Dr. Siddharth Kharkar

Do I have Parkinson’s disease? This article is meant only for people who have Parkinson’s disease or are taking care of someone with Parkinson’s disease. It is essential to get evaluated by a specialist neurologist to be sure of the diagnosis of Parkinson’s disease. I do provide a simple tool for testing yourself for symptoms of Parkinson’s disease, which can be accessed from the main page. However, this is mostly a memory aid and should not be used for clinical purposes. All clinical diagnoses and treatment should be done only under the direct advice of a certified doctor. What causes Parkinson’s disease? We will go step by step. First, let us understand how normal movement works: The front of the head is the part that decides to make a movement – this is our free “will”. Then the mid-portion of the brain (above your ears) sends the signal to execute this movement. But before this signal reaches our muscles, it has to pass through a complicated maze of circuits deep inside our brain that is called the “Basal Ganglia Circuitry” (see image). This circuitry modulates movement, making it smooth and precise. The substantia nigra is an important part of this circuitry. It is located at the back of the head, just above the neck. It produces a chemical called “Dopamine” – remember the name of this chemical, it is very very important: “Dopamine”. The Substantia Nigra produces an important chemical called DOPAMINE. This dopamine travels forwards, deep into the brain, and helps the basal ganglia circuitry operate correctly. Now, In Parkinson’s disease, for some reason, the cells in the substantia nigra are gradually destroyed. Therefore, less dopamine goes to the basal ganglia. Therefore, the basal ganglia do not function properly, leading to problems with movement. Although there are many such movement problems in Parkinson’s disease, the three most typical are: Uncontrolled shaking or TREMOR Slowness of movements or BRADYKINESIA Stiffness of body parts or RIGIDITY This combination of motor problems is called “Parkinsonism”. What causes the death of dopamine-producing cells? What other processes can cause Parkinsonism? In a minority of cases, the reasons for the death of dopamine-producing cells is known: 1. Toxins: In rare cases, the destruction of cells may be due to ingestion of toxic substances like MPTP & rarely pesticides. However, this is believed to be very, very rare. This kind of Parkinsonism probably occurs only in certain people such as industrial workers and iv drug abusers. 2. Genes: Some patients may have faulty genes that lead to the gradual death of these cells. Several such defective genes including PARK-1, PARK-2, LRRK2 etc. have been identified. However, genetically inherited or familial Parkinson’s disease is also relatively rare – only about 10% of cases have a family history of Parkinson’s disease. Faulty genes can produce Parkinson’s disease. 3. As part of another disease: For example, the death of these cells can occur as part and parcel of a more generalized destruction of cells in the brain. This happens in diseases that cause dementia, such as Alzheimer’s disease, and other illnesses called “Diffuse Lewy Body disease” & “Frontotemporal Dementia”. NOTE: A few other diseases can directly cause basal ganglia dysfunction – e.g. In Wilson’s disease, there is accumulation of copper throughout the entire body. When copper accumulates in the basal ganglia, it produces parkinsonism. Similarly, liver failure can cause parkinsonism due to accumulation of a metal called manganese in the basal ganglia. Parkinsonism can occur as part of a more generalized destruction of cells in the brain, for example as part of Alzheimer’s disease. 4. Medications: Some medications can cause symptoms like Parkinson’s disease. These include medications used for vomiting (metoclopramide, levosulpuride, high doses of domperidone) and for psychiatric problems (haloperidol, risperidone etc). These medications may cause symptoms similar to Parkinson’s disease by temporarily decreasing the production of Dopamine. But there is no death of cells and so this condition is not called Parkinson’s disease. Instead, it is called “Medication Induced Parkinsonism” (“Parkinsonism” means “Parkinsons-like disease”). Medications given for constipation can worsen Parkinson’s disease. Medication Induced Parkinsonism is further explained in another article. Do the reasons above explain most of the cases? No. In most cases, no apparent reason can be identified for the destruction of Dopamine-producing cells. This is called “Idiopathic Parkinson’s disease”. The word “idiopathic” means “without a known cause”. In the vast majority of cases, the cause for destruction of cells in the Substantia Nigra is NOT known. Are there any theories regarding the reason for Parkinson’s disease? As noted before, the cause for destruction of the Dopamine-producing cells in most cases (almost 90%) is not known. What could be the cause of this destruction? If only we could find this cause, it would be a revolution in the treatment of Parkinson’s disease! Of course, scientists are working furiously to find this answer. There are a few theories: Many scientists believe there is no single cause for Parkinson’s disease. It is produced by different mechanisms in different people. For example: in the genetic form of Parkinson’s disease, the faulty genes may produce copious quantities