Síntomas de discontinuación luego de suspensión abrupta de olanzapina / Discontinuation symptoms following olanzapine abrupt withdrawal

Extended use of atypical neuroleptics in clinical practice, may be explained by their effectiveness as antipsychotics and also with recent approvals for therapeutic benefits of this drugs beyond psychotic disorders. Receptor adaptation mechanisms rises critical issues about treatment discontinuation strategies. Clinical data of two patients who have required the use of atypical antipsychotics are discussed. In both cases, abrupt discontinuation of the drug occurred followed by the emergence of extrapyramidal symptoms. Adaptation mechanisms in synaptic structures would be responsible for this phenomena and the subsequent amelioration of this extrapyramidal symptoms when initial treatment is replaced. The authors concluded that atypical antipsychotics, as other psychotropic agents shouldn't be abruptly discontinued even when they are replaced by other drugs from the same family.

El uso de los antipsicóticos atípicos ha ido aumentando con el tiempo entre otras cosas, por el hecho de que se están usando no sólo para los cuadros psicóticos sino que también para otras patologías. Como con otros fármacos que actúan a nivel de receptores deben considerarse los mecanismos de adaptación receptorial que se producen con su uso. Lo anterior es de suma importancia cuando pensamos en la discontinuación del tratamiento y en sus formas de hacerlo. En este trabajo presentamos dos casos clínicos de pacientes que han requerido el uso de antipsicóticos atípicos. En ambos casos se ha realizado una suspensión brusca del fármaco lo que ha generado la aparición de síntomas extrapiramidales, que en nuestra opinión, son explicados por mecanismos de adaptación a nivel sináptico y que han disminuido con el reinicio del tratamiento inicial. Debemos tener presente que estos fármacos no deben ser discontinuados en forma súbita aun cuando sean remplazados por otros de la misma familia.

One-year multicenter, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia.

OBJECTIVE: To evaluate the safety and efficacy of the relatively selective M(1)-antagonist, pirenzepine ophthalmic gel (gel), in slowing the progression of myopia in school-aged children. DESIGN: Parallel-group, placebo-controlled, randomized, double-masked study. PARTICIPANTS: Three hundred fifty-three healthy children, 6 to 12 years old, with a spherical equivalent (SE) of -0.75 to -4.00 diopters (D) and astigmatism of

Safety and efficacy of 2% pirenzepine ophthalmic gel in children with myopia: a 1-year, multicenter, double-masked, placebo-controlled parallel study.

OBJECTIVE: To evaluate the safety and efficacy of the relatively selective M(1) antagonist pirenzepine hydrochloride in slowing the progression of myopia in school-aged children. METHODS: This was a parallel-group, placebo-controlled, double-masked study in healthy children, aged 8 to 12 years, with a spherical equivalent of -0.75 to -4.00 diopters (D) and astigmatism of 1.00 D or less. Patients underwent a baseline complete eye examination and regular examinations during a 1-year period. The setting was 13 US academic clinics and private practices. Patients were randomized in a 2:1 ratio to receive 2% pirenzepine ophthalmic gel or a placebo control twice daily for 1 year. RESULTS: At study entry, the spherical equivalent was mean +/- SD -2.098 +/- 0.903 D for the pirenzepine group (n = 117) and -1.933 +/- 0.825 D for the placebo group (n = 57, P = .22). At 1 year, there was a mean increase in myopia of 0.26 D in the pirenzepine group vs 0.53 D in the placebo group (P < .001). No patients in the placebo group and 13 (11%) of 117 patients in the pirenzepine group discontinued participation in the study because of adverse effects (5 [4%] of 117 due to excessive antimuscarinic effects). CONCLUSIONS: Pirenzepine is effective and relatively safe in slowing the progression of myopia during a 1-year treatment period.

Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a geriatric population in the United States.

