Prevalence of movement disorders in adolescent patients with schizophrenia and in relationship to predominantly atypical antipsychotic treatment

Objective To examine prevalence of movement disorders (MDs) such as tardive dyskinesia (TD), parkinsonism or akathisia in an adolescent population with schizophrenia and in relationship to predominantly atypical antipsychotic treatment. Method Ninety-three patients (aged 19.6±2.2 years) were ascertained in this cross-sectional/retrospective study. 76 patients (81.7%) received atypical, 10 (10.8%) typical antipsychotics and 7 (7.5%) combinations of atypical/typical antipsychotics. MD symptoms were assessed using Tardive Dyskinesia Rating Scale (TDRS), Abnormal Involuntary Movement Scale (AIMS), Extrapyramidal Symptom Scale (EPS), Barnes Akathisia Scale (BAS). Results Movement disorder symptoms were found in 37 patients (39.8%) fulfilling strict/subthreshold criteria for TD (5.4/11.8%), parkinsonism (2.2/25.8%) or akathisia (1.1/11.8%), respectively. Patients treated with typical antipsychotics displayed a significantly higher EPS-score (P=0.036) and a tendency towards a higher BAS-score (P=0.061) compared to patients with atypical antipsychotics. Treatment durations with typical/atypical antipsychotics showed trends towards advantages of atypical antipsychotics with regard to parkinsonism/akathisia symptoms (P=0.061; P=0.054), but not with regard to TD symptoms (P=0.003), possibly due to confounding effects. Conclusion Under treatment with atypical antipsychotics MD symptoms are less prevalent and less pronounced than under typical antipsychotics. We speculate that the finding of relatively high prevalence rates of subthreshold MD symptoms may be, at least partially, explained by previous or combined therapy with typical antipsychotics.     

Metabolic syndrome in antipsychotic naïve patients diagnosed with schizophrenia

Aim: The article aims to study the prevalence of metabolic syndrome (MS) and subthreshold MS in antipsychotic naïve patients with schizophrenia. Materials and methods: Forty‐six antipsychotic naïve patients diagnosed with schizophrenia were evaluated for the presence of metabolic abnormalities using International Diabetes Federation and modified National Cholesterol Education Program – Third Adult Treatment Panel criteria. Results: Five patients (10.86%) fulfilled International Diabetes Federation criteria for MS and six patients (13.04%) met modified National Cholesterol Education Program – Third Adult Treatment Panel criteria for MS. Additionally, 14 (30.43%) more patients fulfilled 2 out of the 5 criteria for MS and another 19 (41.3%) fulfilled 1 criterion for MS. Of the 19 patients who fulfilled one criterion for MS, 18 had an abnormality other than increase in waist circumference. Conclusion: Findings of the present study suggest that although only few antipsychotic naïve patients diagnosed with schizophrenia have MS, a significantly large proportion of patients have subsyndromal MS. Awareness of this in clinicians can have implications in the selection of antipsychotic medication.     

Incidence of tardive dyskinesia with typical versus atypical antipsychotics in very high risk patients.

Our aim was to study the risk of developing tardive dyskinesia in highly vulnerable patients (i.e., middle-aged and older adults with borderline dyskinesia) treated with conventional versus atypical antipsychotics.We examined the cumulative incidence of definitive tardive dyskinesia at 1, 3, and 6 months during antipsychotic treatment among 240 outpatients at least 45 years of age who had borderline tardive dyskinesia at baseline.Patients treated with conventional antipsychotics were approximately two times more likely to develop definitive tardive dyskinesia during the study period compared with those treated with atypical antipsychotics (p <.001). This difference was found despite patients in the atypical antipsychotic group being significantly older and having more severe extrapyramidal symptoms at baseline than those prescribed typical antipsychotics.Among patients at a very high risk for worsening tardive dyskinesia, the use of atypical antipsychotics was associated with a significantly lower risk of developing definitive tardive dyskinesia compared with conventional antipsychotics.     