of a toxic waste product. This waste product is called alpha-synuclein, and it can damage the substantia nigra. In some genetic forms, very reactive free oxygen radicals may directly damage the substantia nigra. In some patients, the body’s immune system may go haywire and start destroying the substantia nigra (a process called “autoimmunity”). Faulty genes may produce too much waste called “alpha-synuclein” An interesting theory that has come up recently is that at least some forms of Parkinson’s disease may be caused by a viral infection that starts in the gut. Is Parkinson’s disease the result of a Viral infection? Constipation is a very early symptom of Parkinson’s disease. This constipation may be due to a viral infection of the intestines. From the gut, the viruses gradually move towards the brain through a large nerve called the vagus nerve that connects the intestine to the brain. Such a process is known to happen in other diseases such as Polio. The theory is, when the viruses eventually reach the brain, after many years, they cause havoc

Sleep problems in Parkinson’s include difficulty staying asleep (Insomnia), trashing in bed while sleeping (REM Behavior Disorder), cramping of the legs or arms while sleeping (OFF-dystonia) and finally, sleepiness or sleeping throughout the day. Each one of these has a specific treatment. Parkinson’s Sleep Problems discussed in this article 1. REM Behavior Disorder (RBD) (“I trash around in bed while sleeping”)2. Insomnia (“I keep waking up!”)3. Cramping at night (“What is Off-Dystonia?”)4. Excessive daytime sleepiness (“I feel like sleeping all the time!”) Certainly, other sleep problems can occur in Parkinson’s – like having the urge to urinate frequently in the night (nocturia). But in my experience, the 4 sleep problems above are very common and frequently the most troublesome. Let us talk about these 4 sleep problems. Table Of Contents Parkinson’s – REM Behavior disorder (RBD) Parkinson’s – REM Behavior disorder (RBD) treatment Parkinson’s – Insomnia & Parkinson’s OFF-Dystonia Parkinson’s – Insomnia Treatment Parkinson’s – Sleepiness all the time, including daytime sleepiness Parkinson’s – Sleepiness Treatment Dr. Siddharth Kharkar NeuroPlus Epilepsy & Parkinson’s Clinic – Dr. Kharkar Parkinson’s – REM Behavior disorder (RBD) Usually, when we dream, the body does not move. Our brain is smart enough to completely relax our muscles while we are dreaming. Thus, we are “paralyzed” during our dreams. In patients with Parkinson’s disease, the body is not paralyzed during the dream, so that the person “acts out” what they are dreaming. This is called Parkinson’s – REM Behavior Disorder (RBD). Patients with Parkinson’s disease may talk, move excessively while sleeping, and sometimes hit their bed partner while sleeping. Some patients have only mild symptoms such as talking in their sleep or restlessness. But occasionally patients may have dramatic movements – such as thrashing or kicking. The patient may fall off the bed. Rarely the kicking and thrashing movements may even hurt the patient’s partner! Parkinson’s – REM Behavior disorder (RBD) treatment A. Melatonin for Parkinson’s – REM Behavior Disorder treatment: is a natural hormone that helps the brain to sleep. Melatonin is a natural chemical that helps us to sleep soundly. Melatonin is quite effective in treating mild to moderate Parkinson’s – REM behaviour disorder. It is taken orally before going to bed. Melatonin is exceptionally safe. Usually, doctors start with a low dose (for example 3 mg at night). Newer studies have shown that higher doses (for example 6 mg and above) may be more effective.  Therefore, if the low dose of melatonin does not control your REM behavior disorder (RBD), talk to your doctor to see if you can be given a larger dose. B. Clonazepam for Parkinson’s – REM Behavior Disorder treatment: In severe cases, sedative medications are very helpful. Usually, Clonazepam is given – it is exceptionally effective and resolves RBD in almost all patients. But Clonazepam frequently causes sedation, even during the day. Clonazepam can also be habit-forming. Taking too much clonazepam at one time can cause very severe sedation. Higher doses of Clonazepam can cause you to become very sleepy, even during the day. Therefore, many doctors including myself treat with melatonin first and use clonazepam only if melatonin fails to treat the REM Behavior Disorder. c. Other Medications: Memantine is a drug usually given for dementia (memory problems). A few studies indicate that Memantine may help in treating REM Behavior Disorder (RBD). Memantine is not used frequently for REM Behavior Disorder. If a patient has both dementia and RBD, it may be worth trying. Parkinson’s – Insomnia & Parkinson’s OFF-Dystonia Many patients with Parkinson’s have Insomnia. Patients with Parkinson’s disease may have trouble falling asleep (Initiation Insomnia). This problem may be exacerbated if you take medications other than levodopa just before your bedtime. In my practice, I find that Amantadine frequently causes initiation insomnia. But even more commonly, Parkinson’s patients report that they are unable to stay asleep. This is called Maintainance Insomnia. One of the most frequent causes is wearing off of medications in the night. Sue: A patient with OFF-Dystonia Let us talk about a hypothetical patient – Sue. Sue has Parkinson’s & Maintainance Insomnia. She wakes