Drug-induced stuttering: A comprehensive literature review

Table 1 Number of episodes of drug-induced stuttering reported in the online literature and included in the present review

Therapeutic category	Number of episodes of stuttering, n = 86 (%)
Antipsychotics
Clozapine	30 (34.9)
Olanzapine	8 (9.3)
Risperidone	4 (4.6)
Aripiprazole	3 (3.5)
Trifluoperazine	1 (1.2)
Chlorpromazine	1 (1.2)
Fluphenazine	1 (1.2)
Levomepromazine	1 (1.2)
Anticonvulsants
Phenytoin	2 (2.3)
Divalproex	2 (2.3)
Pregabalin	2 (2.3)
Gabapentin	1 (1.2)
Lamotrigine	1 (1.2)
Central nervous system agents
Methylphenidate	3 (3.5)
Memantine	2 (2.3)
Levodopa	4 (4.6)
Dextroamphetamine and amphetamine salts (Adderall®)	1 (1.2)
Atomoxetine	1 (1.2)
Pemoline	1 (1.2)
Antidepressants
Sertraline	3 (3.5)
Bupropion	3 (3.5)
Desipramine	1 (1.2)
Bipolar agents
Lithium	3 (3.5)
Respiratory tract agents
Theophylline	4 (4.6)
Anxiolytics
Alprazolam	1 (1.2)
Antineoplastics
Methotrexate	1 (1.2)
Pyrethrin	1 (1.2)
Total	86 (100)

Table 2 Demographic characteristics and clinical history of patients

Characteristic/history1	n (%)
Gender
Female	28 (34.6)
Male	53 (65.4)
Age (yr)
< 12	15 (18.5)
12-20	3 (3.7)
21-30	15 (18.5)
31-40	16 (19.7)
41-50	13 (16)
51-60	10 (12.3)
> 60	9 (11.1)
History of speech dysfluency	11 (13.4)

¹The total number of the patients is 82, but the age and gender of one patient was not reported.

Table 3 Summary of the case reports of drug-induced stuttering

Offending drug (dosage)	Patients’ gender/age (yr)	Main indication of drug administration	Concomitant medications (dosage)	Onset/aggravation of stuttering	Primary behaviors	Concomitant symptoms	Management, response	Recurrence of stuttering after medication resumption	Concomitant disorders	Ref.
Adderall XR® (20 mg/d)	Male/10	ADHA	No other drugs	Within two weeks after the initiation of Adderall XR®	Single word and syllable repetitions and audible/silent sound prolongations	Increased tic behaviors, increased levels of social anxiety and communication related frustration	DC of Adderall XR® and start of atomoxetine (10 mg/d), significant reduction of stuttering	NR	Developmental stuttering, Tourette Syndrome, allergies, chronic ear infections, frequent phonic and motor tics	Donaher et al[82]
Alprazolam (1 mg)	Female/22	Anxiety and depression	No other drugs	Shortly after increasing the dose	Not restricted to initial syllables, occurred on small grammatical words and substantive words, persisted during singing, not associated with secondary symptomatology such as facial grimacing or fist clenching	A right carotid bruit and a grade II/IV systolic murmur without a click, Minimal late systolic mitral valve prolapse and mild stenosis of both internal carotid arteries	DC of alprazolam, complete relief after two days	Within one hour after a single morning dose of 0.5 mg alprazolam, stuttering started, then 10 to 12 h later it was stopped. Stuttering did not happen with placebo	No history of speech dysfluency	Elliott et al[83]
Aripiprazole (2 mg/d)	Male/8	ADHD combined-type	Atomoxetine (25 mg/d)	After 10 d of starting aripiprazole	NR	NR	DC of Aripiprazole, complete relief	NR	Developmental stuttering	Ünay et al[84]
Aripiprazole (10 mg/d)	Male/11	Mild intellectual disability	No other drugs	4 wk after increasing the dose to 10 mg/d	NR	Addition of clonazepam 0.75 mg/d, no improvement. Reduction of aripiprazole dose to 5 mg, complete relief over 10 d	NR	Increasing the dose to 10 mg resulted in re-emergence of stuttering which responded to DC of aripirazole	No history of speech dysfluency	Naguy et al[85]
Atomoxetine (started at 25 mg/d and gradually increased to 40 mg/d)	Male/14	ADHD	No other drugs	Three weeks after the initiation of atomoxetine	NR	NR	Dose reduction to 25 mg/d, no improvement. DC of atomoxetine and initiation of methylphenidate, complete relief of atomoxetine-induced stuttering and considerable reduction of developmental stuttering	NR	Developmental stuttering since the age of 7 yr. ADHD predominantly inattentive	Cicek et al[86]
Bupropion (SR) 150 mg BID	Female/59	Major depressive disorder	No other drugs	Four days after starting the drug	Sound prolongations, silent blocking, word production with excess physical tension, and monosyllabic whole-word repetitions. The stuttering was anxiogenic and restricted to initial syllables	Slight finger dysdiadochokinesia	DC of bupropion, complete relief of stuttering after 2 d	NR	No history of speech dysfluency	Fetterolf et al[78]
Bupropion SR (300 mg/d)	Male/38	Major depressive disorder	No other drugs	Two days after increasing the dosage from 150 to 300 mg/d	Involuntary silent pauses or blocks, repetitions, prolongations of sounds, syllables, and words, affected rhythm of speech	NR	DC of bupropion, complete relief of stuttering	Re-administration of bupropion 150 mg after 1 wk caused stammering, and the drug was stopped immediately	A history of occasional smoking, no history of speech dysfluency	Bhatia et al[79]