OBJECTIVES: The objective of this study was to investigate risk of diabetes among elderly patients during treatment with antipsychotic medications. DESIGN: We conducted a longitudinal, retrospective study assessing the incidence of new prescription claims for antihyperglycemic agents during antipsychotic therapy. SETTING: Prescription claims from the AdvancePCS claim database were followed for 6 to 9 months. PARTICIPANTS: Study participants consisted of patients in the United States aged 60+ and receiving antipsychotic monotherapy. The following cohorts were studied: an elderly reference population (no antipsychotics: n = 1,836,799), those receiving haloperidol (n = 6481) or thioridazine (n = 1658); all patients receiving any conventional antipsychotic monotherapy (n = 11,546), clozapine (n = 117), olanzapine (n = 5382), quetiapine (n = 1664), and risperidone (n = 12,244), and all patients receiving any atypical antipsychotic monotherapy (n = 19,407). MEASUREMENTS: We used Cox proportional hazards regression to determine the risk ratio of diabetes for antipsychotic cohorts relative to the reference population. Covariates included sex and exposure duration. RESULTS: New antihyperglycemic prescription rates were higher in each antipsychotic cohort than in the reference population. Overall rates were no different between atypical and conventional antipsychotic cohorts. Among individual antipsychotic cohorts, rates were highest among patients treated with thioridazine (95% confidence interval [CI], 3.1- 5.7), lowest with quetiapine (95% CI, 1.3-2.9), and intermediate with haloperidol, olanzapine, and risperidone. Among atypical cohorts, only risperidone users had a significantly higher risk (95% CI, 1.05-1.60; P = 0.016) than for haloperidol. Conclusions about clozapine were hampered by the low number of patients. CONCLUSION: These data suggest that diabetes risk is elevated among elderly patients receiving antipsychotic treatment. However, causality remains to be demonstrated. As a group, the risk for atypical antipsychotic users was not significantly different than for users of conventional antipsychotics.

Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia.

Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.

A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial.

This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population, in comparison to haloperidol, a conventional antipsychotic with established efficacy. Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth, but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied. Subjects, selected because of prominent positive psychotic symptoms, were randomly assigned to double-blind, parallel treatment with risperidone, olanzapine, or haloperidol for 8 weeks. The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination. An exploratory, descriptive analysis was done to compare the three treatments. A total of 50 patients, 8-19 years, participated. All treatments reduced symptoms significantly with p-values (corrected for multiple comparisons) of 0.0018 for each of the atypical agents and 0.012 for haloperidol. In all, 88% of subjects treated with olanzapine, 74% treated with risperidone, and 53% treated with haloperidol met response criteria. The primary side effects observed in all patients were mild to moderate sedation, extrapyramidal symptoms, and weight gain. Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample. Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol. However, youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults.

A 1-year open-label trial of olanzapine in school-age children with schizophrenia.

OBJECTIVE: To determine the response of children with childhood-onset schizophrenia to a 1-year prospective, open-label trial of olanzapine. METHODS: Twenty children (age range 6-15 years) with childhood-onset Diagnostic and Statistical Manual of Mental Disorders (fourth edition) schizophrenia participated. The treating clinician was free to vary or discontinue dosing and use additional medications. Symptoms were assessed by the Brief Psychiatric Rating Scale-Child version (BPRS-C), Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms. Extrapyramidal symptoms, akathisia, temperature, and weight were monitored. RESULTS: BPRS-C subscales of thought disturbance and psychomotor excitation, and the Scale for the Assessment of Positive Symptoms demonstrated significant decreases by 6 weeks of treatment; BPRS-C anxiety and the Scale for the Assessment of Negative Symptoms (SANS) showed significant improvement after 1 year of treatment. Seventy-four percent of subjects were considered treatment responders, with a greater than 20% reduction in total BPRS-C score and overall impairment of mild or better. Weight gain (body mass index) was above that expected for normal development in every child. No child developed neuroleptic-related dyskinesias. Seventy-four percent (n = 14) of patients completed this 1-year, open-label trial. Of the 5 subjects who discontinued, weight gain was noted as the reason for 4 subjects. CONCLUSIONS: Olanzapine appears useful in the treatment of childhood-onset schizophrenia, although there may be a delayed onset of benefit for anxiety and negative symptoms. Weight gain is problematic, but the emergence of dyskinesias may be rare. Additional controlled trials are indicated.

Olanzapine treatment in chronic drug-resistant childhood-onset schizophrenia: an open-label study.