up often in the night! But why? You may have difficulty turning around in bed if the effect of levodopa wears off in the middle of the night, Sue takes a dose of Levodopa before dinner at 7 PM. She usually goes to bed at 10 PM and wakes up at 8 AM. Then, from 7 PM to 8 AM – a duration of 13 hours – Sue’s brain is not getting any dopamine! Therefore, in the late-night or early-morning hours, frequently between 3 AM – 5 AM, Sue turns OFF! Sue’s body becomes stiff. It becomes difficult to change your position or turn from one side to another in bed. Her muscles – especially those in legs – may cramp up. This cramping up of muscles is called OFF-dystonia. The feeling of Levodopa wearing off can be very uncomfortable for some patients. You may wake up multiple times in the night – this is called Maintenance Insomnia. Parkinson’s – Insomnia Treatment A. Avoid non-levodopa medications close to bed-time: Do not take medications other than levodopa very close to bed-time. Thus, if you are taking Amantadine, Dopamine Agonists & Anticholinergics, make sure you take the last dose many hours before you go to sleep. B. Treat OFF-Dystonia / cramping at night: The solution is to take a dose of Levodopa (preferably the controlled release or CR formulation) just before you go bed. Do it as the last thing you do, just before you close your eyes. Taking a dose of levodopa just before you close your eyes at night may prevent OFF-dystonia in the night. If that doesn’t work, a long-acting dopamine agonist (e.g. Ropinirole XL) may help you avoid an OFF-state & OFF-dystonia at night (But note problem 1!). Deep Brain Stimulation (DBS) may help to reduce OFF-dystonia and also improve the quality of sleep. While at King’s College, I had the opportunity to research this topic with the world-renowned expert of Parkinson’s disease – Dr Kallol Ray Chaudhuri (see below). Relevant references:Changes in Parkinson’s

Is Depression & Anxiety common in Parkinson’s disease? Yes. Depression & Anxiety are common in Parkinson’s disease. These problems can produce significant disability. About 1 in every 5 patients with Parkinson’s disease may have Depression (Rejinders et al. 2008). Anxiety is even more common – about 1 in 4 patients with Parkinson’s disease have significant symptoms of Anxiety (Broen 2016). Depression is common in Parkinson’s disease. Thankfully, detection and treatment is helpful in almost all cases. Other than these two problems, patients with Parkinson’s disease can also have other psychiatric issues. Impulse control Disorders: Patients may have difficulty in controlling their impulses. They may start spending a lot of money online or may start gambling or have excessive weight gain due to overeating. This lack of impulse-control can occur as a side-effect of medications called “Dopamine Agonists” (Pramipexole, Ropinirole, Rotigotine). Agitation and hallucinations/psychosis : This is particularly worrisome and should be promptly treated to prevent injury to family members. Medications such as Quetiapine, Donepezil, Pimvanserin and if all else fails – Clozapine – are usually helpful. Let us focus on Depression here. We can discuss Impulse control disorders and Agitation/Psychosis in a future article. What are the symptoms of Depression or Anxiety? Most people believe that all patients with Depression actively cry, talk to people about their mental pain, or in some way express their grief actively. This is frequently not the case. Many people with Parkinson’s disease have a passive form of Depression. This passive Depression may manifest in the following ways: Symptoms of ‘Passive’ Depression 1. Feeling guilty, worthless or hopeless.2. Loss of interest in previously enjoyable activities (for example, watching a movie)3. Fatigue or loss of energy.4. Thinking about the same things over and over again (Obsessive ruminations)5. Difficulty in paying attention, concentrating or remembering things6. Reduced or increased appetite. Losing or gaining weight without a clear cause.7. Sleeping too much or too little. Early morning awakening. Inability to focus or lack of interest in regular activities may be a sign of depression. In fact, patients with Parkinson’s disease may become so passive that they are diagnosed with a related psychiatric condition called “Apathy” – or a complete lack of interest and motivation. Is there a test for Depression & Anxiety? There is no test to confirm the diagnosis of Depression and Anxiety. This diagnosis can be made only after you have a detailed conversation with your doctor or a qualified mental health professional. However, there are numerous, fairly accurate screening questionnaires for Depression. One of them is the PHQ-2 Questionnaire, displayed below. PHQ-2 Questionnaire In the last two weeks, how often did you have little interest or pleasure in doing things? – Not at all (0 points)– Several days (1 point)– More than half the days (2 points)– Nearly every day (3 points) . In the last two weeks, how often did you feel down, depressed or hopeless? – Not at all (0 points)– Several days (1 point)– More than half the days (2 points)– Nearly every day (3 points) Add up your points for the two questions. If your score is 3 points or more, you may be suffering from Depression. Please remember that even if this Questionnaire indicates you may have Depression, the diagnosis needs to be confirmed by a doctor. Why is Depression and Anxiety common