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<P><FONT size=3>精 神 药 物 与 口 吃</FONT></P><P><FONT size=3>作者：刘连启　王爱青　唐济生 (250014,山东省精神卫生中心)</FONT></P><P><FONT size=3>摘自：《中国行为医学科学》 2000年第5期第9卷 综述  【摘要】：口吃和其他语言表达形式异常是在应用某些药物时偶然能够见到的副反应，本文就所能够检索到的有关精神药物引起的口吃的病例报道及相关文献进行了综述，对此类口吃的定义、特点、诊断及发病机制进行了探讨，同时也对易造成混淆的其他两种语言障碍——言谈阻滞（speech blockage）和构语障碍(dysarthria） 进行了鉴别。</FONT></P><P><FONT size=3>　　 一、口吃的定义及鉴别</FONT></P><P><FONT size=3>　　 1．口吃　DSM-Ⅳ关于口吃的定义为：一种语言流畅性和节奏方面的障碍，以如下几种情况的频繁出现为特点：语音或音节重复，语音拖长，感叹声，词句破裂，有声或无声的阻断期，表达困难，讲话时身体过分紧张，以及单音节词的重复等。　　 口吃分为习得性和获得性（神经源性）两类。习得性口吃比较常见，多在儿童期或青少年期起病，常呈渐进性病程；获得性或神经源性口吃可在任何年龄阶段出现，为突然发病，且总伴有明显的脑功能损害，如脑中风、脑外伤、脑肿瘤等。一般情况下临床上比较容易鉴别这两种口吃：如果让习得性口吃病人重复朗读一段短文，会一次比一次读得流畅，当读到第10至15遍时，就能非常流利地把短文读下来。但当第二天让该患者重读这一段时，又会重复前一天的情形。这种现象称为“适应效应”。而获得性口吃则无此效应。习得性口吃的另一个特点是在发开始的音节和词汇时尤为困难（如表现为重复或阻滞等），获得性口吃则不会或很少在发初始的音节时存在障碍［1］。　　 口吃直到最近几十年才被大多数临床工作者认为是一种与心因有关的障碍。虽然有越来越多的证据表明口吃患者存在中枢神经系统异常的基础，但这并不能说明心理因素不重要，心理因素毫无疑问影响着口吃的病程、严重性和功能缺损的程度。个体和集体心理治疗、行为性语言矫正仍是目前治疗口吃最有效的手段［2］。</FONT></P><P><FONT size=3>　　 2．构语障碍　构语障碍患者明白自己想要说什么，但由于发音肌的虚弱、不协调或瘫痪而很难完成说话的动作。患者虽能发音，但这种歪曲的声音无法被人理解。构语障碍可以合并口吃，但二者通常比较容易进行鉴别［3］。</FONT></P><P><FONT size=3>　　 3．言谈阻滞　言谈阻滞通常指词汇记取方面存在问题，患者清楚自己想要表达的思想或感情，但不能找出恰当的词汇来应用。患者一旦记起所需要的词汇，就会毫无困难地用恰当的声音表达出来。口吃与言谈阻滞明显不同，口吃患者知道自己想要应用的词汇，但是难以不带有音节重复、声音拖长或其他口吃特点就将这些词汇表达出来［3］。</FONT></P><P><FONT size=3>　　 二、精神药物引起口吃的病例报道 </FONT></P><P><FONT size=3>　　 本文共综述了23例由精神药物引发的口吃病例。所有的病例在停用有关药物后不久口吃即均消失，其中有7例还经过了双盲、安慰剂对照的重复验证，即在停用影响药物且口吃消失以后，再次给予原药物口吃又重新出现［3～4］。另外14例病人的口吃的出现和消失与相关药物的启用和停用相平行［5～8］。因此，足以能够证实这些口吃与药物的因果关系。</FONT></P><P><FONT size=3>Nernberg 等［5］报道的一例病人的口吃与吩噻嗪类抗精神病药物三氟拉嗪、氯丙嗪有关，为排除该病人的口吃为锥体外系副反应，作者应用了抗胆碱能药物苯托品，但未见效果。</FONT></P><P><FONT size=3>Alder 等［6］报道了两例同样由吩噻嗪类药物奋乃静和氯丙嗪引起的口吃，由于这两例病人在出现口吃的同时还都伴有静坐不能，于是作者应用了心得安，竟使两例病人的口吃和静坐不能同时消失。当停用心得安时，口吃和静坐不能又都出现了。</FONT></P><P><FONT size=3>McCall 等［8］ 也注意到口吃和静坐不能同时存在的现象，并由此提出了这两种症状相关联的推论。由氯氮平引起的口吃也有两篇报道［4，7］ 。三环类抗抑郁剂（TCAs），选择性5-羟色胺再摄取抑制剂（SSRIs）舍曲林和氟西汀等也可引起口吃［8～10］。抗癫痫药物苯妥英、卡马西平，苯二氮类药物二钾氯氮、利眠宁，中枢兴奋剂匹莫林等，也有引起口吃的报道［3，5，6］。</FONT></P><P><FONT size=3>　　 三、精神药物引起口吃的特点</FONT></P><P><FONT size=3>　　 1．性别差异　一般人群中成年口吃患者性别比率男女之比为5：1。