Parkinson's Disease. Should You Fear Taking Levodopa? Season 1, Episode 2 of the podcast 'Odyssey of Healing. Medicine is Changing to Change Your Life'. Cover.
In the latest episode of our podcast “Odyssey of Healing ” answers to questions about levodopa and Parkinson’s disease treatment from neurologist-Parkinsonologist, PhD Gulnara Nailyevna Akhmadeeva
Do not take these answers as medical advice for your case and do not self-medicate! Each case is individual and requires specialist consultation, You can easily get an online consultation with a Parkinson’s specialist here. Answers to frequently asked questions are provided for educational purposes.
Levodopa is a prodrug that is a precursor of dopamine, a substance that is deficient in the brain in Parkinson’s disease. Levodopa is used for replacement therapy to compensate for this deficiency. It is considered the most effective medication for treating the symptoms of Parkinson’s disease.
Before the introduction of levodopa into medical practice, patients with Parkinson’s disease had a short life expectancy—on average, 5 to 7 years after the onset of the first symptoms. This is explained by the lack of effective treatments that could slow the progression of the disease and alleviate its symptoms.
Levodopa is a precursor of dopamine. When introduced into the body, it converts into dopamine, compensating for its deficiency in the brain, which helps improve the condition of patients and reduce the symptoms of Parkinson’s disease.
The comparison is based on a similar principle of action: just as insulin compensates for the deficiency of this hormone in patients with diabetes, levodopa compensates for the deficiency of dopamine in patients with Parkinson’s disease. Both medications help normalize the body’s condition and improve the quality of life for patients.
There is a myth that levodopa is toxic and causes many side effects. However, numerous studies conducted over the past 50 years have proven that levodopa does not have a toxic effect on brain neurons and does not contribute to the progression of Parkinson’s disease.
No, this is a misconception. Research has shown that levodopa does not destroy brain neurons and does not accelerate disease progression. It is safe when prescribed and used correctly under a doctor’s supervision.
Over time, patients experience a decrease in the neurons’ storage capacity. This means that neurons lose the ability to retain levodopa for extended periods, leading to the need for increased doses of the medication to maintain its effect.
Reduction in the storage capacity of neurons is a process in which neurons lose the ability to retain dopamine synthesized from levodopa. This results in the medication’s effect becoming less prolonged, requiring patients to take it more frequently or in larger doses.
Phenomenon “dose depletion ” occurs when the effect of a single dose of levodopa becomes insufficient, and the symptoms of the disease return before the next dose. This is related to the progression of the disease and the reduced ability of neurons to retain levodopa.
Starting levodopa too early can lead to a faster development of side effects, such as the “wearing-off” phenomenon. Therefore, doctors use a “delayed-start” strategy, prescribing less effective medications in the early stages of the disease to postpone the initiation of levodopa.
Levodopa is prescribed at later stages of the disease, for example, in cases of balance disorders, falls, or other serious manifestations characteristic of the third stage of Parkinson’s disease.
In the early stages, antiparkinsonian drugs from other groups are more commonly used. This allows delaying the need for levodopa and avoiding side effects associated with its long-term use.
Levodopa is prescribed for symptoms such as stiffness, slowness of movement, balance disorders, and frequent falls, which are characteristic of the third stage of the disease.
In the early stages, antiparkinsonian drugs from other groups are used, which are less effective but allow delaying the start of levodopa treatment.
The “delayed start” strategy involves using less effective drugs in the early stages of the disease to postpone the initiation of levodopa. This helps avoid the rapid development of side effects and prolong the effectiveness of treatment.
Patients over 70 years old with risks of dementia, hallucinations, and somatic diseases most often need levodopa, as it is a safer option compared to other medications.
Levodopa causes fewer side effects than other antiparkinsonian drugs and can be used in smaller doses, reducing risks for elderly patients.
Surgical methods include the implantation of brain stimulators and MRI-guided focused ultrasound. These methods help reduce levodopa doses and improve patients’ quality of life.
This procedure allows for a reduction in the doses of levodopa taken, prolongs the beneficial effects of treatment, and improves the overall quality of life for patients.
Focused ultrasound is a non-invasive method suitable for patients over 70-80 years old . It helps improve quality of life without the risks associated with surgical intervention.
Patients can take levodopa for more than 20 years. Their condition is maintained through combined treatment methods, including modern surgical technologies.
