Neuroprotective Effect Of Methanolic Extract Of Sargassum Wightii On Haloperidol Induced Catalepsy And Tardive Dyskinesia In Albino Rats

Objective: The present study was designed to evaluate the neuroprotective effect of methanolic extract of Sargassum wightii on haloperidol-induced catalepsy and tardive dyskinesia in Wistar albino rats. Methods: In this study, thirty Wistar albino rats were randomly divided into six groups. Gr-I served as control. Haloperidol (1 mg/kg intraperitoneally) was administered to rats of Gr-II to Gr-V for twenty-one consecutive days to induce catalepsy and tardive dyskinesia. Animals of Gr-II to Gr-V were orally administered with vehicle, levodopa carbidopa combination (30 mg/kg), Sargassum extract 200 and 400 mg/kg respectively. All the drugs and vehicles were given orally one hour before haloperidol injection for twenty one consecutive days. The cataleptic scores were recorded using standard bar test. Tardive dyskinesia was assessed in terms of vacuous chewing movement (VCM) and tongue protrusion (TP) scores. After behavioural testing, all animals were sacrificed on twenty-second day and various biochemical parameters like MDA, SOD and GSH were estimated in brain tissue. Results: Chronic administration of haloperidol significantly increased cataleptic scores, VCM and TP scores. (p<0.001) Sargassum wightii extract (400 mg/kg) significantly inhibited haloperidol-induced catalepsy, VCM and TP (p<0.001) Haloperidol increased MDA and decreased SOD and GSH in brain tissue to a highly significant extent (p<0.001) Sargassum extract at 400 mg/kg also significantly reversed the haloperidol-induced alteration in brain oxidative stress markers. Conclusion: Sargassum wightii inhibits haloperidol-induced catalepsy and tardive dyskinesia. Thus it may be used as a unique therapeutic adjunct for the prevention of neuroleptic-induced extrapyramidal symptoms, however, it has to be explored more.

The study on the effect of ginkgo biloba extracts on MnSOD activity in the treatment of tardive dyskinesia / 中国神经精神疾病杂志

To investigate if ginkgo biloba extract (Egb-761) can improve tardive dyskinesia (TD) symptoms through increasing the activity of plasma MnSOD. Methods We enrolled a total of 384 schizophrenia patients including 157 TD patients and 227 non-TD patients, as well as 280 normal subjects. The difference of MnSOD level in plasma among these groups were compared. TD patients were then randomly divided into two groups. The treatment group (n=77) and the placebo group (n=75) were treated with 240 mg of Egb-761 or placebo per day for 12 weeks, respectively. The abnormal involuntary movement scale (AIMS) and the positive and negative symptoms scale (PANSS) were used to evaluate the severity of the symptoms in baseline, the sixth week and the twelfth week after treatment. The level of MnSOD activity in plasma was also detected before and after the treatment. Results The level of MnSOD activity was lower in schizophrenia groups than in healthy control group (P＜0.01). In addition, the level of MnSOD activity was significantly lower in TD group than in non-TD group (P＜0.05). Repeated measures analysis of variance showed that group effect (F=4.00, P=0.05), time effect (F=32.17, P＜0.01) and interactive effect of group and time (F=39.04, P＜0.01) were significant in AIMS total score. The AIMS total score of treatment group was significantly lower than that of placebo group at 6-week and 12-week time points (all P＜0.01). Repeated measures analysis of variance showed that time effect (F=23.04, P＜0.01) and interactive effect of group and time (F=6.41, P＜0.05) were significant in the level of MnSOD activity. In addition, the level of MnSOD at baseline was significantly correlated with the reduction of AIMS total score during the treatment period (r=0.27, P=0.018). Conclusion Treatment of Egb-761 can improve symptoms of TD and activity of MnSOD.