in Parkinson’s disease? We could assume that depression is common because of the significant problems with movement in Parkinson’s disease. This intuitive assumption certainly is true up to a certain extent. However, a major cause of depression in Parkinson’s disease is due to chemical changes inside our brain which are caused by the disease. In fact, Depression can actually happen even before the movement problems of Parkinson’s disease start. The exact mechanism by which accumulation of synuclein causes Depression is still being worked out. Chemicals such as Serotonin & Dopamine keep you happy. The leading theory is that just like synuclein causes damage to brain cells that secrete Dopamine, it also causes damage to brain cells that produce a chemical called “Serotonin”. Serotonin (just like Dopamine) is one of the chemicals in the brain that causes feelings of happiness or satisfaction. Therefore, a decrease in the activity of this chemical causes Depression. What are the natural / no-medication methods for treatment of depression? Depression should not be neglected. But all cases of depression do not need medication. Counselling and exercise can be beneficial in many cases. Exercise: Any form of exercise decreases Depression and Anxiety. The effect is marked. In non-Parkinson’s disease patients, exercise can have the same effect on depression as taking an antidepressant medication. Even walking in the open for 15-30 minutes daily can help with depression. Counselling: Cognitive behavioral therapy in particular, may be very helpful. An insider tip – sometimes psychiatrists may not have adequate time to participate wholeheartedly in counselling because of their extremely hectic schedule. You can request a referral to a professional counsellor if you want to try counselling. Talking to a trained professional about your depression can be very helpful Bright light therapy: This is useful if your Depression is seasonal, i.e. it is worse in winter when you get less sunlight. This kind of Depression is called “Seasonal Affective Disorder” or SAD. You can buy “daylight spectrum” bright lights online (see an example below) and keep these on in your house for at least 8 hours a day. Regular use of these lights decreases Depression due to SAD. Bright lights can help with winter-time depression. If specialized lamps are not available, you can try using commonly available bright fluorescent tubes. Even in patients who need medication, participating in a regular exercise program and counselling leads to greater relief than taking the medication alone. Which anti-depressant medications are safe in Parkinson’s disease? Since low levels of Serotonin could be one of the reasons for Depression in Parkinson’s disease, medications which increase serotonin activity are helpful. These medications are SSRIs (short for Specific Serotonin Reuptake Inhibitors). A few examples of these medications are Escitalopram, sertraline, fluoxetine etc. Increasing the levels

What causes Constipation in Parkinson’s disease? Parkinson’s disease affects nerves going to the intestines. As a result, the intestines, just like the rest of the body, move slowly in Parkinson’s disease. This is the major reason why almost all patients of Parkinson’s disease also have constipation. Patients with Parkinson’s disease may also find it difficult to relax the anal sphincter (the outlet valve) sufficiently so that stools can be passed. Other factors increase constipation, and it is straightforward to treat these other factors: Patients with Parkinson’s disease may not get up frequently to drink water. As a result, they might become dehydrated, and their stools may become hard. Physical immobility by itself, and lying in bed all the time can delay the downwards passage of food. Physical inactivity can cause constipation. Patients prefer to eat softer things in Parkinson’s disease because these are easy to swallow. Frequently, these softer things (e.g. rice) do not provide enough fibre. Fiber in our food absorbs water and makes stools soft, making them easy to pass. When the urge comes, patients with Parkinson’s disease may not be able to get up to pass stool. This may cause stools to become hard and impacted (stuck). Some medications such as opioids (e.g. tramadol, given for pain), antidepressants (e.g. Amitriptyline), antihypertensives (diltiazem, furosemide, chlorothiazide etc) may worsen constipation. What should you eat if you have Parkinson’s disease & constipation? Ideally, you should eat a high-fibre diet. Particularly, you should eat a diet rich in insoluble fibre which is found in raw vegetables and fruits. It is essential to be careful about the kind of vegetables and fruits you should eat. Try to eat vegetables and fruits that are easy to swallow. For example, having 1-2 bananas every day would be a great idea! Fruits and vegetables that are difficult to chew and swallow (e.g. apples and pears) may get stuck in your throat if you try to swallow them whole. Therefore, you can mash them nearly into a pulp, or even better pulverize them in a mixer before you eat them. Bananas are easy to swallow, especially after they are mashed. If you have diabetes, try to avoid fruits with high sugar content (e.g. grapes and mangoes). Vegetables such as spinach, mushrooms or well-cooked cauliflower, broccoli and other soft, easy to swallow vegetables would be excellent choices. If you have a lot of trouble