Clozapine and Speech Dysfluency: Two Case Reports

Samuels et al Staff and carers’ views of learning disability service

LACEY,Y.& THOMAS, P. (2001) A survey ROSE, D. (2001) Users’ Voices.The References of psychiatrists’and nurses’ views of Perspectives of Mental Health Service ALLEN, D. (1999) Mediator analysis: an documents/ mental health advocacy. Psychiatric Users on Community and Hospital Care. original overview of recent research on carers MentalHealthGLGuide.pdf. Bulletin, 25, 477-480. Sainsbury Centre for Mental Health. supporting people with intellectual papers GRALTON, E., PEARSON, S., MOSS, S., PATEL, P., PROSSER, H., et al SAINSBURY CENTRE FOR MENTAL disability and challenging behaviour. SUTHERLAND, A., et al (2001) The (1993) Psychiatric morbidity in older HEALTH (1998) Acute Problems: A Journal of Intellectual Disability environment psychiatric patients create people with moderate and severe Survey fo the Quality of Care in Acute Research, 43, 325-339. for themselves.The varyingperceptions learning disability. II. Development and PsychiatricWards. Sainsbury Centre for of professional staff. Psychiatric reliability of the patient interview Mental Health. DEPARTMENT OF HEALTH (2001) Bulletin, 25,134-137. (PAS-ADD). BritishJournal of Valuing People: A New Strategy for Psychiatry, 163,471-480. Learning Disability for the 21st Century. HALL, I., PARKES, C., HIGGINS, A., et al TSO (The Stationery Office). (2006) The development of a new integrated mental health service for people with learning disabilities. British DEPARTMENT OF HEALTH (2004) Green Sarah Samuels Royal Free and University College Medical School, London, Journal of Learning Disabilities, 34, Light for Mental Health: How Good Are Ian Hall Islington Learning Disabilities Partnership, London, 82-87. Your Services for People with Learning Charles Parkes Camden Learning Disabilities Service, London, Disabilities? A Service Improvement HERVEY, N. & RAMSAY, R. (2004) *Angela Hassiotis Department of Mental Health Services, Royal Free and Toolkit.http:// Carers as partners in care. Advances in University College Medical School, 48 Riding House Street, LondonW1W 7EY, www.valuingpeople.gov.uk/ PsychiatricTreatment, 10,81-84. email: [email protected]

Psychiatric Bulletin (2007), 31,16-18 MARC LYALL, ANGELA PRYOR AND KEVIN MURRAY Clozapine and speech dysfluency: two case reports

AIMS AND METHOD progress towards recovery. Deviant history of stuttering might be at We describe two patients, both speech dimensions and voice quality increased risk of developing speech diagnosed with psychotic illnesses, were consistent with dysarthria and problems with clozapine. Speech who developed stuttering while dystonia. dysfluency might be a consequence being treated with clozapine. of clozapine’s action in lowering the CLINICAL IMPLICATIONS seizure threshold. Potential manage- RESULTS Patients who develop abnormal ment strategies include the use of In both patients the stuttering was electroencephalogram activity and sodium valproate and changing the severe and significantly impaired thosewhohaveafamilyorpersonal type of antipsychotic.

