Tag Archives: speech

“A little duloxetine to loosen my tongue”

Posted on by

The drug duloxetine, marketed under the brand name Cymbalta, was originally developed for depression or anxiety but is now prescribed mostly for pain management.  An article from neurologists in Russia and Malaysia now reports that three people with PSP who were receiving duloxetine for their mood issues experienced important, unexpected improvement in their speech. 

The article’s first author is Dr. Oybek Turgunkhujaev of the Semeynaya Clinic in Moscow and its senior author is Dr. Shen-Yang Lin of Universiti Malaya in Kuala Lumpur.  Unfortunately, the journal, Movement Disorders Clinical Practice, is not open-access and because it’s only a brief article, there is no abstract in PubMed for me to link to.

The mechanism of action duloxetine is to enhance the action of the neurotransmitters serotonin and norepinephrine by blocking the brain cell’s ability to re-absorb those molecules from the synapse.  That’s a standard way for brain neurons to regulate and sharpen its signals to other neurons.  That process is called “reuptake” and you’ve probably heard of the SSRIs or selective serotonin reuptake inhibitors. Duloxetine works on norepinephrine as well as serotonin, so it’s an SNRI.   Other SNRIs in common use include venlafaxine (Effexor) and desvenlafaxine (Pristiq). The figure below shows the mechanism of action of duloxetine and venlafaxine. 

Nerd alert: This mostly takes place in the pons, specifically the locus ceruleus (for norepinephrine), raphe nuclei (for serotonin), but to a lesser extent in prefrontal cortex of the cerebrum (both norepinephrine and serotonin).

The journal article is accompanied by before-and-after videos of two of the three patients.  They all had difficulties not only with slurring, but also with difficulties initiating speech and stuttering.  The delay to onset of the drug’s benefit is described only as “within weeks.”  All three patients also experienced an improvement in their mood, which could have been a direct effect of the drug on the natural reaction to their improved ability to speak.

The authors do a good job of describing how the drug’s known mechanism of action might address the parts of the brain that when impaired, are known to cause those symptoms.  But they also recognize that the general alerting and energizing effect of duloxetine could explain the result as well.  Placebo effect seems unlikely, as the durations of benefit were too long: “> 3 months,” “15 months until death” and “>5 months.” 

Bottom line: This is encouraging and I hope further reports of duloxetine in PSP from other centers are forthcoming. BUT . . . and MEANWHILE . . .

Physicians considering prescribing duloxetine off-label for speech problems in PSP should be aware that it can have important side effects and drug/dietary interactions.  I can’t get into those here, but they are described in detail in the 31-page FDA-approved package insert and its one-page summary. Needless to say, there has been no formal trial of duloxetine in PSP, so that population could have different/additional/worse side effects relative to the mostly younger people in the depression and pain trials on which the package insert was based. 

Speech therapy in PSP?

Posted on by

The Lee Silverman Voice Training (LSVT) “Loud” program is a popular method used by speech/language clinicians to improve vocal volume and clarity in people with Parkinson’s disease.  I’ve never been all that enthusiastic about it because there is no literature demonstrating superiority to traditional forms of speech therapy for PD.  For another thing, I’m a little suspicious of its proprietary financial model, where a clinician pays anywhere from $300 (for a student) to $990 (for a professional) for a two-day course that yields a certificate permitting them to advertise that they offer LSVT.   The courses and certificates are available only from LSVT Global, Inc.

Potential evils of capitalism aside, it’s good to see someone finally trying to help the dysarthria of PSP.  Our heroes are a group in Rome headed by the well-regarded movement disorders authority Fabrizio Stocchi, MD PhD.  The paper‘s first author is Patrizio Sale, MD PhD. a neuro-rehabilitation specialist.  The work appeared in the European Journal of Physical and Rehabilitation Medicine.

The study compared the benefit of LSVT Loud in 16 patients with PSP to the same four-week course of treatment in 23 patients with PD.  Both groups did improve in most of the measures applied.  Probably the most positive result was in the reading task, where the maximum volume for the patients with PSP improved from an average of 82.5 dB to an average of 87.5 dB. Somewhat more modest benefits accrued for nonverbal phonation and for non-reading speech.

Unfortunately, there were no control patients receiving sham treatment, traditional treatment or no treatment.  We don’t know if the improvement will long persist, but the literature suggests that it does so in PD.  Equally important is that the study did not evaluate articulation — only volume.  Furthermore, the study was quite small, inviting flukey results.  Clearly, more work is needed, but for now, I’ll try sending some of my patients with PSP and hypophonia (low vocal volume) for LSVT.  I’ll let you know what happens.