上述23例患者中19例为成年人，4例为儿童，成年患者中男女比例为8：7（有4例报道没有给出性别，4例儿童男女比例为2：2）［6］。因此，同一般人群相比，本资料提示由药物引起的口吃更多地出现在女性当中。</FONT></P><P><FONT size=3>　　 2． 口吃的特点　由精神药物引起的口吃，有的具有习得性口吃的特点，有的具有获得性口吃的特点。有影响作用的药物可能会使以往的语言模式重现，故过去有口吃病史的人（如50岁的患者在儿童或青少年期患过口吃）现在由药物引起的口吃会表现出习得性口吃的特点［3］。本文所综述的由药物引起的口吃大多数具有获得性口吃的特点。</FONT></P><P><FONT size=3>　　 3． 治疗口吃的药物　有的药物能引起口吃，但同时也能治疗口吃，神经阻滞剂就是这样一类药物。吩噻嗪类抗精神病药已被证明可以引起口吃，但也同时被用来治疗口吃。Menkes［11］等报道了一例同时患有口吃和精神分裂症的25岁男性病例，三氟拉嗪治好了他的口吃，也改善了他的精神病状态；有两次停用了三氟拉嗪，口吃均重新出现，充分证明了三氟拉嗪对口吃的疗效。甲硫哒嗪合并语言矫正疗法治疗口吃效果明显优于安慰剂合并语言矫正疗法；丁苯酰类抗精神病药氟哌啶醇治疗口吃效果最好，但存在易引起锥体外系副反应进而降低治疗依从性的不足之处［2］。</FONT></P><P><FONT size=3>　　 TCA类的氯丙咪嗪对口吃有治疗作用［12］。Stager等［13］对16例成年口吃患者用氯丙咪嗪或去甲丙咪嗪进行安慰剂单盲、药物双盲的交叉治疗，也发现两药物均有治疗口吃的作用，且前者疗效要优于后者，作者认为氯丙咪嗪的显著疗效来自于它对5-羟色胺再摄取的选择性抑制。属于SSRIs类的帕罗西汀也被成功地用来治疗口吃［12，14］。</FONT></P><P><FONT size=3>　　 四、 精神药物引起口吃机制的探讨</FONT></P><P><FONT size=3>　　 1．胆碱能机制　有研究者认为TCAs之所以能够引起口吃，可能与其抗毒蕈碱能作用有关［6，11］。Brady 等［3］对两例由精神药物引起的口吃患者运用拟胆碱能药物bethanechol 进行了双盲交叉试验，发现两例患者的口吃症状都得到了显著改善。Kampman 等［15］的另外一项研究用bethanechol对10例口吃患者进行双盲交叉安慰剂对照研究，发现有2例获得了显著而持久的疗效。这两项研究提示，在口吃患者中有可能存在一个对bethanechol敏感的亚组。</FONT></P><P><FONT size=3>　　 2． 多巴胺能机制　神经阻滞剂能够引起口吃的现象提示这种口吃可能与多巴胺有关，且是通过抗胆碱能机制而起作用的［6］。Menkes［11］等发现引起口吃的神经阻滞剂多为低效价药物，具有内在的抗毒蕈碱能活性，而很多用神经阻滞剂治疗的病人同时也在应用具有抗胆碱能作用的抗巴金森氏病药物，因此与锥体外系副反应的出现相类似，多巴胺/乙酰胆碱平衡问题可能也是精神药物引起的口吃的缓解和加重的机制。此机制可以解释神经阻滞剂既能引起口吃又能治疗口吃的现象。</FONT></P><P><FONT size=3>　　 3． 去甲肾上腺素能机制　由精神药物引起的口吃患者中有的同时伴有静坐不能现象存在，而有研究发现心得安能同时缓解这种口吃和静坐不能［6］。由此可以推测，去甲肾上腺素能机制在精神药物引起的口吃加重或缓解过程中起了一定作用。</FONT></P><P><FONT size=3>　　 4．5-羟色胺（5-HT）能机制　本文资料中由SSRIs引发的口吃患者共有6例，其中有3例同时伴发静坐不能，提示SSRIs较其他抗抑郁剂似更易引起静坐不能发生。Hamilton 等［10］认为SSRIs 使体内5-HT浓度升高，5-HT浓度的升高可能通过影响黑质—纹状体多巴胺能通路的功能而引发静坐不能，同样的机制可能也是引发口吃的原因，从而提示药物引起的口吃可能存在5-HT能机制。</FONT></P><P><FONT size=3>　　 五、结论　　 多种精神药物可以引发口吃，这种口吃患者的男女比例与普通人群中口吃患者的男女比例不同。一些能够引发口吃的药物在另外一些人身上又可以用来治疗口吃。精神药物引发口吃的机制，可能是通过脑内几种神经递质系统单独或共同起作用的结果。临床医师应及时对由精神药物引发的口吃进行识别和处理，以提高患者的生活质量。</FONT></P><P><FONT size=3>参考文献</FONT></P><P><FONT size=3>1． Helm A, Bulter R, Benson D. Acquired stuttering. Neurology, 1978, 28:1159～1165.</FONT></P><P><FONT size=3>2．