Stuttering is defined as a disturbance in the normal women prescribed clozapine, one at a dose of 125 mg, fluency and time patterning of speech, characterised by the other at 400 mg (Thomas et al, 1994; Ebeling et al, sound and syllable repetitions, sound prolongations and 1997). In two other patients the development of stut- broken words (American Psychiatric Association, 1994). tering has been associated with seizure activity. Supprian The prevalence of stuttering in the general population is et al (1994) described a 49-year-old woman who began slightly less than 1%, with a peak age at onset in early to stutter when prescribed 700 mg clozapine. On 750 mg childhood (Craig et al, 2002). Causation remains uncer- clozapine she suffered a generalised epileptic seizure tain, but many have argued that people who stutter have accompanied by polyspike wave activity on an electro- a subtle neurological dysfunction that disrupts the precise encephalogram (EEG). She was treated with sodium timing required to produce speech (Guitar, 1985). A family valproate; the stuttering remitted and did not recur when history of stuttering is evident in about 60% of people she was prescribed 600 mg clozapine daily. Duggal et al with an onset in childhood (Andrews et al,1988). (2002) reported a 28-year-old man who developed A link between schizophrenia and stuttering is stuttering on 300 mg clozapine daily. At 450 mg recognised and Rogers (1985) reported a 2% prevalence clozapine he suffered a generalised seizure. As the dose rate in patients with chronic schizophrenia. The relation- was reduced to 200 mg the stuttering stopped. Sodium ship between stuttering and antipsychotic treatment is valproate was later started. complex. There are a number of case reports of patients In this paper, we describe two patients who devel- who have developed stuttering when prescribed oped stuttering while being treated with clozapine on the phenothiazines (Nurnberg & Greenwald, 1981; Adler et al, same ward in a high secure hospital. 1987). Conversely, trifluoperazine and haloperidol have been shown to be effective treatments for the stuttering associated with schizophrenia (Menkes & Ungarvi, 1993). Case reports There are no previous reports in the British medical literature of a link between clozapine and stuttering. Patient1 However, four cases have been reported in North A 62-year-old man, a former market trader, was detained America. Two reports describe stuttering in young in hospital following an assault on his partner. He has no

16 Lyall et al Clozapine and speech dysfluency

family history of speech dysfluency. He first displayed of speech dysfluency. He appears to have developed symptoms of psychosis at the age of 31. Over the course paranoid schizophrenia in his early 20s. of several months he developed persecutory beliefs In 1993 the patient suffered a head injury. Subse- original centring on the actions of his partner. He was admitted quent neuropsychological testing revealed problems with papers for a short period to a psychiatric hospital and treated executive functioning and a significant discrepancy with medication. The patient did not report speech between the patient’s verbal and performance IQ, which dysfluency at this time. was felt to be related to frontal and temporal lobe His symptoms appear to have diminished and damage. Magnetic resonance imaging (MRI) of the head continued in remission for many years. In the late 1990s, and an EEG were normal. however, the patient developed a belief that his partner At the time of the patient’s arrest in the late 1990s was plotting to kill him. Over the course of a year the he described an elaborate system of delusions and patient’s mental state deteriorated further and he received a hospital order disposal. Before any treatment eventually attacked his partner. was begun he was noted to make various clicking noises Initially the patient was considered to have a and blowing sounds. Treatments attempted for his personality disorder and received a lengthy prison psychosis included flupenthixol decanoate, haloperidol sentence. However, his paranoia became increasingly decanoate, olanzapine and risperidone, but with little evident