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痙攣を誘発する薬が吃音を重くすると言う内容。抗てんかん薬が吃音に効く理由の説明に成る。
私は現在、頻用されるジプレキサを試し飲みして、てんかん発作を超したことがある。気が付いたら脳外科病院でCT検査を受けて、若手の医師（実は私と知り合い）が病院長に説明していた。助手席に１歳の子供を乗せて、クルマ運転中に発作を起こしたのだった。
私はてんかん発作を超しながらも、無意識のうちにクルマを道の端に停めたらしい。そして１歳の息子が助手席でベビーチェアで泣いている処に警察官が駆けつけ、私は脳外科病院に運ばれたらしい。
オートマチックのクルマであり、私は発作が起こると、無意識のうちにギアをニュートラルへ入れたらしい。私はとにかくオートマチックを好んでいた。
そしてクルマを道の端に停めて意識を失ったらしい。てんかん発作を起こすと直前の記憶が消えて（飛んで）しまうことが多いが、それも有るだろう。クルマは傷も何も無かった。
私には脳波異常は無いが、“てんかん”の素因がある。
Practice tip: medication-induced stuttering in psychiatric patients
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By Mary V. Seeman MD (biography, no disclosures)
What frequently asked questions I have noticed
Fellow psychiatrists often ask whether their patients with schizophrenia are aging prematurely. They point to the fact that several of their patients seem slowed down, forgetful, fidgety, and that they garble their words and stutter. These are, of course, all side effects of antipsychotic medication. Frequently attributed to stress and usually not recognized as a drug side effect, stuttering can occur in psychiatric patients as a result of treatment with a variety of psychotropic drugs. These include antidepressants, memantine, mood stabilizers, propranolol, stimulants, and antipsychotics. Out of the many published case reports on drug-induced stutter, clozapine emerges as the most common culprit (1-3). Because clozapine is typically only used after two or more other drug trials have failed to produce results, clozapine-treated patients cannot simply be switched to another similar antipsychotic. There is no similar antipsychotic. Patients characteristically present with severe psychotic symptoms so neither can the clozapine dose be safely reduced. Because such patients have been on a number of prior antipsychotic drugs, usually at high doses, they have accumulated a variety of tics and grimaces and idiosyncratic manners of speaking and moving. in this context, acquired stuttering can easily be overlooked by the treating physician. Sometimes the patient will complain about it, but sometimes not. Should the physician notice the stutter and recognize that it wasn’t present earlier, the clozapine dose is often paradoxically raised, on the assumption that the stutter is stress-induced.
Data that answers these questions
Patients with schizophrenia can, in fact, age prematurely, but many of the outward signs of aging can be prevented or buffered. With respect to stuttering, it is defined in DSM-5 (the diagnostic and statistical manual of the American Psychiatric Association) as the involuntary, sometimes spasmodic, repetition of speech sounds, usually the consonants at the beginning of words. Syllables are often prolonged and speech flow is often interrupted by short periods of silence (4). When whole words are repeated, the speech disfluency is called palilalia (5). A spasmodic quiver of the mouth often accompanies the disfluency. When stutter emerges in adult life, it is referred to as acquired stuttering. When it begins within a few days after a drug dose increment or the initiation of a new drug, it is referred to as drug-induced acquired stuttering. When drug-induced stuttering occurs with clozapine, it sets in at an average dose of 200-250mg/day (2), but can start at as a low a dose as 50mg (1).
While stuttering in childhood is quite common, its lifetime prevalence is below 1% because children lose their stutter before puberty 80% of the time (6). Like most neurodevelopmental disorders, stuttering affects more boys than girls. By adulthood, the prevalence ratio of stuttering is approximately four males to every female because, not only are there more boys to start with, but, in addition, proportionally more girls overcome childhood stuttering (6).
When stuttering emerges de novo in adulthood, the cause can be psychogenic, a reaction to a significantly stressful event (7,8). It can also be neurogenic, secondary to cerebrovascular accident, brain tumor, brain injury, dementia, or Parkinson’s disease (9), although the two forms, psychogenic versus neurogenic, are often difficult to distinguish. Drug-induced stutter is considered a subcategory of neurogenic stutter. While its prevalence has not been established, a retrospective study in Ireland estimated clozapine-induced stuttering at 0.92%, 6 out of 654 patients (3), with no significant sex difference.
Neurogenic stuttering has been associated with lesions in the left supplementary motor area, the putamen and internal capsule, the striatum, thalamus, and cerebellum (10), not necessarily linked to structural impairment of these structures but, rather, to interruption of brain networks (11). The main network thought to be involved is the cortico-striato-cortical loop, which includes the inferior frontal cortex, the superior temporal cortex, the intraparietal cortex, the basal ganglia, and their white matter connections (12).
The drugs that have been reported to induce stuttering target several different neurotransmitter systems: the cholinergic systems (tricyclic antidepressants), dopaminergic systems (bupropion, methylphenidate, antipsychotics), noradrenergic systems (propranolol, theophylline), serotonergic systems (selective serotonin reuptake inhibitors) and NMDA systems (memantine). This means that theories of causation need to take into account the properties of the drug that triggers the stutter. Because clozapine is known to be active at many brain neurochemical receptors (13), clozapine-induced stuttering could potentially be triggered in a number of different ways.
As do all antipsychotics, clozapine lowers the seizure threshold (14) and can, therefore, lead to focal seizures that manifest as stuttering. This is a mechanism frequently discussed in the literature (15), although EEGs in most reported cases are considered normal. A further problem with the seizure theory is that anticonvulsant drugs can also sometimes induce stuttering.
As mentioned, clozapine is prescribed after several other antipsychotic drugs have failed to produce benefits. While symptoms have not benefited, the earlier drugs have very frequently produced extrapyramidal side effects (EPS) including tardive dyskinesia (TD). Many case reports of clozapine-induced stuttering note that, prior to clozapine, the patient had had severe EPS and/or TD (1), which disappeared when clozapine was started. Clozapine has a well-recognized ability to reverse these adverse effects. This raises the possibility that it is not clozapine alone that is responsible for clozapine-induced stutter but, rather, the combination of clozapine and a prior extrapyramidal disorder.