MRI volumetric and 31P MRS metabolic correlates of caudate nucleus in antipsychotic-naïve schizophrenia

Objective: To examine the volumetric and metabolic correlates of caudate nucleus in antipsychotic‐naïve schizophrenia patients in comparison with healthy controls. Method: Twelve antipsychotic‐naïve schizophrenia patients and 13 healthy controls underwent ³¹P magnetic resonance spectroscopy of basal ganglia. Magnetic resonance imaging volume of caudate nuclei was measured using scion image software. Results: Patients had significantly smaller caudate volume than healthy controls. Phosphocreatine (PCr)/total phosphorous and PCr/total adenosine tri‐phosphate ratios of both caudate nuclei were significantly lower in patients than controls. Significant negative correlation was found between the left caudate volume and left PCr/total phosphorus ratio in the patients. Age at onset of psychosis had i) significant negative correlation with right and left caudate volumes and ii) significant positive correlation with left PCr/total phosphorus ratio. Conclusion: The metabolic and volumetric abnormalities of caudate nucleus in antipsychotic‐naïve schizophrenia patients support neurodevelopmental etiopathogenesis.     

Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine

Aims: Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second‐generation antipsychotics in dopamine D₂ receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D_2/3 receptor apparent binding potential (BP_app) and occupancy in midbrain and temporal cortex among clozapine‐, olanzapine‐ and haloperidol‐treated schizophrenia patients. Methods: Dopamine D_2/3 binding was studied on single‐photon emission computed tomography ligand [¹²³I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug‐naïve patients and seven healthy controls. Results: Statistically significant differences in midbrain dopamine D_2/3 receptor BP_app (P = 0.015) and occupancy (P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine‐treated patients (5%), followed by olanzapine‐treated patients (28%), compared to haloperidol‐treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug‐naïve vs healthy controls) in the examined brain areas (P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used. Conclusion: Both typical and second‐generation antipsychotics occupy cortical dopamine D_2/3 receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D_2/3 occupancy between classical antipsychotics and second‐generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.     

Patterns of clinical use of antipsychotics in hospitalized psychiatric patients

The ways of using antipsychotic drugs have greatly changed over the last 10 years. The aim of this study was to evaluate such changes in psychiatric patients admitted to the Psychiatric Department of Milan's Ospedale Maggiore in 1989 (n=350), 1999 (n=718) and 2002 (n=628). The medical records of the hospitalized patients were evaluated by analyzing the anamnestic and clinical data with particular reference to age, gender, diagnosis and medication use. In 2002, atypical antipsychotics were more frequently prescribed as monotherapy upon discharge than typical antipsychotics (32.64% vs. 30.10%). Combinations of two or more antipsychotic drugs were prescribed upon discharge for 20.63% of the patients in 1989, 31.24% in 1999 and 23.09% in 2002. The combinations of one typical and one atypical drug increased from 4.04% in 1999 to 13.06% in 2002. The mean (+/-S.D.) daily antipsychotic drug dose (expressed in chlorpromazine equivalents) was significantly higher in 2002 than in 1999 and 1989. The results of this study confirm the trend to use combinations of one typical and one atypical antipsychotic, and higher doses.     

The use of antipsychotic medication in child and adolescent psychiatric treatment in Denmark. A cross-sectional survey

The number of children and adolescents with psychiatric disorders being treated with antipsychotic medication is increasing significantly; however, only a limited evidence-base is available on this topic, especially when children are concerned. This study reports and discusses the use of antipsychotic medication in children and adolescents below 19 years of age in Denmark. A national cross-sectional survey registered the use of antipsychotic drugs on a given date. A questionnaire was sent to all child and adolescent psychiatric departments and all consultants in child and adolescent psychiatry throughout the country. All children and adolescents, aged 0–18 years, registered in treatment with antipsychotic medication, were included. Sixty-seven per cent of clinics and 63% of consultants participated. The total number of subjects registered in examination or treatment in the participating units was 3854. Antipsychotic medication was used in n=244 (6.4%) of these cases. Eighty-eight patients received additional medication, of which 24% received antidepressants, 8% sedative medication and 4% psychostimulants. The age of the patients was 4–18 years, and 63% was male. The most frequent diagnoses for patients in antipsychotic treatment were: schizophrenia, schizotypal disorder, autism spectrum disorders and personality disorders. Monotherapy was used in 87% of cases. Sixty-four per cent of patients treated with antipsychotics, received a second-generation antipsychotic as the main treatment. All 244 patients received one or more additional treatment modalities other than medication. Antipsychotic medication has a definite role in the treatment of children and adolescents with psychiatric disorders. Second-generation antipsychotics used as monotherapy prevail.     

