Sedation clozapine

The daily dose of clozapine ranges from as low as 200 mg/day to as high as 900 mg/day, though most patients with mania require lower doses than those with schizophrenia. Due to side effects such as dizziness and sedation, patients must be titrated gradually to the effective dose range. 

NSAID and warfarin ACE inhibitors and K-sparing dinretic Verapamil and beta-adrenergic antagonists Nenromnscnlar (NM) blockers and aminoglycosides Alcohol and benzodiazpines Thioridazine and halofantrine Clozapine and co-trimoxazole Increased risk of bleeding Increased risk of hyperkalaemia Bradycardia and asystole Increased NM blockade Increased sedation Increased risk of QT interval prolongation Increased risk of bone marrow suppression... 

Neurological Extrapyramidal side effects, sedation, seizures Dopamine 2, histamine Examine for Parkinsonism, akath-isia, and abnormal involuntary movements at each visit Baseline electroencephalogram if treated with clozapine. 

Because of prominent sedation and orthostatic hypotension, clozapine therapy is initiated at a dose of 12.5 mg/day, with a rapid increase to 12.5 mg twice a day. The dose is then increased as tolerated, generally in 25- or 50-mg increments every day or every other day. Clozapine is... 

Sedation. Sedation is the most common side effect of clozapine, and it is particularly prominent early in treatment. Sedation generally attenuates when the dose is reduced, when tolerance to this side effect develops, or when a disproportionate amount is given at bedtime. 

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... 

Concomitant use of a BZD and clozapine may increase the risk of sedation, dizziness, collapse with loss of consciousness, respiratory distress, and fluctuating blood pressure (196). 

Sedation, ataxia, and cognitive impairment occur more frequently with high BZD dosages. Other adverse effects reported when BZDs were used to treat schizophrenia include behavioral disinhibition, exacerbation of psychosis, and increase in anxiety and depression ( 163, 188, 189,190, 191,192, 193,194 and 195, 351). Concomitant use of a BZD and the atypical antipsychotic clozapine may increase the risk of sedation, dizziness and collapse with loss of consciousness ( 196). Respiratory compromise has also been reported with this combination (395, 396). 

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. 

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... 

Clozapine s anticholinergic effects can cause confusion and delirium as well as sedation and lethargy. The severity of withdrawal psychosis may be due to cholinergic rebound. Clozapine can aggravate or cause hypersalivation, glaucoma, constipation and ileus, and urinary retention (Baldessarini et al., 1991). Weight gain is also a potentially very serious problem. 

In nine men who were given a single dose of clozapine 50 mg on two separate occasions with a 2-week interval, fluvoxamine increased clozapine plasma concentrations, and the total mean clozapine AUC was increased by a factor of 2.6 all the patients were sedated during combined therapy (38). 

Prior TI. Is there a way to overcome over-sedation in a patient being treated with clozapine J Psychiatry Neurosci 2002 27 224. 

Clozapine has also been compared with risperidone in 60 treatment-resistant patients with schizophrenia in India (16). There was clinical improvement (a more than 20% reduction from baseline PANSS scale scores) in 80% of the clozapine-treated patients and 67% of the risperidone-treated patients. The predominant adverse effects with clozapine (n = 30) were tachycardia (77%), hypersalivation (60%), sedation (60%), weight gain (43%), and constipation (30%) one patient had a seizure. The adverse effects of risperidone (n = 30) were constipation (50%), dry mouth (47%), weight gain (43%), akathisia (37%), insomnia (33%), tachycardia (30%), and impotence (27%). The final mean daily doses after 16 weeks of treatment were 343 mg for clozapine and 5.8 mg for risperidone. 

In a retrospective open study of 46 patients taking clozapine for 4 years, clozapine had to be discontinued in 10 patients (21%) and serious adverse effects were rare no patient had agranulocytosis (6). The most troublesome adverse effects were drooling, sedation, and weight gain, and three patients had seizures. 

Experiences in uncontrolled open studies in Chinese patients have been summarized (7). The most common adverse effect of clozapine was hypersalivation, followed by sedation. Mandatory blood monitoring is considered an obstacle in persuading some patients to undergo a trial of clozapine, mainly for cultural reasons, summed up by the Chinese proverb that a hundred grains of rice make a drop of blood. ... 

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