Stuttering has been present across almost every culture with similar incidence and prevalence. In the early days of medical sciences, experts considered stuttering to be the result of physical abnormalities of the tongue and larynx. As a result, surgeries to correct these anomalies were frequent.

However, clinical treatments that targeted the larynx and the tongue rarely showed any improvement of the symptoms. Finally, in the early 1900s, Travis and Orton postulated that stuttering may have its roots in brain function rather than a physiological abnormality of the tongue or larynx.

Most modern theories of stuttering are based on the work of Travis and Orton in the 1930s. The establishment of the possibility that stuttering emerges from anomalous cerebral activity paved the way for new theories and inspired modern medical research. After much debate, research and taboo, the Diagnostic and Statistical Manual of Mental Disorders (DSM 5) now defines stuttering as a childhood fluency disorder. It typically results from the underactivation of the primary speech centres in the brain.

Why is there no stuttering medicine yet?

Why is there no medicine for Stammering

Individuals who stutter and their loved ones have always hoped for a pharmacological cure for stuttering. Currently, there are no pharmaceutical compounds that can fully alleviate the symptoms of stuttering. There are no FDA-approved drugs for the cure of stammering.

Genetics play a significant role in the incidence of developmental stuttering. Familial studies and twin studies by Yairi and Ambrose suggest genetic dependence of stuttering. Genes related to stuttering have been mapped to chromosome numbers 1, 7, 12, 13, 15 and 16 in recent genetic studies linked to stuttering in children and adults.

Newer studies by Montag et al published in 2012 and Chen et al in 2014 show that there is an association between the dopaminergic genes (SLC6A2 and DRD2) and stammering. However, almost all available dopamine blockers come with significant side effects that dilute their efficacy in reducing the repetitions, blocks and prolongations in dysfluent speech.

Like most genetic and developmental disorders therapists and doctors can prescribe medication for the management of stuttering. However, there is no medicinal treatment that cures the childhood onset fluency disorder. Combining cognitive behavioural therapy with medication often shows better outcomes than using medication only.

Haloperidol and reduction in stuttering intensity

Data from the 1980s show that there is enough correlation between first-generation dopamine-blocker haloperidol. The compound can improve the fluency by increasing brain activity in the primary speech centres, but haloperidol can have serious side effects. The constant use of haloperidol has been linked with extrapyramidal symptoms, dysphoria, sexual dysfunction and tardive dyskinesia.

Research shows a relationship between stuttering and elevated dopamine levels. Moreover, drugs that enhance dopamine activity like L-dopa make stuttering much worse in people who stutter.

Another dopamine blocking agent – Pimozide, which is similar to haloperidol, has shown positive responses in clinical trials. However, it has significant side effects upon prolonged usage. Contraindications include an elevation in the prolactin levels, tardive dyskinesia, extrapyramidal symptoms, dysphoria and cardiac conduction concerns.

Not all antipsychotics and antidepressants reduce the stuttering intensity

On the other hand, paroxetine, the antidepressant that reduces the reuptake of serotonin (SSRI) does not exhibit any clinical response in stammering. Similarly, tricyclic antidepressants show little effect on the symptoms of stuttering. A comparative study of clomipramine and desipramine show that clomipramine show increased improvement as compared from the latter based on self-reported fluency scales according to two studies published in 1995 by Gordon et al. and Stager et al.

New-age dopamine blockers work better with fewer side effects

Second generation dopamine blockers like olanzapine and risperidone have better effects on stuttering symptoms and exhibit lower side effects as compared to first-generation dopamine blockers like Haloperidol. Both these compounds have are better tolerated than haloperidol.

Risperidone shows increased activity in the cortical speech areas and striatum. According to research, doses between 0.5mg and 2mg per day decreases stuttering intensity significantly. Although risperidone is well-tolerated, it can increase overall plasma concentration of prolactin leading to severe side effects including sexual dysfunction, amenorrhea, galactorrhea and dysphoria upon prolonged use. Patients treated with risperidone also exhibit increased metabolism of the left striatal function as per FDG PET studies conducted by Maguire et al in 2000 (as compared to patients treated with placebo).

Olanzapine has a different tolerability profile as compared to risperidone. It has lower risks of causing dysphoria, sexual dysfunction and amenorrhea, but it can contribute to drastic weight gain in patients. Doses of olanzapine between 2.5mg and 5mg can effectively reduce stutter, but these doses can also result in an average of 4 kg (11 pounds) of weight gain.

A recent study shows that olanzapine might be more effective than haloperidol in reducing the intensity of stuttering. The compound downregulates the post-synaptic GABA-A receptors. They act as complete or partial GABA-A agonists and contribute to decreasing the intensity of stuttering in the targeted population.

Treatment of stuttering with new and unique pharmaceutical compounds

Ziprasidone is another compound that is well-tolerated and effective for the treatment of stammering. It is also an atypical antipsychotic. Another newer compound that has fewer side effects but reduces the intensity of stuttering is asenapine. It leverages the sublingual administration and does not contribute to unwarranted weight gain like olanzapine. Aripiprazole is another compound that acts as a partial agonist of the D2 and 5HT1a receptors. Aripiprazole is an FDA-approved drug for the treatment of Tourette’s in children.

Other alpha receptor agonists like Clonidine, calcium channel blockers like nimodipine and verapamil, and selective GABA-A agonists like Pagoclone have limited efficacy with a flurry of side effects.

New drugs as stuttering medicine

Drugs for stammering treatment

A new category of drugs that inhibit the vesicular monoamine transporter 2 (VMAT2) is under review as you read this blog. These compounds decrease the synthesis of dopamine through the VMAT2 inhibition. These drugs including valbenazine and deutetrabenazine have shown significant promise in the treatment of tardive dyskinesia, Tourette’s, and abnormal movements associated with Huntington’s Chorea. At the same time, these compounds pose the risk of precipitating depression via the non-selective inhibition of monoamines and a sharp decrease in serotonin levels in the brain.

Should you take medication for stuttering?

The perfect medicine for the treatment of stuttering is still far away. The ongoing research does hold promise and keep the hope for a medicinal cure of stuttering alive. Right now, almost every pharmaceutical compound available in the market for the treatment of stuttering belongs to groups of antipsychotics, atypical antipsychotics or medication for Tourette’s syndrome. Therefore, there are scores of side-effects the patient and their loved ones have to deal with during constant use.

There is no replacement for a good speech language pathologist for the treatment of stuttering. Even if you are taking medication, you should not discontinue speech therapy. A combination of speech exercises and medication has been most effective in treating the signs and symptoms of stuttering.