Successful Treatment of a Child with Difficult-to-Treat Chronic Selective Mutism Using Pramipexole

To the Editor:

Selective mutism (SM), historically called aphasia voluntaria by Kussmaul, and elective mutism by Tramer, is an anxiety disorder, characterized by lack of verbal communication in specific settings. Children with SM can speak well in certain environments, but they are mute or extremely hesitant to communicate in other social settings. This inability then becomes a pattern of behavior (Muris et al. 2015). It must be ongoing for at least 1 or 6 months if in the first year of school. Speech impairment, stuttering, autism, and so on, should be ruled out. There is a continuum of severity. It impacts 1% of elementary school population (Wong 2010). Age of onset is 2.7–4.1 years of age. However, 1- to 3-year lag between onset and referral to treatment is commonplace. This negatively impacts the prognosis as SM is notorious to become less responsive to treatment over time. Girls outnumber boys by 2:1 ratio (Standart and Le Couteur 2003).

It is rare that SM occurs independent of other anxiety issues (shy bladder, enuresis, generalized anxiety, obsessive-compulsive disorder, etc.). Seventy percent to 100% of children with SM eventually receive an additional diagnosis of social phobia (Muris and Ollendick 2015). SM has a genetic component, coupled with overactive amygdale—a neurobiological underpinning common to anxiety disorders in general. Temperamentally, it is linked to innate behavioral inhibition (BI) as a precursor to SM. High rates of anxiety disorders are reported in families of SM. It was described in twins and in association with fragile-X syndrome. Inconsistent parenting was reported as well as bilingualism at home (Berger et al. 2002). Treatment capitalizes chiefly on age-appropriate cognitive-behavioral/behavioral therapy. Selective serotonin reuptake inhibitors at higher doses are effective and superior to placebo, with efficacy rates of 65% (Kaakeh and Stumpf 2008). Outcome depends on duration of SM, comorbidities, and family/teachers engagement. Through appropriate handling and treatment, most children overcome SM, bearing in mind that the older they are, the longer it takes (Oerbeck et al. 2015).

Case Report

A 9-year-old Kuwaiti female youngster was referred to our outpatient clinic for long-standing difficult-to-treat SM that started at age of 5 when she first joined Kindergarten. She failed 2-year therapy sessions. Also, she was tried on fluoxetine, coupled with therapy by a private child psychiatrist, up to 15 mg/d over 8 weeks, but to no avail. Only headaches and gastric upset were reported initially. Sertraline was then tried, up to 100 mg/d on two divided doses for another 6 weeks, but deemed futile too. Infrequent diarrhea was noted. She was followed-up by school psychologist. She is now in grade 3, but at risk of being dismissed for nonparticipating in scholastic activities and classroom discussions. She is the product of elective caesarean section of nonconsanguineous monogamous family. She ranks the third among five sibs. Uneventful developmental trajectories with the exception of occasional nocturnal enuresis that was addressed at large with desmopressin. Family history of note is for paternal uncle obsessive-compulsive disorder. No relevant medical history, apart from occasional bronchial asthma with nebulized salbutamol on when-needed basis. No history of traumatic experience.

She is well relating and socializing within her family context. She has otherwise socially inhibited temperament, only barely whispering during the interview. She was ostensibly under marked distress during office visit despite presence of parents and repeated reassurance. She looked fretful, trembling, and pallid, with fleeting eye contact and perspiration. Toward the end of intake interview and in subsequent sessions, she was more engaging but kept totally mute. No indicators of autism spectrum disorder or obsessive compulsive disorder were elicited. Physical examination was unremarkable. More elaborative work-up was pursued in our facility to rule out/in organicity that might have contributed to treatment apparent refractoriness. Baseline laboratory, including thyroid, electroencephalography, and neuroimaging, was totally unrevealing. Projective testing pursued with negative yield, including House-Tree-Person test. Pediatric Anxiety Rating Scale revealed marked anxiety.

Pramipexole is a D2/D3 dopamine agonist of the nonergoline class, FDA-approved for Parkinson disease and restless leg syndrome (Constantinescu 2008). In psychiatry, it has been tried in bipolar depression. In child psychiatry, it has been reported in de la Tourette syndrome. Since dopamine has been tied to motivation (Brankovic 2015), we hypothesized that SM might be regarded as a motivational deficit, and hence, boosting dopamine might help. This might explain the reported utility of phenelzine in SM (Golwyn and Sevlie 1999). Bromocriptine has been used similarly in some cases of poststroke aphasia, an obviously extreme neurologic model (Gupta and Mlcoch 1992).

Parents' consent was obtained beforehand, and we embarked on a trial of pramipexole 0.125 mg/d, uptitrated to 0.25 mg tds. By week 3, it was markedly obvious that the child was more engaging with therapist, starting to reciprocate few responsive audible phrases for the first time outside family social sphere. With positive reinforcement, and at the same dose, by week 4, she was utterly verbal and more socially adept. Response was maintained at week 6, 8, and 12 follow-ups. Apart from initial transient nausea, that wore off very soon, this was achieved with high tolerability. Previous failure of multiple drug trials would defy a placebo response in this case.

“Booster” therapy sessions were then reinstituted. Three months have elapsed since that report; the case has been seen to be faring perfectly well. Pramipexole was tapered down (0.125 mg/week) over 6-week duration. Clinical response was well sustained.

Literature on pharmacotherapy of SM is quite limited to two RCTs, one open-label trial, and case reports like this. Therapy remains the treatment modality of choice.

A small (n = 5), double-blind, placebo-controlled, multiple baseline/across participants trial of sertraline documented improvement in sertraline group but not between-group differences (Carlson et al. 1999)

A double-blind placebo-controlled study of 16 subjects with SM showed superiority of fluoxetine arm on parents' ratings and global change but not on clinician and teacher ratings (Black and Uhde 1994)

Dummit et al. (1996) conducted a 9-week open trial of fluoxetine for 21 children with SM and demonstrated that 76% were improved.

Fluvoxamine was also reported to be effective for SM (Lafferty and Constantino 1998).

MAOI, phenelzine, was effective for treatment of SM in four prepubertal children but gave serious drug and food interactions; authors recommended to reserve it for cases unresponsive to behavioral therapy and fluoxetine (Golwyn and Sevlie 1999).

To the best of our knowledge, this is one of earliest reports illustrating a tangible response on DA agonists in cases of pediatric long-standing difficult-to-treat SM. This might open new treatment venues in these clinical scenarios that definitely need to be replicated in larger trials.