Neuroleptic-related dyskinesias in children and adolescents.

BACKGROUND: Few studies have investigated the comparative risk of neuroleptic-related dyskinesias in children and adolescents receiving typical versus newer, atypical antipsychotics. This prospective study was completed to test whether clinical use of atypical antipsychotics is associated with less risk for developing neuroleptic-related dyskinesias than clinical use of typical neuroleptics in an unselected heterogeneous population of seriously emotionally disturbed youths admitted to acute residential treatment. We also tested a novel model of predictive risk for neuroleptic-related dyskinesias in children and adolescents. METHOD: 102 children and adolescents receiving typical neuroleptics, atypical antipsychotics, or the combination were studied. Youths developing neuroleptic-related dyskinesias were compared with youths free of dyskinesias over a 3-month study period on demographic, diagnostic, and treatment variables. Logistic regression was utilized to develop a novel model of predictive risk. RESULTS: Of neuroleptic-treated youths, 5.9% had probable tardive dyskinesia, a rate less than the prevalence of tardive dyskinesia in chronic neuroleptic-treated adults. Use of typical neuroleptics was significantly (p = .03) associated with dyskinesia compared with use of atypical antipsychotics. Four variables including IQ, initial Abnormal Involuntary Movement Scale score, type of antipsychotic, and cumulative number of risk factors accounted for 35.8% of the variance when predicting dyskinetic status. CONCLUSION: Use of atypical antipsychotics appears to be associated with less dyskinesia risk than typical neuroleptics in an unselected group of seriously emotionally disturbed children and adolescents. Results support a cumulative risk model of neuroleptic-related dyskinesia in youths.     

Glatiramer acetate in treatment-naïve and prior interferon-beta-1b-treated multiple sclerosis patients

Objective – This prospective, open‐label study evaluated the efficacy, safety, and tolerability of glatiramer acetate (GA) in treatment‐naïve relapsing–remitting multiple sclerosis (RRMS) patients and in patients who had previously received interferon‐β (IFN‐β)‐1b therapy. Methods – Two treatment cohorts were defined based on prestudy IFN‐β‐1b use. At entry, prior IFN‐β‐1b patients (n = 247) were older, had longer disease duration, and had higher mean Expanded Disability Status Scale (EDSS) scores, relapse rates, and ambulation indexes than treatment‐naïve patients (n = 558). Safety was assessed every 3 months and EDSS every 6 months for up to 3.5 years. Results – Overall, 247 treatment‐naïve and 107 prior IFN‐β‐1b patients discontinued before study end. Median GA treatment durations were 36 and 24 months in treatment‐naïve and prior IFN‐β‐1b patients, respectively. At last observation, annual relapse rates had declined by 75% in both cohorts (0.42 ± 0.84 and 0.34 ± 0.71 in treatment‐naïve and prior IFN‐β‐1b groups, respectively, P = 0.1482). Mean changes in EDSS were less than 0.5 in both cohorts, regardless of entry EDSS, at 12 and 18 months and at last observation. Conclusions – Prior IFN‐β‐1b treatment does not negatively influence the efficacy, safety, or tolerability of subsequent GA therapy. Switching to GA can benefit patients who discontinue IFN‐β therapy.     

Expected incidence of tardive dyskinesia associated with atypical antipsychotics

Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol.     

