In 1888, neurologist Dr. William Gowers described that “the movement of the fingers at the metacarpal-phalangeal joints is similar to that by which Orientals beat their small drums” (Gowers, 188, as cited in Goetz, 2011). This comparison expresses one of many Parkinson’s diseases symptoms: tremors. Parkinson’s disease has been medically recorded since the late 1800s, and was commonly defined by patients’ Parkinsonian tremor and rigid form. Parkinson’s disease is a neurodegenerative disorder caused by the impairment and death of nerve cells in the brain. This results in the reduction of dopamine, a neurotransmitter responsible for regulating movement. Parkinson’s disease, or PD, is associated with motor abnormalities such as tremor, stiffness, and postural instability. Today, there is still no cure to PD. However, there are pharmacologic treatments that are able to provide symptomatic relief. The issue with PD treatments is that although they do provide some regulation of symptoms, the treatments may also lead to worsening the disease. That being said, what is the most effective treatment for Parkinson’s disease?
According to an article from Medscape, the objective to treat PD is to medically manage the symptoms while attempting to minimize adverse effects (Hauser, 2018). Having Parkinson’s disease affects people’s overall quality of life, including their physical and emotional health. People with PD are limited to certain ranges of motion and are limited in controlling various movements. Emotionally, they can suffer with anxiety and depression. The geriatric population is more likely to experience a lessening of quality of life, as their age makes it more probable for them to be diagnosed with PD. Thus, treatments for PD should be evaluated on their effectiveness so that people with PD will have the knowledge they need to decide on how to take care of themselves. People will also be able to help their loved ones that are diagnosed with PD. With focus on the pharmacologic treatment of PD, the common types of medications are monoamine oxidase (MAO)-B inhibitors, levodopa, and dopamine agonists (Hauser, 2018).
Within the brain are enzymes called monoamine oxidase (MAO)-B. They are responsible for breaking down neurotransmitters, one of them being dopamine. PD is treated with MAO-B inhibitors, meaning that they stop the catabolization or breaking down of dopamine. PD is caused by the lack of dopamine and the mechanism of MAO-B inhibitors slows the breakdown of dopamine. By slowing this catabolization of dopamine, more dopamine remains available. In a review about how PD is managed, MAO-B inhibitors are described as providing “higher levels of dopamine” while “decelerating metabolization” (Pedrosa, 2013). MAO-B inhibitors are often used as stand alone initial treatment for early PD or in adjunct with the dopamine-increasing levodopa treatment.
An article discussing why MAO-B inhibitors are beneficial for initial treatment of PD states that MAO-B inhibitors have a reputation of being safe, providing mild symptomatic effects along with the capability to be neuroprotective (Lohle & Reichman, 2011). Studies have shown that MAO-B inhibitors are safe because they don’t usually appear to have substantial or adverse effects like other PD pharmacologic treatments. The mild symptomatic effects also support the efficacy of MAO-B inhibitors, especially for early PD since the symptoms during that phase are usually mild. Other treatments such as levodopa and dopamine agonists are known to be superior for managing the symptoms of PD, but MAO-B inhibitors help to delay these treatments, which also delays their adverse effects. One type of MAO-B inhibitor is called selegiline; although it may cause negative side effects such as nausea and dizziness, however, “it is important to note that a meta-analysis of placebo controlled trials found no difference in dropouts due to adverse events between patients treated with selegiline and patients treated with placebo” (Lohle & Reichman, 2011). The conclusion of this study indicates that, despite the adverse effects of selegiline, they are tolerable enough to patients that they are likely to continue therapy. This differs from other treatments such as levodopa; the adverse effects of levodopa can cause patients to discontinue levodopa treatment. MAO-B inhibitors are not known to be as clinically significant as other pharmacological treatments such as levodopa, but they may still prove their effectiveness by assisting in determining the treatment that is to be later administered as PD progresses in patients.
Multiple sources have referred to levodopa as the gold standard treatment for PD, a position it has occupied for many years. It is a precursor to dopamine, meaning that the medication converts to dopamine and therefore leads to an increase of dopamine levels in the brain. It is known as the most effective treatment that is available because it is able to control the PD symptoms as they worsen over time, whereas treatments like MAO-B inhibitors are only able to manage the mild symptoms of PD. During the early stages of PD, the motor symptoms are regulated well when Levodopa is applied. This is because levodopa allows greater levels of dopamine in the brain, so body movements are better controlled, even for patients who experience more moderate symptoms of PD. It is important to note that levodopa is often paired with carbidopa, a dopamine promoting drug. This is because carbidopa assists in preventing the nausea side effect of levodopa. Levodopa can be used to have long-lasting effects or it can be used if immediate relief is needed (Pedrosa, 2013). Through years of being used as primary treatment and its success in controlling motor symptoms of PD, levodopa is considered to be one of the more efficacious treatments.
