Sedation olanzapine

There were moderate but significant improvements in neurocognition (including executive function, working memory, and declarative memory) in a randomized, double -blind, 8-week study in 52 patients with schizophrenia assigned either to olanzapine (10-20 mg/day n = 18) or amisulpride (400-800 mg/day n = 18) (11). Of 16 dropouts, six were due to adverse events olanzapine—sedation (n = 2) and increased transaminases (n = 1) amisulpride—rash, extrapyramidal symptoms, and galactorrhea (n — 1 each). 

Prochlorperazine is a potent phenothiazine antipsychotic drug that is associated with a high risk of extrapyramidal side-effects, a low degree of sedation and of antimuscarinic side-effects. Chlorpromazine is less likely to induce extrapyramidal side-effects but has increased risks of inducing sedation and antimuscarinic side-effects. Olanzapine is classified as an atypical antipsychotic having characteristically much fewer incidences of extrapyramidal... 

Olanzapine has shown encouraging results, in doses ranging from 2.5 to 20 mg/day, in two open trials involving a total of 30 adults with TS (Budman et al., 2001 Stamenkovic et al., 2000). A 52-week doubleblind crossover study of olanzapine (5 or 10 mg) versus pimozide (2 or 4 mg) in four adult patients with TS conducted by Onofrj et al. (2000) found olanzapine superior to pimozide in terms of tic reduction, sedation, and patient preference. The small sample size limits the clinical import of these findings. 

Antipsychotic drugs with strong sedative clinical effects (e.g. chlorpromazine. clozapine, olanzapine) produce subjective and objective sedation and impair most areas of performance in healthy volunteers, usually at doses far below those typically used in patients. Antipsychotic drugs with little sedative clinical action (e.g. pimozide, sulpiride, amisulpride) produce few subjective and objective effects in healthy... 

Quetiapine (3) has the lowest affinity for the D2 and 5-HT2a receptors among the atypicals therefore, relatively high doses are required for maximal efficacy. Quetiapine causes significant weight gain, but less than that of olanzapine. Other side-effects include sedation, dizziness and hypotension. 

In the development of new antipsychotics, cQT intervals are routinely evaluated but it is currently unclear how predictive these are of clinically significant cardiotoxicity or sudden death. For this reason, the heart rate variability (HRV) index has been developed. It has been shown that the HRV decreases after TCAs and clozapine. In a comparison of the acute effects of olanzapine, risperidone and thioridazine in healthy male volunteers, olanzapine was shown to increase, thioridazine to decrease while risperidone was without effect on the HRV. A decrease in the HRV is an established predictor of poor cardiac outcome. The cardiac changes were unrelated to the degree of sedation caused by the drugs. 

Recreational drug users note the same effects. Several comment on similarities between olanzapine and quetiapine and the benzodiazepine drugs, such as diazepam (Valium), because of the intense sedation. However none report the euphoria that characterises benzodiazepine effects. One correspondent reported protracted insomnia after stopping olanzapine, comparing it to benzodiazepine withdrawal (Sixseal.com 2007). 

Clozapine, olanzapine, and quetiapine display significant affinity to histamine Hj receptors, and it is widely accepted that some side effects of these agents (e.g., weight gain liability, sedation) are attributed to their histamine antagonism... 

There was a highly significant reduction in rating scale scores for the syndrome with olanzapine 10 mg versus baseline and versus pimozide 2 mg, and a significant reduction with olanzapine 5 mg versus pimozide 4 mg only moderate sedation was reported by one patient during olanzapine treatment while three complained of minor motor adverse effects and sedation during pimozide treatment. 

Olanzapine, mean dose 5.4 mg/day, has been given to 21 patients with apathy in the absence of depression after long-term treatment with SSRIs for non-psychotic depression in an open, flexible-dose study (111). The more frequent adverse effects were sedation (n = 12), increased appetite (n = 8), stiffness (n = 7), edema (n = 6), and dry mouth (n = 5). 

Of 14 consecutive patients with bipolar I disorder, who were inadequately responsive to standard psychotropic agents and who were given olanzapine, 8 improved (20). The most common adverse effects were sedation, tremor, dry mouth, and increased appetite with weight gain. 

In contrast, olanzapine was discontinued in five preadolescent children (aged 6-11 years) within the first 6 weeks because of adverse effects or lack of therapeutic response (23). The adverse effects included sedation (n = 3), weight gain (n = 3), and akathisia (n = 2). 

The medical records of 151 hospitalized elderly psychiatric patients (mean age 71 years) have been analysed (25). Of 37 patients treated with olanzapine (mean duration of treatment 20 days, mean dose 10 mg/day), 75% responded. Adverse effects were reported in six patients sedation in four patients and extrapyramidal signs and postural hypotension in one each. 

Olanzapine was effective in an open trial in 10 patients with obsessive-compulsive disorder refractory to selective serotonin reuptake inhibitors, who were given additional olanzapine they had minimal adverse effects, primarily sedation (27). 

In 23 patients with obsessive-compulsive disorder who had not responded to a 6-month course of fluvoxamine (300 mg/day), olanzapine (5 mg/day) was added in an open comparison (28). There was a significant reduction in the mean score on the Yale-Brown Obsessive-Compulsive Scale concomitant schizotypal personality disorder was the only factor significantly associated with a response. The most common adverse effects were mild to moderate weight gain and sedation. 

In a prospective open 12-week study in eight children, adolescents, and adults with developmental disorders, the most significant adverse effects of olanzapine were increased appetite and weight gain in six patients and sedation in three (31). 

In 18 patients with trichotillomania given olanzapine (maximum dose 10 mg/day) in a 3-month open study the most common adverse effects were sedation and weight gain (43). The authors claimed that olanzapine may be effective monotherapy for trichotillomania. 

In a recent non-randomized, open study in 37 patients (21 women, 16 men) with essential tremor, the most common movement disorder, olanzapine significantly reduced the median tremor score from 3.3 to 1.1 (47) seven of the patients reported adverse effects such as sedation, which disappeared in about 7 days, and three complained of weight gain. 

In an 8-week study, pre-school-age children with bipolar disorder (aged 4-6 years) took either olanzapine (n = 15 mean age 5.0 years 10 boys mean dose 6.3 mg/day) or risperidone (n = 16 mean age 5.3 years 12 boys mean dose 1.4 mg/day) (59). There were significantly more dropouts with olanzapine (6 versus 1), including one patient who withdrew because of adverse events (increased appetite and hand tremor). The main adverse events, found with both treatments, were significant increases in prolactin concentrations and weight gain. With both treatments, increased appetite, flu-like symptoms, headaches, and sedation were the most commonly reported adverse effects. 

There have been reports that selective serotonin reuptake inhibitors, which inhibit CYP1A2, increase plasma olanzapine concentrations (SEDA-24, 71 SEDA-26, 63). In a recent open add-on trial, 21 patients with obsessive-compulsive disorder unresponsive to treatment with paroxetine 60 mg/day for at least 12 weeks, took additional olanzapine 10 mg/day (280). Steady-state plasma concentrations of paroxetine were not changed, and 7 patients were rated as responders at final evaluation. Sedation (n = 12), weight gain up to 3 kg (n = 8), dry mouth (n = 6), and constipation (n = 3) were the most frequent adverse effects. 

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