The use of typical antipsychotics is limited in children with schizophrenia, owing to the high rate of response failure and early appearance of extrapyramidal syndromes as well as tardive and withdrawal dyskinesia. The aim of the present study was to examine the effectiveness of the atypical antipsychotic olanzapine in the treatment of childhood-onset schizophrenia. The study sample included nine children hospitalized for schizophrenia who had proven refractory to treatment with at least two antipsychotic drugs. Olanzapine was administered after a 2-week washout period in gradually increasing doses to a maximum of 5 mg/day on day 5 and 10 mg/day in week 3; six patients received up to 20 mg/day as of week 5. The duration of the study was 12 weeks. Patient psychiatric status was measured with three scales at onset of therapy and thereafter once weekly. Patients also underwent regular blood, laboratory, and liver function tests, and we also monitored their blood pressure and weight and performed electrocardiography and electroencephalography. A reduction in all psychopathology scores was obtained at 12 weeks from baseline. All extrapyramidal symptoms of previous medications resolved, and there were no new incidents. Side effects were mild. There were no adverse changes in blood chemistry, hematological tests, or electrocardiography parameters, but the treatment was associated with a significant weight gain (6.10 +/- 3.25 kg). At 1-year follow-up, the improvement in psychiatric symptoms was sustained in eight children. We conclude that olanzapine may have potential as a first-line drug in the treatment of drug-resistant childhood-onset schizophrenia. Large-scale, double-blind, placebo-controlled comparative studies are needed to clarify the role of the various atypical antipsychotics in both treatment-resistant and treatment-naïve populations with psychotic symptoms/disorders.

A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment of acute mania.

BACKGROUND: This randomized controlled trial compares the efficacy and safety of olanzapine vs haloperidol, as well as the quality of life of patients taking these drugs, in patients with bipolar mania. METHODS: The design consisted of 2 successive, 6-week, double-blind periods and compared flexible dosing of olanzapine (5-20 mg/d, n = 234) with haloperidol (3-15 mg/d, n = 219). RESULTS: Rates of remission (Young-Mania Rating Scale score of < or =12 and 21-item Hamilton Rating Scale for Depression score of < or =8 at week 6) were similar for olanzapine- and haloperidol-treated patients (52.1% vs 46.1%, respectively; P =.15). For the subgroup of patients whose index episode did not include psychotic features, rates of remission were significantly greater for the olanzapine group compared with the haloperidol group (56.7% vs 41.6%, P =.04). Relapse into an affective episode (mania and/or depression) occurred in 13.1% and 14.8% of olanzapine- and haloperidol-treated patients, respectively (P =.56). Switch to depression occurred significantly more rapidly with haloperidol than with olanzapine when using survival analysis techniques (P =.04), and significantly more haloperidol-treated patients experienced worsening of extrapyramidal symptoms, as indicated by several measures. Weight gain was significantly greater in the olanzapine group compared with the haloperidol group (2.82 vs 0.02 kg, P<.001). The olanzapine group had significant improvement in quality of life on several dimensions compared with the haloperidol group. CONCLUSIONS: These data suggest that olanzapine does not differ from haloperidol in achieving overall remission of bipolar mania. However, haloperidol carries a higher rate of extrapyramidal symptoms, whereas olanzapine is associated with weight gain.

Long-term antidepressant efficacy and safety of olanzapine/fluoxetine combination: a 76-week open-label study.

BACKGROUND: The olanzapine/fluoxetine combination has demonstrated effectiveness in treatment-resistant depression (TRD). Although this combination is being used by prescribers, this is the first study to examine long-term use. Long-term efficacy and safety were therefore investigated in a group of patients with major depressive disorder (MDD) with and without TRD. METHOD: 560 patients who met DSM-IV diagnostic criteria for MDD were enrolled in this 76-week, open-label study (Feb. 2000-July 2002). The Montgomery-Asberg Depression Rating Scale (MADRS) total score was the primary efficacy measure. Safety was assessed via adverse events, vital signs, laboratory analytes, electrocardiography, and extrapyramidal symptom measures. RESULTS: MADRS mean total scores decreased 7 points from baseline (31.6 [N = 552]) at 1/2 week of treatment, 11 points at 1 week of treatment, and 18 points at 8 weeks of treatment. This effect was maintained to endpoint with a mean decrease of 22 points at 76 weeks. Response and remission rates for the total sample were high (62% and 56%, respectively), and the relapse rate was low (15%). Response, remission, and relapse rates for TRD patients (N = 145) were 53%, 44%, and 25%, respectively. The most frequently reported adverse events were somnolence, weight gain, dry mouth, increased appetite, and headache. At endpoint, there were no clinically meaningful changes in vital signs, laboratory analytes, or electrocardiography. There were no significant increases on any measure of extrapyramidal symptoms. CONCLUSIONS: The olanzapine/fluoxetine combination showed rapid, robust, and sustained improvement in depressive symptoms in patients with MDD, including patients with TRD. The long-term safety profile of the combination was similar to that of its component monotherapies.