Brady JP. The pharmacology of stuttering: a critical review. Am J Psychiatry, 1991, 148:1309～1316.</FONT></P><P><FONT size=3>3．Brady JP. Drug-induced stuttering: a review of the literature. J Clin Psychopharmacol, 1998, 18:50～54.</FONT></P><P><FONT size=3>4．Thomas P, Lalaux N, Vaiva G, et al. Dose dependent stuttering and dystonia in a patient taking clozapine. Am J Psychiatry, 1994, 151:1096.</FONT></P><P><FONT size=3>5．Nernberg HG, Greenwald B. Stuttering: an unusual side effect of phenothiazines. Am J sychiatry, 1981, 138:386～387.</FONT></P><P><FONT size=3>6．Adler L, Leong S, Delgato R. Drug-induced stuttering treated with propanolol. J Clin Psychopharmacol, 1987, 7:115～116.</FONT></P><P><FONT size=3>7．Ebeling TA, Compton AD, Albright DW. Clozapine-induced stuttering. Am J Psychiatry, 1997, 154:1473.</FONT></P><P><FONT size=3>8．McCall WV. Sertraline -induced stuttering. J Clin Psychiatry, 1994, 55:316.</FONT></P><P><FONT size=3>9．Christenson RC, Byerly MJ, McElroy RA. A case report of sertraline-induced stuttering. J Clin Psychopharmacol, 1996, 16:92～93.</FONT></P><P><FONT size=3>10．Hamilton MS, Opler LA. Akathisia, suicidality and fluoxetine. J Clin Psychiatry, 1992, 53:401～406.</FONT></P><P><FONT size=3>11．Menkes DB,Ungvari GS. Adult-onset stuttering as a presenting feature of schizophrenia: restoration of fluency with trifluoperazine. J Nerv Ment Dis, 1993, 181:64～65.</FONT></P><P><FONT size=3>12．Brady JP, Ali Z. Alprazolma, citalopram and clomipramine for stuttering. J Clin Psychopharmacol, 2000, 20:287.</FONT></P><P><FONT size=3>13．Stager SV, Ludlow CL, Gordon CT, et al. Fluency changes in persons who stutter following a double blind trial of clomipramine and desipramine. J Speech Hear Res, 1995, 38:515～525.</FONT></P><P><FONT size=3>14．Murray MG, Newman RM. Paroxetine for treatment of obsessive-compulsive disorder and stuttering. Am J Psychiatry, 1997, 154:1037.</FONT></P><P><FONT size=3>15．Kampman K, Brady JP. Bethanechol in the treatment of stuttering. J Clin Psychopharmacol, 1993, 13:284～285.</FONT></P><P><FONT size=3> </FONT></P>

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