A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder

Atypical antipsychotics have been shown to improve disruptive and repetitive behaviors in pervasive developmental disorders (PDDs), but they require assessment of potential side effects. This is the first placebo-controlled trial of olanzapine in the treatment of children and adolescents with PDD. Eleven patients with a diagnosis of either autism, Asperger's syndrome, or PDD not otherwise specified (PDD-NOS) and aged 6-14 years were randomized into an 8-week double-blind, placebo-controlled, parallel treatment study with olanzapine. There was a significant linear trend x group interaction on the Clinical Global Impressions- Improvement (CGI-I) and 50% on olanzapine versus 20% on placebo were responders. Olanzapine was associated with significant weight gain (7.5 +/- 4.8 lbs vs. 1.5 +/- 1.5 lbs on placebo). Olanzapine may be a promising treatment for improving global functioning of PDDs, but the risk of significant weight gain remains a concern. Additional studies are needed to determine the efficacy and safety of olanzapine in the treatment of children with PDD.     

Olanzapine therapy in treatment-resistant psychotic mood disorders: a long-term follow-up study

BACKGROUND: Recent studies suggest a role for the atypical antipsychotic olanzapine in the acute treatment of psychotic mood disorders, but long-term data are unavailable. The purpose of this naturalistic study was to determine the long-term effectiveness and tolerability of olanzapine as add-on therapy in psychotic mood disorders. METHOD: Hospital records were reviewed for 125 inpatients at the state psychiatric hospital in Buffalo, N.Y., who received at least 6 weeks of add-on olanzapine treatment for psychotic mood disorders (schizoaffective disorders [bipolar and depressive type], bipolar disorders [I, II, and NOS], and major depressive disorder). A group of schizophrenic patients served as a control group (N = 50). Baseline measures, including age, gender, number of hospitalizations in the 2 years prior to olanzapine treatment, concomitant medications, the Clinical Global Impressions scale (CGI), and the Global Assessment of Functioning-Equivalent (GAF-EQ) and Kennedy Axis V psychological impairment, violence, social skills, and activities of daily living subscale scores, were obtained. Follow-up information was obtained from the patients at least 6 months after initiation of olanzapine or by chart review and discussion with the treating psychiatrist. Patients with a diagnosis of psychotic mood disorders were compared with patients with the non-affective psychotic disorder (schizophrenia) on a variety of outcome measures. RESULTS: Follow-up information was available on 102 patients (82%). Mean follow-up was 15 months; 50 (49%) of the 102 patients remained on olanzapine treatment at follow-up (32 psychotic mood disorder, 18 schizophrenic). The primary reason for discontinuation in both groups was lack of response. Both the psychotic mood disorder and schizophrenic groups had comparable outcomes on the CGI and GAF-EQ. Improvement on the Kennedy Axis V psychological impairment and social skills subscales was seen only in the psychotic mood disorders group (p < .01); both groups showed significant (p < .02) improvement in the violence subscale. Sustained mood-stabilizing effect was evident in only 7/27 (26%) of the psychotic mood disorders patients continuing on add-on olanzapine treatment at follow-up. CONCLUSION: Lack of response was the primary reason for discontinuation of add-on olanzapine in both groups. Mood symptoms predicted a better response to add-on olanzapine in patients with psychotic mood disorders on selective outcome measures. However, only 26% of the patients with psychotic mood disorders sustained a clinically meaningful mood-stabilizing effect with add-on olanzapine treatment at follow-up.     

Use of atypical antipsychotics in a Veterans Affairs hospital

In a retrospective chart review, efficacy and drug costs were compared in 91 consecutive outpatients receiving risperidone (n=70) or olanzapine (n=21) at the Veterans Affairs Medical Center in Syracuse, NY. Between-group differences in background characteristics, diagnoses (schizophrenia in more than half of each group) and antipsychotic efficacy [Clinical Global Impressions (CGI) scale scores] were not significant. The mean doses were 3.6+/-2.4 mg/day of risperidone and 10.7+/-7.6 mg/day of olanzapine. The VA costs of these mean doses were S3.32/day for risperidone and $6.67/day for olanzapine. Mean duration of treatment was significantly longer for risperidone (21 months) than for olanzapine (13 months). Incidence of parkinsonian symptoms (14% of both risperidone and olanzapine patients) and tardive dyskinesia (3% of risperidone patients and 5% of olanzapine patients) was similar in the two groups. Akathisia tended to occur more often in patients receiving olanzapine than risperidone (14% versus 3%, P=.08). The results of this retrospective survey indicate that, in comparable VA populations of patients with psychotic and other disorders, risperidone and olanzapine are equally efficacious but olanzapine may be more likely to produce akathisia and is twice as expensive as risperidone.     

