Are drug holidays in the treatment of attention deficit/hyPeractivity disorder(ADHD)iustified？

Yasong DUMinjie WANG

·Forum·

Are drug holidays in the treatment of attention deficit/hyPeractivity disorder(ADHD)iustified？

Yasong DU1*Minjie WANG2

Forum：Advantages and disadvantages of drug holidays in ADHD theraPy

Drug holidays are temporary physicianmonitored breaks in the course of continuous drug therapy that usually have the goal of reversing the receptor desensitization and adverse effects of chronic drug treatment.Initially used to describe intermittent breaks in long-term treatment with antipsychotic medication，in child psychiatry drug holidays in the treatment of attention deficit/hyperactivity disorder(ADHD)typically involve stopping medication when the child is not at school—weekends，holidays and，summer or winter vacations.However，there are conflicting views about the benefits of drug holidays in the treatment of ADHD.

Arguments in favor or drug holidays in ADHD include the following：1)reduction in the drug tolerance that occurs with gradual increases in dosage;2)it provides an opportunity to assess the efficacy of the drug by comparing medicated and nonmedicated states;3)alleviation of side effects like difficulties falling asleep，loss of appetite，increased blood pressure，inhibited growth，and so forth;4) return of the child to normal life，free from the need to‘depend’on daily medication;5)decrease in concerns of parents about the side-effects of the medication;and 6)decreased need for medication when the child is not in the school environment.

Determining the appropriateness of drug holidays in the treatment of ADHD requires the clinician to assess several factors.1)Therapeutic effect：if psychostimulants effectively help the child complete cognitive tasks that require maintaining attention［1］then drug holidays should not be undertaken when the child is routinely undertaking such activities(e.g.，during school).But during recreational and leisure activities the need for maintaining attention is less and so the need for medication is also less.2)ADHD Subtype：the benefits of psychostimulants are greatest in the attention-deficit subtype of ADHD so drug holidays would be expected to result in the most marked deterioration of attention in this subgroup.3)The expectations of the primary care-givers for the child：for example，mothers who monitor the child’s homework may have greater expectations in terms of focused attention than fathers who interact with children in routine daily activities or recreational activities.4)Side effects：when dose-dependent side effects such as loss of appetite，difficulty falling asleep，headache and so forth cannot be tolerated by the child，then a drug holiday may be necessary.And 5)Symptom recovery：when symptoms have resolved and there is doubt about whether or not the child needs to continue the medication，a drug holiday can be used to assess the continued need for the medication.

Martins and colleagues［2］（2004）carried out a randomized，double-blind，placebo-controlled study on drug holidays in 40 children with ADHD.In one group methylphenidate was administered twice a day seven days a week and in the other group the children received methylphenidate during weekdays and a placebo during the two week-end days. As assessed both by parents and teachers，the therapeutic effect(school functioning)and side effects (sleep and appetite)in the week following the drug holiday week-end were not different between the groups.This study supports the use of drug holidays in children being treated for ADHD.Hugtenburg and colleagues［3］（2005）report that 24%of ADHD children treated at mental health centers and 17% of those treated in community health centers routinely take physician-sanctioned drug holidays.Moreover，in the early phase of ADHD treatment 57% of parents intermittently stop their child’s medication against physician advice.

Despite these arguments，we believe that drugholidays are not necessary and can be harmful.A multi-center retrospective study conducted by Velilla-Picazo and colleagues［4］in Spain(only available as a meeting abstract)with 802 children who had been treated for ADHD with psychostimulants continuously for at least four months compared the functioning of 440 children who stopped taking drugs for 30 days or longer over the summer vacation with that of 362 children who continued taking drugs during the vacation.They found that at the end of the vacation the core symptoms of ADHD and CGI-S scores in the drug holiday group were significantly worse than in children who did not take a drug holiday.Other studies find that episodes of arson and traffic accidents are more common in ADHD children who are not taking medication［5］.And despite the concerns of parents and some professionals that long-term treatment with psychostimulants inhibits growth and development or leads to addiction，multi-center studies assessing these problems do not confirm these dangers［6］.

ADHD is a continuous disease state that starts in early childhood and usually persists through adolescence into early adulthood.It needs continuous—not intermittent—treatment，both pharmacological and behavioral.

1. Banaschewski T，Coghill D，Danckaerts M，Dopfner M，Rohde L，Sergeant JA，et al.ADHD and Hyperkinetic Disorder.Oxford University Press，2010：54-72.

2. Martins S，Tramontina S，Polanczyk G，Eizirik M，Swanson JM，Rohde LA.Weekend holidays during methylphenidate use in ADHD children：a randomized clinical trial.Child Adolesc Psychopharmacol，2004，14(2)：195-206.

3. Hugtenburg JG，Griekspoor JE，De Boer I，Heerdink ER，Tso YH，Egberts AC.Methylphenidate：use in daily practice.Pharm World Sci，2005，27(3)：197-201.

4. Velilla-Picazo M，Garcia-Giral M，Caballero-Correa M，Martinez-Jimenez.Benefits/risks of treatment discontinuation on patients diagnosed of attention deficit hyperactivity disorder during summer holidays：The AESTAS study.Poster at the 2nd International Congress on ADHD，Vienna，May 2009.Available online at http：//www.neurologia.tv/bibliopsiquis/bitstream /10401/1507/1/AESTAS_IIADHDDanubeCongress_Vienna2009%20%282%29.pdf(accessed 23 October 2011).