and he was eventually transferred to hospital effect; the patient reported that he developed a where a delusional disorder was diagnosed. He was initi- stammer on risperidone, with associated unusual limb and ally treated with flupenthixol decanoate, but with limited trunk movements. effect. After 2 months of oral risperidone, clozapine was Clozapine was started and prescribed up to a dose started. of 450 mg; however, the patient was noted to stammer Within a month of taking 50 mg clozapine daily, the and belch. He developed persistent hiccups and his facial patient’s speech was noted to be abnormal. As the dose tic worsened. A repeat MRI scan was normal and these of clozapine was increased to 125 mg these difficulties symptoms improved as the dose of clozapine was became more prominent and the patient’s speech reduced to 125 mg daily. When zuclopenthixol decanoate became almost unintelligible. However, when the dose was prescribed instead of clozapine, because of uncertain was subsequently reduced to 75 mg, giving a serum adherence, the patient’s speech improved significantly to clozapine level of 0.09 mg/l (normal therapeutic range the extent that he demonstrated no dysfluency although 0.35^0.42 mg/l; Taylor et al, 2005), there was some his dyskinetic movements remained. Unfortunately the improvement. patient’s mental state deteriorated and clozapine was A speech and language therapy assessment revealed restarted. a constant and severe orofacial dyskinesia, which had not At a dose of 75 mg daily (serum level 0.07 mg/l) the been noted previously. The quality of the patient’s voice speech problems re-emerged. A speech and language was harsh and strangulated. He was unable to sustain therapy assessment revealed orofacial dyskinesia invol- phonation and his speech rate was characterised by irre- ving the lips and tongue. A ‘tic-like’ movement of the gular articulatory breakdown, hesitations and sound upper lip was observed, and sudden, involuntary repetitions. The repetitions were not associated with any contractions of the jaw resulted in the patient’s teeth particular speech sound and occurred at irregular word clicking together, characteristics associated with quick positions throughout his speech utterances. The deviant hyperkinetic dysarthria (Murdoch, 1990). The patient’s speech dimensions and voice quality were consistent speech output was characterised by occasional blocking, with slow hyperkinetic dysarthria and dystonia (Murdoch, prolongation on word-initial sounds and repetitions of 1990). An EEG was normal and the patient’s stuttering speech elements, including one-syllable words at the was felt to likely result from clozapine-related tardive beginning of his speech utterances. A diagnosis of a dystonia affecting the laryngeal and pharyngeal muscles. clozapine-induced stutter was made. His family’s history Tetrabenazine was prescribed and the patient was of speech problems may have increased his vulnerability. then able to tolerate an increase in the dose of clozapine Despite a normal EEG, 600 mg sodium valproate daily was to 100 mg daily (serum level 0.09 mg/l). However, attempts to increase the dose of clozapine further prescribed as an adjunct to clozapine and the patient’s resulted in unacceptable dysarthria, despite increases in speech difficulties improved considerably. tetrabenazine dosage. Eventually clozapine was with- drawn. The patient’s speech pattern returned to normal. After a washout period, quetiapine was started. This did Discussion not cause any side-effects, but made little difference to Who is at risk? the patient’s mental state. Given the widespread prescription of clozapine and the small number of case reports linking its use to stuttering, Patient 2 the problem seems small. However, there appear to be A 55-year-old man was convicted of a violent attack on a two groups of patients at particular risk: those who friend. The patient’s father and paternal uncle had a develop abnormal EEG activity on clozapine and those pronounced stammer, and the patient’s brother has a who have either a family history of stuttering or have mild stammer. The patient denies any personal history themselves stuttered as a child.

