olanzapine and Parkinson-Disease--Secondary

The incidence of acute extrapyramidal symptoms (EPS)--akathisia, dystonia, and parkinsonism--associated with traditional antipsychotics varies, but most researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients who take conventional antipsychotics. Atypical antipsychotics were developed to widen the therapeutic index and to reduce EPS. Although the mechanisms are unclear, the risk of EPS is less with the novel antipsychotics than with conventional drugs, and agents that produce low levels of acute EPS are likely to produce less tardive dyskinesia. Nevertheless, clinicians should exercise caution when comparing data from investigations of the novel antipsychotics and, until long-term data become available, should administer the new drugs at doses below the EPS-producing level.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance Withdrawal Syndrome

Clinical safety data for treatment of acute schizophrenia with olanzapine, a new atypical antipsychotic agent, are summarized. The primary clinical trial safety database included 2500 patients treated with olanzapine, 810 with haloperidol, and 236 with placebo. The overall discontinuation rate from olanzapine treatment was low. Significant adverse events included somnolence, weight gain, and asymptomatic treatment-emergent transaminase elevation. Minimal parkinsonism and akathisia with rare dystonia were noted. No hematotoxicity was noted. The incidence of seizures and sexual dysfunction was rare.

Topics: Acute Disease; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Clinical Trials as Topic; Cross-Over Studies; Dizziness; Double-Blind Method; Dystonia; Haloperidol; Heart Rate; Humans; Liver; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Sleep; Transaminases; Treatment Outcome; Weight Gain

Most traditional neuroleptics have a narrow therapeutic-to-toxic index, and thus, the novel antipsychotics are the result of a search to substantially widen the distance between the dose that treats psychosis and the one that produces adverse effects. In vitro binding profiles have been created for the atypical antipsychotics that have been approved by the U.S. Food and Drug Administration (FDA)-clozapine, olanzapine, and risperidone and those that are under FDA review-quetiapine and sertindole. These profiles, which were compared with that of the typical neuroleptic haloperidol, provide guidance for predicting the adverse effects produced by these drugs. Most conventional antipsychotics have central nervous system effects, particularly extrapyramidal symptoms (EPS) and tardive dyskinesia, sedation, and dulling of cognition. Other adverse effects of the typical antipsychotics include the neuroleptic malignant syndrome, orthostatic hypotension, changes in liver function, anticholinergic and antiadrenergic side effects, sexual dysfunction, and weight gain. The newer agents have a lower incidence of EPS and tardive dyskinesia, while weight gain and changes in blood pressure and liver function tests are adverse effects that have been associated with the use of the newer agents. The favorable side effect profile of these new antipsychotics is likely to make patients more willing to continue treatment, and thus these agents represent a step forward in the treatment of patients with severe, chronic mental illness.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Receptors, Neurotransmitter; Seizures; Sleep; Weight Gain

To compare the blood lactate levels between patients with psychotic disorder receiving first- and those receiving second-generation antipsychotics.. The study was conducted at the psychiatric inpatient and outpatient clinics of the Split Clinical Hospital from June 6, 2008 to October 10, 2009. Sixty patients with psychotic disorder who were assigned to 6-month treatment were divided in two groups: 30 received haloperidol (first generation antipsychotic) and 30 received olanzapine (second generation antipsychotic). Blood lactate levels, other metabolic parameters, and scores on the extrapyramidal symptom rating scale were assessed.. Patients receiving haloperidol had significantly higher blood lactate levels than patients receiving olanzapine (P < 0.001). They also more frequently had parkinsonism, which was significantly correlated with both haloperidol treatment at 1 month (P < 0.001) and 6 months (P = 0.016) and olanzapine treatment at baseline (P = 0.016), 3 months (P = 0.019), and 6 months (P = 0.021). Also, patients receiving haloperidol had significant correlation between blood lactate and dystonia at 1 month (P < 0.001) and 6 months (P = 0.012) and tardive dyskinesia at 1 month (P = 0.032). There was a significant difference between the treatment groups in lactate levels at all points from baseline to month 6 (P < 0.001).. It is important to be aware of the potential effect of haloperidol treatment on increase in blood lactate levels and occurrence of extrapyramidal side effects. Therefore, alternative antipsychotics should be prescribed with lower risk of adverse side effects.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dopamine Antagonists; Drug Monitoring; Haloperidol; Humans; Lactic Acid; Male; Middle Aged; Movement Disorders; Olanzapine; Parkinson Disease, Secondary; Psychiatric Status Rating Scales; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