Bupropion XL (300 mg/d)	Male/53	Depression	No other drugs	After increasing the dosage of Bupropion	Difficulty starting words and repetition of syllables	NR	Administration of 5 mg oral haloperidol, stuttering was improved after 3 h and completely relieved after 7 h	Medication was continued	No history of speech dysfluency	McAllister et al[80]
Clozapine (up to 400 mg/d)	Female/32	Paranoid schizophrenia	No other drugs	4 wk after the initiation of clozapine	NR	Pharyngeal dystonia and buccolingual and facial dyskinesia associated with laryngeal dystonia	DC of clozapine, complete relief after 5 d	Clozapine was reintroduced at 100 mg/d. All symptoms reoccurred and relieved by clozapine cessation	History of neuroleptic-induced parkinsonism but not concomitant with dysarthria, no history of speech dysfluency	Thomas et al[63]
Clozapine (was initiated at 400 mg/d and gradually increased to 900 mg/d)	Female/28	schizoaffective disorder	No other drugs	Shortly after the initiation of clozapine at 400 mg/d and not relieved during the gradual increase in the dosage to 900 mg/d	NR	NR	Dosage reduction to ≤ 700 mg/d, complete relief	The dose was not increased again	No history of speech dysfluency	Ebeling et al[87]
Clozapine (450-750 mg/d)	Female/49	Psychosis	No other drugs	Stuttering was initiated when the clozapine dosage was increased to 700 mg/d	NR	Generalized seizure followed by myoclonic jerks of her arms at the clozapine dosage of 750 mg/d	The addition of phenytoin and then sodium valproate and the reduction of clozapine dosage to 600 mg/d, complete relief	Clozapine was continued at 600 mg/d in addition to sodium valproate 900 mg/d with no recurrence of stuttering	History of neuroleptic- induced acute dystonia, no history of speech dysfluency	Supprian et al[59]
Clozapine (300 mg/d)	Male/28	Paranoid schizophrenia	No other drugs	Stuttering was initiated when the dosage of clozapine was increased from 150 mg to 300 mg/d and worsened with further increases in the clozapine dosage	NR	Generalized tonic colonic seizure at 425 mg/d along with the increased severity of stuttering	The reduction in the dosage of clozapine to 200 mg/d and addition of sodium valproate, significant improvement	The clozapine dosage was increased to 300 mg/d, but stuttering was not reoccurred albeit in the presence of sodium valproate 800 mg/d	No history of speech dysfluency	Duggal et al[64]
Clozapine (300 mg/d)	Male/57	Schizoaffective disorder	Lithium (900 mg/d), sodium valproate (600 mg/d)	Four days after the initiation of clozapine	NR	NR	Dose reduction and DC of clozapine, complete relief after 7 d	NR	History of alcohol dependency, diabetes mellitus, no history of speech dysfluency	Bar et al[15]
Clozapine (up to 500 mg/d)	Not mentioned	Schizophrenia	No other drugs	A few days after the initiation of clozapine at 300 mg/d	NR	Myoclonic jerks at night and facial tics	Addition of sodium valproate, significant improvement, reducing the dosage of clozapine from 500 to 300 mg/d, complete relief	Clozapine was not discontinued	No history of speech dysfluency	Begum et al[11]
Clozapine (700 mg/d)	Female/33	Schizophrenia	No other drugs	After reaching the daily dose to 700 mg (interval was not reported)	NR	Facial tics, seizure (seizure was initiated after the occurrence of stuttering)	Reduction in the dosage of clozapine to 600 mg/d, remarkable improvement, addition of sodium valproate to control seizure, no effect on stuttering	Clozapine was not discontinued	No history of speech dysfluency	Hallahan et al[58]
Clozapine (300 mg/d)	Female/34	Schizophrenia	No other drugs	2 wk after the initiation of clozapine	NR	Orofacial dyskinesia	Clozapine dosage reduction to 50 mg/d, complete relief	Clozapine was not discontinued	No history of speech dysfluency	Hallahan et al[58]
Clozapine (50-125 mg)	Male/62	Delusional disorder	No other drugs	NR	Unsustained phonation, hesitation, irregular articulatory break down, sound repetition (not related to any specific sound, occurred at irregular word positions)	Orofacial dyskinesia, laryngeal and pharyngeal tardive dystonia, harsh and strangulated voice	Addition of tetrabenazine, patient could not tolerate the clozapine dosages more than 100 mg/d, DC of clozapine, complete relief	Clozapine was not restarted	No history of speech dysfluency	Lyall et al[9]
Risperidone and then clozapine (450 mg/d and 75 mg/d)	Male/55	Schizophrenia	No other drugs	NR	Occasional blocking, prolongation on word-initial sounds and repetitions of speech elements including one-syllable words at the beginning of his speech utterances	Stammering and unusual limb and trunk movements related to risperidone, belching, persistent hiccupping, worsening of the facial tic, and the orofacial dyskinesia involving the lips and tongue related to clozapine	Risperidone-induced stuttering: NR, the first episode of clozapine-induced stuttering, dose reduction to 125 mg/d and cessation of clozapine; significant improvement and complete relief of stuttering; the second time of clozapine-induced stuttering: addition of sodium valproate, considerable improvement	Clozapine was restarted at 75 mg/d, recurrence of stuttering, the addition of sodium valproate, 600 mg/d, significant improvement in the stuttering	History of head injury resulting in problems with executive functioning and a significant discrepancy, between the patient’s verbal and performance IQ, making various clicking noises and blowing sounds when speaking before the initiation of antipsychotic drugs	Lyall et al[9]
