The art of an injection

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This page is in response to an article from the Pittsburgh Post-Gazette, "The Hoarse Whisperer." I have since expanded the page to address issues that would help in obtaining appropriate informed consent.

A common complaint

Just getting the correct diagnosis of spasmodic dysphonia goes a long way towards treating the disorder. However, dosing the medication that is the currently the most acceptable treatment for spasmodic dysphonia is a bit of an art and one that is perhaps not well explained or not well detailed by some physicians. The major complaint of losing one’s voice is the side effect of the dosing of the medication. Commonly patients receive too large of a dose. 

Variable effects

Botulinum toxin has a variable effect on different people but is usually consistent in a given individual. This makes getting the proper dose a trial and error procedure at the beginning, since the amount needed by any one person may vary by a factor of 20 or more. The best dosage does not seem to be related to sex, age, weight, or any of the other usual measures physicians use.

Side effects

Since the medication treats the symptoms of the disorder and not the actual cause of the disorder (which remains unknown) the goal of the treatment should be in the hands of the patient. The two opposing factors to be weighed by the patient are side effects versus the duration of the benefit of the treatment. In broad terms, the benefit of a large dose is an increased duration of beneficial effect; the downside are the initial side effects. The benefit of a smaller dosage is few or no side effects but the duration of the beneficial effects may be limited.

More specifically, the maximum duration of benefit for the “average” person with ADductor spasmodic dysphonia is about 18 weeks or roughly 4 months. Some individuals last longer and some are always much shorter. Once the dose of botulinum toxin is large enough to get this duration, a diminishing return is obtained by going to a larger dosage. In a typical patient, to get this 4 months of benefit before requiring a return visit to the physician with the necessary needle poke, the patient will suffer through about a week of hoarseness. Patients variously experience a breathy voice, a high pitched squeaky voice, a non-projecting voice, a laryngitis-type voice, and possibly trouble swallowing liquids.

Decreasing the dosage can totally eliminate these initial side effects though at the price of more frequent injections. By the time the dose is low enough to eliminate all breathiness, the duration of beneficial effect will typically shorten by a few weeks to perhaps 3 months resulting in four shots per year instead of three.

What if I get too big a dose the first time?

If your first dose is too large, you will likely have side effects which have been described by patients as a laryngitis-type voice, a squeaky voice, a whispery voice, or hoarseness. These side effects are because the initial weakness of the vocal folds prevents them from closing very well. Basically, the weaker the vocal folds from the injection, the worse the voice. When the vocal folds fail to come together for speech, it requires a lot of air to talk and patients complain of running out of breath, exhaustion when talking, and even general fatigue. Additionally, if the vocal folds do not close well, swallowing becomes a problem. Liquids tend to leak into the wind pipe and cause choking and coughing. If the dosage of the injection is way too much, these vocal effects might last three to four weeks and the swallowing problems one to two weeks. To some extent, these side effects can be dealt with by not talking much and thickening any liquids or tucking the chin to the chest when swallowing liquids. Fortunately, Botox treatments are temporary and these side effects will resolve. Then the most important issue is to decrease any subsequent doses of Botox.

What if I get too small a dose the first time?

Side effects are not an issue here. You may note improvement in your voice in one to seven days, but improvement will be short lived, perhaps as little as a week or two. The difficult judgment here is whether the dose was really too low or it was a missed injection. If in doubt, a small increase with the next dose is in order. If not, then a larger increase may be appropriate. At worse, you will experience the difficulties associated with the previous question. If more than one injection is unhelpful, then another consideration would be to make sure the diagnosis is correct.

Patients who might prefer a large dose

Patients make decisions based on many factors but perhaps some examples would be helpful. For example, take a patient who lives alone, talks little, and has to travel a long distance to get the medication. Her insurance coverage is not wonderful and she abhors needles. She takes Valium just to tolerate the thought of getting a needle poked in her neck. She chooses a dose large enough that she loses her voice for a month and has to avoid thin liquids for a week after the injection. She waits six months before returning for another treatment and her spasms and difficulty speaking are quite bad before she even thinks about making the trip. This is the best scenario in her mind, given that she has this disorder. The price: a roller coaster voice and two injections per year.