Damir Lukmanov: Opposite me is a neurologist specializing in Parkinson’s at the V.S. Buzaev International Medical Centre, a specialist in movement disorders, PhD Gulnara Nailevna Akhmadeeva. Hello!
Gulnara Akhmadeeva: Hello, Damir, nice to meet you!
Damir Lukmanov: Nice to meet you, yes. Unlike people who have encountered some problems and are currently facing a choice: which treatment methods to choose? We are talking about this from the perspective of modern medicine. And I would like to ask you about Levodopa. It does decline, doesn’t it?
Gulnara Akhmadeeva: Declines, yes.
Damir Lukmanov: I hope so. In conversations with the buzaevclinic team doctors, I learn a lot of new things, and our podcast is dedicated not to doctors, but to those who are currently addressing these issues. We have already found out that Parkinson’s disease is not a verdict. Let’s put it in a few words: what is it, and most importantly, why are Levodopa medications so feared?
Gulnara Akhmadeeva: Levodopa medications were discovered and approved for use in patients with Parkinson’s disease about 50 years ago or even longer. Before these medications, patients with Parkinson’s disease had a very limited lifespan, living only about 5-7 years from the onset of the first symptoms. Why is Levodopa actively used and applicable? The reason is that it is a prodrug—a precursor of dopamine, which is deficient in the brain in Parkinson’s disease. A simple analogy can be drawn with diabetes and insulin. In diabetes, the amount of insulin decreases, causing all the problems. Patients with diabetes can inject insulin to bring themselves, conditionally, back to normal, stabilizing their carbohydrate metabolism. The same happens here. We use the most effective medication—the substance lacking in the brain, we administer it to patients, and, accordingly, they feel better. Essentially, it is replacement therapy. That’s why it is so effective.
Damir Lukmanov: We understand that it is effective. But why does Levodopa cause some fear? Could it be some misinformation, maybe a small amount of quality information available?
Gulnara Akhmadeeva: What is the fear in patients? The fear is that Levodopa is considered toxic and has a huge number of side effects. In fact, this is not the case, to get ahead. Over these 50 years, many studies have been conducted on many thousands of patients, proving that it has no toxic effect on brain neurons and, accordingly, does not contribute to their destruction or the progression of Parkinson’s disease. As for the myth of increased or new side effects, they certainly exist, but this is not related to Levodopa itself. It is related to the natural progression of Parkinson’s disease, with a decrease in the number of cells that remained at the onset of the disease, and this progression is increasing. Accordingly, a property of the brain manifests, such as an increased need for Levodopa.
Damir Lukmanov: Is this addiction?
Gulnara Akhmadeeva: This is not habituation, but a decrease in the cumulative capacity, the buffering capacity of neurons. If at the beginning of the disease we give a certain amount of Levodopa to a patient, and the neurons can capture and hold that one tablet for a day or two, in principle, the patient can be in good condition for those days. However, over time, these neurons become “leaky,” and through a certain number of “holes,” the amount of Levodopa gradually decreases, it “seeps out.” And over time, due to the progression of the disease, the number of “holes” simply increases. This leads to the need for Levodopa, the need for multiple doses throughout the day. So, it is no longer enough to take Levodopa once, because the dose depletion occurs. Patients, not knowing that this is caused by the progression of the disease and thinking that it is due to Levodopa itself, of course, are mistaken. Our task, the task of doctors, Parkinson’s specialists, is to explain that Levodopa is not toxic, it does not shorten life expectancy, and it does not have pronounced side effects. There are limitations to its use, of course, but again, it is up to the doctors who can adjust the regimen to improve the patient’s condition and, most importantly, add Levodopa when it is necessary for a particular patient, because there are specific indications. It is important not to miss that critical point for a particular patient when Levodopa is needed. This is the doctor’s task.
Damir Lukmanov: So, Levodopa is not a panacea, not everyone is prescribed it, am I understanding correctly?
Gulnara Akhmadeeva: In fact, all patients with Parkinson’s disease eventually turn to Levodopa, one way or another. It’s just that each person does so at their own stage, depending on when they see a doctor and how their disease progresses.
Damir Lukmanov: But nevertheless, this medication is not always necessary, right?