incorporating fibre into your diet, think about buying a smoothie machine or maybe you can even use your regular mixer. If it is strong enough, it pulverizes any fruit or vegetable into a fine smoothie that is very tasty! “Ninja” is one such good brand for blenders. You can increase the taste further by adding reasonable quantities of sugar, chocolate powder, honey and other condiments. Bananas are easy to swallow, especially after they are mashed. If you have trouble swallowing, remember to make the smoothie on the thicker side, almost like custard. This can be achieved by putting a banana or two in each smoothie. Make sure there are no large chunks of fruits/vegetables. You can take it in a bowl and eat it with a spoon. Thick smoothies eaten with a spoon are easier to swallow than very thin smoothies. Is it important to drink enough water? Absolutely!!! Water is essential to keep the stools soft. It is absorbed by the fibre in the diet. This swollen up fibre increases the bulk of stool. This bulk makes it easier for intestines to push it forwards and ultimately out of the body. Keep a bottle of water close to your bed, so that you can drink water whenever you want to. Patients with Parkinson’s disease often don’t drink enough water because of two problems: They find it difficult to get water when they are thirsty. They find it difficult to go to the bathroom when they have to pass urine. Some of my patients were used to drinking only 2-3 glasses of water when they visited me! Of course they were very constipated! Consider drinking at least 7-8 glasses of water daily. If you want, you may drink less water towards the end of the day so that you don’t have to get up in the middle of the night to pass urine. If you do have a lot of trouble getting up in the night, you may need adjustment of your medications so that they keep working throughout the night. Do two things: Keep a bottle of water near your bed / the place where you sit. Make sure you drink at least 7-8 glasses of water daily. What are some useful home remedies? Other than eating a healthy, high-fiber diet and drinking enough water you may try the following home-remedies for constipation: Walk at least 30 minutes daily. When resting, sit upright in a chair. Do not spend the day lying down in bed. Substances called “Probiotics” may help in maintaining a regular bowel schedule. Don’t buy expensive medications for this purpose! Yoghurt or “Dahi” is a rich source of probiotics. You can try eating half to one bowl of yoghurt/Dahi daily. Probiotics present in yogurt may help to have regular bowel movements. There is no reason to buy expensive brands, in fact home made yogurt probably is the best kind. Prunes provide some laxative effect. They can be difficult to swallow, so make sure you smash them or cut them up into tiny pieces before you eat a few pieces daily. Maintain a regular bowel schedule. Try to use the bathroom at the same time every day. When you get an urge to pass stool, do not wait. Try to use the bathroom as soon as it is possible. Which medications should you avoid for Constipation in Parkinson’s disease? You should NEVER take any medications without the prescription and advice of a Doctor. Taking medications without a prescription is illegal and may be life-threatening. Levosulpuride (e.g. PAN-L tablets) Metoclopramide (e.g. Perinorm) High doses of domperidone (e.g. PAN-D tablets) Medications given for constipation can

People with Parkinson’s disease may be afraid of being “trapped” in difficult situations: – What if I go to a marriage and start to have a tremor? – What if I am travelling and develop sudden slowness? Luckily, there are “On-Demand” therapies for such situations: Sublingual Apomorphine =======================– You place a thin film below your tongue. – Acts in ~15 min & lasts for ~ 1.5 hours.–Most common side-effects are nausea and mouth or throat irritation. Injectable Apomorphine =======================– The “Pen” is filled with medication.– You can inject yourself. – Acts in ~10 min & lasts for ~ 1 hour. – Possible side-effects are nausea, excessive movements, sleepiness or dizziness. Inhaled Levodopa =================– You place a thin film below your tongue. – Acts in ~10 min & lasts for 1 hour or more. – Most common side-effect is coughing. – Should not be used by people with problems in breathing. Simple: Additional tablet ==========================– Ask your doctor if you can take 1/2 or 1 tablet extra during such occasions. – You can use regular levodopa tablets.– Dissolve 1 tablet in a glass of carbonated water or orange juice. Drink as needed. – Acid in the soda/juice helps in absorption. – Starts slowly (>20 min), acts longer (>1hr) Tadalafil 5mg can last up to 36 hours, aiding erectile dysfunction management. Its efficacy duration depends on individual physiology. When discussing medication, note factors such as cialis 5mg price in malaysia for economic considerations. ***********************************Dr. Siddharth D Kharkar More info: https://drkharkar.com/ Keywords – On-Demand Therapy for OFF Episodes in, on demand therapy for off episodes in parkinson’s disease, on-demand therapy for parkinson’s disease patients: opportunities and choices, On‐Demand Therapy for OFF Episodes in Parkinson’s Disease Caution: This information is not a substitute for professional care. Do not change your medications/treatment without your doctor’s permission.