Clozapine (up to 600 mg/d)	Male/35	Schizotypal personality disorder	No other drugs	At clozapine dosage of 250 mg/d and progressive worsening with dose escalation	NR	NR	Reducing the dosage of clozapine to 200 mg/d, complete relief	Clozapine was continued at 200 mg/d without causing stuttering	History of trifluoperazine-induced truncal dystonia, no history of speech dysfluency	Krishnakanth et al[88]
Clozapine (200 mg/d)	Male/24	Paranoid schizophrenia	No other drugs	After increase in the dosage of clozapine to 200 mg/d	NR	NR	DC of clozapine, complete relief	Clozapine was not restarted, amisulpiride was started and did not cause stuttering	No history of speech dysfluency	Krishnakanth et al[88]
Clozapine (250 mg/d)	Male/23	Paranoid schizophrenia	No other drugs	At clozapine dosage of 250 mg/d (interval was not reported)	NR	NR	Clozapine dosage reduction to 150 mg/d, complete relief	Clozapine was not discontinued	History of neuroleptic-induced tardive dyskinesia, no history of speech dysfluency	Krishnakanth et al[88]
Clozapine (350 mg/d)	Male/15	Undifferentiated schizophrenia	Clomipramine (225 mg/d)	Three years after the initiation of clozapine and clomipramine	Repetitions of syllables and transient accelerations of speech rate	Involuntary paroxysmal perioral movements, facial tic-like movements, myoclonic jerks of the upper limbs, GTC seizure	Addition of valproic acid at 500 mg/d, complete relief of stuttering within days	Clozapine was continued with valproic acid without reoccurrence of seizure and speech dysfluency during 2 yrs of follow-up	Symptoms of obsessive-compulsive disorder, no history of epilepsy or speech dysfluency	Horga et al[66]
Clozapine (up to 250 mg/d)	Male/29	Undifferentiated schizophrenia	No other drugs	After the clozapine dosage titration from 137.5 mg/d to 150 mg/d	Frequent repetition and prolongation of syllables or words with frequent hesitations, blocking and pauses	No focal dystonia or any evidence of seizure-like activity	Reducing and splitting the dose of clozapine to 50 mg in morning and 75 mg at night, improvement of stuttering	Reoccurrence of stuttering at clozapine dosage of 250 mg/d, improvement of stuttering after dose reduction to 225 mg/d, a later increase in the dosage to 300 mg/d did not cause recurrence of stuttering	History of antipsychotic-induced extrapyramidal symptoms, no history of speech dysfluency	Grover et al[61]
Clozapine (400 mg/d)	Female/33	Severe MDD with psychotic features	No other drugs	Stuttering was started after increasing the dosage of clozapine to 400 mg/d and worsened when the dosage was increase to 450 mg/d	Excessive prolongation of syllables or words	Sialorrhea	Addition of benztropine, no improvement. Reduction of the dosage of clozapine to 350 mg/d, complete relief	Stuttering recurred 16 d after increasing the clozapine dosage to 400 mg/d, but completely relieved after dosage reduction to 300 mg/d	None	Kumar et al[89]
Clozapine (up to 650 mg/d)	Male/32	Paranoid schizophrenia	Sertraline (300 mg/d), lamotrigine (500 mg/d), haloperidol (4 mg/d), clonazepam (1 mg/d)	Noticeable stuttering at clozapine dosages of ≥ 600 mg/d	Expressive speech dysfluency with hesitancy and frequent pauses	Involuntary twitching of muscles of jaw	Clozapine dose reduction by 25 mg, improvement of stuttering	Clozapine was not discontinued	No history of speech dysfluency	Murphy et al[20]
Clozapine (400 mg/d)	Male/43	Schizoaffective disorder	Paroxetine (20 mg/d)	Stuttering became noticeable when the clozapine daily dose was increased to more than 350 mg	Expressive speech dysfluency	NR	Clozapine dose reduction by 50 mg, improvement of stuttering	Clozapine was not discontinued	No history of speech dysfluency	Murphy et al[20]
Clozapine (450 mg/d)	Male/33	Paranoid schizophrenia	No other drugs	Stuttering was developed during the initiation and dose titration of clozapine	Intermittent stuttering of speech	NR	Reducing the rate of dose titration, improvement of stuttering	Clozapine was not discontinued	No history of speech dysfluency	Murphy et al[20]
Clozapine (up to 300 mg/d)	Female/46	Delusional disorder	No other drugs	Stuttering was developed during the initiation and dose titration of clozapine	Hesitancy with specific syllables	Orofacial dyskinesia	Clozapine dose reduction to 50 mg, improvement of stuttering	Clozapine was not discontinued	No history of speech dysfluency	Murphy et al[20]
Clozapine (325 mg/d)	Male/67	Schizoaffective disorder	Duloxetine (60 mg/d), hyoscine (30 mg/d), aripiprazole (10 mg/d)	Stuttering was developed during the initiation and dose titration of clozapine	Expressive speech dysfluency	Orofacial twitching, upper limb jerking, hypersalivation	Reducing the rate of clozapine dose titration, improvement of stuttering	The clozapine dose was increased again to control psychotic symptoms, but nothing about the recurrence of stuttering was reported	Hearing impairment, hypertension	Murphy et al[20]