Patients who might prefer a small dose

Another patient sells financial investment advice. His job suffers when his voice is strained. When he no longer "sounds" confident about his advice, no one trusts him, and he loses income. He chooses a very low dose of botulinum toxin that gives him no hoarseness at all. He returns for another injection at the tiniest vocal struggle. Thus, he has almost no dips and peaks in terms of vocal performance. The price: perhaps four injections per year.

Technique issues

Unfortunately, injection technique also affects the outcome of the injections. If injections have extremely variable results, despite the same dosage each time, it is possibly a result of more or less medication reaching the intended muscles. Thus, a person who is hoarse for a month one injection and the next has the perfect injection with no breathiness at all, likely had two different amounts actually enter the muscle rather than the medication having a different effect each time.

Physician philosophy

Philosophy of the injecting physician has a role at the initial treatment. Some physicians may treat the patient with a dose that is sure to have an effect, given that the patient has traveled far or paid a large amount of money for the injection. Many of these patients will tend to have a marked amount of initial breathiness. Other physicians will tend to start with a lower than average dosage so the patient gets a whiff of the benefit of the medication without the side effects. Later, the dose is increased to give the patient a longer beneficial effect, with cautions about the side effects. For Dr. Thomas, an average dosage is about 2 1/4 units total split into two parts, one for each vocal fold. Dr. Thomas usually starts at a low dosage and increases. He recommends a starting dose of about 1.8 units total with a range from 1/2 unit total up to 20 units total. Following patient requests with appropriate precautions is priority. Dr. Thomas doses what the patient requests and will use various injection techniques, again based on patient request. Patients seem most satisfied with this approach.

What if I decide not to have any treatment?

At this time, we do not know the cause of spasmodic dysphonia so we do not have a cure for the disorder. Botox treatments are directed at relieving the symptoms of the disorder. The condition tends not to be progressive and many patients have tolerated it’s difficulties for many years. As far as we know, nothing should happen if you decide not to treat your problem with Botox. Those who undergo treatment with Botox have returns spasms after several months, but they are usually not as severe as they were initially, so there seems to be some small prolonged benefit from the injections.

Cost of treatment

The treatment is relatively expensive. Costs will vary markedly across the United States and presumably other countries. There are typically three or four costs associated with the injection and it would be reasonable for you to ask about them before your injection. Pricing information is given to patients. Charges typically include the actual injection by the physician, the EMG machine charge, to determine accurate placement, and the medication charge. Other charges might include an evaluation and management charge if a significant amount of time is spent evaluating your illness and outcomes that day, apart from the actual injection.

A special consideration in the use of Botox is that the wholesale price for a single vial of the medication (100 units) is about $400 (year 2001 price), $525 (2012, 2013 price). The cost of one vial is usually split among a number of people. Thus, for the small doses required for spasmodic dysphonia, clinics may be held where multiple patients receive injections on the same day. The medication is delivered dried and frozen and potentially loses potency after it is constituted and thawed for a day. Medicare has regulated the insurer of the last person injected on a day should cover the cost of any medication remaining unused in the vial. We had struggled in vain to persuade Medicare representatives to allow distribution of the cost of unused medication over all patients receiving injections on a given day. Failing, Dr Thomas and medical fellow, Nora Siupsinskiene MD, PhD in 2006 studied the efficacy of using fresh versus frozen Botox. (see http://www.ncbi.nlm.nih.gov/pubmed/16890068).   They found there was no statistically significant difference in the duration of action of the drug, and patients were satisfied with the results.  Hence, Dr Thomas uses both fresh and re-frozen Botox for the convenience of his patients.   Once a vial is opened and reconstituted, any remainer not used on a given day, is frozen in small aliquots for reuse by individual patients on a later day.    It is this use technqiue from which the study was designed.

A little fine print

The US Food and Drug Administration has not approved Botox for use in laryngeal dystonia. What does this mean? In the United States, a drug must be approved for at least one disorder before physicians may use it. However, once approved for one indication, physicians may apply their judgment and utilize the medication in question at their reasonable discretion for other uses. That is the case for Botox. It has been quite successfully used by many physicians and patients in many dystonias other than blepharospasm, the only one for which Botox is FDA approved. The cost of getting approval for other indications is likely prohibitive for Allergan, especially when it is already being used for these indications. When Medicare began covering charges for Botox use in spasmodic dysphonia, most insurance companies followed suit and began covering charges. You, of course, should be sure yours does, before proceeding with an injection.