Comparison of Risperidone and Olanzapine in Bipolar and Schizoaffective Disorders

OBJECTIVE: To compare risperidone and olanzapine for efficacy, tolerability, need for concomitant mood stabilizers, and cost of treatment in bipolar and schizoaffective disorders. METHOD: We conducted a retrospective chart review of 36 consecutive outpatients with DSM-IV bipolar or schizoaffective disorder seen in 3 settings who received risperidone or olanzapine for at least 1 month between May and August 1997. RESULTS: The mean +/- SD doses were 3.7 +/- 3.5 mg/day of risperidone and 12.0 +/- 5.4 mg/day of olanzapine. Between-treatment differences in patient characteristics, psychiatric history, Clinical Global Impressions scale ratings, and duration of treatment were not significant. Similar proportions of patients in the 2 groups reported side effects, including extrapyramidal symptoms, akathisia, tardive dyskinesia, and precipitation of mania by the respective drug. Patients in the olanzapine group received a significantly higher dose of concomitant lithium than those receiving risperidone (mean daily lithium doses: risperidone group, 750 +/- 150 mg; olanzapine group, 1211 +/- 186 mg; p =.006). The total daily acquisition cost per patient was $11.84 for olanzapine versus $5.81 for risperidone. CONCLUSION: Olanzapine and risperidone were equally efficacious and safe in the treatment of patients with bipolar or schizoaffective disorder, but treatment costs and dose of concomitant lithium were lower in risperidone-treated patients.     

A retrospective assessment of topiramate in children and adolescents with pervasive developmental disorders

An open-label retrospective study was conducted to assess the effectiveness and tolerability of topiramate in children and adolescents with pervasive developmental disorders (PDD). Topiramate is a novel antiepileptic drug approved as an adjunctive treatment for seizure disorders. A retrospective chart review was conducted in an outpatient clinic specialized in treating individuals with developmental disabilities, to identify all children and adolescents with PDD who received topiramate. Patients were included if concomitant medications remained unchanged. Treatment response was assessed using the Global Improvement item of the Clinical Global Impressions scale (CGI-GI), based on a review of medical records and the Conners Parent Scale (CPS), as completed by parents. Fifteen patients were identified (12 male, 3 female; age = 14.7 +/- 3.3 years), including 11 patients with autistic disorder, 2 patients with Asperger's disorder, and 2 patients with PDD not otherwise specified (PDD, NOS). Eight patients (4 patients with autistic disorder, 2 patients with Asperger's disorder, and 2 patients with PDD, NOS) were judged to be responders, as defined by a score of 1 or 2 on the CGI-GI. Treatment duration was 25 +/- 16 weeks, and the mean dose was 235 +/- 88 mg. Differences between baseline and the end-of-trial period were observed in the following CPS subscales: conduct, hyperactivity, and inattention. No differences were noted in the psychosomatic, learning, and anxiety subscales. Three patients discontinued topiramate because of side effects, with 2 patients experiencing cognitive difficulties and 1 patient a skin rash. Topiramate may be beneficial for treating secondary symptoms of PDD, and prospective openlabel studies and double-blind, placebo-controlled studies to assess its efficacy and safety are needed.     

An open-label,flexible-dose study of olanzapine in the treatment of trichotillomania

BACKGROUND: Thus far, only selective serotonin reuptake inhibitors have been systematically studied in the treatment of trichotillomania, and the results are conflicting. This open-label study is the first to systematically evaluate an atypical neuroleptic, olanzapine, as a monotherapy in the treatment of trichotillomania. METHOD: Twenty-one patients were screened and 18 patients were enrolled in a 3-month open-label study of olanzapine for trichotillomania (diagnosis based on modified DSM-IV criteria). Patients with comorbid psychiatric disorders or on treatment with psychoactive medication were excluded. Olanzapine was titrated gradually in 2.5-mg/week increments up to a maximum dose of 10 mg/day. RESULTS: Seventeen patients who completed at least 1 week of olanzapine treatment were evaluated. Hair pulling, as measured by the Massachusetts General Hospital Hairpulling Scale, decreased by 66% from baseline (p < or =.001), and mean scores on the Hamilton Rating Scale for Anxiety decreased by 63% (p < or =.05). Clinical Global Impressions scale scores also revealed significant improvement as a whole (p < or =.001), with 4 patients having complete symptom remission at the end of the study period. CONCLUSION: Findings suggest that olanzapine may be an effective monotherapy for trichotillomania.     