Aside from levodopa’s performance in early treatment, its timely selectiveness of providing relief, and capability for treating more than just PD’s mild symptoms, the use of levodopa debatable due to its adverse effects after patients have used levodopa for several years. In an article exploring the approaches to PD treatment, many patients who use levodopa suffer from motor fluctuations and dyskinesias after 5 years of treatment (Jankovic & Aguilar, 2008). Dyskinesia is the term for uncontrolled and seemingly involuntary movement. These motor complications can greatly impact patients and their quality of life, so they may choose to discontinue treatment and use other pharmacological treatments. Another option is to utilize drugs that can ameliorate or better the adverse effects of levodopa, such as MAO-B inhibitors or dopamine agonists. Due to the negative reports on the long-term use of levodopa, doctors suggest putting off the application of levodopa to help patients avoid the adverse effects until they progress to the later stages of PD. During the delay of levodopa, other treatments such as MAO-B inhibitors and dopamine agonists would be applied. Considering the later consequences of levodopa, it is important to re-evaluate its effectiveness. Then, the substantial effects of levodopa would highlight the effectiveness of other treatments like MAO-B inhibitors or dopamine agonists.
Dopamine agonists are known to be more potent than MAO-B inhibitors, however majority of medical professionals still agree that levodopa is the most effective. The mechanism of dopamine agonists involve mimicking the dopamine neurotransmitter, tricking the brain into thinking that it has dopamine. The function of the dopamine neurotransmitter helps to control movement. With the application of the dopamine agonist, the brain believes it has dopamine, so it will try to regulate body movement. Like MAO-B inhibitors, dopamine agonists can be used to to treat the negative effects of long-term levodopa treatment. In an article published by The Canadian Journal, Dr. Paul J Bedard mentions that “Longitudinal studies have shown that dopaminergic agonists such as pergolide, ropinirole and pramipexole can be used as drugs of choice, such as levodopa. They are effective, but slightly more difficult to titrate and manipulate” (2001). That being said, dopamine agonists can be considered as an effective drug like levodopa, the gold standard treatment.
The effectiveness of dopamine agonists (DA) have been assessed through its performance in comparison with levodopa and MAO-B inhibitors. An article discusses one type of DA called pramipexole, which presents “several advantages over levodopa such as direct simulation of striatal dopaminergic neurons” and a “longer half-life providing a more continuous stimulation at the dopamine receptors” (Constantinescu, 2008). These advantages can be explained beginning with the basal ganglia: a part of the brain associated with controlled movements. One major component of the basal ganglia is the striatum, which regulates the body’s voluntary movements with the help of dopaminergic neurons. Since pramipexole interacts directly with the striatal dopaminergic neurons, it is able to better alleviate PD symptoms. Pramipexole also proves to have a longer half-life, meaning that the drug functions and remains in the bloodstream for a greater duration of time. Half-life is a measurement of the time it takes for the concentration of a drug to be reduced to half within one’s blood. DAs such as pramipexole provide motor symptomatic relief, and studies have also shown that DAs are effective in treating the non-motor symptoms of PD such as depression (Constantinescu, 2008). The motor and non-motor symptoms of PD impact people’s quality of life; if both types of symptoms are able to be treated by pramipexole, it could have the same level of effectiveness as levodopa. Studies have been conducted to represent scores for the quality of life in levodopa and pramipexole patients. In the beginning, the group who received levodopa had better scores than pramipexole. However, after three to four years of being treated with either pramipexole or levodopa, the scores for the pramipexole group were favored (Constantinescu, 2008). There are several benefits to receiving DA treatment, but there complications can also arise using this treatment.
Just as the other PD treatments, DAs have adverse effects; these effects increase over time as patients age and their PD This includes hallucinations, edema, and somnolence (Constantinescu, 2008). Studies have shown that patients treated with pramipexole were more likely to develop and experience hallucinations more than patients treated with levodopa. Edema, known commonly as swelling, is a side effect also associated especially with pramipexole treated patients. Edema is likely to occur in patients who have history relating to cardiac disease. Somnolence is a state of sleepiness, and evidence suggests that pramipexole increases the risk for somnolence compared to levodopa. These adverse effects can decrease one’s quality of life, but as stated previously, there have been studies suggesting that DAs can better the quality of life in the long-term. DAs such as pramipexole is able to treat both motor and non-motor symptoms, while also helping to increase the quality of life.
MAO-B inhibitors, levodopa, and DAs are three common pharmacologic treatments of PD. Their overall effectiveness can be examined in comparison to one another. Each treatment can be used as monotherapy, or in adjunct with another. MAO-B inhibitors are not known to be as effective as levodopa or DAs, but they are safer and are often used to delay the use of levodopa to avoid its adverse effects. Most professionals agree that levodopa is the most efficacious treatment of PD; however it is reported that their adverse effects such as motor fluctuations potentially decrease patients’ quality of life. Thus, some professionals question the use of levodopa. Studies suggest that DAs could be one of the top choices for PD treatment, just as levodopa. DAs appear to have certain advantages over the use of levodopa, but they also increase the risk for other adverse effects. After researching and comparing each treatment to each other, I consider levodopa to be the most efficacious treatment for PD because it is able to treat the mild and more moderate symptoms PD. Although levodopa’s complications can negatively impact patients and their quality of life, levodopa can be paired with MAO-B inhibitors or dopamine agonists in attempt to relieve the adverse effects. When deciding upon the treatment for PD patients, it is critical to be knowledgeable of each treatments’ mechanism, potential adverse effects, and results from studies conducted for that treatment. Moreover, it is important to be aware of the status of each PD patient, as their needs are very individualized. That being said, one treatment may be generally considered as the most effective for PD patients, but treatments should be administered to fit the needs of every individual in order to increase their qualities of life.