Clozapine (650 mg)	Female/63	Paranoid schizophrenia	Amisulpride 200 mg/d, amitriptyline 25 mg/d, paroxetine 20 mg/d, zopiclone 3.75 mg/d	Stuttering was developed on a stable dose of clozapine	Expressive speech dysfluency with hesitancy	NR	Reducing the dose of clozapine by 50 mg, no improvement	Clozapine at 650 mg/d was recommenced, but authors did not report its effects on the recurrence of stuttering	No history of speech dysfluency	Murphy et al[20]
Clozapine (100 mg), aripiprazole (7.5 mg/d)	Female/21	Schizophrenia	No other drugs	At clozapine dosage of 100 mg/d and aripiprazole dosage of 7.5 mg/d	NR	NR	Reduction of the dose of clozapine and addition of aripiprazole (5 mg/d), complete relief. Reduction of the dose of aripiprazole from 5 to 7.5 mg/d, complete relief	The drugs were not discontinued	Turner syndrome, no history of speech dysfluency	Ertekin et al[8]
Clozapine (gradually increased to 450 mg/d)	Male/16	Schizoaffective disorder	Citalopram (NR), clonazepam (NR), atenolol (NR), lithium (NR)	Approximately 22 d after increasing the clozapine dosage to 400 mg/d	Persistent stuttering (difficulties with the pronunciation of letters “I,” “D,” and “T”)	Orofacial dyskinesia with perioral twitching (started at clozapine dosage of 350 mg/d), microseizure according to EEG (at clozapine dosage of 400 mg/d)	Substituting lithium with divalproex sodium, improvement in stuttering 4 wk after receiving divalproex sodium at 500 mg BID	Clozapine was not discontinued because of its considerable therapeutic effects	History of type 1 DM, DKA with episodic hallucinations, GERD, cerebral contusion, occasional cocaine use, anxiety-induced intermittent stuttering, family history of stuttering	Rachamallu et al[62]
Clozapine (up to 600 mg/d)	Female/22	Schizophrenia	Fluoxetine (60 mg/d)	Stuttering was developed after the clozapine dose escalation to 300 mg/d	NR	NR	Reduction in the clozapine dose and initiation of ECT, minimal improvement	Clozapine was not discontinued	NR	Das et al[19]
Clozapine (450 mg/d)	Man/in early 40s	NR	No other drugs	After increasing the clozapine daily dose from 400 mg to 450 mg	NR	Marked increase in seizure activity	DC of clozapine, nothing was clearly reported by the authors	NR	NR	Kranidiotis et al[24]
Clozapine (200 mg/d)	Male/38	Schizophrenia	No other drugs	Stuttering was evident at 200 mg/d and became so disabling at 350 mg/d	NR	NR	Dose reduction of clozapine and addition of amisulpiride and BDZ, reduction of stuttering, DC of clozapine, complete relief	Clozapine was not restarted	NR	Kranidiotis et al[24]
Clozapine (300 mg BID)	Male/57	Paranoid schizophrenia	Risperidone, IM injection (37.5 mg every 2 wk), Risperidone, oral (1.5 mg/d which increased to 2 mg BID on admission)	Two days after admission (the dosage of clozapine, 300 mg BID, was not changed on admission)	NR	Orofacial and extremities myoclonic jerks, drop attacks	Clozapine dosage reduction to 100 mg BID, resolution of stuttering within two days	The patient was discharged on clozapine 150 mg BID, but author reported nothing about stuttering at follow-up	History of COPD, hypertension, DM, and chronic back pain, cigarette smoking	Chochol et al[60]
Clozapine (125 mg/d)	Male/29	Schizophrenia	No other drugs	A few days after titrating the clozapine dosage to 125 mg/d	Frequent repetitions of words that included broken words	NR	Reducing the clozapine dosage to 100 mg/d, significant improvement	Clozapine dosage was not re-escalated	No history of speech dysfluency	Nagendrappa et al[90]
Clozapine (up to 200 mg/d)	female/25	Schizophrenia	No other drugs	At clozapine dosage dose of 150 mg/d (interval was not mentioned)	NR	Tonic-clonic epileptic seizure	DC of clozapine and start of amisulpiride and biperiden, complete relief of stuttering and seizure	Clozapine was not rechallenged	No history of speech dysfluency	Gica et al[65]
Divalproex sodium (600 mg/d)	Male/45	Affective instability and irritability	Citalopram (30 mg/d), promazine (100 mg/d)	Four days after initiation of divalproex sodium	Sound repetitions and prolongations (not restricted to the initial syllable and caused pronounced difficulty in starting and completing his sentences)	NR	DC of divalproex, complete relief after 3 d	Divalproex sodium was not restarted	A 10-yr history of post-traumatic stress disorder and alcoholism, no history of speech dysfluency	Aukst-Margetić et al[91]
Divalproex sodium (1500 mg/d in divided dose)	Male/56	Bipolar affective disorder	Olanzapine (10 mg/d), lorazepam (4 mg/d, gradually stopped along with increase in the dose of divalproex)	Two weeks after increasing the dosage of divalproex from 1000 to 1500 mg/d	A moderately pressured speech, articulation of speech, alterations in intensity and timings of utterance segments, Involuntary repetitions and prolongations of sounds, syllables, words or phrases, involuntary silent pauses or blocks	NR	DC of divalproex, instant amelioration of the stuttering	Re-initiation of the drug after one week caused resurgence of symptoms, so the drug was stopped	No history of speech dysfluency	Mukherj et al[92]
