September 1, 2016

Excellent Mayo Clinic Update on Parkinson's Disease and its Latest Therapy Options

I subscribe to many health newsletters. These two are my favorites:

This month’s issue of the Mayo Clinic Health Letter leads off with one of the best descriptions I’ve seen of Parkinson's disease (PD) and its treatment. I was going to summarize the article but decided to run it in full, below. 

I didn't learn anything startlingly new from the article. But the section on supportive drugs used to extend the benefits of carbidopa-levodopa -- for those of us with more advanced PD -- reminded me it was time to check some of them out. 

Here's the full text:


Parkinson’s disease is widely recognized but poorly understood by most people. It seems to be a bad disease, but then many people who can have it appear to be doing fairly well.

However, Parkinson's disease signs and symptoms progressively worsen, and the beneficial response to drug therapy is likely to diminish. In addition, Parkinson's disease can result in numerous other health problems — such as dementia, bladder and bowel difficulties, and sleep trouble. Working closely with your doctor can help you stay abreast of standard and newer treatment options as signs and symptoms change for you over time. It's true that people diagnosed with Parkinson's disease — most of whom are 60 or older — typically have many more active and productive years of life ahead of them. Drug treatment aimed at managing the better-known signs and symptoms such as tremor and difficulty with movement is often very effective for years.

Lost connections
The primary process that causes Parkinson's disease signs and symptoms is when dopamine-producing nerve cells in the brain die prematurely. Brain cells communicate with each other through chemical messengers called neurotransmitters. Dopamine is one of the main neurotransmitters in the brain.

In a healthy brain, ample dopamine is produced so that the brain cells can coordinate smooth and precise muscle movements. However, when dopamine-producing cells are lost, brain cells communicate abnormally with muscles, which can lead to impaired body movement.

The hallmark of Parkinson's disease is the gradual and progressive loss of movement control. In fact, a diagnosis of Parkinson's disease requires the presence of two of the four main features:
  • Shaking (tremor) that's more pronounced at rest — This often begins with your hand or fingers on one side of the body and may be intermittent. It then spreads to the other side over a period of years and becomes more noticeable. It often first becomes noticeable as a rubbing together of your thumb and forefinger, called pill-rolling. Not everyone with Parkinson's disease develops a visible tremor, and tremor can also occur as a result of other problems.
  • Slowed movement (bradykinesia) — You or your family notice you're much slower doing things, such as walking. It may be difficult to use an arm or leg. Simple tasks such as buttoning a shirt, typing, lifting coins from a pocket or getting out of a chair become more difficult. You may start shuffling or dragging your feet when walking. Later on, episodes may occur where you freeze up or start to take shorter, quicker steps when walking. 
  • Rigid muscles — Muscle stiffness causes stiff movement of arms, legs or your body. It usually begins on one side of the body before progressing to the other side. Often, an early sign is reduced arm swing with one arm while walking. Stiff muscles can also cause pain.
  • Instability of balance — Diminished reflexes and impaired balance with falls are serious issues, but these often don't occur until later in the course of Parkinson's disease.

Maintaining movement
Treatment of Parkinson's disease addresses signs — such as tremor — but it doesn't change the progressive course of the disease. Medication for movement problems is usually very effective for several years. However, eventually adjustments in drug therapy will be needed.

The most effective therapy for older adults is the combination drug carbidopa-levodopa (Sinemet) that replaces dopamine. This can have a dramatic effect on improving slowness and can also help with tremor and rigid muscles. The drug is started at a low dose, and the dose is gradually increased over time until your signs and symptoms are controlled at the lowest possible dose. It's recommended that carbidopa-levodopa be taken an hour before eating so that digestion of food doesn't alter the absorption of the drug. Avoid snacking on foods containing protein, such as ice cream, nuts, cheese and meat. Also avoid large, high-protein meals that can take a particularly long time to digest.

Nausea is a primary side effect of carbidopa-levodopa, which can usually be managed by taking the drug with a few soda crackers, fruit juice or a piece of fruit, rather than on an empty stomach. If nausea persists, adding more carbidopa to the drug formulation may be helpful.

After years of carbidopa-levodopa therapy and advancing Parkinson's disease, the beneficial effects of the drug become less predictable. It's a double-edged sword, where too little carbidopa-levodopa can cause problems, but so can too much. The drug effect from a dose can begin to wear off too soon before the next dose, resulting in a change from being nearly normal to having severe signs and symptoms before the next dose takes effect.

Added to that, higher doses of carbidopa-levodopa can cause involuntary movements (dyskinesia), and lessening or adjusting doses of carbidopa-levodopa may be needed to control this. Adjustments in carbidopa-levodopa therapy that may be considered to address this include:
  • Shortening the interval between carbidopa-levodopa doses
  • Transitioning to a newer extended release form of carbidopa-levodopa called Rytary, which provides a more sustained effect

For select people with difficult-to-control signs and symptoms, a continuous infusion of a carbidopa-levodopa gel (Duopa) is released directly into the digestive tract through a surgically implanted feeding tube.

Supportive drugs
A number of other drugs may be used to reduce the symptoms of Parkinson's disease. When used earlier on in therapy, some may be used instead of carbidopa-levodopa, or along with it to allow a lower carbidopa-levodopa dose.

With more-advanced Parkinson's disease, these drugs are used to extend the benefit of carbidopa-levodopa between doses. These drugs are usually started at a low dose, and then gradually increased over time to minimize side effects, such as nausea, lightheadedness upon standing, sleepiness, confusion or hallucinations.

Options include:
  • Dopamine agonists such as pramipexole (Mirapex), ropinirole (Requip) and rotigotine (Neupro) which is a skin patch. In early Parkinson's disease, these drugs are sometimes used instead of carbidopa-levodopa. Unusual side effects can include problematic behaviors such as compulsive gambling or shopping, binge eating, or hypersexuality.
  • Monoamine oxidase type B inhibitors such as selegiline (Eldepryl, Zelapar) and rasagiline (Azilect). These drugs are sometimes used in early Parkinson's disease to relieve mild signs and symptoms. More commonly, they're used to complement the use of carbidopa-levodopa. These drugs sometimes interact with certain antidepressant medications.
  • Catechol O-methyltransferase inhibitors such as entacapone (Comtan). This drug is only useful if given with carbidopa-levodopa. This is primarily used in advanced Parkinson's disease. 
  • Amantadine may be used alone in very early Parkinson's disease to provide short-term relief of mild signs and symptoms. It may be used with advanced Parkinson's disease to help control dyskinesia caused by carbidopa-levodopa.
  • Anticholinergic drugs such as trihexyphenidyl or benztropine (Congentin) can help control tremor, but they usually aren't recommended for older adults due to side effects such as worsened cognitive problems and constipation.

Deep brain stimulation
When drug therapy is no longer enough to satisfactorily manage Parkinson's disease signs and symptoms, the next step may be to consider deep brain stimulation. This surgical procedure involves implanting thin electrodes into a specific part of the brain.

The electrodes are connected to a pacemaker-like generator implanted in your chest near your collarbone. The generator sends finely tuned electrical pulses to your brain and can — when effective — control Parkinson's disease movement-related signs and symptoms as well as the best drug options can. Research suggests that the beneficial effect of deep brain stimulation lasts for at least five years, or even much longer.

In addition to risks associated with surgery, downsides of deep brain stimulation include that it doesn't work for everyone, it's not an option for those with dementia, and it doesn't help with signs and symptoms that aren't helped by carbidopa-levodopa, such as unsteadiness and freezing of gait.

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