Depression in Schizophrenia Patients with Tardive Dyskinesia

OBJECTIVES: This study aimed to investigate the relationship between depressive and anxiety symptoms and tardive dyskinesia (TD) and reveal the association of cognitive function and TD in patients with schizophrenia. METHODS: We recruited 30 schizophrenia patients with TD and 31 without TD from a national mental hospital in South Korea. To assess depressive and anxiety symptoms, the Beck Depression Inventory-II (BDI–II) and the Beck Anxiety Inventory (BAI) were conducted. Using the five-factor structure of the BDI-II and BAI, somatic anxiety, cognitive depression, somatic depression, subjective anxiety, and autonomic anxiety were assessed. Computerized neurocognitive function test (CNT) was performed to assess levels of cognitive functions. We compared the clinical characteristics, levels of cognitive functions, and depressive and anxiety symptoms between schizophrenia patients with TD and without TD. Chi-square test, Fisher's exact test, independent t-test and Mann Whitney U test were conducted to compare two groups. Pearson correlation analysis was conducted to evaluate relationships among the abnormal involuntary movement scale (AIMS), BDI-II, BAI, somatic anxiety, cognitive depression, somatic depression, subjective anxiety, and autonomic anxiety. RESULTS: The subjects with TD had significantly lower score on the cognitive depression than those without TD (t = −2.087, p = 0.041). There were significant correlations between the AIMS score and the BDI-II score (r = −0.386, p = 0.035) and between the AIMS score and cognitive depression score (r = − 0.385, p = 0.035). CONCLUSIONS: Our findings suggest the inverse relationship between severities in TD and depression and support the assumption that there is an inverse relationship between the pathophysiology of TD and depression.

Vitaminas B1, B6, B12 e complexo B na prevenção da discinesia orofacial induzida porhaloperidol em ratos: avaliação comportamental e mecanismos associados

A Discinesia tardia (DT) é caracterizada por movimentos involuntários, principalmente na parte inferior da face, próximos da boca, com espasmos que podem ser leves ou severos. É uma alteração motora grave relacionada, mas não restrita à terapia antipsicótica. Tratamentos com antipsicóticos principalmente os da classe dos típicos, como o haloperidol (HAL) aumentam os riscos de DT. A fisiopatologia da DT é associada a um desequilíbrio em sistemas de neurotransmissão, dentre eles dopaminérgico e colinérgico, bem como com desequilíbrio oxidativo, principalmente em áreas cerebrais relacionadas ao controle do movimento, como o corpo estriado. As vitaminas (vit.) B, por sua vez, apresentam efeitos antioxidantes sendo cofatores para enzimas relacionadas à síntese de neurotransmissores. Neste contexto, o presente trabalho teve como objetivo determinar os efeitos preventivos das vit. B1, B6, B12 ou Complexo B na discinesia orofacial (DO) induzida por HAL em ratos. Foram utilizados ratos Wistar machos tratados por via intraperitoneal com HAL (1 mg/kg, i.p.) por 21 dias ou concomitantemente com HAL e as vit. B1 (60 mg/kg), B6 (60 mg/kg) ou B12 (0,6 mg/kg) por via subcutânea, sozinhas ou em associação (complexo B). O complexo B consistiu na mistura das 3 vitaminas em iguais proporções. Um grupo de animais foi administrado clozapina (25 mg/kg), um antipsicótico atípico não relacionado ao desenvolvimento de DO. Os testes comportamentais foram realizados após 30 minutos no 1º, 7º e 21º dias de administração das fármacos e consistiram na determinação da atividade locomotora, catalepsia e movimentos de mastigação no vazio...