Prospective long-term follow-up of patients with pervasive developmental disorders

We conducted a 12-year prospective study of children with pervasive developmental disorders from North Dakota. In a prospective longitudinal follow-up study, of 59 patients, we found 52 patients with pervasive developmental disorders (88%). Ten (17%) declined to participate. We collected data on 42 (71%) of the original cohort. Of the 42 subjects, 1 died (1.7%). The other 41 were followed up for 492 person-years. Severity scores for the Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) declined 20% and for DSM-IV 23%. Global Assessment of Functioning improved 19%, and the average number of comorbidities decreased 45%. Thirty-seven percent of patients improved in all four measures, whereas only 5% improved in only one measure. Pervasive developmental disorders are developmental disorders with a long-term course of limited improvement for most patients. Male subjects demonstrated substantially more variability in improvement but, overall, demonstrated more improvement than female subjects.     

Safety and tolerability of olanzapine compared with other antipsychotics in the treatment of elderly patients with schizophrenia: a naturalistic study.

OBJECTIVE: To evaluate the safety and tolerability of olanzapine in the treatment of elderly patients with schizophrenia. METHODS: A total of 135 outpatients with schizophrenia > or =60 years of age were treated with olanzapine (n = 105) or another antipsychotic (n = 30) and followed up for 6 months. Safety measures included the recording of spontaneous adverse events and extrapyramidal symptoms (EPS). Clinical status and effectiveness of the medications were measured using the Clinical Global Impressions-Severity of Illness and the Global Assessment of Function (GAF) scales. Quality of life was assessed by means of the Spanish version of the EuroQol. The Awad scale was applied to evaluate patients' subjective attitude towards medication. RESULTS: The incidence of overall adverse events and EPS was non-significantly lower in patients treated with olanzapine than in patients treated with other antipsychotics. The use of anticholinergic drugs was significantly lower (P = 0.04) in patients treated with olanzapine. Both groups of patients experienced similar improvements in Clinical Global Impressions-Severity and GAF scores. Non-significantly greater improvement in the acceptance of medication occurred at endpoint in olanzapine-treated patients than in control patients as measured by the Awad scale. The improvement in the EuroQol quality of life scale achieved at the end of study did not differ between both treatment groups. CONCLUSIONS: Results from this naturalistic study showed that olanzapine was as safe and effective as other antipsychotic drugs in the treatment of elderly patients with schizophrenia.     

Six-month outcomes for patients who switched to olanzapine treatment

OBJECTIVE: This study evaluated the outcomes of patients in a community mental health center who switched from treatment with another antipsychotic to olanzapine treatment. It also sought to determine whether simultaneous access to case management and psychosocial rehabilitation and olanzapine leads to enhanced functional improvement. METHODS: Six-month outcomes for a consecutive series of 104 patients who switched from a conventional antipsychotic medication to olanzapine were evaluated. Forty-nine patients in the same treatment program who continued to take conventional antipsychotics were also monitored as a reference group. Outcomes of the group receiving olanzapine were compared with their own baseline status and with outcomes of the reference group. RESULTS: At six months, patients in the olanzapine group demonstrated significant improvement over baseline across multiple measures of symptoms and psychosocial function. Compared with the reference group, the olanzapine group was more symptomatic at baseline and demonstrated significantly greater improvement at follow-up on the Brief Psychiatric Rating Scale and all subscales; Mini Psychiatric Rating Scale negative symptom, disorganization, anxiety, depression, and medication side effects items; and Clinical Global Improvement scale and Case Manager's Rating Scale-Plus illness factors. There was a trend toward superior improvement in psychosocial functioning among patients in the olanzapine group that achieved significance when patients in acute relapse at baseline were excluded. CONCLUSIONS: Olanzapine is effective in managing markedly to severely ill patients with psychotic disorders in a community mental health center. Simultaneous treatment with olanzapine, case management, and psychosocial rehabilitation leads to enhanced functional improvement among nonrelapsing patients.     

Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders

Atypical antipsychotics are emerging as the first-line pharmacologic treatment for irritability (i.e., aggression, self-injurious behavior, and severe tantrums) in children and adolescents with autistic and other pervasive developmental disorders. Results from placebo-controlled and open-label studies of clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole in this subject population are reviewed. Additional placebo-controlled trials and studies of longer-term safety and tolerability are needed.     

Olanzapine vs. haloperidol in the treatment of elderly chronic schizophrenia patients

OBJECTIVE: Most of the data supporting the use of atypical antipsychotics (AA) is based on studies in young adult patients. The present study is an open-label naturalistic follow-up study of olanzapine treatment vs. haloperidol for elderly chronic schizophrenia patients. MEHTOD: 20 patients (mean age 72.7+/-5.9 years, mean disease duration 33.1+/-12.0 years) who met the DSM-IV criteria for schizophrenia were randomly assigned to olanzapine (n=10) or haloperidol (n=10) treatment during acute exacerbation. Primary outcome measure was rating on the Clinical Global Impression (CGI) scale and the Positive and Negative Symptom Scale (PANSS). RESULTS: Between-group differences were computed using analysis of covariance. PANSS Total score decreased from 84 at baseline to 65 after treatment with olanzapine while decreased only from 79 to 74 with haloperidol treatment (F= 6.66, P=.02). PANSS Negative subscale decreased from 19 at baseline to 15 with olanzapine treatment while increased (deteriorated) from 18 to 20 with haloperidol treatment (F=23.37, P=.0003). CGI decreased from baseline with both olanzapine and haloperidol treatments (1.1 vs. 0.4) but the decrease in the olanzapine group was significantly greater (F=4.63, P=.05). Mean weight increased in both groups but without statistical difference between groups. CONCLUSIONS: In elderly chronic schizophrenia patients, olanzapine treatment is superior to haloperidol in reducing negative symptoms as well as less induction of extrapyramidal symptoms (EPS).     

Prescription of olanzapine in children and adolescent psychiatric patients

INTRODUCTION: A review of the literature from 1996-2004 on the indications and adverse reactions concerning the use of olanzapine, a second generation antipsychotic agent, in children and adolescents with psychiatric illness is made in this article. Studies lasted for 2 to 3 months and a few had a follow up period up to a year. Olanzapine, dosed from 2.5 to 20 mg/day, is shown to be a useful drug in the treatment of child and adolescent onset schizophrenia, bipolar disorder, anorexia nervosa with delusions, pervasive developmental disorder, tic disorders, and aggression. OPEN AND DOUBLE-BLIND STUDIES: In 4 open labeled studies (26, 34, 39, 43) and 2 case reports (25), 53 patients, aged from 6-18 years old, afflicted by child onset schizophrenia, were treated with olanzapine for 1 1/2 weeks to one year; 19 had treatment resistant childhood schizophrenia and 34 a first episode. In the first group 13/19 showed improvement whereas, in the second group 27/34 were considered responders. Four patients in the first group who had responded to clozapine (stopped because of adverse events) did less well on olanzapine. In 5 studies, 4 open labeled (15, 20, 44) and 1 double blind (27), 59 adolescent onset schizophrenic patients were treated by olanzapine from 8 to 26 weeks; 50/59 patients were considered responders. In the open label study (20) comparing 43 adolescents treated by olanzapine (19 patients), risperidone (17 patients), or haloperidol (7 patients), improvement was significant in the three groups after 4 weeks of treatment and continued after 8 weeks. It is most interesting to mention that 2 months after the end of the study 71% (12/17) of the olanzapine group that had completed the study, 10/15 (67%) of the risperidone group, and 43% (3/7) of the haloperidol group had continued their treatment. Dropouts were for inefficacy and non-compliance in the olanzapine and risperidone groups whereas they were also for adverse events in the haloperidol group (2/4). A final double blind study of 263 adult and adolescent schizophrenic patients (latter are not separated from the former) confirmed the superiority of olanzapine compared to haloperidol and its use for a long period: 67% of the olanzapine and 54% of the haloperidol patients completed the 12-week study. CASE-REPORTS: 12 case reports of children and adolescents diagnosed with acute mania (8, 25, 46, 47) and 23 in an open labeled study (16) were treated by olanzapine; 26/35 were considered to respond well. Some of the patients were on mood stabilizers before adjunction of olanzapine, others on olanzapine monotherapy; 10 case reports of patients with anorexia nervosa associated with psychotic symptomatology, aged from 10-17 years old, relate the use of olanzapine as adjuvant treatment. Improvement was spectacular in these patients who not only gained considerable weight, but were also more compliant to the therapeutic program and their obsessions, delusions, agitation and anxiety became less intense. In this form of anorexia nervosa, olanzapine appears to have an interesting therapeutic role and, in particular, its most important adverse effect, weight gain, became a therapeutic goal. In 2 preliminary studies (24, 30) 31 children and adolescents diagnosed with pervasive developmental disorder were treated by olanzapine from 6 to 13 weeks; 18/25 had good or moderate symptomatic improvement: they were less irritable and hyperactive, and their speech less excessive. In 17 case reports of children and adolescents with aggression (42, 45), associated with tics in 10 patients (49), treatment with olanzapine from 2 weeks to 10 months lowered the presenting symptoms, enhanced the cooperation, and improved the mood of the patients. Only one patient's treatment was changed for inefficacy. DISCUSSION: No matter what the disorder treated, when olanzapine was compared to haloperidol and risperidone, it proved to be as effective as risperidone, and as or more effective than haloperidol; but when compared to clozapine, it was less effective. The most prominent adverse reaction was excessive weight gain, even more so than in adult patients treated with olanzapine. Also weight gain was greater in children and adolescents treated by olanzapine than those treated by risperidone or haloperidol. Though few treatments had to be interrupted because of this side effect, child and adolescent psychiatrists are wary of the long-term disease related to obesity and glucose dysregulation. All should be done to under-stand the process of weight gain better and to prevent or stall excessive caloric intake, encourage activity, and eventually treat by corrector drugs. Secondly, sedation may bother up to 50% of patients even at the end of the study periods, as many as those treated by haloperidol and more than those treated by risperidone. Extrapyramidal symptoms were mild or moderate compared to those that appear with haloperidol, but may be more frequent than in adult patients. Liver enzymes and blood sugar may be slightly elevated. Prolactemia may be elevated but less so with risperidone and haloperidol. CONCLUSION: All the authors emphasized the unfortunate lack of randomized double blind studies for the use of olanzapine in this age group.     

Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia

OBJECTIVE: The efficacy and safety of olanzapine were compared with those of ziprasidone. METHOD: This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight. RESULTS: The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level. CONCLUSIONS: Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.     

Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia

BACKGROUND: Patients with chronic schizophrenia (DSM-IV criteria) often receive depot antipsychotic medications to assure longer administration and better compliance with their treatment regimen. This study evaluated whether patients stabilized on depot antipsychotic medication could be successfully transitioned to oral olanzapine. METHOD: In a 3-month open-label study, 26 clinically stable patients with schizophrenia taking depot antipsychotics for over 3 years were randomly assigned to continue on their current depot dose or to switch to oral olanzapine. Clinical ratings (Positive and Negative Syndrome Scale [PANSS], Global Assessment of Functioning [GAF] scale, and Clinical Global Impressions [CGI] scale) and side effect parameters (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Scale, AMDP-5 scale, vital signs, and weight) were obtained monthly. RESULTS: Oral olanzapine patients (N = 13) demonstrated significant clinical improvement over the depot control group (N = 13) from baseline to 3-month endpoint (PANSS total, p =.012; PANSS general, p =.068; PANSS negative, p =.098; CGI-Improvement, p =.007; CGI-Severity, p =.026; GAF, p =.015). Side effect rating scales showed no statistical differences between the 2 groups (AIMS, Barnes Akathisia Scale, AMDP-5, vital signs). The depot control group showed no statistical superiority in any measure except weight change (p =.0005). After 3 months, all olanzapine patients preferred olanzapine to their previous depot medications and chose to continue on olanzapine treatment. CONCLUSION: Clinicians may expect clinical improvement when switching chronically psychotic patients from traditional depot antipsychotic drugs to oral olanzapine. Switching may be completed within a 4-week period with relative compliance being maintained and patients preferring oral olanzapine to their previous depot medications.     