Anticholinergics: Trihexyphenidyl, Benztropine. Brandnames in India: Pacitane, Parkin etc… How do these medications work? Dopamine has an enemy in the brain, called Acetylcholine. Acetylcholine actually is a good chemical with a lot of beneficial effects, but one of the things it does is to reverse some of the actions of Dopamine. Acetyl-choline & Dopamine are both “nice” but are enemies of each other. These medications are anticholinergic. That is, these medications by destroying the effect of acetylcholine, give Dopamine a free hand in the brain. Uses / Advantages: There are no real advantages to the use of acetylcholine, over and above the usual Parkinson’s medications described earlier. Sometimes, symptoms like Parkinson’s disease produced by the side-effects of other medications (Medication Induced Parkinsonism). These medications are effective in that situation. But, so is Amantadine – and it is much safer. Disadvantages: Oh Boy! First, they are not as effective as levodopa. And they cause serious side-effects! I (and many other doctors) believe that Trihexyphenidyl (Pacitane) and related medications should not be used in the elderly, at least not routinely. Acetylcholine has many vital roles to play in the body, including proper functioning of the brain, passing urine and keeping your pupils at the appropriate size. Therefore the most common, and frequently serious side-effects with the use of these medications are: Confusion – The patient may lose track of day and night. He/She gets confused easily, has trouble paying attention or remembering anything. In very severe cases, the patient can have visual hallucinations and become physically violent! Anticholinergics can cause confusion. Acute urinary retention – This happens more frequently in males. The urinary bladder fills up with urine, but because of the anticholinergics, the path for urine to get out is closed! The patient starts becoming very, very uncomfortable because of the ever-increasing size of the bladder, which causes severe abdominal pain. This sometimes requires the urgent insertion of a catheter. Anticholinergics can make it very difficult to pass urine. Glaucoma – Similar to what happens with urine, these medications can cause shut off the flow of fluid away from the eye. They make the pupil very large, blocking all the drainage pipes in the periphery of the eye. As a result, fluid keeps accumulating within the eye, and it starts becoming larger. The eye is not a very flexible, and therefore the pressure inside it increases rapidly, and this can cause severe eye pain and blindness. Immediate medical treatment is needed! Sometimes, anticholinergics can cause “Glaucoma” – which is uncontrolled increase in pressure inside the eye. Bottom Line: Who would you much rather have on your side? Arnold Schwarzenegger (Levodopa) or a potentially villanous side-kick (Trihexyphenidyl/Pacitane)? Caution: This information is not a substitute for professional care. Do not change your medications/treatment without your doctor’s permission.

Remember: Levodopa’s best friends are: Entacapone & Amantadine. The medications discussed here (the MAO-B inhibitors) are also supposedly “friends of levodopa/dopamine”. Except, two of them,  like the older brothers Karamazov, these medications are somewhat useful but full of flaws. These medications probably belong to an older generation. I use them very sparingly, if at all. The newest amongst them, Safinamide, is a promising baby. Considering the reputation of its brothers, it’s difficult not to be slightly wary about it. The flawed elder brothers: Rasagiline & Selegiline Rasagiline & Selegiline are the bad brothers that you should probably avoid. How do Rasagiline / Selegeline work? Their mechanism of action is similar to Safinamide: They prevent the destruction of dopamine and therefore preserve it in the body, prolonging it’s action. Uses/Advantages: Two studies indicate that these medications may slightly slow the progression of Parkinson’s disease. However researchers and doctors have ferociously debated the results of these studies. Most doctors believe that there is either no effect, or a very minor effect that should not affect the choice of medication. The effects of Rasagiline & Selegiline in slowing progression of Parkinson’s disease are very minimal. Many researchers believe there is no such effect. Most doctors start by using levodopa (or rarely, the dopamine agonists) for a patient with newly diagnosed Parkinson’s disease. The thought process is as follows – Levodopa is the most potent medication for Parkinson’s disease. If I delay using levodopa, this patient will continue to have symptoms of Parkinson’s disease. Therefore, let me give him levodopa which I am sure will control most if not all of his symptoms, right now. These side-kicks are probably of no use in protecting the brain and produce too many side-effects. It may be worthwhile, for the astute reader, to know about the details of these two studies: The ADIAGO study published in 2009 – Rasagiline at 1 mg per day seemed to slow Parkinson’s disease progression. But 2 mg per day had no beneficial effect! Many doctors believe that the positive result is just due to statistical chance, and is not real. The DATATOP study published in 1993 – Selegiline was useful in relieving the early symptoms of Parkinson’s disease, and therefore using the boss medication – levodopa – could be delayed by a few years.However, there was no direct comparison to the usual strategy of starting levodopa as the first medication. Although often cited as one of the studies that shows possible neuroprotection with these medications, it does not look at this question directly. Disadvantages: These medications have all of the same