Tardive dyskinesia (TD) is characterized by involuntary movements, mostly at lower face, near the mouth, with convulsion that can be light or hard. Is one severe disorder related, but restricted the antipsychotic therapy. Antipsychotic treatments above all the class of typical, like haloperidol (HAL) increase the risk of TD. The pathophysiology of TD is associated to a instability in neurotransmission system, such as dopaminergic and cholinergic, among others, as well as with oxidative instability mainly in brain areas related to the control of movement, as the striatum. B vitamins, in turn, show antioxidants effect and are cofactors to enzymes related to the synthesis of neurotransmitters. In this context, the present study aimed to determine the preventive effects of B1, B6, B12 vitamins or B complex against orofacial dyskinesia (OD) induced by HAL in rats. To do this male Wistar rats were intraperitoneally administered HAL (1 mg/kg, i.p.) for 21 days or concomitantly received HAL, B1 (60 mg/kg), B6 (60 mg/kg) or B12 (0,6 mg/kg) vitamin subcutaneously alone or in association. B complex consisted in the mix of 3 vitamins in equal proportions. One group of animals was administered with clozapine (25 mg/kg), an atypical antipsychotic not related to the development of OD. Behavioral tests were performed at the 1st, 7th and 21st days of drugs administration. The behavioral tests performed were locomotor activity, catalepsy and chewing vacuous movements. At 21stday the animals were sacrificed and had their brain areas dissected for neurochemical analysis. The results showed that HAL increased catalepsy time at 7th day and OD at 21stday...

The efficacy of treatment and prevention of vitamin E on haloperidol-induced tardive dyskinesia and its pos-sible mechanisms in rats / 中国神经精神疾病杂志

Objective To investigate the efficacy of treatment and prevention of VitE on vacuous chewing move-ments (VCMs) of haloperidol-induced tardive dyskinesia (TD) rats and serum levels of brain-derived neurotrophic fac-tor ( BDNF) and total antioxidant capacity ( TAC) , and to explore the possible mechanisms.Methods Thirty-two male Sprague-Dawley (SD) rats were randomly divided into TD, P-Vit E, T-Vit E and control group (n=8), receiving to-week treatment with Haloperidol (Hal)+NS, Hal+Vit E (medicated at the baseline), Hal+VitE (medicated at the fifth week) or normal saline (NS), respectively.VCM was evaluated at each week.ELISA and spectrophotometer were used to detect the serum levels of BDNF and TAC, respectively.Results The VCM score of both TD group and T-Vit E group increased at the 2nd weekend, reached the peak at the 5th weekend.VCM score of T-Vit E group declined gradually at the 6th weekend and was significantly lower than that in the TD group [(6.5 ±3.3) vs.(27.9 ±5.8), P0.05) at the 10th weekend.There was no significant difference in VCM score between P-Vit E group and control group for ten weeks(P>0.05).At the 10th weekend, serum BDNF [(6.9 ±1.0) pg/mL] and TAC [(11.9 ±3.2) U/mL] levels of TD group were significantly lower than those of the controls [BDNF (8.6 ±2.5) pg/mL, TAC (18.2 ±5.5) U/mL] and T-Vit E group [BDNF (8.7 ±2.0) pg/mL, (18.6 ±5.9) U/mL] (P0.05).Conclusions Vit E may relieve and prevent VCM in TD model rats though alleviation of free radical damage.

Elaeocarpus ganitrus: its beneficial antiparkinsonian effect in MPTP induced motor and non-motor impairments in mice.

Aim: Elaeocarpus ganitrus (Family: Elaeocarpaceae), has shown beneficial role in the treatment of depression, convulsions and asthma. This study was undertaken to evaluate the antiparkinson effect of E.ganitrus. Materials and methods: Swiss albino mice of either sex were divided into 06 groups (n =12). 1st group mice were given 0.5% carboxy methyl cellulose (orally), 2nd group were administered MPTP (2 doses, each dose 20 mg/kg at 2 hr. interval, i.p.). Whereas 3rd, 4th and 5th groups - were administered with E. ganitrus (100, 200, and 400 mg/kg/day, orally), respectively, along with MPTP. Group 6- received Levodopa (30mg/kg, i.p,) along with MPTP. To evaluate anti-Parkinson effect, hanging wire test, tardive dyskinesia test and elevated plus maze test were performed on the1st day and on 8 th day. One way ANOVA followed by post-hoc Tukey test, with p<0.05 was considered statistical significant. Results: E.ganitrus (200 and 400 mg/kg, p.o.) was found to increase the hanging time significantly (p <0.001) in hanging wire test and significantly decreased (p <0.001) the Vacuous Chewing Movements (VCMs) in tardive dyskinesia test as compared to MPTP group. E.ganitrus (200 and 400 mg/kg, p.o.) was found to significantly increase (p <0.001) the no. of entries and time spent in open arm and significantly decreased the no. of entries and time spent in closed arm (p <0.001) compared to MPTP treated group. Conclusion: The results of the present study conclusively showed that E.ganitrus has beneficial effect in MPTP induced experimental model of Parkinson’s disease.

