Mulher jovem, de 33 anos, em tratamento psiquiátrico para depressão maior no Hospital Mount Sinai, em Nova Iorque (EUA), desenvolve gagueira ao receber uma dose diária de 400mg ou mais de clozapina. Mas quando a dose é reduzida para menos de 400mg diários, a gagueira melhora e, por fim, desaparece.

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AJP-334; No. of Pages 2
Asian Journal of Psychiatry xxx (2012) xxx–xxx
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Letter to Editor
Dose dependent stuttering with clozapine: A case report inpatient unit, she was followed by our consultation and liaison
service. They increased her dose of clozapine again to 200 mg in am
To the Editor, and 200 mg at bedtime. She stayed on medical floor for about 12
days and was transferred back to the psychiatry inpatient unit.
Stuttering is the involuntary disturbance in normal fluency or After being on 400 mg of clozapine (200 mg BID) for about 16 days,
pattern of speech and is characterized by sound repetitions, sound she was noticed to have stuttering again. After review of her old
prolongations or broken words which leads to marked speech records, her medication was decreased to 300 mg daily (100 mg in
dysfluency. Stuttering as a side effect has been reported in the past am and 200 mg at bedtime) which she tolerated well and her
with the use of risperidone, olanzapine, chlorpromazine, fluphen- stuttering disappeared. Ms. S continued on the same medication
azine, sertraline and clozapine. A literature search suggested that but later required ECT treatment for her psychosis.
stuttering with the use of clozapine has been linked to epileptic Association of Clozapine with stuttering has been described in
activity or is considered as another extrapyramidal symptom. We literature. These literature references are mostly case reports
present a case of young women suffering from major depressive suggesting that stuttering with Clozapine occurs more frequently
disorder with psychotic features that was refractory to most of the in males and most of the cases described in literature had either
atypical antipsychotics and developed dose dependent stuttering seizure like activity (Duggal et al., 2002; Ebeling et al., 1997;
with clozapine. Patient developed stuttering at a dose of 400 mg or Supprian et al., 1999) or orofacial dyskinesias and dystonia
above but when the dose was lowered to less than 400, stuttering (Thomas et al., 1994). Authors did not come across any case
improved and finally disappeared. Our patient was readmitted due report which reported appearance of stuttering above a particular
to relapse of symptoms and was restarted on clozapine and dose and its complete absence below that dose. Grover et al. (2012)
developed stuttering again when we tried to increase the dose reported a similar case recently where the patient had stuttering at
beyond 400 mg/day. a dose but the patient was able to tolerate even higher dose after
Ms. S, a 33-year-old female with past psychiatric history of initial reduction of doses. In our case, every time the dose of
Major Depressive Disorder, severe, with psychotic features with Clozapine was increased to or above 400 mg/day, the patient
multiple prior psychiatric hospitalizations since 2001, was started stuttering with complete resolution of stuttering below
admitted to the forensic psychiatry inpatient unit at our hospital 400 mg/day (350 mg in 1st admission and 300 mg at 2nd
for management of her psychotic symptoms. She was started on admission).
clozapine as she had documented history of failed attempts with It has been suggested that addition of antiepileptics like sodium
multiple antipsychotics including risperidone and olanzapine. valproate or reduction in clozapine dose helps with stuttering. Our
Prior to starting clozapine, her full blood counts, EKG, and CT head case calls for more research into pharmacokinetics and pharma-
did not reveal any abnormality. She was started on clozapine with codynamics of Clozapine to better understand this dose related
weekly monitoring of her white counts. Her clozapine dose was phenomenon.
gradually increased. She did fine up to a dose of 150 mg in am and
200 mg at bedtime. But when her dose was increased to 200 mg Conflict of interest
BID, she started experiencing excessive salivation and stuttering
speech (excessive prolongations of syllables or words). When the None of the authors have any proprietary or commercial
dose of clozapine was further increased to 450 mg a day (200 mg in conflicts of interest.
am and 250 mg at bedtime), her stuttering worsened. No other
symptoms of dystonia or seizure like activity were reported by the References
patient or staff. She was started on benztropine which provided
Duggal, H.S., Jagadheesan, K., Nizamie, S.H., 2002. Clozapine-induced stuttering and
benefit with sailorrhea but her stuttering still persisted despite seizures. American Journal of Psychiatry 159 (2), 315.
increasing the dose of benztropine from 0.5 mg BID to 2 mg BID. Ebeling, T.A., Compton, A.D., Albright, D.W., 1997. Clozapine-induced stuttering.
The dose of clozapine was decreased to 150 mg in am and 250 mg American Journal of Psychiatry 154 (10), 1473.
Grover, S., Verma, A.K., Nebhinani, N., 2012. Clozapine-induced stuttering: a case
at bedtime to which Ms. S responded well and her stuttering report and analysis of similar case reports in the literature. General Hospital
improved a little but it disappeared when dose was decreased to Psychiatry.
350 mg a day (100 mg in am and 250 mg at bedtime). During her Supprian, T., Retz, W., Deckert, J., 1999. Clozapine-induced stuttering: epileptic
brain activity? American Journal of Psychiatry 156 (10), 1663–1664.
stay, she remained depressed and stopped eating in the context of
Thomas, P., Lalaux, N., Vaiva, G., et al., 1994. Dose-dependent stuttering and
her delusions. She was transferred to the medical service for dystonia in a patient taking clozapine. American Journal of Psychiatry 151
stabilization as she required a nasogastric tube. In medicine (7), 1096.
1876-2018/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ajp.2012.08.004
Please cite this article in press as: Kumar, T., et al., Dose dependent stuttering with clozapine: A case report. Asian J. Psychiatry (2012),
http://dx.doi.org/10.1016/j.ajp.2012.08.004

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AJP-334; No. of Pages 2
2 Letter to Editor / Asian Journal of Psychiatry xxx (2012) xxx–xxx
Tarun Kumar* *Corresponding author. Tel.: +1 718 334 4736;
Archana Kathpal fax: +1 718 334 5721
Carrol Tim Longshore E-mail address: drtarundhingra@gmail.com (T. Kumar)
Department of Psychiatry, Mount Sinai School of Medicine,
Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373, USA 31 July 2012
Please cite this article in press as: Kumar, T., et al., Dose dependent stuttering with clozapine: A case report. Asian J. Psychiatry (2012),
http://dx.doi.org/10.1016/j.ajp.2012.08.004