A simple switching strategy for inadequately treated patients with schizophrenia to olanzapine: changes in psychopathology and subjective well-being

INTRODUCTION: The aim of the study was to assess the feasibility of abruptly switching inadequately treated psychotic outpatients from another oral antipsychotic to olanzapine and to evaluate subjective well-being under olanzapine. METHODS: Previous medication was switched to olanzapine 10 mg/day and continued for 4 weeks (5-20 mg/day). Successful switch was predefined as no change or any improvement on the Clinical Global Impression-Improvement (CGI-I) scale after one week. A successful switch rate of > or = 70 % was considered a positive study outcome. Well-being was evaluated using the Subjective Well-being under Neuroleptics (SWN) scale. RESULTS: 198 patients (100 %) were switched to olanzapine. In 177 patients (89 %), CGI-I was unchanged (29 %) or improved (60 %) after one week of olanzapine treatment, indicating a positive study outcome (p < 0.001). SWN total score significantly improved from 127.9 (+/- 32.5) at baseline to 139.2 (+/- 31.5) at week 1, continuing to 149.3 (+/- 30.3) at week 4 (LOCF). DISCUSSION: The findings suggest that an abrupt switch from another antipsychotic to olanzapine 10 mg/day can be performed successfully in psychotic patients, while rapidly improving subjective well-being.     

Effectiveness and tolerability of olanzapine in the treatment of adolescents with schizophrenia and related psychotic disorders: results from a large, prospective, open-label study

OBJECTIVE: The aim of this study was to assess effectiveness and tolerability of oral olanzapine treatment of adolescents with schizophrenic disorders. METHOD: Adolescent patients (12-19 years) with schizophrenia, schizoaffective, or schizophreniform disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) were enrolled in a multicenter, prospective, open-label study. Following a 2- to 9-day washout period, patients initially received 10 mg/day olanzapine. Dose modification was allowed during week 2 (dose range 5-15 mg/day) and during weeks 3-6 (dose range, 5-20 mg/day). Responders (improvement > or =30% on the Brief Psychiatric Rating Scale, BPRS) continued olanzapine for additional 18 weeks. Psychopathology was assessed using BPRS and Clinical Global Impressions (CGI) scales; side effects were assessed by adverse event reporting. RESULTS: Out of 96 patients enrolled at 10 sites, 60 (62.5%) met response criteria at week 6. Mean BPRS total scores decreased significantly (p < 0.001) from baseline (39.2 +/- 13.4) to week 6 last observation carried forward (LOCF) (22.2 +/- 14.7). The rate of patients considered markedly ill or worse (CGI-S) decreased from 83.3% (baseline) to 37.5% (week 6, LOCF). The most common reported adverse event was weight gain (30.2%, 29/96). Three patients (3.1%) discontinued due to adverse events. CONCLUSIONS: In this study of young patients with schizophrenia, schizoaffective, or schizophreniform disorders, olanzapine treatment was associated with marked symptom improvement. As changes in weight and prolactin levels may be greater in adolescent than in adult patients, potential risks and benefits of olanzapine treatment in adolescents should be considered carefully.     

Olanzapine orally disintegrating tablet: a review of efficacy and compliance

Medication nonadherence, especially in psychiatric disorders, has been associated with treatment failure and other negative outcomes. Orally disintegrating formulations have been developed as an alternative to improve medication adherence. This report reviews the properties, efficacy, and safety profile of olanzapine as an orally disintegrating tablet, and explores their association with medication compliance compared with standard oral formulation. Medical literature, published on orally disintegrating formulation of olanzapine identified using Pubmed and EMBASE, was used. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug. Studies evaluating the biostability, biodisposability, pharmacokinetics, efficacy, and safety of orally disintegrating olanzapine as treatment of patients with psychiatric disorders were reviewed. Measurement tools included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale, and Nursing Assessment of Medication Acceptance (NAMA). Orally disintegrating olanzapine, an effective atypical antipsychotic with an acceptable safety profile, can facilitate the burden of treatment on patients and caregivers due to its ease of administration. This is especially important in diseases such as schizophrenia and bipolar disorder, which can be chronic and require long-term treatment.     

