|Year : 2015 | Volume
| Issue : 1 | Page : 25-27
Divalproex-induced stuttering: A rare case report
Shatavisa Mukherjee1, Sukanta Sen1, Seshadri S Chatterjee2, Arunava Biswas1, Santanu K Tripathi1
1 Department of Clinical and Experimental Pharmacology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India
2 Department of Psychiatry, Medical College and Hospital, Kolkata, West Bengal, India
|Date of Web Publication||23-Jul-2015|
Dr. Sukanta Sen
Department Clinical and Experimental Pharmacology, Calcutta School of Tropical Medicine, 108 C R Avenue, Kolkata - 700 073, West Bengal
Source of Support: None, Conflict of Interest: None
This report describes development of stuttering with divalproex sodium in a patient of bipolar disorder. The treatment was started with twice a day regime which was well-tolerated and the patient started showing some improvement in symptoms. After a week, as the dosing was switched to three times a day, the patient experienced decreased and labored speech. His articulation altered as were the intensity and timings of utterance. Speech rhythm was also affected. Patient reported that such a problem he never experienced earlier. As he reverted to twice a day regime on advice of the doctor, there was improvement in his speech.
Keywords: Bipolar disorder, divalproex sodium, stuttering
|How to cite this article:|
Mukherjee S, Sen S, Chatterjee SS, Biswas A, Tripathi SK. Divalproex-induced stuttering: A rare case report. Eur J Psychol Educ Studies 2015;2:25-7
|How to cite this URL:|
Mukherjee S, Sen S, Chatterjee SS, Biswas A, Tripathi SK. Divalproex-induced stuttering: A rare case report. Eur J Psychol Educ Studies [serial online] 2015 [cited 2020 Feb 25];2:25-7. Available from: http://www.ejpes.org/text.asp?2015/2/1/25/161419
| Introduction|| |
Stuttering is a neuro-developmental disorder which interferes with academic and/or occupational achievement as well as social communication. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5) described stuttering as frequent occurrences of one or more of the following: Sound and syllable repetitions, sound prolongations, interjections, broken words, audible or silent blocking, circumlocutions, words produced with an excess of physical tension and monosyllabic whole word repetitions. It should be classified as a disorder only if its severity is such as to markedly disturb the fluency of speech. 
Developmental stuttering, the most common type of stuttering, is a disorder of early childhood with mean age of onset of approximately 33 months. In rare cases, stuttering may be acquired in adulthood as the result of a neurological event such as a head injury, tumor, stroke, or drug use.  The stuttering has different characteristics from its developmental equivalent: It tends to be limited to part-word or sound repetitions, and is associated with a relative lack of anxiety and secondary stuttering behaviors. Published reports on drug induced stuttering have been noted with bupropion,  clozapine,  topiramate,  lithium,  tricyclic antidepressants, , phenothiazines, , selective serotonin reuptake inhibitors (sertraline and fluoxetine),  risperidone,  olanzapine  and memantine  as responsible agents. French Pharmacovigilance Database reported that drug suspected stuttering were mainly with psychoactives: Seven cases with antiepileptic drug, six cases with neuroleptic drug (particularly clozapine and olanzapine) and five cases with antidepressive agent. Two cases involved antihistaminic and antineoplastic agents. Other classes of drug were also involved (one case for each class: TNF-α antagonist, vaccine, antibiotics, immunosuppressive agent. 
Divalproex sodium has diverse side-effects, but an extensive review of the literature has shown only one published case report stuttering as one of the complications. 
We also present a rare case in which divalproex sodium was implicated as a potential cause of stuttering. To best of our knowledge it is the first report of its kind from India.
| Case Report|| |
A 56-year-old married man reported in the outdoor patient unit, Department of Psychiatry of a tertiary care teaching hospital, Kolkata with complaints of inflated self esteem, increased energy, over talkativeness, decreased sleep, hypersexuality and occasional aggressiveness; increasing gradually for last 2 months. A similar episode happened 3 years ago. He was educated up to class 12, and having history of similar disease in elder brother.
His mental status examination (MSE) revealed psychomotor agitation and elevated, expansive mood. Speech was increased in rate and volume with decreased reaction time. There were grandiose delusion and delusion of reference. He was diagnosed as a case of bipolar affective disorder (F-31) according to International Classification of Disease: Clinical Descriptions and Diagnostic Guidelines (ICD 10).  Young Mania Rating Scale (YMRS)  scored 34 which further corroborated the diagnosis.