Gulnara Akhmadeeva: Levodopa is not always necessary. For a patient in the early stages of the disease, for example, if one hand is trembling, if symptoms are predominantly on one side, we usually do not start with Levodopa. I can explain when we do start with Levodopa. For example, a patient comes to the doctor with hand tremors, stiffness, slowness, and complains of instability when walking, balance issues leading to falls. These symptoms are characteristic of the third stage of the disease, and there are five stages in total. The manifestation of the third stage in the form of falls dictates the need for the quickest possible prescription of the most effective medications. In this case, to improve the patient’s condition and reduce the risk of falls and injuries, we will prescribe Levodopa immediately. But this is not the only example. In fact, there is a group of patients in the so-called age group, 70+, especially those with high risks of dementia, possible hallucinations, and risks of somatic diseases. These are patients to whom we cannot prescribe medications from other antiparkinsonian groups because they have higher risks of other side effects. Other medications, compared to Levodopa, may cause more hallucinations, lower blood pressure, and more swelling. For such patients “70+” with high risks, prescribing Levodopa is safer. Since Levodopa is generally more effective than other antiparkinsonian drugs, we can prescribe it in lower doses, thereby reducing the risk of side effects. This must be understood. So, this is the age group with a high number of potential side effects and patients in the third stage.
Damir Lukmanov: If Levodopa is so effective, then why mention any alternative medication options at all?
Gulnara Akhmadeeva: Due to the fact that with age and as the disease progresses, there is a greater need for Levodopa, which unfortunately also depends on the dosage. Often, patients come to the appointment who were prescribed Levodopa at an early stage when it was not yet indicated. It was prescribed, and patients have been taking the drug for, say, 7 years, only Levodopa. During this time, they have reached a higher dose of Levodopa, and of course, they have developed the “wearing-off” phenomenon, the “on-off” phenomenon—the very “side effects” we fear. All of this could have been avoided if we had used the “delayed start” strategy from the beginning. What is this? It means that at the first stage, we usually use (for middle-aged patients, especially younger ones) antiparkinsonian drugs from other groups, not Levodopa. They are, of course, slightly less effective. But their use over a certain period, for example, 2-5 years, can improve the quality of life for the patient and delay the use of Levodopa. Of course, we will eventually come to Levodopa for this patient, but it will be a little later. Therefore, there are different strategies for patients, and it is important to understand that starting with Levodopa is not always necessary due to the higher risk of “side effects,” which we also do not need. Levodopa is needed at the right time: neither too late nor too early.
Damir Lukmanov: It seems to me that nothing scares a person as much as the lack of alternatives. We say that sooner or later a patient facing Parkinson’s disease will turn to Levodopa. But it is only necessary to explain that it is safe. And everything that happens regarding side effects – unfortunately, that’s how our body is structured. Right?
Gulnara Akhmadeeva: In reality, the body is such an interesting thing. For example, if we take two patients comparable in age, gender, education level, and number of comorbidities… We might give Levodopa to one and not to the other, and we will get completely different effects. And even if we give the same amount of medication, we will still likely get different effects because each patient has their own social interactions, level of physical activity, habits, hobbies, and communication level—all of which influence how the patient ultimately lives with their Parkinson’s disease. Everything is very individual, of course.
Damir Lukmanov: Based on your experience at the V.S. Buzaev International Medical Centre, how long have you been observing a patient who was prescribed Levodopa, and how many years has it lasted?
Gulnara Akhmadeeva: Do you mean from the start of taking Levodopa or in general?
Damir Lukmanov: I’m interested in the duration of the “distance,” how long is it? 5 years, 10 years, 15 years?
Gulnara Akhmadeeva: No, definitely, it’s more than that. I’ve been working with such patients for almost 20 years. So, all this time I’ve been observing patients to whom I once prescribed Levodopa, and they still live with this disease, using Levodopa. Naturally, progress does not stand still. Along with Levodopa, we definitely resort to more advanced treatment methods, meaning neurosurgical operations. It must be understood that when a patient starts taking Levodopa at some point, we are preparing them for the fact that a side effect will arise sooner or later. But this is a feature of the disease. It’s just important to be ready for the moment when side effects occur, we will have the very alternative you mentioned. An alternative of additional treatment, radical treatment with the help of neurosurgery. And then, depending on the age and condition of the patient when the need for the same neurosurgery arises. If the patient is “preserved,” if the patient is not 70 years old, for example, if they do not have hallucinations, serious diseases such as diabetes, heart problems, coronary heart disease, etc. – we can recommend them for the installation of brain stimulators. Yes, this operation is invasive, yes, this operation involves craniotomy, with the installation of electrodes. But this method allows reducing the amount of Levodopa taken, extending their good quality of life, that is, not only life expectancy but also quality. If we mean that the patient, to some extent, “could not preserve” until this age, or they have crossed the threshold of 70 years, for example, and then there is a need for a more progressive method of treatment – then we can recommend a non-invasive method. For example, operations conducted in our center – MRI-guided focused ultrasound, and then we are not limited by the age of the patients. We have a patient, for example, 75+ or 80+, when we have exhausted all possibilities of drug therapy, we take them for our operation, which is called an operation, but in fact, it is non-invasive, and we similarly improve their quality of life and extend life precisely in good quality.
