Stager Sheila V, Calis Karim, Grothe Dale, Bloch Meir, Berensen Nannette M, Smith Paul J, Braun Allen
Voice and Speech Section, NIDCD, Bethesda, MD 20892-1416, USA.
J Fluency Disord. 2005;30(4):319-35. doi: 10.1016/j.jfludis.2005.09.004. Epub 2005 Oct 24.
Medications with dopamine antagonist properties, such as haloperidol, and those with serotonin reuptake inhibitor properties, such as clomipramine, have been shown to improve fluency. To examine the degree to which each of these two pharmacological mechanisms might independently affect fluency, a selective serotonin reuptake inhibitor, paroxetine, and a selective dopamine (D-2) antagonist, pimozide, were evaluated. Both types of medications also affect mood and anxiety, factors that could influence fluency levels. Therefore, we also evaluated the medications' effects on generalized and speech-related anxiety and the relationships between changes in anxiety and changes in fluency in 11 subjects with a history of developmental stuttering. The randomized, double blind, placebo-controlled crossover study that was designed had to be terminated prior to completion due to severe side effects following withdrawal from paroxetine. Even with a reduced sample size (n=6), significant improvement in percent fluent speaking time (p=0.02) was found using a telephone task between baseline and pimozide (n=6), with average duration of dysfluencies significantly shorter (p=0.04) but no significant difference in the estimated number of dysfluencies per minute. This significant improvement was associated with non-significant increases in generalized anxiety, but non-significant decreases in speech-related anxiety. No significant differences were found in fluency between baseline and paroxetine (n=5). These preliminary results suggest that fluency improvement is more likely to be mediated by dopaminergic rather than serotonergic mechanisms. Due to its side effects, however, pimozide may be considered a risk for treatment of stuttering.
As a result of reading this paper the reader will describe and explain: (1) how medications may affect fluency and the rationale for selecting medications for treatment trials; (2) the interrelationship between fluency and anxiety; and (3) factors important in developing clinical trials using medications.
具有多巴胺拮抗剂特性的药物，如氟哌啶醇，以及具有血清素再摄取抑制剂特性的药物，如氯米帕明，已被证明可改善流畅性。为了研究这两种药理机制各自独立影响流畅性的程度，我们评估了一种选择性血清素再摄取抑制剂帕罗西汀和一种选择性多巴胺（D-2）拮抗剂匹莫齐特。这两种药物也会影响情绪和焦虑，而这些因素可能会影响流畅性水平。因此，我们还评估了这两种药物对广泛性焦虑和言语相关焦虑的影响，以及11名有发育性口吃病史的受试者焦虑变化与流畅性变化之间的关系。由于停用帕罗西汀后出现严重副作用，设计的随机、双盲、安慰剂对照交叉研究在完成前不得不终止。即使样本量减少（n = 6），在基线和匹莫齐特（n = 6）之间使用电话任务发现，流利说话时间百分比有显著改善（p = 0.02），不流畅的平均持续时间显著缩短（p = 0.04），但每分钟不流畅次数的估计值无显著差异。这种显著改善与广泛性焦虑的非显著增加相关，但与言语相关焦虑的非显著降低相关。在基线和帕罗西汀（n = 5）之间的流畅性方面未发现显著差异。这些初步结果表明，流畅性的改善更可能是由多巴胺能机制而非血清素能机制介导的。然而，由于其副作用，匹莫齐特可能被认为是治疗口吃的一种风险药物。
阅读本文后，读者将描述并解释：（1）药物如何影响流畅性以及选择药物进行治疗试验的基本原理；（2）流畅性与焦虑之间的相互关系；（3）在使用药物进行临床试验中重要的因素。