Desipramin (300 mg/d)	Male/28	Dystimia, primary type, major depression	Doxepin (50 mg at bed time)	Two months after increasing the dosage of desipramine	Stuttering with difficulty in articulation	Minimal dryness of mouth before stuttering, myoclonic jerking (twitching movements around his jaw) concomitant with stuttering	DC of both drugs, complete relief after 48 h	Twenty-four hours after restarting both drugs stuttering happened again, the desipramin dosage was decreased to 250 mg/d, but stuttering was persisted occasionally, on 4 different occasions, desipramin was discontinued and stuttering was solved within 24-48 h; an increase in the doxepin dosage to 200 mg at bed time had not resulted in stuttering	Opiate and alcohol dependence in remission, retinal detachment and ruptured disc and chronic back pain in the past, no history of speech dysfluency	Masand et al[93]
Fluphenazine (up to 50 mg/d)	Male/35	Schizophrenia	Benztropine mesylate (4 mg/d)	12 d after increasing fluphenazine dosage to 50 mg/d	NR	EPS	Dosage reduction to 30 mg/d, complete relief	Increasing the dosage of fluphenazine to 40 mg/d caused stuttering recurrence	No history of speech dysfluency	Nurnberg et al[10]
Gabapentin (NR)	Female/58	Intractable seizure	Phenytoin (NR)	NR	NR	NR	DC of gabapentin, relief after 4 d	NR	No history of speech dysfluency	Nissani et al[94]
Lamotrigine (up to 5 mg/kg/d)	Female/5	BECTS	Valproic acid (30 mg/kg/d)	Stuttering was initiated after increasing the dosage of lamotrigine to 5 mg/kg/d	NR	Frequent diurnal absence seizures, poor concentration and forgetfulness, clumsiness and poor coordination, emotional lability, dysarthria, and slurred speech	DC of lamotrigine, speech improvement in a couple of days	Lamotrigine was not rechallenged	NR	Catania et al[95]
Levodopa/carbidopa (100/25 mg TID)	Male/44	PD	NR	Patient had a history of PDS, and stuttering was exacerbated during on periods, 1 h after levodopa/carbidopa intake	NR	Dyskinesia during drug-on phases and akinesia, bradykinesia, resting tremors, and rigidity in drug-off phases	The severity of stuttering return to baseline during levodopa-off periods	Levodopa was not discontinued	PDS	Anderson et al[25]
Levodopa (200 mg/d)	Male/72	PD	None	Nearly one month after increasing the dosage to 200 mg/d	NR	Palilalia, speech freezing	DC of levodopa and initiation of pramipexole, return to the baseline level of dysfluency	Reinitiating levodopa caused stuttering	Speech dysfluency due to PD	Louis et al[22]
Levodopa (up to 1000 mg/d)	Male/42	PD	Pergolide (1.5 mg/d), quetiapine (50 mg at bed time)	After increasing the levodopa dosage to 300 mg/d	Pressured speech and sound repetition	Palilalia, speech freezing	NR	NR	None	Louis et al[22]
Levodopa 600 mg/d	Male/57	PD	Cabergoline (4 mg/d), selegeline (10 mg/d), amantadine (300 mg/d)	Patient had a history of PDS, and stuttering was exacerbated during on phases after levodopa consumption	Speech repetitions and speech blocks	Speech problems associated with PD including hypokinetic dysarthria and hypophonia occurred during levodopa-off phases	Severity of stuttering return to baseline during levodopa-off periods	Levodopa was not discontinued	PDS	Burghause et al[26]
Levomepromazine (50 mg at bed time)	Male/65	Bipolar disorder	Quetiapine (NR), valproate semisodium (NR), zolpidem, moxonidin (NR), propafenone (NR), insulin (NR)	Five days after the initiation of levomepromazin	NR	NR	DC of Levomepromazin, complete relief three days later	Levomepromazin was not recommenced	History of drug induced EPS, supraventricular tachycardia, type 2 DM, HTN, and mild cognitive impairment	Margeticet al[96,97]
Lithium (1200 mg at bed time)	Male/48	Bipolar affective disorder	Fluoxetine (20 mg/d)	One month after the initiation of lithium	Worsening his developmental stuttering, a repetitive word stutter that severely limited his verbal communication ability	Lightheadedness, hand tremor	Tapering off lithium, stuttering returned to baseline within a few weeks	Valproic acid (2750 mg/d) was started instead of lithium	PDS, depression	Netski et al[98]
Lithium (900 mg twice daily)	Male/10	Bipolar disorder	Risperidone (4 mg bed time), clonidine (0.1 mg 3 times daily), melatonin (3 mg at bed time), famotidine (20 mg BID)	Two days after increasing the dose of lithium, stuttering was worsened	Syllable repetitions, occurred only at the beginning of sentences	NR	Dose adjustment of lithium to 600 mg in the morning and 900 mg at night, stuttering returned to baseline after 2 d	Lithium was not discontinued	History of developmental stuttering, bipolar disorder not otherwise specified, ADHD, and conduct disorder	Gulack et al[99]