shortcomings as safinamide, except to a much greater degree. Sometimes they can cause or worsen high blood pressure They may occasionally cause liver problems. Some antidepressants including SSRIs (e.g. fluoxetine) and TCAs (e.g. amitriptyline, nortriptyline, amoxapine) Stimulants such as Amphetamine & Methlyphenidate Painkillers that contain opioids Some muscle relaxants such as cyclobenzaprine A few other medications such as the antibiotic linezolid. Fermented and pickled food e.g. fermented cheeses and Red Wine – these can cause a very uncomfortable, and occasionally serious condition called “Cheese reaction” due to accumulation of a chemical called tyramine in the body.The affected person has severe flushing of the skin, his/her heart starts beating faster, and he/she has a marked increase in BP. This can last hours – certainly not a good thing to go through! These medications can interact with fermented foods & cause a terrifying, very uncomfortable reaction. More importantly, they can interact with a large number of medications. You should avoid the following medications if you are taking rasagiline/selegiline: The new kid on the block: Safinamide. How does Safinamide act? Safinamide acts just like Rasagiline and Selegiline. It inhibits an enzyme called MAO, which prevents the destruction of dopamine and keeps it in the body for a longer period of time. It seems to be the less harmful brother of the older brothers Karamazov (Rasagiline & Selegiline), but only time will tell. This is 2019: Safinamide was released only 4 years ago. No one is perfectly sure how useful it will be. Uses/Advantages: Since it is a very new medication, its uses are still being worked out. However, it seems to be effective in late-stage Parkinson’s disease. Addition of Safinamide again seems to smoothen-out the effect of levodopa, so that patients experience fewer fluctuations in their functioning throughout the day. Safinamide is very unlikely to cause liver injury. Safnamide is less likely to interact with other medications. But you should probably avoid the medications mentioned above, if you can. Safinamide is less likely to interact with fermented foods. But perhaps it would be wise to avoid the foods mentioned above until we have more experience with the medications. Disadvantages: The side-effects of Safinamide seem to be the same as Rasagiline/Selegiline, but they occur less commonly. Just like its brothers, Safinamide can cause or worsen high blood pressure. Caution: This information is not a substitute for professional care. Do not change your medications/treatment without your doctor’s permission.

(Brand names in India: Amantrel, Parkitidin) How does Amantadine act? Amantadine is a another friend of levodopa (remember: its other friend is entacapone). While it can decrease the symptoms of Parkinson’s disease, it works best when it is given to support the action of levodopa. While Entacapone can sometimes increase the side-effects of levodopa, Amantadine is the friend who smoothens out your rough edges, makes you a better person. Amantadine decreases some side-effects of levodopa and makes it more wonderful. Levodopa’s two friends: Entacapone & Amantadine. No one quite understands how Amantadine works for Parkinson’s disease. It was originally designed to kill the influenza virus. However, doctors accidentally discovered that it makes Parkinson’s disease better as well. It has one, fantastic and unique effect in Parkinson’s disease that is described below. Use/Advantages: Treatment of “Dyskinesias”: Some patients with Parkinson’s disease start getting bothersome movements of the hands, legs and neck after a few years of treatment. I want you to understand these movements. So with all respect: please allow me to describe these movements in the simplest way possible. These movements are dance-like movements, somewhat similar to the way Michael Jackson dances on stage. The Latin word for dance is chorea, and therefore these movements are called chorei-form (dance-like) movements. Since that word is very complicated, they are also called “Dyskinesias”. These movements are often time-linked to levodopa. They are maximum in intensity 30 min – 1 hour after taking levodopa. Dyskinesias are dance-like movements. Amantadine has one fantastic effect – it decreases these movements tremendously. For patients who have not been able to take enough levodopa because of these movements, it enables intake of an adequate quantity of levodopa, so that they can have a much better quality of life. It may smoothen-out the effect of levodopa, and can help in relieving “Predictable wearing OFF” to some degree. But, other stratergies such as entacapone, long-acting medications etc are much more useful for this purpose. Rarely, it can be given as the only medication for Parkinson’s disease. But when used by itself, its effectiveness is limited. Disadvantages: Most people don’t have any side-effects from Amantadine. Some people can have mild swelling or slight purplish discolouration of the feet. Since it is an anti-viral, it can decrease the effectiveness of some viral vaccines. If a live viral vaccine (e.g. Hepatitis B vaccine) needs to be given, Amantaide should be stopped 2 weeks prior and 2 days after the vaccine is administered. Amantadine can decrease the effectiveness of some vaccines. Bottom-line: It is used to control troublesome dance-like movements caused by high doses of levodopa. Although it is only modestly effective by itself, it is extremely good at smoothing out the rough edges of our superstar (levodopa), hence the sorbiquet – The lawyer of levodopa. Caution: This information is not a substitute for professional care. Do not change your medications/treatment without your doctor’s permission.

