotic drugs, among others, is thought to interfere with the function of the
dopamine D2 receptor (DRD2) resulting in clinical improvement. Accumulating evidence
suggest the role of epigenetic mechanisms in the pathophysiology of schizophrenia.
Despite this, specific evidence linking the DRD2 DNA methylation with schizophrenia is
insufficient mainly due to the poor accessibility and limited brain samples. Of late, new
data has suggested the global impact of DNA methylation in the development of
schizophrenia, thus methylation in the peripheral blood could infer changes in the brain.
The aim of this study was to assess the DRD2 DNA methylation in the peripheral blood of
schizophrenia.
The dopamine hypothesis of schizophrenia is based on the fact that hyperdopaminergic
state is involved in causing psychosis and antipsychotic drugs block the
dopamine receptor. COMT regulates the homeostatic levels of neurotransmitter
dopamine in the synapses and plays a role in the neurocognitive function. The
dysregulation of dopamine in the prefrontal cortex influences the cognitive function and
the severity of the psychotic symptoms in schizophrenia. During epigenetic event,
methylated COMT gene may cause reduction in its expression and contribute to the
clinical presentation of schizophrenia. Therefore, the aim of this study was to assess the
feasibility of using COMT DNA methylation for the prediction of specific psychotic
presentation of schizophrenia. (Copied from article).
AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients.
METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis.
RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P
Objective: To report the use of Paliperidone in an adolescent with bipolar disorder primarily concerning its effectiveness and safety. Method: We present a case report of an adolescent with atypical presentation of bipolar disorder. The problem was complicated by poor liver function and poor compliance. Progress of the patient was recorded. Results: The patient showed dramatic improvement after 2 weeks on Paliperidone and has achieved the best level of functioning after almost 4 years on other treatment. Conclusion: The usage of Paliperidone was effective and safe in an adolescent with atypical bipolar disorder.
The use of atypical antipsychotic agents in early onset schizophrenia is rising despite its limited data on efficacy, safety and tolerability. Early onset schizophrenia warrants effective pharmacological treatment that is safe and well tolerated by children and adolescent population. Existing atypical agents are not completely free of side effects. Aripiprazole has unique properties that differ from other atypical antipsychotics and fill up the missing gaps, as it is associated with minimal metabolic complications and extrapyramidal side effects that are more commonly seen in other atypical agents. It offers a better option for this population and may possibly be considered as first line treatment in future. This case report demonstrates the efficacy and safety of Aripiprazole in children and adolescent population.
INTRODUCTION: The present study investigated the relationship between psychological symptoms and psychosocial function and the role of relevant sociodemographic data and antipsychotic use in the prediction of psychosocial function among multiracial schizophrenia outpatients in Malaysia.
METHODS: A total of 223 participants were recruited in this cross-sectional study conducted from December 2010 to April 2011. Psychological symptoms were assessed using the Positive and Negative Syndrome Scale whilst the psychosocial function was assessed using the Personal and Social Performance scale. Sociodemographic and treatment variables were gathered through interview or review of the medical records.
RESULTS: All dimensions of psychosocial functions were inversely correlated with Positive and Negative Syndrome Scale sub-domains. Only the disorganization sub-domain significantly predicts all dimensions of psychosocial function. For social data, body mass index and employment status were significant predictors of all dimensions of psychosocial functions. Typical antipsychotics significantly predict social function negatively as compared to sulpiride (β = -0.152, P = 0.028).
DISCUSSION: We found that the relationship between psychological symptoms and psychosocial functions were relatively consistent with the findings from the Caucasian population. Additionally, disorganization was the only significant predictor of all dimensions of psychosocial functions. This further emphasized the importance of cognition in psychosocial function. The roles of sulpiride, body mass index and employment status as predictors of psychosocial function were also discussed.
KEYWORDS: antipsychotics; psychosocial function; schizophrenia; symptoms
Study site: Psychiatric clinic, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia
OBJECTIVES. Obesity is an issue of concern among patients with schizophrenia as it is a co-morbid condition that is closely related to metabolic syndrome. The present study assessed the correlation of body mass index with antipsychotic use among multiracial schizophrenia outpatients. The study also compared the patients' body mass index with Malaysian Adult Nutrition Survey (MANS) data.
METHODS. A total of 216 participants were recruited into a cross-sectional study conducted over 5 months, from December 2010 to April 2011. Body weight and height were measured using the standard methods. Demographic data and treatment variables were gathered through interview or review of the medical records.
RESULTS. There were differences in mean body mass index between men and women (p = 0.02) and between Malay, Chinese and Indian races (p = 0.04). Stratified by sex, age, and race, the body mass index distributions of the patients were significantly different to those of the reference MANS population. The prevalence of obesity among patients was more than 2-fold greater than among the reference population in all variables. Although body mass index distribution was related to antipsychotic drugs (χ(2) = 33.42; p = 0.04), obesity could not be attributed to any specific drug.
CONCLUSION. The prevalence of obesity among patients with schizophrenia was significantly greater than that in the healthy Malaysian population, and affects the 3 main races in Malaysia.
Study site: Psychiatry Clinic, Tengku Ampuan Afzan Hospital, Kuantan, Pahang, Malaysia.