Olanzapine versus placebo in the treatment of borderline personality disorder

BACKGROUND: Atypical antipsychotics are increasingly used in clinical practice in the management of borderline personality disorder (BPD), and a small but growing body of literature supports their efficacy. Here, we report the results of a double-blind, placebo-controlled study of olanzapine as a treatment for BPD. METHOD: Forty BPD patients (25 female, 15 male) were randomly assigned in equal numbers to olanzapine and placebo. Diagnoses were made using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders and the Mini-International Neuropsychiatric Interview. Patients with schizophrenia, bipolar disorder, or current major depression were excluded. Olanzapine dosage was flexible, and the dose range was 2.5 to 20 mg/day, with most patients receiving 5 to 10 mg/day. No concomitant psychotropic medications were allowed. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks. The primary outcome was change in the total score for the 9 BPD criteria on a 1-to-7 Likert scale, the Clinical Global Impressions scale modified for borderline personality disorder (CGI-BPD), using an analysis of covariance model including baseline score as covariate. Data were collected from July 2000 to April 2002. RESULTS: Olanzapine was found to be significantly (p <.05) superior to placebo on the CGI-BPD at endpoint, with separation occurring as early as 4 weeks. Similar results were found for the single-item Clinical Global Impressions scale. Weight gain was significantly (p =.027) greater in the olanzapine group. CONCLUSIONS: This study supports the efficacy of olanzapine for symptoms of BPD in a mixed sample of women and men. Further studies with olanzapine and other atypical antipsychotics are needed.     

Olanzapine treatment in adolescents with severe conduct disorder.

The most severe forms of conduct disorder (CD) are highly stable and disabling disorders, more likely to persist in time and to evolve into disruptive or antisocial behaviors. One crucial issue in the prognosis of these forms of CD is the high resistance to both non-pharmacological and pharmacological treatments, with antipsychotic drugs being frequently used in refractory cases. Aim of this study was: (1) to explore efficacy and tolerability of olanzapine treatment in adolescents with severe CD; (2) to identify predictors of olanzapine treatment outcome. This was a retrospective study, based on clinical records of the first 23 adolescents diagnosed as having a CD, diagnosed with a clinical interview (K-SADS), either pure or with comorbid diagnoses, and treated with olanzapine. All these patients did not respond satisfactorily to non-pharmacological intervention and to adequate dosages of mood stabilizers (lithium and/or valproate). The sample consisted of 16 males and seven females, 16 inpatients and seven outpatients (mean age 13.6 +/- 1.9 years, range 11-17.2 years), followed-up for a period ranging from 6 to 12 months (mean 8.8 +/- 2.7 months). Outcome measures included the Modified Overt Aggression Scale (MOAS), Clinical Global Impression-Improvement (CGI-I) and Children Global Assessment Scale (CGAS). During the follow-up, all patients were involved in non-pharmacological treatments (psychotherapy, family therapy, or day-hospital group treatments). Based on both an improvement of at least 50% at MOAS and a score 1 or 2 at CGI-I, 14 out of 23 patients (60.9%) were classified as responders at the end of the follow-up. Significant improvement at the last observation was found in MOAS (P < 0.001) and CGAS (P < 0.001) scores. Olanzapine dosage was 8 +/- 3.2 mg/day (range 5-20 mg/day). Mean weight gain at the end of the follow-up was 4.6 +/- 3 kg. The predictors of a positive treatment response was an impulsive-affective versus controlled-predatory type of aggression. Age at onset of CD and comorbid disorders did not affect treatment response. These preliminary findings suggest that olanzapine may improve behavior in adolescents with severe and treatment-refractory CD and impulsive aggression.     

Quality of life in children with psychiatric disorders: self-, parent, and clinician report

OBJECTIVE: To study the relationship between child psychiatric disorders and quality of life (QoL). METHOD: In a sample of 310 children (ages 6-18 years) referred for psychiatric problems, children, parents, and clinicians reported on psychopathology and subjective and objective QoL indicators. RESULTS: Six diagnostic categories were distinguished: attention-deficit and disruptive behavior disorders, anxiety disorders, pervasive developmental disorders, mood disorders, other disorders, and no diagnosis. In overall QoL, no differences were found between the diagnostic categories, except in clinician's ratings, who rated children with pervasive developmental disorder as having a poorer QoL than children with other diagnoses. In each diagnostic category specific QoL subdomains were affected: for children with attention-deficit and disruptive behavior disorder, school functioning and social functioning; for children with anxiety disorder, emotional functioning; for children with pervasive developmental disorder, social functioning; and for children with mood disorder, emotional functioning. CONCLUSIONS: Across multiple raters, the distinguished child psychiatric disorders had a different impact on QoL. Knowledge about domains of QoL that are affected in specific child psychiatric disorders can help clinicians to focus on particular QoL domains during the diagnostic process and to define adequate treatment goals.