A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease

Background: Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use.  Objective: Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable. Methods: In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability. Results: Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ‑39, Schwab-England ADL assessment, and sleep scores). Conclusion: This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease

A pilot study of basal ganglia and thalamus structure by high dimensional mapping in children with Tourette syndrome

Background: Prior brain imaging and autopsy studies have suggested that structural abnormalities of the basal ganglia (BG) nuclei may be present in Tourette Syndrome (TS). These studies have focused mainly on the volume differences of the BG structures and not their anatomical shapes.  Shape differences of various brain structures have been demonstrated in other neuropsychiatric disorders using large-deformation, high dimensional brain mapping (HDBM-LD).  A previous study of a small sample of adult TS patients demonstrated the validity of the method, but did not find significant differences compared to controls. Since TS usually begins in childhood and adult studies may show structure differences due to adaptations, we hypothesized that differences in BG and thalamus structure geometry and volume due to etiological changes in TS might be better characterized in children. Objective: Pilot the HDBM-LD method in children and estimate effect sizes. Methods: In this pilot study, T1-weighted MRIs were collected in 13 children with TS and 16 healthy, tic-free, control children. The groups were well matched for age.  The primary outcome measures were the first 10 eigenvectors which are derived using HDBM-LD methods and represent the majority of the geometric shape of each structure, and the volumes of each structure adjusted for whole brain volume. We also compared hemispheric right/left asymmetry and estimated effect sizes for both volume and shape differences between groups. Results: We found no statistically significant differences between the TS subjects and controls in volume, shape, or right/left asymmetry.  Effect sizes were greater for shape analysis than for volume. Conclusion: This study represents one of the first efforts to study the shape as opposed to the volume of the BG in TS, but power was limited by sample size. Shape analysis by the HDBM-LD method may prove more sensitive to group differences

Clinical features and comorbidity of mood fluctuations in Parkinson\u27s disease

Parkinson\u27s disease (PD) patients commonly develop fluctuations in their motor responses to levodopa within several years of initiation of treatment; some also develop nonmotor fluctuations. The authors performed a case-control study comparing the frequency of comorbid symptoms in 70 PD patients who experienced clinically apparent mood changes during their motor on or off states with two control groups with no mood fluctuations. Mood fluctuators had significantly younger age at onset and longer disease duration and were significantly more likely to have dementia, psychosis, clinical depression, and motor complications. This association remained after removing effects of age and disease duration

A voxel-based morphometry study of Tourette syndrome

<p>We used T1-weighted MRI to compare brain structure in 15 adult TS volunteers and 15 carefully matched tic-free controls. No significant results after correction for multiple comparisons; trend decrease in GM concentration in voxels centered in left precentral gyrus (primary motor cortex) (-26, -12, 66).</p> <p>The official published abstract is available online at http://neuro.psychiatryonline.org/article.aspx?articleid=101807</p> <p>Support: NARSAD, NINDS (NS41248, NS01898),<br>and the Charles A. Dana Foundation. We thank<br>the Tourette Syndrome Association for referral of<br>volunteers.</p> <p>More information: [email protected]</p

Negative results from a randomized controlled trial of olanzapine for psychosis in Parkinson disease: data, CONSORT checklist and initial study protocol

<p>CONSORT checklist</p> <p>Subject characteristics at study entry: S#, subject ID for this study; DRUG, olanzapine dose (mg) this patient took; ADJUST, whether the dose of antiparkinsonian medication was adjusted at the week 2 visit. For remaining columns, the trailing zero in the column heading refers to the score at the baseline (week 0) visit; see Methods section for references. BPRST, BPRS total score; BPRSP, BPRS psychosis items subscore; PDQ, PDQ39 score; BDI, Beck Depression Inventory; HamD, Hamilton Depression Rating Scale; CGIMDo/a, Clinical Global Impression score for overall clinical state as rated by investigator; INS, insomnia score from sleep rating scale; HYPIN, hypersomnia score from sleep rating scale; SEADLS, Schwab-England score; BlindKB, investigator guess at week 4 as to drug assignment; BlindPt., patient guess at week 4 as to drug assignment.</p> <p>Outcomes other than blinded BPRS ratings: S#, subject ID for this study; DRUG, olanzapine dose (mg) this patient took; ADJUST, whether the dose of antiparkinsonian medication was adjusted at the week 2 visit; change, details of that change; use0-2, analyze this subject’s data in the ANOVA for weeks 0-2; use2-4, analyze this subject’s data in the ANOVA for weeks 2-4; WD, ended study participation early; WDSE, withdrew from study because of side effects; WDnowork, withdrew from study because of lack of benefit; WDcure, withdrew from study because subject pronounced self “cured” after one dose; SAEs, serious adverse events; mild SEs, mild side effects; other, other comments on efficacy or side effects; handed, right- or left-handed. For remaining columns, the trailing numeral in the column heading refers to the score at the visit from week 0, 2, or 4. See Methods section for additional information. VH, visual hallucinations present; AH, auditory hallucinations present; Del, delusions present; BPRST, BPRS total score; BPRSP, BPRS psychosis items subscore; 1UPDRS, UPDRS subscale 1; 2UPDRS, UPDRS subscale 2 (etc.); PDQ, PDQ39 score; BDI, Beck Depression Inventory; HamD, Hamilton Depression Rating Scale; CGI, Clinical Global Impression scale; CGIMD, CGI rated by investigator; CGI…overall, CGI score for overall clinical state; CGIPT, CGI rated by patient; CGI…hall, CGI for hallucinations; CGI…improve, CGI improvement from study initiation; INS, insomnia score from sleep rating scale; BlindJH, study RN guess at week 4 as to drug assignment; BlindKB, investigator guess at week 4 as to drug assignment; BlindKBdrug, same, collapsed to simply olanzapine vs placebo (no dose category); BlindPt., patient guess at week 4 as to drug assignment; BlindBR, guess of study neurologist at week 4 as to drug assignment; 0/5/10, whether this subject was enrolled under the initial study drug assignment (placebo vs 5 or 10mg); HYPIN, hypersomnia score from sleep rating scale; SEADLS, Schwab-England score.</p> <p>Blinded BPRS ratings from videotape: video ID#, code by which blinded videotape reviewer scored each video segment; BPRS-T, BPRS total score; BPRS-P, BPRS psychosis items subscore.</p

Data file (subject characteristics, volume and shape)

<p>In this data file the columns from left to right represent Diagnosis (dx=diagnosis, T = TS or chronic tic disorder, C = Control), Sex (m = male, f = female), Age at scan (in years), and handedness (L = Left, R = Right, A = Ambidextrous). Then the shape principal component (eigenvector) values are represented as demonstrated by the following example: “NaLpc01” = nucleus accumbens (Na) Left (L) principal component (pc) 01. (“Na” = nucleus accumbens, “Cd” = caudate, “Pl” = globus pallidus, “Pu” = putamen, “Th” = thalamus). Next the volumes are listed using similar notation, e.g. “volCdL” = volume in mm3 (vol) Caudate (Cd) Left (L). Finally, Freesurfer analysis values are listed using their standard notation, which can be found in the table at: http://ftp.nmr.mgh.harvard.edu/fswiki/FsTutorial/AnatomicalROI#aseg.stats - See more at: http://62.231.116.94/black/#sthash.OO28vyHo.dpuf</p