High-dose olanzapine and prolactin levels.

BACKGROUND: This study evaluates whether high-dose olanzapine is associated with elevation of serum prolactin levels. METHOD: Twenty-four patients taking daily doses of olanzapine of 20, 25, 30, and 40 mg for DSM-IV schizophrenia or schizoaffective disorder had serum prolactin levels measured. The patients were all from one author's (J.L.K.'s) clinical practice. The mean duration of olanzapine therapy was 15.3 months at a dose of at least 20 mg/day. Data were gathered in 2000 and 2001. RESULTS: There was no significant correlation between olanzapine dose and prolactin level (Pearson product moment correlation coefficient = 0.09). No significant differences were found between mean prolactin values in each dose group. CONCLUSION: There was no significant elevation of prolactin with higher doses of olanzapine. Thus, preliminary evidence suggests that using higher doses of olanzapine is generally safe with regard to prolactin levels.

Olanzapine for self-injurious, aggressive, and disruptive behaviors in intellectually disabled adults: a retrospective, open-label, naturalistic trial.

BACKGROUND: The effectiveness of olanzapine in treating challenging behaviors in the intellectually disabled and its ability to substitute for conventional antipsychotic drugs were evaluated. METHOD: A total of 20 institutionalized adults with a mean age of 42.7 years (range, 18-55 years) with intellectual disability and aggression, self-injurious behavior, destructive/disruptive behavior, or combinations of these behaviors were studied. These individuals were receiving multiple psychotropic medications at baseline and were given additional treatment with the atypical antipsychotic agent olanzapine. The mean dose of olanzapine was 9.1 mg/day (range, 2.5-22.5 mg/day). Effectiveness was determined by retrospective review of the summaries of quarterly neuropsychiatric behavioral reviews and retrospective review of longitudinal behavioral graphs of target symptoms. Data were collected from 1995 to 2000. RESULTS: A significant decrease in global challenging behaviors and specific target behaviors (i.e., aggression, self-injurious behaviors, destructive/disruptive behaviors) occurred (p <.05). A numerical decrease in the dosage of concurrent conventional antipsychotic medications occurred over the course of the first 6 months of olanzapine therapy, and a statistically significant (p <.005) decrease from the start of olanzapine therapy occurred in those subjects who received olanzapine for longer than 6 months (mean = 20.3 months). A significant increase in weight occurred in the subject group during the first 6 months of olanzapine treatment (p <.006), and sedation and constipation were the other common side effects noted. CONCLUSIONS: Olanzapine was found to be effective in the treatment of challenging behaviors in the intellectually disabled and in part could be substituted for administration of conventional antipsychotic drugs.

Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial.

CONTEXT: Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug. OBJECTIVE: To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia. DESIGN AND SETTING: Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers. PARTICIPANTS: Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine percent fully completed and 36% partially completed follow-up assessments. INTERVENTIONS: Patients were randomly assigned to receive flexibly dosed olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n = 159); or haloperidol, 5 to 20 mg/d (n = 150), for 12 months. MAIN OUTCOME MEASURES: Standardized measures of symptoms, quality of life, neurocognitive status, and adverse effects of medication. Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole (ie, consumption of all resources on behalf of these patients). RESULTS: There were no significant differences between groups in study retention; positive, negative, or total symptoms of schizophrenia; quality of life; or extrapyramidal symptoms. Olanzapine was associated with reduced akathisia in the intention-to-treat analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug. Small but significant advantages were also observed on measures of memory and motor function. Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs, ranging from 3000 dollars to 9000 dollars annually. Differences in societal costs were somewhat smaller and were not significant. CONCLUSION: Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost.

Switching treatment-resistant patients with schizophrenia or schizoaffective disorder to olanzapine: a one-year open-label study with five-year follow-up.