Investigation of antiparkinsonian effect of Aloe vera on haloperidol induced experimental animal model.

Background: Aloe vera (Family: Liliaceae) has been used for the treatment of diabetes, skin disorders and as an anti-inflammatory agent. There is increased concern about the side effects of conventional medicine in the treatment of Parkinson’s disease (PD). As A.vera has found to have antioxidative property, it may be a safer alternative. Methods: Parkinson’s disease was induced by administering haloperidol (1 mg/kg i.p. daily x 1 week).The mice of either sex were divided into 06 groups (n =12). 1 st day group mice were given distilled water (orally), 2nd group were administered haloperidol (20 mg/kg i.p.).The 3rd, 4th and 5th groups were administered A.vera (100, 200, and 400 mg/kg/day, orally) respectively, along with haloperidol. Group 6- received Levodopa (30mg/kg, i.p,) along with haloperidol. To evaluate anti-Parkinson effect, hanging wire test, tardive dyskinesia test and hole board test were performed on the1st day and 8th day. One way ANOVA was used to detect statistical significance followed by post-hoc Tukey test. Results: A.vera (200 and 400 mg/kg, p.o.) was found to increase the hanging time significantly (p <0.001) in hanging wire test and significantly decreased (p <0.001) the Vacuous Chewing Movements (VCMS) in tardive dyskinesia test as compared to haloperidol group. A.vera (200 and 400 mg/kg, p.o.) was found to significantly increase (p <0.001) the number of dips and no. of line crossings in hole board test when compared to haloperidol group. Conclusion: The results of the present study conclusively showed that A.vera has beneficial effect in haloperidol induced experimental model of Parkinson’s disease.

Tardive Dyskinesia and Tardive Dystonia with Second-Generation Antipsychotics in Bipolar Disorder Patients Unexposed to First-Generation Antipsychotics

OBJECTIVES: Second-generation antipsychotics (SGAs) are frequently used in the treatment of bipolar disorder. However, there is still no consensus on their risk of tardive movement syndromes especially for first-generation antipsychotics (FGAs)-naive patients. This study aimed to investigate the prevalence and associated factors of SGAs-related tardive dyskinesia and tardive dystonia in patients with bipolar disorder, in a naturalistic out-patient clinical setting. METHODS: The authors assessed 78 non-elderly patients with bipolar (n = 71) or schizoaffective disorder (n = 7) who received SGAs with a combined use of mood stabilizers for more than three months without previous exposure to FGAs. Multiple direct assessments were performed and hospital records longer than one recent year describing any observed tardive movement symptoms were also reviewed. RESULTS: The prevalence rates of tardive dyskinesia and tardive dystonia were 7.7% and 6.4%, respectively. These patients were being treated with ziprasidone, risperidone, olanzapine, quetiapine, or paliperidone at the time of the onset of the movement symptoms. Tardive dyskinesia was mostly observed in the orolingual area, and tardive dystonia was most frequently detected in oromandibular area. A past history of acute dystonia was significantly associated with presence of both tardive movement syndromes. CONCLUSIONS: Our findings suggest that SGAs-related tardive movement syndromes occur in a substantial portion of bipolar disorder patients. Acute dystonia, a reported risk factor of tardive movement syndromes in the era of FGAs is confirmed as a risk factor of both tardive dyskinesia and tardive dystonia that were induced-by SGAs.

Dextromethorphan for tardive dyskinesia.

