Атипичные антипсихотики: сон, седация и эффективность

"In general, the high-milligram, low-potency antipsychotics, such as chlorpromazine and mesoridazine, produce more sedation than the low-milligram, high-potency antipsychotics such as haloperidol and fluphenazine (Table 1).6 This principle tends to hold true for the atypical antipsychotics as well. For example, the high-potency, low-dose atypical antipsychotic risperidone is less sedating than the lower-potency, high-dose atypical antipsychotics quetiapine and clozapine. However, dose does not always determine sedation. Olanzapine, which has a common dose range of 15 to 30 mg/day, is more sedating than ziprasidone, which has a common dose range of 80 to 160 mg/day. Studies have indicated that sedation may also be related to the affinity of the medication for the histamine H1 receptors. The antipsychotics vary in their ability to block these receptors.4,7 A study by Richelson and Souder7 of the binding profiles of antipsychotic medications found that olanzapine has the highest affinity for the histamine H1 receptors, followed by clozapine (Figure 1Figure 1.). This may explain why olanzapine has a relatively large sedative effect even though it is a high-potency medication. Of the antipsychotics studied, haloperidol had the lowest affinity for the histamine H1 receptors. Quetiapine and risperidone had the lowest affinity of the atypical antipsychotics. Although both dosage and affinity for histamine H1 receptors play a part in the sedative effect of a medication, what ultimately determines sedative effect is the amount of the drug reaching the histamine H1 receptors in the central nervous system. For example, quetiapine, which has little affinity for the histamine H1 receptors, is a less potent antipsychotic medication and requires many more milligrams to be effective than do higher-potency medications such as risperidone and ziprasidone. Because of this, quetiapine has a greater sedative effect on patients in clinical use than do risperidone and ziprasidone."

"If sedation is bothersome to patients taking antipsychotic medications, physicians can take steps to minimize it. According to the 1999 Expert Consensus Guidelines on the treatment of schizophrenia,15 physicians should consider eliminating other sedating agents from the patient's list of medications. This includes antidepressants, such as the tricyclics and mirtazapine, and mood-stabilizing medications such as valproic acid. Instructing the patient to take his or her medication at bedtime can also reduce daytime sedation. If the entire dose cannot be given at bedtime, then the majority of the dose should be taken at night. If necessary, the physician should consider reducing the dose of the antipsychotic medication, but this should be done slowly and cautiously. The physician could also consider switching the patient to a less sedating antipsychotic. Also, the physician might consider checking the patient for hypothyroidism, which can cause individuals to feel sedated. If these efforts do not work, caffeine or bupropion might help the patient feel more alert. Many patients taking antipsychotic medications drink several cups of coffee every morning to feel less sedated.
The 1999 guidelines recommended prescribing stimulants for patients who were persistently sedated, but this has become highly controversial. Generally, I do not recommend prescribing stimulants for psychotic patients because sedation can usually be controlled using other means and the physician may be held liable for the patient's actions while medicated with stimulants.
A medication that has recently emerged as an option to treat drug-induced sedation is modafinil. The treatment mechanism of modafinil is unknown, and although it is a schedule IV controlled substance, it is not a stimulant. It has been used successfully in clinical settings to combat sedation, but there is concern that it may worsen psychotic symptoms. Modafinil was reported to have exacerbated psychosis in 1 patient who was taking a dose of 200 mg 4 times daily,16 but no adverse effects were reported in 3 patients who were taking 200 mg/day along with antipsychotic medications.17"

Atypical Antipsychotics: Sleep, Sedation, and Efficacy