Use of the atypical antipsychotics Olanzapine and Risperidone in adults with intellectual disability

The present study was designed to monitor the use of atypical antipsychotics in adults with intellectual disability and to evaluate the clinical effectiveness of these drugs. Twenty‐one patients were commenced on an atypical antipsychotic: 12 on Olanzapine and nine on Risperidone. The ICD‐10 diagnoses of the subjects were mild (13 cases) or moderate (8 cases) mental retardation, and psychiatric disorders (17 cases) with significant impairment of behaviour in 10 cases. Tolerability was good for 15 patients experiencing minimum or no side‐effects, and medication was only stopped as a result of side‐effects in one case. Clinical global outcome was rated as minimally improved or better for 16 cases. The present findings suggest that the atypical antipsychotics Olanzapine and Risperidone are well tolerated by patients with intellectual disability and psychiatric disorders, and are broadly effective against target symptoms.     

Atypical antipsychotic medication improves aggression, but not self-injurious behaviour, in adults with intellectual disabilities

Objective Atypical antipsychotic medications have largely supplanted their typical counterparts, both for psychosis and for the treatment of aggression and/or self‐injurious behaviour (SIB), in persons with intellectual disabilities (ID). However, with the exception of risperidone, little systematic research supports their use in such persons. Method A retrospective review of 31 adult residents of a state developmental centre, who were treated for aggression and/or SIB with atypical antipsychotics. Average monthly counts of aggression and SIB for 1 year of treatment with typical antipsychotics, were compared with monthly averages for the next 12 months of treatment with atypical antipsychotics. Results Twenty‐seven of 31 subjects (87%) completed a full year of atypical antipsychotic treatment. Subjects ranged in age from 24 to 54 years (mean = 39); 18/31 (58%) had profound ID. Twelve of 26 (46%) had typical antipsychotics discontinued within the year of atypical treatment; another 7/26 (27%) had their typical antipsychotic dose decreased. Twenty‐three of 31 trials involved risperidone; 7/31 olanzapine; 1/31 quetiapine. Subjects gained an average of 6.6 pounds during the year of atypical treatment, but no significant changes in glucose or cholesterol were found. Subjects with aggression alone (N = 14) had significant decreases in the number of aggressive acts per month during the year of atypical treatment (P = 0.03); those with both aggression and self‐injury (N = 12), or those with self‐injury alone (N = 5) had no significant improvement. Conclusion The findings suggest that atypical antipsychotics can be successfully substituted for typical agents in individuals with ID and decrease the frequency of aggression over one year of treatment. The weight gain seen in our sample reinforces the necessity of regular monitoring of weight and metabolic changes in persons with ID treated with atypical antipsychotics.     

Tardive dyskinesia: eliminated, forgotten, or overshadowed?

PURPOSE OF REVIEW: The present review focuses on atypical antipsychotics and tardive dyskinesia. RECENT FINDINGS: We have known for many years that clozapine has a diminished risk of tardive dyskinesia compared with typical antipsychotics. The last decade has seen the introduction of a number of other atypical antipsychotics, allowing us to begin evaluating whether they too share this attribute. In addition, the opportunity to use these drugs as first-line treatment permits a more precise means of establishing risk. While longer-term data are required, the limited evidence available clearly indicates that the atypical antipsychotics have a decreased liability of tardive dyskinesia, approximately 1% compared with 5% for typical agents annually. Like clozapine, the other atypical antipsychotics also demonstrate antidyskinetic properties in individuals with preexisting tardive dyskinesia. The underlying mechanisms remain unclear, and without such information it is not possible to say what clinical conditions, if any, might diminish or even eliminate these advantages. SUMMARY: An update is provided regarding the atypical antipsychotics and tardive dyskinesia. This information is critical in our decision-making regarding choice of antipsychotic and optimal use in the clinical setting.     

Influence of antipsychotic agents on neurological soft signs and dyskinesia in first episode psychosis

First episode psychosis patients treated with atypical antipsychotics had significantly fewer signs of dyskinesia than patients treated with classical antipsychotics, but there were no significant differences regarding the total number of neurological soft signs (NSS). This suggests that the type of antipsychotic medication does not influence NSS, but that atypical antipsychotics are associated with less dyskinesia in the early stages of treatment.     

