Child Psychopharmacology – Gaps in Knowledge.docx

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1、4Editorial! 播 v* vy ,朝 #Child Psychopharmacology - Gaps in Knowledge1 Sharma1Department of PsychiatryInstitute of Medical SciencesBanaras Hindu UniversityVaranasi (UP), INDIAChild psychopharmacology is a relatively new field The 1937 publication by CharlesBradley reporting the effects of administeri

2、ng racemic amphetamine sulphate to 30children 5 to 14 years of age with various behavioural disturbances is usuallyconsidered to mark the beginning of the modern era of child psychophar macology.The rapid growth of child psychopharmacology has been nothing short cf beingphenomenal Not only have the

3、1ypes of medications available increaseddra maticall but so have their annual rates of production and prescription But Thereis however; inadequate research on the physiological and behavioural effects ofpsychoactive medications; their long term effect the mechanisms of 1heir action,their side effect

4、s and their interactions with other treatments both pharamacologicaland psychoeducationaLBecause of several diffilties in conducting psychopharmacological research on thesafety and efficacy of psychoactive drugs in children and younger adolescent theinvestigation and introduction into clinical pract

5、ice of psychoactive drugs in childrenhas always lagged somewhat behind that for adultsExtreme caution is required in employing psychoactive medications The long termseffects of psychoactive medications on the maturation and development of childrenand adolescents are at best only partially known, and

6、 many of their known untowardeffects are potentially han f uLChildren are not simply miniature adults You cari t just make milligram-per-kilogram assumptions with psychotropic drugs From the perspective ofpharmacotherapy, the process of development and growth in childhood represents anunstable and d

7、ynamic ndition The immaturity of the paediatric patient and thecontinuous state of development of body and oian functions influence both drugeffects and drug disposition Age-related differences in drug handling(phar ma co kinetics) and drug sensitivity (pharmacodynamics) occur throughoutchildhood an

8、d account for many of the differences between drug doses at variousstages of childhood (Routledge 1994).Therefore children should not be considered as scaled down adults as the differencesin doses are not purely dependent upon body mass Processes controlling theabsorption, distribution, metabolism,

9、excretion and pharmacologic effects of drugs arelikely to be immature or altered in infants (Ebert, 2003).A full 75% of the psychotropic drugs prescribed for children have not been tested fortheir use in well controlled trials according to AA P. Instead, weight based dosing isused to estimate the ne

10、cessary dosages for younger; smaller patients (Kaufmann,2005).W i de variations in drug dose recommendations for children of the same or differentages reflect the inadequacy of data on pharmacokinetics and pharmacodynamics inchildren Selected aspects of available literature on pharmacokinetics of dr

11、ugs used inchildren have been reviewed with special attention to calculation of an age-appropriate dose In childhood, a greater rate of elimination from plasma than inadults has been observed for many drugs, notably phenobarbitone, phenytoin,carbamazepine, ethosuximide. Consistent with this it has b

12、een shown that drugsexhibit a lower plasma level /dose ratio in childhood as compared with in adulthoodThis is true for phenobarbitone, phenytoin and ethosuxi mi da Some age groups ofchildren remain uninvestigated with regard to pharmacokinetics even for the drugsredewed Therefor paediatric therapy

13、remains empirically based formany drugs(Rane & Wilson, 1976).A number of physiologic and metabolic processes differ qualitatively as well asquantitatively when compared to adults For example, different metabolic pathwayspredominate in the biotransfor mation of drugs The i mpact of develop me nt on h

14、epaticphase I (e oxidation, reduction, hydroxylation) and phase II (Le glucuronidation,glutathione conjugation, sulfonation, methylation) enzymes can result in differentmetabolic profiles for a particular drug in children and some pathways may also beproportionally more active in children than in ad

15、ults (Schwab, 2004).Children and adolescents may require larger doses of psychoactive medication perunit of body weight than adults to attain si milar blood levels and therapeutic efficacy.It is usually assumed that two factors explain this situation: 1) more rapid metabolismby the liver and an incr

16、eased glomerular filtration rate in children compared with thatin adults (Campbell et a 1984).The catecholamine (norepinephrine, epinephrine and dopamine) systems are not fullyanatomically developed and operationally functional until adulthood The relativelyhigh prevalence of ADHD in younger children and its spontaneous improvement in