The purpose of this study was to examine the incidence of Parkinsonism in new users of second-generation antipsychotics (SGAs) in older adults (≥65 years). In the secondary analyses, we examined the risk of Parkinsonism by type and dose of SGA and conducted age-sex interactions.. This population-based study included older adults who had a new-onset diagnosis of Parkinsonism and who started taking olanzapine, risperidone or quetiapine between 1 January 2005, and 30 December 2016. The Cox proportional hazard (COXPH) model with inverse probability treatment weighted (IPTW) covariates was used to evaluate the risk of new-onset Parkinsonism associated with SGAs, using quetiapine as the reference. We used the Generalized Propensity Score method to evaluate the dose-response risk of Parkinsonism associated with SGAs.. After IPTW adjustment for covariates, the COXPH model showed that compared to quetiapine, the use of olanzapine and risperidone were associated with an increased risk of Parkinsonism. The IPTW-hazard ratios are 1.76 (95% confidence interval 1.57-1.97) and 1.31 (95%CI 1.16-1.49), respectively. The dose-response risk of Parkinsonism was highest for olanzapine with a hazard ratio of 1.69 (95%CI 1.40-2.05) and the least for quetiapine with a hazard ratio of 1.22 (95%CI 1.14-1.31). The risk of Parkinsonism in the 65 to 74-year age group was higher for both sexes with risperidone compared to olanzapine, but the risk increased with olanzapine for both sexes in the 85+ age group.. The study found that the risk of new-onset Parkinsonism in older adults is 31% and 76% higher with risperidone and olanzapine respectively compared to quetiapine.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Databases, Factual; Female; Humans; Incidence; Male; New Zealand; Olanzapine; Parkinson Disease, Secondary; Propensity Score; Quetiapine Fumarate; Retrospective Studies; Risk Assessment; Risk Factors; Risperidone; Time Factors

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium Compounds; Male; Olanzapine; Parkinson Disease, Secondary

Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS.. Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS.. In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS.. In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.

Topics: Adolescent; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Male; Mental Disorders; Multivariate Analysis; New York; Olanzapine; Parkinson Disease, Secondary; Piperazines; Prospective Studies; Quetiapine Fumarate; Regression Analysis; Risperidone; Thiazoles

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Flupenthixol; Humans; Male; Mumps; Olanzapine; Parkinson Disease, Secondary

The aim of this study was to evaluate demographic, clinical, and treatment factors that may impact on neurological adverse effects in naive and quasi-naive children and adolescents treated with antipsychotics.. This was a 1-year, multicenter, observational study of a naive and quasi-naive pediatric population receiving antipsychotic treatment. Two subanalyses were run using the subsample of subjects taking the 3 most used antipsychotics and the subsample of antipsychotic-naive subjects. Total dyskinesia score (DyskinesiaS) and total Parkinson score (ParkinsonS) were calculated from the Maryland Psychiatric Research Center Involuntary Movement Scale, total UKU-Cognition score was calculated from the UKU Side Effect Rating Scale. Risk factors for tardive dyskinesias (TDs) defined after Schooler-Kaine criteria were studied using a logistic regression.. Two hundred sixty-five subjects (mean age, 14.4 [SD, 2.9] years) with different Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. DyskinesiaS (P < 0.001) and ParkinsonS (P < 0.001) increased at 1-year follow-up. Risperidone was associated with higher increases in DyskinesiaS compared with quetiapine (P < 0.001). Higher increases in ParkinsonS were found with risperidone (P < 0.001) and olanzapine (P = 0.02) compared with quetiapine. Total UKU-Cognition Score decreased at follow-up. Findings were also significant when analyzing antipsychotic-naive subjects. Fifteen subjects (5.8%) fulfilled Schooler-Kane criteria for TD at follow-up. Younger age, history of psychotic symptoms, and higher cumulative exposure time were associated with TD at follow-up.. Antipsychotics increased neurological adverse effects in a naive and quasi-naive pediatric population and should be carefully monitored. Risperidone presented higher scores in symptoms of dyskinesia and parkinsonism. Quetiapine was the antipsychotic with less neurological adverse effects. Younger subjects, psychosis, and treatment factors predicted an increased risk of TD.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Male; Olanzapine; Parkinson Disease, Secondary; Quetiapine Fumarate; Risperidone

Differences between atypical antipsychotics in their potential to cause parkinsonism and risk factors for antipsychotic-induced parkinsonism are not well established. There is a particular paucity of information on this in real-world use of these drugs, outside of clinical trial settings.. We compared the incidence of parkinsonism after new treatment with risperidone, olanzapine, or quetiapine in patients with dementia and examined the effects of dose and sex on the risk of parkinsonism.. Administrative data from Ontario, Canada between 2002 and 2010 were used to compare the incidence of a diagnostic code for parkinsonism or prescription of an anti-Parkinson medication among patients with dementia who were newly prescribed quetiapine, olanzapine, or risperidone.. From 15,939 person-years of observation, 421 patients developed parkinsonism. Using low-dose risperidone as the reference group, the adjusted hazard ratios for developing parkinsonism were 0.49 (95% CI, 0.07-3.53) for low-dose olanzapine and 1.18 (95% CI, 0.84-1.66) for low-dose quetiapine. Comparing across drugs within the most commonly prescribed dose ranges, the incidence of parkinsonism was higher in the medium-dose olanzapine group compared with the low-dose risperidone group (hazard ratio 1.66; 95% CI 23-2.23). The adjusted hazard ratio for developing parkinsonism for men (compared with women) was 2.29 (95% CI, 1.88- 2.79).. We found no evidence that the risk of drug-induced parkinsonism in older adults with dementia was different among quetiapine, olanzapine, or risperidone, challenging the notion that the drugs differed in their propensity to cause parkinsonism. Men appeared to be at higher risk of parkinsonism as a adverse event than women.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Incidence; Male; Olanzapine; Parkinson Disease, Secondary; Proportional Hazards Models; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Sex Factors