Lithium (the dose was not mentioned, but lithium was used for a long time)	Female/86	Bipolar disorder	Donepezil (NR), primidone (NR), risperidone (NR)	After a chronic use of lithium, stuttering was started and stayed for 3 more mo. The lithium level was elevated (2.0 mmol/L)	Starting a few words fluently, then repeating syllables and words and terminating the sentence abruptly	NR	DC of lithium, complete relief of stuttering after two weeks	Lithium was not restarted	Past medical history of dementia and epilepsy, no history of speech dysfluency	Sabillo et al[100]
Memantine (10 mg/d)	Male/9	Autistic disorder	No other drugs	After increasing the dose	Deterioration of primary behaviors of developmental stuttering includingsound repetition, and sound prolongation on first and middle vowels, and difficulty for starting to speak. His parents explained that the child could only start to speak after a deep and audible breath	NR	Reduction of memantine dosage to 7.5 mg/d, improvement of acquired stuttering after several days. DC of memantine, stuttering was reduced to baseline after 3 wk	Risperidone was used instead	Developmental stuttering	Alaghband-Rad et al[17]
Memantine (5 mg/d)	Male/4	Autism	No other drugs	After increasing the dose	The difficulty was with the start of the speech and the child could only start to speak after a deep and audible breath	NR	The drug was continued at the same dose as the difficulty was tolerable, and gradually was increased to 7.5 mg/d, relief of speech difficulty	Medication was continued, and its dose was gradually increased	No history of speech dysfluency	Alaghband-Rad et al[17]
Methotrexate (cumulative dose of 62.5 mg, IT)	Female/22	Pre-B acute lymphoblastic leukemia	NR	After achieving cumulative dose of 62.5 mg (26 d after initiating IT MTX)	NR	Dysphasia progressed to aphasia, mild headache, low-grade fever, behavioral problems	Three months after initiation of symptoms (no intervention was described)	NR	No history of speech dysfluency	Shuster et al[21]
Methylphenidate (10 mg/d)	Male/7	ADHD	No other drugs	10 d after the initiation of the drug	Sound prolongations, silent blocking, word production with excess physical tension, monosyllabic whole-word repetitions	NR	DC of methylphenidate, speech returned to normal after 1 wk	Atomoxetine was used instead	No history of speech dysfluency	Alpaslan et al[101]
Methylphenidate (5 mg in the morning and 5 mgat noon)	Male/7	ADHD	No other drugs	One day after drug initiation	Troubles during the pronouncing the first syllables and repetitions of some syllables	NR	DC of Methylphenidate, improvement after 10 d	Methylphenidate was restarted at 10 mg in the morning and5 mg at noon. After 10 d, stuttering was returned	NR	Copur et al[102]
Methylphenidate (2.5 mg BID) and pemoline (9.375 mg/d) after DC of methylphenidate	Girl/3	Pervasive hyperactivity	None	Three days after starting methylphenidate, four days after starting pemoline	Repetition of the first syllable of word which gradually worsened	NR	DC of methylphenidate, relief of stuttering, DC of pemoline, relief of stuttering	Methylphenidate and pemoline were not restarted	NR	Burd et al[7]
Olanzapine (15 mg/d)	Male/56	Depression	Intrathecal morphine (7.5 mg/d), clomipramine (225 mg/d)	Four days after the initiation of clozapine	Constant word repetition (acquired)	NR	DC of olanzapine, complete relief after two days	NR	Chronic pain syndrome, no history of speech dysfluency	Bar et al[15]
Olanzapine (7.5-10 mg/d)	Male/72	Psychotic depression	Clomipramine (50-150 mg/d)	3 wk after the initiation of olanzapine	Repetition and retention of first syllables and prolongation of phonemes	NR	DC of olanzapine, complete relief after 5 d	NR	Brain cortical atrophy, no history of speech dysfluency	Bar et al[15]
Olanzapine (5 mg/d)	Female/36	Manic episode	Sodium valproate (300 mg/d), prednisolone (75 mg/d)	7 d after the initiation of olanzapine	Repetition of syllables and words	NR	DC of olanzapine, complete relief after 4 d	NR	Ulcerative colitis and celiac disease, no history of speech dysfluency	Bar et al[15]
Olanzapine (10 mg/d)	Female/43	Schizophrenia	No other drugs	Approximately 21 d after the initiation of olanzapine	Repetition of first syllables and word prolongation	NR	DC of olanzapine, complete relief after 3-5 d	NR	Mild cluttering at the age of 19	Bar et al[15]
Olanzapine (2.5 mg/d)	Female/51	Depression	Sertraline (100 mg/d), promethazine (50 mg at night); both was started 14 wk before initiation of olanzapine	14 d after the initiation of olanzapine	Blocking of speech and prolongation of phonemes	NR	Increase in olanzapine dose to 5 mg/d, relief of stuttering during the next weeks	Olanzapine was not discontinued	Symmetrical cerebellar hypoplasia and generalized cortical atrophy, no history of speech dysfluency	Bar et al[15]
Olanzapine (10 mg/d)	Male/42	Schizophrenia	Zopiclone (7.5 mg/d)	Two days after the initiation of olanzapine	Difficulty in articulating words properly	NR	DC of olanzapine, complete relief after two days	NR (patient was not followed-up)	A fall without loss of consciousness 2 d before initiation of stuttering, no history of speech dysfluency	Bar et al[15]