OBJECTIVE: To determine whether patients with treatment-resistant schizophrenia or schizoaffective disorder would respond when switched to olanzapine and whether they could maintain their response on this atypical antipsychotic. RESEARCH DESIGN AND METHODS: In this single-center, observational, 1-year open-label study, a cohort of patients was switched to olanzapine due to failure on previous treatment. The patients were followed up (retrospectively) for an additional 5 years. Patients had schizophrenia or schizoaffective disorder and all but one were treatment-resistant. The starting dose was 10 mg/day, with dosage adjustments based on physician judgment. MAIN OUTCOME MEASURES: The CGI-S and CGI-I scales were the primary outcome measures. During the observation period, positive and negative symptoms, hospital readmission rates and duration of hospitalization were measured, and treatment-emergent adverse events recorded. RESULTS: Mean age of patients (n = 25) was 39.7 years; 19 were male, and all were Caucasian. The mean number of antipsychotics used prior to olanzapine was 4.6 with risperidone (76%) being the most common. The mean duration of olanzapine therapy was 8.6 months. The average number of hospital admissions per patient dropped from 1.32 during the year prior to olanzapine therapy to 0.39 after starting olanzapine. Total number of hospital days was 1042 the year before and 258 the year after olanzapine treatment. The mean CGI-S score improved from markedly ill at baseline to borderline/mildly ill at study end. The mean CGI-I score was rated much improved at study end. Few adverse events occurred during the study. Twelve patients remained on olanzapine monotherapy after 5 years of treatment (mean duration of 62 months). CONCLUSIONS: Olanzapine may be a treatment option for patients who fail to respond to treatment with other antipsychotics. Importantly, this is one of the first reports showing that patients with schizophrenia can be maintained on atypical antipsychotic monotherapy for at least 5 years.

Investigation of target plasma concentration-effect relationships for olanzapine in schizophrenia.

Olanzapine is an atypical antipsychotic effective in the treatment of schizophrenia. The present study has examined the potential use of target concentration monitoring of olanzapine in plasma as a marker of clinical response and an aid in patient management. Fifty-three patients (mean age 32 years; 40 M, 13 F) with a DSM-IVR diagnosis of schizophrenia completed a 6-week trial of oral olanzapine. Participants received once-daily olanzapine, and their psychotic symptoms were measured with the PANSS (Positive and Negative Symptom Scale) on admission and again after 6 weeks. Responders were classified as having a >/=20% decrease in PANSS scores. Plasma olanzapine was quantified by high-performance liquid chromatography. Receiver operator characteristic (ROC) curve analysis was used to identify a break point in plasma olanzapine that might serve as a surrogate for PANSS classification, and the two methods were compared using the McNemar chi2 test. After 6 weeks the median olanzapine dose was 15 mg/d (range 5-30 mg/d), and the mean plasma olanzapine was 32 micrograms/L at a mean of 13.5 hours after dose. With the PANSS (total), there were 42 responders and 11 nonresponders. ROC curve analysis for total PANSS identified a break point at 23 micrograms/L plasma olanzapine, with the proportions of responders and nonresponders identified by PANSS and the plasma break point being similar. Similar break points were found for the positive, negative, and global PANSS subscores. Nevertheless, these relationships were very modest, and at best the target plasma olanzapine concentration identified only 20% more responders than nonresponders. We suggest that plasma olanzapine monitoring can be used for dose-response optimization, but only to complement the normal clinical evaluation process.

[Neuroleptic malignant syndrome in a patient treated with olanzapine]. / Malignt nevroleptikasyndrom hos pasient behandlet med olanzapin.

BACKGROUND: Neuroleptic malignant syndrome is a potentially fatal reaction to antipsychotic drugs, characterised by hyperthermia, rigidity, autonomic instability and muscle injury. The syndrome was originally associated with traditional neuroleptics, but may also occur during treatment with second-generation atypical antipsychotic drugs. MATERIAL AND METHODS: We present a case of neuroleptic malignant syndrome in a 52-year-old patient who had been treated for 2(1/2) years with olanzapine, a new atypical antipsychotic agent. He had previously been treated with a conventional neuroleptic for 25 years. RESULTS: For 2-3 days the patient's condition was serious and unstable, requiring care in the emergency unit. When he was discharged after 12 days' hospitalisation, he was still physically disabled and needed care in his home. INTERPRETATION: Neuroleptic malignant syndrome may develop even after long and stable treatment with atypical antipsychotic agents. The condition should be suspected in psychiatric patients who present with unclear hyperthermia and muscular rigidity. Essential therapeutic principles are cooling, rehydration, correction of electrolytic disturbances, cardiac monitoring, regular tests of renal function and creatine kinase. Treatment of malign hyperthermia with dantrolene should also be considered.