Aims: To report three cases of successful treatment of tardive dyskinesia (TD) with dextromethorphan. Study Design: Retrospective chart review. Place and Duration of Study: Private outpatient practice in Syracuse, NY. Methodology: A retrospective chart review of patients with TD who were treated with dextromethorphan between 2003 and 2013 was conducted. Results: Three consecutive patients experienced marked improvement of TD with dextromethorphan. Conclusion: Dextromethorphan may be a useful drug for treating TD. Further prospective studies are needed.

Late-onset Quetiapine-related Tardive Dyskinesia Side Effects in a Patient with Psychotic Depression

The atypical antipsychotics were believed to induce less extrapyramidal syndrome, including tardive dyskinesia (TD). Since the introduction of the quetiapine, it is also reported with less TD side effects. It even can relieve the symptoms of severe TD and reduce the risk of TD. The quetiapine's low affinity and fast dissociation from postsynaptic dopamine D2 receptors should give the least risk of producing the symptoms of TD. The quetiapine even can reduce the TD side effects related to clozapine, which has the lowest risk for TD. However, since the first case report of TD side effects related to quetiapine published on 1999, the safety of quetiapine in TD aspect has been questioned. Therefore, we want to share this case report, which was written to describe the severe late-onset TD side effects after long-term use of quetiapine in a patient with psychotic depression. The patient had no significant findings after concurrent comprehensive neurological examinations, magnetic resonance imaging of brain and electroencephalogram since the onset of TD.

A Case of Aripiprazole Induced Tardive Dyskinesia in a Neuroleptic-Naive Patient with Two Years of Follow Up

Tardive dyskinesia (TD) is arguably the most serious and potential irreversible side effect of antipsychotic medication. Traditionally first generation antipsychotics are the neuroleptics considered to have higher risk of TD as compared to second and third generation antipsychotics. Aripiprazole is a third-generation antipsychotic with a novel mechanism of action. Risk of developing TD with use of aripiprazole has been unknown. Recently many cases of aripiprazole associated TD have been reported. A case of 52 year old Caucasian woman is discussed who presented to us with first manic episode. Patient had never been treated with any antipsychotic medication in her life before. During current episode, she was treated with aripiprazole 30 mg/day. During follow up, patient was found to have developed dyskinetic oro-facial movements within 2 months of starting aripiprazole. She was not taking any other antipsychotic/anti-dopaminergic medication at that time. Patient's abnormal oro-facial movements could not be reversed in spite of immediate discontinuation of aripiprazole. Multiple medications are tried over the next 2 years but her movement disorder never remitted. Above case (along with other recent reports) suggest that risk of movement disorder with aripiprazole use could be higher than previously thought. Further studies are required to find out incidence of movement disorder with aripiprazole. Aripiprazole use should be preferably restricted to FDA approved indications. Clinician needs to be very vigilant about emergence of any movement disorder while using aripiprazole, especially in patients with risk factors for TD.

Association between Tardive Dyskinesia and Polymorphisms of TNF-alpha Gene in Korean Schizophrenia Patients / 대한정신분열병학회지

OBJECTIVES: There are emerging evidences suggest that the development of tardive dyskinesia (TD) is related to the oxidative stress, excitotoxicity, and immune activation. The purpose of this study is to investigate whether single-nucleotide polymorphisms (SNPs) of tumor necrosis factor (TNF)-alpha genes are associated with the susceptibility of TD and schizophrenia. METHODS: We investigated two hundred and eighty Korean schizophrenic patients. The schizophrenic participants consisted of patients with (n=105) and without (n=175) TD who were matched for antipsychotic drug exposure and other relevant variables. The TNF-alpha gene -308G/A SNPs were analyzed by polymerase chain reaction (PCR)-based methods. RESULTS: The frequencies of genotype (chi2=0.33, p=0.848) of the TNF-alpha gene -308 G/A SNP did not differ significantly between schizophrenic patients with and without TD. The difference of allele frequencies (chi2=0.28, p=0.594) of the TNF-alpha gene between the schizophrenic patients with and without TD were not significant. CONCLUSION: These results suggest that the TNF-alpha gene -308 G/A SNPs are not associated with TD and schizophrenia in a Korean population. Further association studies of TD with other candidate genes for cytokines would help us understand the pathophysiological mechanisms of TD.