5. Nada-Raja S，Langley J，Mcgee R，Williams SM，Begg DJ，Reader AI.Inattentive and Hyperactive Behaviors and Driving Offences in Adolescents.J Am Acad Child Adolesc Psychiatry，1997;36(4)：515-522.

6. MTA Cooperative Group.Moderators and mediators of treatment response for children with Attention Deficit/Hyperactivity Disorder：The multimodal treatment study of children with Attention-Deficit/Hyperactivity Disorder.Arch Gen Psychiatry，1999，56(12)：1088-1096.

·論壇·

論壇：注意缺陷/多動障礙治療中藥物假日的利弊

藥物假日是醫(yī)生根據(jù)病情需要有意識地、暫時性停止用藥的過程，目的是逆轉(zhuǎn)抗精神病藥物慢性治療過程中的受體不敏感和不良反應(yīng)。最初用于描述長期抗精神病藥治療中的間歇性停藥，在兒童精神科，當(dāng)注意缺陷多動障礙（Attention Deficit/Hyperactivity Disorder,ADHD）患者不上學(xué)時——周末、節(jié)假日、寒暑假，會采用藥物假日的治療方式。然而，對ADHD治療中藥物假日的利弊存在爭議。

ADHD治療中藥物假日的使用理由包括：①減輕持續(xù)用藥的不良反應(yīng)和藥物劑量增加的耐受性；②可以檢測一段時間治療后的藥物療效；③緩解藥物不良反應(yīng)，如入睡困難、食欲下降、血壓升高和生長抑制等；④使患兒恢復(fù)正常生活，從對每日用藥的“依賴”中恢復(fù)正常生活；⑤減少家長對藥物不良反應(yīng)的擔(dān)心；⑥兒童未在校時，使他們對藥物的需要減少。

是否需要“藥物假日”，需要對藥物假日使用的必要性進行評估：①藥物治療作用：如果精神興奮劑有助于ADHD患兒在完成認知活動任務(wù)時保持良好的注意力［1］，那么當(dāng)患兒常規(guī)地在從事這些活動時（如上學(xué)），不應(yīng)該減少藥物。但在閑暇娛樂時，對維持注意力的需要減少，所以藥物也應(yīng)相應(yīng)的減少。②ADHD亞型：在ADHD的3種亞型中，以注意缺陷為主型的藥物治療效果最好。③養(yǎng)育者的期望：例如負責(zé)孩子學(xué)習(xí)的母親與帶孩子活動的父親相比，母親可能認為孩子更需要集中注意力。④藥物不良反應(yīng)：當(dāng)藥物治療過程中出現(xiàn)與劑量相關(guān)的不能耐受的不良反應(yīng)時，例如食欲下降、入睡困難、頭疼等，“藥物假日”可能是必要的；⑤考察癥狀恢復(fù)程度：當(dāng)ADHD患兒治療一段時間后，癥狀恢復(fù)較好，專業(yè)人員和家長對是否需要繼續(xù)用藥感到疑惑時，也可以嘗試藥物假日，以評估是否需要持續(xù)用藥。

Martins及其同事［2］（2004）做了一項針對藥物假日的隨機、雙盲、安慰劑對照研究。他將40例ADHD患兒隨機分配到兩組：非藥物假日組，1 d 2次用藥，連續(xù)7 d接受哌甲酯治療；藥物假日組，哌甲酯治療5 d，周末使用安慰劑。由老師和家長評定療效，藥物假日之后的1周兩組間治療效應(yīng)（學(xué)校功能）與藥物不良反應(yīng)（睡眠和食欲）無差異。該研究支持治療ADHD患兒采用藥物假日的方式。Hugtenburg等［3］（2005）報道精神衛(wèi)生專業(yè)機構(gòu)中24%、社區(qū)醫(yī)療機構(gòu)有17%的ADHD患兒接受醫(yī)生批準(zhǔn)的假日停藥。在治療初期，57%的ADHD患兒家長自行間斷的選擇使用藥物假日。

盡管存在上述爭議，我們認為藥物假日不是必要的，并且存在弊端。Velilla-Picazo等［4］（2009）在西班牙進行的多中心回顧性研究（僅見于一次會議的摘要），研究對象為連續(xù)服用精神興奮劑4個月以上的802例ADHD患兒，其中440例暑假停藥30 d以上（藥物假日組），362例持續(xù)用藥（非藥物假日組）。暑假結(jié)束時藥物假日組患兒的核心癥狀及CGI-S評分顯示的病情均比非藥物假日組嚴重。其他研究發(fā)現(xiàn)不服藥期間患兒的縱火及交通事故發(fā)生率增加［5］。盡管家長和部分專業(yè)人員擔(dān)心長期精神興奮劑治療的不良反應(yīng)，如影響生長發(fā)育（身高、體重）、成癮，但多中心研究并未證實會出現(xiàn)上述危害［6］。

參考文獻

注意缺陷/多動障礙治療中的藥物假日合理嗎？

杜亞松1王民潔2

1上海交通大學(xué)醫(yī)學(xué)院附屬精神衛(wèi)生中心200030；2南京醫(yī)科大學(xué)附屬南京腦科醫(yī)院210029。

杜亞松，電子信箱yasongdu@yahoo.com.cn

doi(combining all the papers in the Forum Section)：10.3969/j.issn.1002-0829.2011.05.010

1Shanghai Mental Health Center，Shanghai Jiao Tong University School of Medicine，Shanghai 2000302Brain Hospital，Nanjing Medical University，Nanjing 210029，China

*Correspondence：yasongdu@yahoo.com.cn

doi(包括論壇欄目中所有的內(nèi)容）：10.3969/j.issn.1002-0829.2011.05.010