非典型抗精神病药在青少年使用性安全性考虑

转载 ：practice parameter for the use of atypical antipsychotic
medications in children and adolescents 

safety issues and concerns

  the aaas are associated with several significant risks and the rates and severity of

particular side effects differ among the aaas. these side effects can occur with treatment 江西省精神病医院精神科朱健民

initiation but some may also develop after sustained use. when evaluating side effects, a

clinician should consider not only the objective severity of the side effects, but also the

subjective distress in the individual patient, as both these factors are important contributors to

non-compliance and treatment failure. when choosing an aaa for a patient, it is essential to

evaluate the potential benefit to the patient in light of the associated risk of the use of the

medication. 

 weight changes, diabetes, and hyperlipidemia: significant weight gain may occur with

the use of the aaas. this weight gain appears to be largest with clozapine and olanzapine,

although clinically significant weight gain occurs during treatment with risperidone and

quetiapine. based primarily on data from adults, aripiprazole and ziprasidone appear to have the lowest propensity for weight gain.studies examining the impact of antipsychotics on weight gain in youths suggest that aaa-associated weight gain may be greater in young people when compared to adults. studies evaluating the impact of aaas on triglycerides and cholesterol have noted an association between alterations in triglyceride levels with weight gain. although limited short-term data failed to find large significant changes in cholesterol and triglyceride levels in youths, no long-term studies have examined these parameters and therefore the long-term implications are unknown.all aaas have a black-box warning regarding the possibility of developing diabetes mellitus during pharmacotherapy with these agents. case reports of diabetes in youths being treated with a variety of the aaas exist.additionally, there is evidence to suggest that the risk of diabetes may be weight independent and differs

cardiovascular: the impact of the aaas on the cardiovascular (cv) system has been of increasing interest. cv changes that have been observed in youths treated with the aaas include prolongation of the qtc interval, orthostatic hypotension, tachycardia, and pericarditis. there are limited short-term data, and even less long-term data concerning the clinical relevance of these changes. however, the limited data available indicate there may be a greater propensity for cv changes in youths as compared to adults.a prolonged qtc is associated with an increased risk of torsades de pointes and lethal ventricular arrhythmias. although concern about the impact of the aaas on the qtc interval has focused mainly on ziprasidone, the cardiovascular safety profile of other agents has yet to be definitively characterized due to the limited amount of data.while no documented cases of sudden death due to cardiac arrhythmias have been reported with the use of aaas, there is sufficient evidence to support the conclusion that aaas do impact the qtc and this should be addressed when using these agents. in addition to concerns about the qtc interval, there are other cardiovascular events, including tachycardia, orthostatic hypotension, and coronary artery disease associated with weight gain, that should also be considered.in adults, clozapine appears to have the highest associated incidence of tachycardia and orthostatic hypotension, while other agents appear to have less impact on blood pressure and pulse. 

agranulocytosis and neutropenia: clozapine may be associated with neutropenia and

potentially fatal agranulocytosis. it is possible that the risk for these events is greater in children

when compared to adults.however, there are also case reports in adults of neutropenia

associated with risperidone, olanzapine and quetiapine.the relationship between neutropenia and agranulocytosis remains unclear and careful consideration of treatment options should follow the development of neutropenia in any youth being treated with an aaa.

hepatic dysfunction: case reports of hepatic dysfunction in youths possibly related to rapid weight gain and steatohepatitis, have been published.though there are case reports in adults and children of aaa associated hepatotoxicity this appears to be a rare occurrence. the possibility of a relationship between rapid weight gain and incidence of hepatic injury does exist and ought to be useful in guiding recommendations for monitoring.  

prolactin: elevation of prolactin levels is associated with several of the aaas. in adults

and youths, risperidone appears to have the largest propensity for prolactin elevation.

olanzapine and ziprasidone appear to have less propensity for increasing prolactin levels, while

clozapine, quetiapine, and aripiprazole do not appear to elevate prolactin levels in adults.

prolactin elevations may lead to symptoms such as amenorrhea, galactorrhea, and gynecomastia.

a recent retrospective study did not find any evidence for delays in growth or puberty in children

treated with risperidone for one year.however, the long-term significance of asymptomatic

prolactin elevations remains uncertain.

seizures: electroencephalogram (eeg) abnormalities have been reported with the use of aaas.while the greatest risk for seizures associated with the aaas appears to be with clozapine, there is a lack of data regarding the eeg changes associated with the prescription of other aaas to youths.

eps, tardive dyskinesia and withdrawal dyskinesias: although the incidence of eps and tardive dyskinesia is significantly lower when using aaas as compared to the traditional neuroleptics, there still exists the potential for the development of eps and movement disorders with these agents. the currently available data suggests that there is a higher risk of movement disorders in youths as compared to adults.

neuroleptic malignant syndrome (nms): while a very rare complication of treatment with antipsychotics, nms, a combination of autonomic instability, elevated temperature, rigidity and elevated levels of creatine phosphokinase (cpk), can be fatal. case reports exist of nms with all of the aaas. this severe, though rare complication, is of concern when using these medications in any age patient.

cataracts: over the years, several ophthalmological side effects have been reported in patients treated with psychotropic medications. animal research reported quetiapine to be associated with the development of cataracts in beagle puppies. for this reason, the manufacturer of quetiapine recommends that an examination of the lens be performed on or around the initiation of treatment and at six month intervals thereafter during chronic therapy, and that a method that is sensitive to detect cataract formation (such as a slit lamp evaluation) be employed. at the present time, there are neither reports of cataracts occurring in youths nor any published studies specifically examining this adverse event in youths.