Association Study between Tryptophan Hydroxylase 2 Gene -703G/T Polymorphism and Tardive Dyskinesia / 대한정신분열병학회지

OBJECTIVES: Tardive dyskinesia (TD) is a serious and sometimes irreversible adverse effect that may develop during long-term antipsychotics treatment. Previous studies have suggested that brain serotonergic systems are related to TD vulnerability and tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. This study aimed to investigate the association between TPH2 gene -703G/T polymorphism (rs4570625) and antipsychotic-induced TD in the Korean schizophrenia patients. METHODS: We investigated whether TPH2 gene -703G/T polymorphism is associated with antipsychotic-induced TD in 280 Korean schizophrenia patients. The subjects with TD (n=105) and without TD (n=175) were matched for antipsychotic drug exposure and other relevant variables. RESULTS: There was no significant difference in the distribution of genotypic (chi2=3.00, p=0.223) and allelic (chi2=0.19, p=0.661) frequencies between patients group with TD and without TD. There was no significant difference in total Abnormal Involuntary Movement Scale score (F=1.95, p=0.362) among the genotype groups, either. CONCLUSIONS: The present study does not support that TPH2 gene -703G/T polymorphism is involved in TD of the Korean schizophrenia subjects.

Association Study between Tryptophan Hydroxylase 2 Gene -703G/T Polymorphism and Tardive Dyskinesia / 대한정신분열병학회지

OBJECTIVES: Tardive dyskinesia (TD) is a serious and sometimes irreversible adverse effect that may develop during long-term antipsychotics treatment. Previous studies have suggested that brain serotonergic systems are related to TD vulnerability and tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. This study aimed to investigate the association between TPH2 gene -703G/T polymorphism (rs4570625) and antipsychotic-induced TD in the Korean schizophrenia patients. METHODS: We investigated whether TPH2 gene -703G/T polymorphism is associated with antipsychotic-induced TD in 280 Korean schizophrenia patients. The subjects with TD (n=105) and without TD (n=175) were matched for antipsychotic drug exposure and other relevant variables. RESULTS: There was no significant difference in the distribution of genotypic (chi2=3.00, p=0.223) and allelic (chi2=0.19, p=0.661) frequencies between patients group with TD and without TD. There was no significant difference in total Abnormal Involuntary Movement Scale score (F=1.95, p=0.362) among the genotype groups, either. CONCLUSIONS: The present study does not support that TPH2 gene -703G/T polymorphism is involved in TD of the Korean schizophrenia subjects.

No Association between PAWR Gene Polymorphisms and Tardive Dyskinesia in Schizophrenia Patients

Tardive dyskinesia (TD) is a hyperkinetic movement disorder associated with the prolonged use of antipsychotic drugs. Since prostate apoptosis response 4 (Par-4) is a key ligand of the dopamine D2 receptor, the Par-4 gene (PAWR) is a good candidate gene to study in the context of TD susceptibility. We examined the association between PAWR gene polymorphisms and TD. Three single nucleotide polymorphisms of PAWR were selected for the analysis: rs7979987, rs4842318, and rs17005769. Two hundred and eighty unrelated Korean schizophrenic patients participated in this study (105 TD and 175 non-TD patients). Genotype/allele-wise and haplotype-wise analyses were performed. There were no significant differences in genotype and allele frequencies between the two groups. Haplotype analysis also did not reveal a difference between the two groups. Within the limitations imposed by the size of the clinical sample, these findings suggest that PAWR gene variants do not significantly contribute to an increased risk of TD.