Clinical features of Sjogren’s syndrome in patients with multiple sclerosis

Annunziata P, De Santi L, Di Rezze S, Millefiorini E, Capello E, Mancardi G, De Riz M, Scarpini E, Vecchio R, Patti F. Clinical features of Sjogren’s syndrome in patients with multiple sclerosis.
Acta Neurol Scand: 2011: 124: 109–114.
© 2010 John Wiley & Sons A/S. Objectives – To assess the frequency of clinical features of Sjogren’s syndrome (SS) in patients with multiple sclerosis (MS) receiving treatment with disease‐modifying drugs (DMDs) or naïve to treatment and the possible association with clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) parameters. Methods – A multicentre cross‐sectional observational study was designed, based on a structured neurologist‐administered questionnaire to 440 patients. Results – Twenty‐eight of 230 (12%) patients receiving treatment with DMDs (DMDs⁺) and 14 of 210 (6.6%) treatment‐naïve patients (DMDs⁻) showed clinical features of SS. Four primary SS were diagnosed, two of which were DMDs⁺ and two were DMDs⁻. Sicca symptoms were significantly associated with higher EDSS scores (P = 0.018), a low frequency of gadolinium‐enhanced MRI‐positive lesions (P = 0.018) and cerebral disturbances (P = 0.001). Conclusions – Screening for the clinical features of SS should be performed in patients with MS both receiving treatment with immunomodulatory drugs and without therapy.     

Tardive dyskinesia and other movement disorders secondary to aripiprazole

The objective of this report is to draw attention to tardive dyskinesia (TD) caused by aripiprazole, a third generation antipsychotic. TD has been traditionally attributed to typical (first‐generation) antipsychotics, but other dopamine receptor blocking drugs and atypical (second‐ and third‐generation) neuroleptics are emerging as an important cause of TD. We reviewed the medical records of patients with TD seen at the Baylor College of Medicine Movement Disorders Clinic between 2002 and 2010 to identify patients with TD associated with aripiprazole. Among 236 patients with TD seen over the specified period, 8 (3.4%) were found to have aripiprazole‐associated TD. In 5 patients, TD occurred after exclusive exposure to aripiprazole. The mean age at onset was 55.8 ± 14.8 years with a female predominance. The average duration of treatment with aripiprazole was 18.4 ± 26.4 months. Oro‐bucco‐lingual stereotypy was seen in all patients. In most patients, TD did not spontaneously improve after stopping aripiprazole. Of the 5 patients treated with tetrabenazine, 4 improved during follow‐up. Although aripiprazole, a third generation antipsychotic, has been promoted to have a low risk of TD, the drug accounts for about 3.5% of patients with TD evaluated in a movement disorders clinic. This largest reported series draws attention to the growing incidence of TD and other drug‐induced movement disorders associated with “atypical antipsychotics.” © 2010 Movement Disorder Society     

Extrapyramidal side effects, tardive dyskinesia, and the concept of atypicality

The most frequent problems associated with the older generation of antipsychotic agents are extrapyramidal side effects (EPS) and tardive dyskinesia. Neuroleptic-induced EPS are thought to be caused by blockade of nigrostriatal dopamine tracts resulting in a relative increase in cholinergic activity; tardive dyskinesia is less well understood but is thought to be a supersensitivity response to chronic dopamine blockade. The leading hypothesis for the mechanism of action of the newer generation of atypical antipsychotics is the presence of a high serotonin-to-dopamine receptor blockade ratio in the brain. When serotonergic activity is blocked-as is the case with atypical antipsychotics-dopamine release increases and balances out the dopamine blockade effect at postsynaptic receptor sites, which results in few or no EPS. Prospective data indicate that the risk of tardive dyskinesia in patients taking atypical antipsychotics is less than that for those taking typical antipsychotics. This article reviews the mechanisms of neuroleptic-induced EPS and tardive dyskinesia and discusses the relationship between these movement disorders and atypical antipsychotic agents.