Olanzapine (10 mg/d)	Male/42	Paranoid ideation	Venlafaxine (150 mg/d), promazine (200 mg/d)	Four days after the initiation of olanzapine	Repetition and retention of first syllables and prolongation of phonemes	NR	DC of olanzapine, complete relief after two days		PTSD, adjustment disorders, no history of speech dysfluency	Lasic et al[103]
Olanzapine (10 mg/d)	Male/21	Psychotic disorder	No other drugs	Three days after the initiation of olanzapine	disturbance in the fluency and time patterning of speech, repetition of sounds and syllables, blocking between words	NR	DC of olanzapine and start of quetiapine, complete relief after three days	Olanzapine was not restarted	No history of speech dysfluency	Asan et al[104]
Phenytoin (200 mg/d)	Male/42	Seizure due to head injury	No other drugs	Shortly after initiation of phenytoin	Predominantly part-word repetitions and prolongation	Abnormality of speech muscle fine motor control	Addition of CBZ and gradual DC of phenytoin, sustain decrease in the frequency of dysfluencies and improved motor performance	Phenytoin was not restarted	No history of speech dysfluency	Mcclean et al[105]
Phenytoin (20 mg/kg LD and 5 mg/kg/d MD)	Male/3	GTC seizure due to head trauma	No other drugs	10 d after the initiation of phenytoin	NR	NR	DC of phenytoin and initiation of sodium valproate, complete relief 10 d after DC of phenytoin	Phenytoin was not rechallenged	No history of speech dysfluency	Ekici et al[106]
Pregabalin (75 mg twice daily)	Female/31	Complex regional pain syndrome	No other drugs	After taking the second dose of pregabalin on the first day	A slurred speech	NR	DC of pregabalin, complete relief after one week	Pregabalin was not restarted	No history of speech dysfluency	Giray et al[107]
Pregabalin (75 mg twice daily)	Female/68	Herpes zoster	Acyclovir (800 mg five times daily)	Three days after the initiation of pregabalin	NR	Frequent blepharospasm	DC of pregabalin;alleviated of symptoms after four days and complete relief after one week	A 75 mg pregabalin capsule consumption after 4 wk resulted in stuttering and frequent blepharospasm	No history of speech dysfluency	Ge et al[108]
Pyrethrin product containing 0.33% pyrethrum extract and 4% piperonyl butoxide (3 times overa period of 12 d left on the scalp for 10 min)	Female/2 (the child’s mother, who was breastfeeding her atleast one time per day, were receiving this topical product)	Repeated episodes of head lice	No other drugs	Two days after the last period of mother’s treatment	An acute onset of stuttering especially at the initiation of the speech	An increase in clumsiness, slight erythematous rash ofapproximately 3 cm × 2 cm on the occiput of the scalp	Six weeks postexposure	Pyrethrin was not repeated	No history of speech dysfluency	Hammond et al[81]
Risperidone (4 mg/d, then 8 mg/d)	Male/32	Aggravated psychotic disorder	Lorazepam (1 mg/d)	Stuttering was initiated after the dose increase to 4 mg/d, and worsened 16 d after the dose increase to 8 mg/d	Severe sound repetitions and interjections in a way that it was difficult to understand his words	Slight akathisia-like symptoms such as anxiety and restlessness (not prominent)	No action, stuttering diminished 23 d later	He continued taking risperidone at 8 mg/d with only a slight stuttering	A 10-yr history of Schizophrenia. His friend during junior high school was a stutter, and the patient used to mimic his stuttering. He began stuttering at that time for 1 yr	Lee et al[16]
Risperidone (4 mg)	Female/48	Psychosis	Lorazepam (1 mg PRN), procyclidine (5 mg BID for treatment of EPS)	11 d after taking risperidone	Repetitions in the speech, pausing within a word and her speech, an excess of physical tension in the speech	NR	A little decrease in risperidone dose, a bit reduction in stuttering	Risperidone was not discontinued	No history of speech dysfluency	Yadav et al[18]
Risperidone (at a dose of 1 mg/d for 2 yr)	Male/21	Behavioral disorder	No other drugs	After chronic treatment with low-dose of risperidone	Prolongation of sounds, hearable blocks, repetitions of single-syllable words	NR	No action, stuttering was decreased to a minimal level after 17 d	Risperidone was not discontinued	Moderate mental retardation because of perinatal asphyxia, no history of speech dysfluency	İnci et al[23]
Sertraline (100 mg daily)	Male/36	Major depression	Alprazolam (0.25 mg 3 TID)	Two weeks after increasing the dosage from 50 to 100 mg/d	Normal vocabulary, decreased rate of speech, normal tone, interrupted words	NR	DC of serteraline, speech problem resolved after one day	Medication was not restarted. Later, administering phenelzine, imipramine, and fluoxetine caused milder speech hesitancy	No history of speech dysfluency	Makela et al[109]
Sertraline (50 mg daily)	Female/32	Recurrent depression	No other drugs	During the third week of starting the drug¸ stuttering occurred and worsened over a 3-d period	Difficulty in starting and completing the sentences	Feeling nervous, increased restlessness, and insomnia two days before the onset of stuttering	DC of sertraline, complete relief of stuttering after 3 d	Previously, patient has received sertraline and experienced stuttering, so discontinued the medication. Medication was not restarted. Desipramine was started and did not cause stuttering	No history of speech dysfluency	Christensen et al[76]