A comparative study of brain iron deposition in schizophrenia with and without tardive dyskinesia / 中华行为医学与脑科学杂志

ObjectiveTo explore the relationship between brain iron deposition and pathogenesis of tardive dyskinesia (TD) in schizophrenia.MethodsThe corrected phase (CP) of basal ganglia was measured in schizophrenia with TD( n=18) and without TD( n =18 ) using susceptibility weighted imaging MRI.Abnormal Involuntary Movement Scale (AIMS) was applied for clinical assessment of TD.ResultsAfter adjusting for age,sexual,and antipsychotic dosage,the mean CP of substantia nigra (SN) and caudate nucleus (CN) were significantly lower in schizophrenia patients with TD ( ( - 0.194 ± 0.040 ) rad,( - 0.089 ± 0.023 ) rad) than those without TD ( ( - 0.163 ± 0.033 ) rad,( - 0.076 ± 0.013 ) rad ; P =0.022,0.023 ).Lower mean CP in CN correlated with higher severity score of AIMS in TD patients ( r =- 0.468,P =0.034).Logistic regression analysis showed that the lower CP vaule in SN (β=-72.12,P=0.029) and CN(β=- 156.43,P=0.037),aging (β=0.379,P=0.042)were associated with the onset of TD.ConclusionThe results imply that the excess iron accumulation in basal ganglia may be associated with pathogenesis of TD in schizophrenia.

Effectiveness of melatonin in tardive dyskinesia / Efectividad de la melatonina en la discinesia tardía

Tardive Dyskinesia (TD) is a movement disorder associated with the clinical administration of antipsychotics. It is believed that TD is due, among other factors, to an increase in the oxidative damage produced by free radicals. Antioxidants, like vitamin E, have been used in the treatment of TD but there is no evidence of their effectiveness. Melatonin (MEL) is 6 to 10 times more effective, as an antioxidant, than vitamin E and it has been used with an apparent higher effectiveness in the treatment of TD, although the results have not been conclusive. A randomized, double blind, placebo controlled design was used to determine the effectiveness of MEL (20mg/day) during 12 weeks in 7 patients with TD. Six patients with TD were treated with placebo. The Abnormal Involuntary Movement Scale (AIMS) was chosen to assess the severity of TD initially and after 4, 8 and 12 weeks. The psychiatric evaluation was done following the Brief Psychiatric Rating Scale. In two patients treated with MEL a significant improvement (more than 60%) of the values of AIMS was detected. In the remainder five, as well as in the patients treated with placebo, no difference was observed during the 12 weeks. When compared the AIMS score in all the MEL-treated patients with the values in the placebo-treated patients, no significant differences were detected during the 12 weeks of the study. However, the significant clinical improvement observed in two patients must be considered before reaching a final conclusion on the usefulness of MEL in TD.

La Discinesia Tardía (DT) es un trastorno de los movimientos asociado al uso crónico de antipsicóticos que parece producirse, entre otros factores, por un incremento en los procesos oxidativos. La vitamina E se ha utilizado en su tratamiento, pero no hay evidencia de su efectividad. Como la melatonina (MEL) es 6 a 10 veces más efectiva como antioxidante que la vitamina E, se ha utilizado con una aparente mayor efectividad, aunque los resultados no han sido concluyentes. Se realizó un estudio doble ciego, al azar y controlado con placebo, para determinar la efectividad de la administración de la MEL durante 12 semanas en 7 pacientes con DT. Seis pacientes con DT fueron tratados con placebo. La Escala de Movimientos Involuntarios Anormales (AIMS) se usó para evaluar la evolución de los movimientos al inicio y a las 4, 8 y 12 semanas de tratamiento. La evaluación clínica psiquiátrica se hizo con la Escala Breve de Evaluación Psiquiátrica. En dos pacientes tratados con MEL se observó una mejoría clínica superior al 60% pero en los restantes, así como en los tratados con placebo los valores de la AIMS no variaron significativamente en el transcurso de las 12 semanas. Cuando se compararon los valores de la AIMS de la totalidad de los pacientes tratados con MEL, con los del grupo placebo, no se detectó ninguna diferencia significativa. Sin embargo, la mejoría clínica significativa de dos de los pacientes estudiados debe considerarse para llegar a una conclusión sobre la utilidad de la MEL en la DT.

