Search

Although life prevalence of substance use disorders among patients with schizophrenia is close to 50%, few studies have been carried out to date to identify an integrated pharmacological treatment for this comorbidity. So far, the most promising results, that we report here, have been obtained with clozapine. To a lesser extent, quetiapine and olanzapine, both clozapine analogues, have also shown promising results. Further to these observations, the present paper critically reviews the advantages associated with clozapine, quetiapine and olanzapine, and their relevance to the treatment of addiction among schizophrenic patients. Six characteristics seem to distinguish clozapine, quetiapine and olanzapine from the first-generation antipsychotics: (1) acting preferentially on the reward system, these second-generation antipsychotics (mainly clozapine and quetiapine) induce almost no extrapyramidal symptoms; (2) quickly dissociating from D(2), theses drugs (mainly clozapine and quetiapine) seem not to induce dysphoria, unlike conventional antipsychotics like haloperidol;(3) these drugs (mainly clozapine) seem more effective in the treatment of negative symptoms than conventional antipsychotics; (4) because of a diversified activity on several serotoninergic and noradrenergic receptors, these drugs positively alter mood, which does not seem to be the case with conventional antipsychotics, except for flupenthixol; (5) these drugs have a positive impact on cognition, which is not the case with the first-generation antipsychotics; (6) unlike conventional antipsychotics, these drugs seem to have a moderate affinity for 5-HT(3), the receptor on which ondansetron, an anti-craving medication, acts.

Randomized controlled trials have demonstrated the efficacy of olanzapine for treating acute mania or depression symptoms in patients with bipolar disorder. We aimed to evaluate the effectiveness of this medication in more usual care outpatient settings. A consecutive series of 15 patients entered an open, uncontrolled 8-week trial of olanzapine monotherapy. Inclusion criteria included significant hypomanic or manic symptoms greater than or equal to 15 on the Young Mania Rating Scale and no psychotic symptoms. The majority of patients experienced significant decreases in mania ratings and more limited improvement on depression ratings. Most patients reported adverse events consistent with other studies, but few discontinued due to these complaints. This case series highlights the individual variation in response to a proven medication. Furthermore, it highlights that those medications effective at one end of the mood spectrum may not be equally or simultaneously effective with other symptoms, emphasizing the complexity of treating bipolar illness.

Risperidone and olanzapine-administration data were collected for schizophrenia patients treated at four Taiwanese medical centres. Only stable patients maintained on a medication at a dose that had remained unchanged for more than 1 month were included in the analysis. Of the 268 cases, 175 were treated with risperidone and 93 with olanzapine at mean daily doses of 3.56 +/- 1.54 mg and 12.21 +/- 4.99 mg, respectively. The majority of the risperidone-treated patients (73.2%) received 2-4 mg per day, with another 19.0% receiving 5-6 mg. A daily dose of 10-20 mg was received by 82.9% of the olanzapine group. Although the mean daily doses for both drugs were slightly higher for inpatients than outpatients, statistical significance was not achieved. Further, no gender or age-group dose differences were demonstrated for either drug.

The effect of a single dose of 10 mg olanzapine on healthy volunteers of both sexes was examined using polysomnography and power spectral analysis. The structure and continuity of sleep were unaffected by olanzapine in both sexes. The increase in both actual sleep time and slow wave sleep in females correlated with the increase in theta power, while delta power was not significantly elevated, suggesting that theta power may be a sensitive indicator of changes in sleep. The changes in sleep had the same tendency in men, but they were not significant. The difference between the sexes could not be explained by differences in body mass index. Olanzapine affects sleep probably through 5-HT(2C) receptors. The receptor gene is located on the X-chromosome, inducing an allelic difference between the females and males. This difference may contribute to the different effects of olanzapine on sleep. Olanzapine seems to preserve the normal structure of sleep and increase the amount of slow-wave sleep, which might be of additional benefit in treatment of schizophrenia. The effective clinical dose may be lower for females than males.