Damir Lukmanov: I wanted to touch on your collaboration, your partnership, your interaction within the medical center. All doctors work as a single coordinated organism, and if a patient comes to you, you solve all tasks together. Tell us, how does the interaction occur? With doctors of which specialties do you also conduct consultations?
Gulnara Akhmadeeva: In fact, we have a very cool collegial decision-making process at our center, and I’ve always liked it. First and foremost, we collaborate with the neurosurgeon, Rezida Maratovna Galimova, who makes decisions in her capacity as a neurosurgeon. The decision to operate on each specific patient is made based on all available data, including MRI, together with the neurosurgeon. We definitely interact with our MRI specialist, Dmitry Konstantinovich Kreotin, because making a decision for such a neurosurgical operation is impossible without assessing risks and possible contraindications. This requires knowledge of MRI and CT, so the MRI doctor is essential. But we also necessarily work with specialists in therapeutic profiles. I have three “best friends” – a psychiatrist who helps with elderly patients, with hallucinations or dementia, which, if present, are contraindications for our surgery, and we continue to manage such patients together. The second excellent doctor who helps navigate all the “intricacies” of the patient, all symptoms, and comorbidities is, of course, our therapist-cardiologist-nephrologist. With her, we decide: to take the patient or not? Most likely to take, of course, but after we adjust medication doses, correct antihypertensive measures, and so on, I mean preoperative preparation activities. The third specialist who usually joins our consultations is, of course, our neurourologist Ivan Alekseevich Kuvin, who helps men with libido issues, male and female problems, the latter often presenting with frequent urination urges, incontinence – the problem known as overactive bladder. These are the three “friends” without whom I, as a neurologist specializing in Parkinson’s, do not see the most effective treatment for my patients. We always work as a team of four where necessary. Plus, two more doctors, as I mentioned, when we make the decision about “to operate or not to operate.”
Damir Lukmanov: As far as I know, the medical center also conducts research and educational activities. Are you involved in educational work?
Gulnara Akhmadeeva: We conduct clinical research, observe patients, and write papers. Rezida Maratovna defended her Doctor of Medical Sciences degree, and we have PhD theses being written in several areas. We constantly hold educational events for doctors. We are engaged not only in research but also in clinical work. Among the moments we are proud of is that in the fall, we held the second session of our in-person educational course for doctors, where physicians even from other countries come to see, integrate into our educational process, and observe our clinical process, including how we perform our operations.
Damir Lukmanov: Patients, their relatives, and doctors are watching us. I know that you are open to collaboration and that medical professionals often reach out to you when they encounter unusual situations that you have already faced, worked through, and are ready to share your knowledge about. Yes, what specifically can you share with the professional world?
Gulnara Akhmadeeva: Well, all I have is my clinical experience over many years. I work with such patients, and among them, of course, there are not only patients with typical classical variants of Parkinson’s disease or Alzheimer’s disease, but also interesting dementias, interesting Parkinsonism, and Parkinsonism plus. These are interesting patients with functional disorders who seem to come with tremor or suspicion of another disease, and it turns out to be some psychiatric condition. And here we have a big advantage – we solve problems with patients collegially. And that’s why we often come to the right decision. We now have really complex patients coming to us so that we can help them diagnose and prescribe treatment. Such cases are becoming more and more frequent. I confirm your words that our center is open to cooperation, open to learning, to exchanging experiences, because such interesting and complex patients, of course, are encountered in the life of every doctor, and certainly, such interesting patients should be shared. We are ready for this and very happy.
Damir Lukmanov: As I look at you, you’ve used the adjective “interesting” several times. I see a doctor with bright eyes who is interested in what they do. That’s great, that’s wonderful. This, by the way, is a distinctive feature of the entire buzaevclinic team. I wish you success in your work!
Gulnara Akhmadeeva: Thank you very much, Damir! It was a pleasure working with you.
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