No Evidence for an Association between Dopamine D2 Receptor Polymorphisms and Tardive Dyskinesia in Korean Schizophrenia Patients

OBJECTIVE: Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. Dopaminergic activity in the nigrostriatal system have been proposed to be involved in development of TD and dopamine D2 receptors (DRD2) has been regarded as a candidate gene for TD because the antipsychotics have potent antagonism DRD2. This study was aimed to find the relationship between DRD2 gene and antipsychotic-induced TD. METHODS: We evaluated whether 5 DRD2 single nucleotide polymorphisms (-141Cins>del/TaqID/NcoI/Ser311Cys/TaqIA) are associated with antipsychotic-induced TD in 263 Korean schizophrenia patients with (n=100) and without TD (n=163) who were matched for antipsychotic drug exposure and other relevant variables. Haplotype analyses were also performed. RESULTS: None of 5 polymorphisms were found to be significantly associated with TD and with TD severity as measured by Abnormal Involuntary Movement Scale. Overall haplotype (-141Cins>del/TaqID/NcoI/Ser311Cys/TaqIA) frequency was also not significantly different between TD and non-TD groups, although one rare haplotype (I-D1-T-G-A1) showed significantly different frequency between TD and non-TD groups (2.7% vs. 8.5%, respectively, p=0.031). CONCLUSION: The present study does not support that DRD2 gene may be involved in TD in the Korean population, although further studies are warranted.

Tardive Dyskinesia: Treatment with Aripiprazole

Tardive dyskinesia is characterized by choreiform movements, or rhythmic abnormal involuntary movements of the face, mouth, tongue, trunk, and limbs. It is frequently associated with the use of neuroleptic medications. The choreiform movements are irreversible in some patients, even after the drug is withdrawn. Although no reliable treatment for tardive dyskinesia exists, atypical antipsychotics are associated with a significantly lower incidence of tardive dyskinesia than typical antipsychotics. Moreover, recent reports suggest that atypical antipsychotics may have a beneficial effect on tardive dyskinesia remission. Until recently, evidence for the effectiveness of aripiprazole on tardive dyskinesia has been mixed. Aripiprazole has a unique mechanism of action and has various effects in tardive dyskinesia. The drug acts as a partial D2 receptor agonist that can stabilize D2 up-regulation, and as a partial 5-HT1A receptor agonist and a 5-HT2A receptor antagonist, and can increase the release of dopamine in the striatum.

An examination of synaptic proteins following chronic haloperidol in a rat model of tardive dyskinesia

Tardive dyskinesia (TD) is a late-onset side effect mainly affecting the orofacial region of patients treated chronically with classic antipsychotic drugs such as haloperidol (HAL). The causes of TD remain unknown. We hypothesized that faulty synaptic re-organization might be related to TD-like syndromes and used the vacuous chewing movements (VCM) model in rats to investigate the expression of four synaptic proteins, synaptophysin, syntaxin, spinophilin and PSD-95, in brains of HAL-treated rats. Male Sprague-Dawley rats were treated for 14 weeks with either haloperidol decanoate (21 mg/kg once every 3 weeks, I.M) or vehicle and VCMs were monitored on a weekly basis. As expected, VCMs developed reliably and were consistently more pronounced in some rats than in others. Using immunohistochemistry in anatomically preserved brain sections as well as Western Blot analyses of whole cells or synaptosomal fractions in striatal tissue, we found no significant effect of chronic HAL on levels of these proteins. Neither did we find significant differences in the levels of the four synaptic markers when comparing rats showing High vs. Low levels of VCMs. These results suggest that structural synaptic alterations (e.g. involving increased number of synapses) may not be the underlying mechanism of oral dyskinesias induced by chronic antipsychotic drug treatment. The possibility that functional neuroplastic changes occur remains to be investigated