17 Lyall et al Clozapine and speech dysfluency

Clozapine is associated with more frequent parox- the secondary effects of stuttering should be addressed ysmal EEG patterns than other antipsychotics (Koukkou appropriately through support, reassurance and original et al, 1979). Three of the four cases in the American appropriate speech and language therapy. papers literature showed EEG abnormalities, including diffuse slowing and increased paroxysmal activity. Two patients suffered tonic^clonic seizures while on clozapine and in Declaration of interest these patients co-prescription of an anticonvulsant, sodium valproate, abolished the stuttering. Sodium None. valproate was also effective in one of the patients we present. Some have ascribed stuttering to abnormal micro- Acknowledgement electrical activity, which often affects the left side of the brain, and as such treatment with anticonvulsants would We thank Professor Thomas Barnes for his helpful make theoretical sense (Weiss et al,1989). comments. Patients with either a family or personal history of stuttering might have a lower threshold for developing stuttering in the future and hence might be vulnerable to References the effects of medication such as clozapine. ADLER, L., LEONG, S. & DELGATO, R. MENKES, D. B. & UNGARVI, G. S. (1993) (1987) Drug-induced stuttering treated Adult-onset stuttering as a presenting with propanolol. Journal of Clinical feature of schizophrenia: restoration of Management Psychopharmacology, 7,115^116. fluency with trifluoperazine. Journal of An accurate diagnosis is an essential first step and this is Nervous and Mental Disease, 181, AMERICAN PSYCHIATRIC 64^65. likely to require specialist assessment by a speech and ASSOCIATION (1994) Diagnostic and MURDOCH, B. E. (1990) Acquired language therapist. Speech and language therapists are Statistical Manual of Mental Disorders (4th edn) (DSM^IV). APA. Speech and Language Disorders: A likely to have a key role in educating the patient, in Neuroanatomical and Functional particular in increasing their self-awareness of their ANDREWS, G., NEILSON, M. & CURLEE, Neurological Approach. Chapman & R. (1988) Stuttering. JAMA, 260,1445. speech output. Techniques such as encouraging the Hall. patient to pause before speaking and to regulate their COLLABORATIVE WORKINGGROUP ON NURNBERG, H. G. & GREENWALD, B. CLINICAL TRIAL EVALUATIONS (1998) breathing so as to speak on an egressive airstream, and (1981) Stuttering: anunusual side effect Adverse effects of the atypical of phenothiazines. AmericanJournal of working with the patient to slow down their rate of antipsychotics. Journal of Clinical Psychiatry, 138,386^387. speech, may also be helpful. Psychiatry, 59 (suppl.12),17^22. ROGERS, D. (1985) The motor disorders The association between clozapine and stuttering CRAIG, A., HANCOCK, K.,TRAN,Y., et al of severe psychiatric illness: a conflict of appears, at least partly, to be dose related. A reduction in (2002) Epidemiology of stuttering in paradigms. BritishJournal of Psychiatry, the communication across the entire 147, 221^232. the dose of clozapine was enough in some patients for life span. Journal of Speech Language the stuttering to stop. This clearly needs to be balanced and Hearing Research, 45,1097^1105. SUPPRIAN,T., RETZ,W. & DECKERT, J. against the requirement to treat a patient’s psychotic (1994) Clozapine-induced stuttering: DUGGAL, H. S., JAGADHEESAN, K. & epileptic brain activity. American illness effectively. A change in medication, perhaps to NIZAMIE, S. H. (2002) Clozapine- Journal of Psychiatry, 156,1663. another neuroleptic with fewer side-effects such as induced stuttering and seizures. TAYLOR, D., PATON, C. & KERWIN, R. quetiapine, may be needed. An EEG examination may be AmericanJournal of Psychiatry, 159, 315. (2005) The South London and helpful. If this reveals abnormalities, consideration should Maudsley NHS Trust Oxleas NHS Trust be given to treatment with an anticonvulsant, for EBELING,T. A., COMPTON, A. D. & 2005^2006 Prescribing Guidelines, ALBRIGHT, D.W. (1997) Clozapine- (8th edn).Taylor & Francis. example, sodium valproate. induced stuttering. AmericanJournal of Although clozapine is not typically associated with Psychiatry, 154,1473. THOMAS,P., LALAUX, N.,VAIVA, G., et al (1994) Dose-dependent stuttering dystonia or extrapyramidal symptoms, in some cases GUITAR, B. E. (1985) Stuttering and and dystonia in a patient taking stuttering appears to have presented as part of general stammering. Pediatric Reviews, 7, clozapine. AmericanJournal of movement side-effects (Collaborative Working Group 163^168. Psychiatry, 151,1096. on Clinical Trial Evaluations, 1998). In such cases KOUKKOU, M., ANGST, J. & ZIMMER, D. WEISS, S. R. B., POST, R. M., SZELE, F., tetrabenazine may be useful. (1979) Paroxysmal EEG activity and et al (1989) Chronic carbamazepine psychopathology during the treatment Patients typically experience more symptoms of inhibits the development of local with clozapine. Psychopharmacology anaesthetic seizures kindled by cocaine speech dysfluency in situations where they feel anxious. 12,173^183. and lidocaine. Brain Research, 497, Used with caution, benzodiazepines may be useful, both 72^79. for their anxiolytic properties and also because of their anticonvulsant action. Marc Lyall Specialist Registrar in Forensic Psychiatry, Angela Pryor Speech and LanguageTherapist, *Kevin Murray Consultant Forensic Stuttering can affect a patient’s self-image and Psychiatrist, Broadmoor Hospital, Crowthorne, Berkshire RG45 7EG, inhibit their willingness to engage with others. Hence email: [email protected]

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