Sertraline (150 mg daily)	Female/22	Bulimia nervosa, anorexia nervosa, posttraumatic stress disorder, recurrent depression, panic disorder	Clonazepam (0.5 mg QID), trimethoprim-sulfamethoxazole (BID)	One week after increasing the dosage of sertraline	NR	Hyperreflexia and mild tremulousness, generalized muscle twitching (myoclonus), restlessness, and mild confusion	DC of sertraline and Antibiotic, gradual normalization of speech over two to three days	Seven days after restarting sertraline at 50 mg/d, stuttering and other symptoms returned, then the drug was discontinued	No history of speech dysfluency	Brewerton et al[77]
Theophylline (200 mg BID to 100 mg QID)	Male/the age of the onset of theophylline-induced stuttering was not reported, but it surely occurred when he was between 1.5 and 4 yr old	Asthma	Nothing was clearly mentioned	The patient only experienced stuttering during the autumn when he was receiving theophylline for the management of asthma attacks	Repeating whole words, six or seven times usually at the beginnings of the sentences, no dysfluency while singing	Being tense, havinginsomnia, and be frustrated by his speech problem	DC of theophylline at the end of autumn before age 4 yr, complete relief of stuttering. Changing the dosage from 100 mg QID to 200 mg BID at age 4 yr, complete relief after 7 d with no recurrence of stuttering	The patients had stuttered each time that he was on Theophyllineregimen 200 mg BID	No history of speech dysfluency	Rosenfield et al[110]
Theophylline (130 mg TID and sometimes QID)	Female/6.5	Asthma	Metaproterenol sulphate (PRN)	Within a few days after increasing the theophylline dosage to 130 mg TID	Multiple repetitions of the word "I", especially at the beginning of sentences, she could speak better when speak more slowly. Stuttering was worse when she was excited	NR	DC of theophylline, complete relief within two days	Resumption of theophylline resulted in the recurrence of stuttering which responded to drug withdrawal. Several months after the discontinuation of theophylline, the drug was resumed without causing any dysfluency	No history of speech dysfluency	Rosenfield et al[110]
Theophylline 200 mg BID to 200 mg TID	Male/4 yr and 3 mo	Asthma	Beclomethasone dipropionate and Theo-Dur sprinkle (200 mg BID) (at age 4 yr and 4 mo). Addition of metaproterenol sulphate, isoetharine HCL andatropine (at age 4 yr and 10 mo, DC of all drugs and initiation of cromolyn capsules (20 mg TID) (at age 5 yr)	Nine months after the initiation of theophylline	Repeating "ah, ah, ah" in the middle of sentences, stuttering was worse when he was excited	Anxiety, sleep problems	Withdrawal of theophylline at age 5 yr, complete relief within two weeks	After complete relief of stuttering, the patient only received theophylline during asthma attacks and experienced no stuttering	No history of speech dysfluency	Rosenfield et al[110]
Theophylline (400 mg BID)	Male/73	A long-standing chronic obstructive lung disease secondary to pneumoconiosis	Steroids and ranitidine as well as being on oxygen	One month after the introduction of theophylline	An intense tonic-clonic stuttering without any extrapyramidal components	NR	DC of theophylline, stuttering was diminished within 48 h	Theophylline was readministered 2 wk later at the same dosage, and the same speech disorder recurred within a few daysand persisted until treatment was stopped	No history of speech dysfluency	Gerard et al[111]
1. Trifluoperazine (30 mg/d)2. Chlorpromazine (up to 800 mg/d)	Male/40	Schizophrenia	Trihexyphenidyl (5 mg/d)	1. Four days after increasing the trifluoperazine dosage to 30 mg/d2. After increasing chlorpromazine dosage to 800 mg/d	NR	NR	1. Increasing dosage of trihexyphenidyl, no improvement. DC of trifluoperazine, complete relief2. Addition of benztropine, no improvement. Reduction of chlorpromazine dose to 400 mg/d, complete relief	Increasing the dosage of chlorpromazine to 700 mg/d caused the return of stuttering; reducing the dosage of chlorpromazine to 400 mg/d caused cessation of stuttering	No history of speech dysfluency	Nurnberg et al[10]

ADHD: Attention-deficit hyperactivity disorder; BECTS: Benign focal epilepsy of childhood with centrotemporal spikes; BID: Two times per day; BDZ: Benzodiazepine; CBZ: Carbamazepine; COPD: Chronic obstructive pulmonary disease; DC: Discontinue, DM: Diabetes mellitus; EPS: Extrapyramidal side effect; GERD: Gastroesophageal reflux disease; GTC: Generalized tonic-colonic seizure; HTN: Hypertension; IM: Intramuscular; IT: Intrathecal; IV: Intravenous; LD: Loading dose; MD: Maintenance dose; MDD: Major Depressive Disorder; MTX: Methotrexate; NR: Not reported; PD: Parkinson disease; PDS: Persistent developmental stuttering; PRN: Pro re nata (as needed); QID: Four times a day; TID: Three times a day; VPA: Valproic acid.