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Electroconvulsive Therapy; Female; Humans; Hyperkinesis; Intellectual Disability; Olanzapine; Parkinson Disease, Secondary; Psychomotor Agitation; Young Adult

The Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) was examined for its usefulness as a subjective measure of drug-induced parkinsonism and akathisia. Eighty-three subjects were assessed using the LUNSERS, the Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS), before and after a 6-week treatment with olanzapine. Significant correlations were found between the changes in scores of parkinsonism items of LUNSERS and SAS. The changes in scores of akathisia item (restlessness), extrapyramidal side effects (EPS) subscale and psychic side-effects subscale of LUNSERS were significantly correlated with those of the BARS. 'Shakiness', one item of the EPS subscale of LUNSERS, correctly classified between parkinsonism and non-parkinsonism groups with 81.0% accuracy. A combination of four items included in EPS and psychic side-effect subscales of LUNSERS identified akathisia and non-akathisia groups with 76.2% accuracy. These results suggest that the EPS and psychic side-effect subscales of LUNSERS may be useful in screening for drug-induced parkinsonism and akathisia.

Topics: Adult; Akathisia, Drug-Induced; Basal Ganglia Diseases; Benzodiazepines; Comorbidity; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Parkinson Disease, Secondary; Patient Participation; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Drug Interactions; Haloperidol; Humans; Male; Olanzapine; Parkinson Disease, Secondary; Pirenzepine

In vivo studies of dopamine D2 receptor occupancy with atypical antipsychotics have suggested good clinical efficacy at occupancy rates less than those observed with typical neuroleptics, and few extrapyramidal side effects (EPS), possibly even at high levels of D2 occupancy. We used [123I]IBZM-SPECT to investigate striatal D2 receptor occupancy in 10 schizophrenic patients who were treated with both a low (5 mg) and a high dose (20 mg) of the novel antipsychotic olanzapine without concomitant medications. The mean D2 occupancy at 5 mg was 59.8% (range 33-81%); the mean D2 occupancy at 20 mg was 82.8% (range 56-97%). Although the D2 occupancy rates on 5 and 20 mg olanzapine were significantly different (P < 0.001), there were no significant differences in clinical ratings for psychiatric symptoms or extrapyramidal side effects between the two doses of olanzapine. These data suggest that: (1) olanzapine doses below those used routinely occupy D2 receptors at levels approaching those associated with therapeutic response; (2) higher doses produce relatively high levels of D2 occupancy rates; and (3) EPS are mild even at relatively high levels of D2 occupancy.

Topics: Adult; Benzamides; Benzodiazepines; Case-Control Studies; Contrast Media; Corpus Striatum; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Pyrrolidines; Receptors, Dopamine D2; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Tomography, Emission-Computed, Single-Photon

Clozapine is the current treatment of choice for drug-induced psychosis (DIP) occurring in Parkinson's disease. However, alternative medications have been sought because of the small but significant risk of agranulocytosis and the need for frequent blood testing. The new "atypical" antipsychotic olanzapine (OLZ) has recently been proposed as a safe and effective option for treating psychosis in this setting. To investigate this, we retrospectively evaluated all 12 of our patients treated with OLZ for DIP. Symptoms of psychosis were improved in nine of 12 patients, but nine of 12 patients also experienced worsening of motor functioning while on OLZ. The worsening was considered dramatic in six of these patients. Overall, there was no significant increase in levodopa doses on OLZ. Only one patient remained on OLZ at the time of the analysis. Nine patients were switched to alternative treatment for DIP. We conclude that although OLZ may improve symptoms of psychosis in parkinsonian patients, it can also worsen motor functioning. In some patients, the degree of motor worsening may be intolerable.

Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Female; Humans; Levodopa; Male; Middle Aged; Motor Skills; Neurologic Examination; Olanzapine; Parkinson Disease; Parkinson Disease, Secondary; Pirenzepine; Psychoses, Substance-Induced; Risk Factors

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Carbon Radioisotopes; Clozapine; Corpus Striatum; Dopamine Antagonists; Female; Humans; Male; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Psychiatric Status Rating Scales; Raclopride; Radioligand Assay; Receptors, Dopamine D2; Salicylamides; Schizophrenia; Tomography, Emission-Computed