Olanzapine vs haloperidol in geriatric schizophrenia: analysis of data from a double-blind controlled trial.

OBJECTIVES: To compare the six-week clinical response and safety profile of schizophrenia patients, age > or =60 years, receiving olanzapine (OLZ) vs haloperidol (HAL) in a double blind, randomized trial. METHODS: Double-blind data on patients age > or =60 randomized to 5 mg/d OLZ (n=83) or 5 mg/d HAL (n=34) (Week 1) then flexibly dosed to 5-20 mg/d over six weeks, with a 48-week extension for responders, were analyzed post-hoc. Efficacy indices included the PANSS Total and PANSS Psychosis Core Total (PPCT). Safety measures included the Simpson-Angus Scale (SAS), Barnes Akathisia Scale (BAS), Abnormal Involuntary Movement Scale (AIMS), treatment-emergent adverse events, and laboratory values. Mixed model, repeated measures (MMRM) analyses were applied to all continuous data measured at each visit. Continuous data recorded only at phase completion or termination were analyzed with a fixed effect last observation carried forward (LOCF) model. Frequencies of categorical response data were analyzed using Fisher's exact methods. Differences were tested for significance at Week 6 using a two-sided alpha value of 0.05. RESULTS: HAL group (n=34; age range 60-80) received a mean modal dose 9.4 mg/d while OLZ group (n=83; age range 60-86) received a mean modal dose 11.9 mg/d. At Week 6, OLZ was superior to HAL on both the PANSS Total (p=0.015) and PPCT (p=0.043). Considering safety, OLZ was superior to HAL for the SAS and BAS (p<0.001; p<0.001). No spontaneous adverse event occurred more frequently with OLZ than with HAL. In patients never receiving adjunct anticholinergic therapy, no significant differences were present for anticholinergic-like side effects including blurred vision, dry mouth, constipation, or urinary difficulties. CONCLUSIONS: In elderly schizophrenia patients, olanzapine was more efficacious and better tolerated for extrapyramidal signs than was haloperidol. Olanzapine was equivalent to haloperidol for anticholinergic-like side effects when corrected for anticholingergic agents.

Comparison of risperidone and olanzapine in the control of negative symptoms of chronic schizophrenia and related psychotic disorders in patients aged 50 to 65 years.

BACKGROUND: This analysis compares the efficacy of risperidone and olanzapine in controlling negative and positive symptoms of chronic psychosis in older patients. METHOD: Post hoc assessments were made in a subset of risperidone-treated (N = 19) and olanzapine-treated (N = 20) older patients (aged 50 to 65 years) from a large international, multicenter, parallel, double-blind, 28-week study of patients aged 18 to 65 years (N = 339) randomly assigned to receive risperidone (4-12 mg/day) or olanzapine (10-20 mg/day). Assessments were made using repeated-measures analysis. RESULTS: At both 8 weeks and 28 weeks, the magnitude of changes in Positive and Negative Syndrome Scale (PANSS) positive symptom subscale scores did not differ between treatment groups (8 weeks: risperidone, -6.5; olanzapine, -6.8, p = .866; 28 weeks: risperidone, -6.5; olanzapine, -7.0; p = .804). However, by the 8-week timepoint, olanzapine had reduced PANSS negative subscale scores significantly more than risperidone (-8.8 vs. -4.9, p = .032). By the 28-week endpoint, olanzapine had continued to maintain significantly greater reduction in baseline-to-endpoint PANSS negative scores (-8.1 vs. -3.5, p = .032) and led to significantly greater reduction in scores on the Scale for the Assessment of Negative Symptoms (SANS) dimensions of affective flattening (-5.2 vs. -0.6, p = .033) and alogia (-3.8 vs. -0.3, p = .007). Patients in the olanzapine treatment group also demonstrated numerically greater reduction of both SANS summary (-3.7 vs. -1.0, p = .078) and SANS composite scores (-14.1 vs. -4.1, p = .075). CONCLUSION: These data demonstrate that, in older patients with schizophrenia and related psychotic disorders, risperidone and olanzapine have approximately equal efficacy in controlling positive symptoms. However, olanzapine appears to be more efficacious in maintaining control over negative symptoms.