It has been suggested that the atypical antipsychotic drugs may induce a rapid improvement in individuals with melancholic depression. This might reflect a specific or non-specific effect on mood and other parameters. To examine this issue, ten consecutive patients, for whom olanzapine augmentation was judged a clinically appropriate strategy, were asked to complete daily ratings of depression severity and component features for 1 week. Of the six rapid responders, there was a 52% group improvement in the first day and 89% improvement at 1 week. Item analyses suggested the most rapid impact was evident for insomnia, compared to a slower and linear improvement in depressed mood. Such findings may assist in an understanding of the mechanisms underlying augmentation with atypical neuroleptic drugs.

The few reports available on olanzapine in Huntington's disease (HD) are insufficiently documented and/or insufficiently dosed. We describe a 30-year-old woman with genetically confirmed HD who presented with severe chorea. She was not able to eat or dress without help and did not respond to haloperidol; the motor scale of the Unified HD Rating Scale (UHDRS-I) revealed 65 of a possible 124 points. After admission, we treated the patient with a high dose of olanzapine (30 mg daily). The chorea almost ceased in the next 2 days, she was able to eat and walk without assistance (UHDRS-I of 21 points), and fine motor tasks improved, as well as gait and eye movements. This effect lasted for 5 months. We conclude that high-dose olanzapine appears to be useful in grave choreatic attacks.

Post-traumatic stress disorder (PTSD) is a common and increasingly diagnosed mental illness. Recent pharmacotherapeutic research on treatments for this condition has focused on antidepressant drugs with serotonergic actions. However, the presence of intrusive, psychotic-like symptoms in a substantial portion of PTSD patients raises the possibility that antipsychotics with serotonergic properties might also prove useful in treating PTSD. We conducted an open-label 8-week study of olanzapine treatment in veterans with combat-induced PTSD. Primary outcome measures in this study were the Clinician Administered PTSD Scale (CAPS) and the Clinical Global Impressions Improvement scale. Secondary outcome measures included the Hamilton Rating Scales for Depression (HRSD) and Anxiety (HRSA). Forty-eight patients enrolled in the study, and 30 completed the 8-week trial. Results of intent-to-treat and completer analyses demonstrated that all outcome measures improved significantly during treatment. Secondary analyses indicate that improvement in the intrusive symptom cluster of the CAPS was independent of improvement on the HRSD and HRSA. In conclusion, the study indicates that olanzapine treatment is useful in alleviating the symptoms of combat-induced PTSD.

Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind, placebo-controlled evaluation in which 15 patients were randomized 2:1 to either olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day. Eleven patients completed the study. Patients in both groups showed improvement in PTSD symptoms, but no between-group differences in treatment response were observed and a high placebo response rate was found. Both treatments were tolerated well, although the olanzapine treatment group had more weight gain. Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD. The lack of difference between olanzapine and placebo may in part be due to olanzapine's not being effective in PTSD or, alternatively, a small sample size, a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients.

Schizophrenia is a chronic and debilitating disorder whose effective pharmacological management is often less than optimal. For several decades, pharmaceutical treatment for this disorder consisted of conventional neuroleptics such as haloperidol and chlorpromazine. However, the limitations of these drugs have driven the development of newer antipsychotics that are designed to be more efficacious and more tolerable than conventional agents. Newer agents available for consideration as first-line treatment options now include risperidone, olanzapine, sertindole and, more recently, quetiapine. Proper dosing has emerged as a vital factor in the effective use of these newer drugs. This report examines data derived from clinical trials and market research with risperidone and olanzapine to help clinicians determine the appropriate dose for efficacy and to appraise the adverse events associated with that efficacious dose. Current information suggests that, for most patients with schizophrenia, the optimal dose with respect to efficacy and tolerability of risperidone is < or = 6 mg/day. The optimal dose of olanzapine is less clear and may be 15 mg/day or higher. With the advent of these newer antipsychotics, clinicians now have more treatment options for the management of patients with psychotic disorders. Knowledge gained through clinical experience is needed to augment clinical trial results and to help define the most effective use of each of these agents.