The laboratory investigations of routine hematology, blood sugar, liver function test and thyroid function test were found to be normal. He was placed on olanzapine 10 mg, divalproex sodium 500 mg twice daily and lorazepam 4 mg/day. But because of affective instability and irritability benzodiapine was gradually stopped and divalproex was titrated to 1500 mg/day in divided dose for a period of 14 days. At 2 weeks follow-up patient showed significant improvement with a repeat YMRS score 8.
But he reported decreased and labored speech. During the initial conversation, patient responded to all questions; but with time his speech was moderately pressured. His wife reported his articulation of speech and alterations in intensity and timings of utterance segments. Involuntary repetitions and prolongations of sounds, syllables, words or phrases as well as involuntary silent pauses or blocks were reported. Rhythm of speech was highly affected. Patient reported that increased dose of divalproex sodium from two times daily to three times daily have resulted in his decreased speech which he has not experienced earlier. He was not confused or cognitively impaired during stuttering.
Hence, we stopped divalproex which resulted instant amelioration of his speech problem. Normal rhythm of speech was restored, intensity normalized. Re-challenge after one week caused resurgence of symptoms and was stopped immediately. Naranjo's adverse drug reaction probability scale  gave a score of 8 which denotes 'probable' Adverse Drug Reaction. Patient was properly counseled.
| Discussion|| |
Valproate semisodium or divalproex sodium consists of a compound of sodium valproate and valproic acid in a 1:1 molar relationship. It is used for the treatment for bipolar disorder, epilepsy and in the prevention of migraines. Interestingly, there are limited reports of stuttering development with divalproex sodium. We are aware of a few reports of stuttering associated with the use of selective serotonin re-uptake inhibitors and the use of phenothiazines. , Thus, it is possible that stuttering was a consequence of the direct influence of divalproex sodium on speech.
A variety of hypotheses and theories suggests multiple factors contributing to stuttering. Role of several neurotransmitters such as Gamma Amino Butyric Acid (GABA), serotonin and dopamine have been proposed in the pathogenesis of stuttering.  Though neuroimaging studies have not yet found specific neural correlates, there is much evidence that the brains of adults who stutter differ from the brains of adults who do not stutter. Several neuroimaging studies have emerged in order to identify areas associated with stuttering. In general, during stuttering, cerebral activities change dramatically in comparison to silent rest or fluent speech between people who stutter and people who do not stutter. There is evidence that people who stutter activate motor programs before the articulatory or linguistic processing is initiated. Brain imaging studies have primarily been focused on adults. Studies utilizing positron emission tomography (PET) have found during tasks that invoke diffluent speech, people who stutter show hypoactivity in cortical areas associated with language processing, such as Broca's area, but hyperactivity in areas associated with motor function. 
There is also evidence of over-activity in the anterior insula, cerebellum and midbrain bilaterally and under-activity in the ventral premotor, Rolandic opercular and sensorimotor cortex bilaterally and Heschl's gyrus on the left. Per et al., hypothysised the core dysfunction is the inability of the basal ganglia to produce timing cues for the initiation of the next motor segment in speech. 
Drug-induced speech disorders  are a concern whose periodic monitoring is a component of comprehensive mental health care. Educating and involving patients and caregivers can facilitate early detection and reporting of drug-induced movement disorders. Therefore, due to limited information on the causality of the relationship between divalproex and stuttering, performing further studies in this area to clarify the mechanism of drug-induced stuttering seem to be necessary.
| References|| |
Maguire GA, Yeh CY, Ito BS. Overview of the diagnosis and treatment of stuttering. J Exp Clin Med 2012;4:92-7.
Fetterolf F, Marceau M. A case of bupropion-induced stuttering. Gen Hosp Psychiatry 2013;35:574.
Grover S, Verma AK, Nebhinani N. Clozapine-induced stuttering: A case report and analysis of similar case reports in the literature. Gen Hosp Psychiatry 2012;34:703.
Brady JP. Drug-induced stuttering: A review of the literature. J Clin Psychopharmacol 1998;18:50-4.
Yadav DS. Risperidone induced stuttering. Gen Hosp Psychiatry 2010;32:559.
Béné J, Auffret M, Fedrizzi S, Valnet-Rabier MB, Caron J, Gautier S. Drug-induced stuttering: A review of the French Pharmacovigilance Database. Available from: http://www.pharmacovigilance-npdc.fr/
[Last accessed on 2014 Nov 6].
Aukst-Margetiæ B, Margetiæ B. Stuttering as a side-effect of divalproex sodium. Psychiatry Clin Neurosci 2008;62:748.
Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: Reliability, validity and sensitivity. Br J Psychiatry 1978;133:429-35.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al
. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.
Alm PA. Stuttering and the basal ganglia circuits: A critical review of possible relations. J Commun Disord 2004;37:325-69.