Click here for the Complete Parkinson’s Patient Guide (Brand names in India: Pramipex, Pramipex ER, Ropark, Ropark XL) How do dopamine agonists work? These chemicals are imitators. They look just like Dopamine itself. They attach themselves to the same sites that Dopamine usually attaches itself. Therefore, they produce similar effects in the brain as Dopamine and relieve the symptoms of Parkinson’s disease. Pramipexole (and Ropinirole) looks like Dopamine. Use/Advantages: “Extended-release” / 24-hour preparations: The effect of a single tablet of “Extended Release” Pramipexole (or Ropinirole) can last for 24 hours. The main advantage is that these medications have “extended-release preparations” that gradually dissolve in the stomach so that they keep gradually entering the blood and then the brain for the entire day. Therefore the effects of a single tablet taken in the morning can last for 24 hours. This infrequent dosing is very convenient! But even more importantly in patients who have Predictable-wearing-OFF or other motor fluctuations with levodopa, these long-acting medications can maintain good movement throughout the day, to “smoothen out the day”. They may produce less dyskinesias than levodopa. They may therefore be used to start treatment in younger patients (e.g. below 45) or may be added to the treatment of a person who cannot tolerate high doses of levodopa due to dyskinesias. Disadvantages: These medications are not as strong as levodopa. When given in smaller doses, they may not relieve all the symptoms of Parkinson’s disease. When given in higher doses, they can produce troublesome side-effects including excessive daytime sleepiness, impulse control problems such as gambling and rarely, sleep disturbances & hallucinations. In particular, the excessive sleepiness during the day often limits their use – restricting their use to smaller doses. Rarely, dopamine Imitators can cause Impulse Control Disorders including gambling, excessive spending or excessive eating. But the most common side-effect is sleepiness. Bottom-line: While good in theory, it is difficult to use these medications in practice. They are sometimes used for the treatment of very young patients with Parkinson’s disease. Also, the fact that 24 hour preparations are available make these medications useful in certain niche situations such as predictable-wearing OFF. Caution: This information is not a substitute for professional care. Do not change your medications/treatment without your doctor’s permission.

(Brand names: Sinemet, Syndopa, Syndopa plus, Syndopa CR, Tidomet etc) Levodopa is the MOST POWERFUL, POSSIBLY BEST medication for Parkinson’s disease. If Parkinson’s was a jungle, Levodopa would be an Elephant. It is the Optimus Prime of Transformers, the Mount Everest of mountains… I could go on… Levodopa is the best medication for Parkinson’s disease, for most people How does levodopa work? In a very simple fashion! Levodopa travels inside the brain, and is converted into Dopamine! As described here, low levels of dopamine in the brain is the main problem in Parkinson’s disease. So, levodopa directly addresses the basic problem. Once it enters the brain, Levdoopa is converted into Dopamine. Use/Advantages: It is one of the strongest medications for Parkinson’s disease. It has a very marked effect on relieving the movement and many of the non-movement problems associated with Parkinson’s disease. Disadvantages / Side-effects of levodopa: Absorption: The absorption of levodopa is decreased if you have food in your stomach at the same time. Ideally, levodopa should be taken on an empty stomach. You should not eat at least 30 minutes (and if possible one hour) before and after taking levodopa. It is mainly protein in the food that hampers the absorption of levodopa. But, you should drink a glass of water with each dose to help the tablet dissolve. Logistics: Levodopa needs to be taken multiple times in a day. In the initial stages, it has to be taken 3 times a day, but in the later stages, it may need to be taken 5 or more times per day. It is sometimes difficult to remember to take each dose on time! It is somewhat inconvenient to take Levodopa. Nasuea: Some patients complain of nausea after taking levodopa. Carbidopa, which is always given with levodopa, does decrease nausea somewhat. High doses of levodopa can cause some people to become nauseous. Usually, levodopa should be taken on an empty stomach because food decreases its absorption. But If the nausea is so very severe, then taking levodopa with a small piece of bread can be permitted. It is mainly protein that hampers the absorption of levodopa, and bread does not contain a lot of protein. Sometimes, your doctor may prescribe medications such as domperidone for this problem. Lightheadedness: Some people may complain that when they take levodopa, they feel lightheaded. This feeling usually goes away. Sometimes, it is caused by a drop in blood pressure when standing up. In this case, drinking enough water (7-8 glasses/day if okay with your cardiologist/nephrologist), and getting up gradually helps a lot.This often is worst in the morning or night. When you get up from bed in the morning, first sit by the side of the bed for some time. Then stand up gradually and stand by the side of the bed for some time. And only after you spend some time standing and feel stable, start walking (after 30 seconds – 1 minute). Some people may feel a bit lightheaded after taking levodopa. Rarely, medications (e.g. fludrocortisone or Pyridostigmine) may need to be given for this problem. Fludrocortisone increases the amount of fluid in the body. No one completely understands how Pyridostigmine works in this scenario. But it is a safe and very effective medication to prevent this kind of drop in blood pressure. “Dyskinesias”: Earlier, some doctors used to believe that levodopa should be avoided in very early Parkinson’s disease. They were concerned that the early use of levodopa leads to the early development of abnormal movements called dyskinesias. However, most recent research shows that this is not a very valid concern. These movements are now believed to be due to the disease itself, rather than any particular medication. In very young patients, below 45 years of age, it may be reasonable to consider using drugs other than levodopa because of this concern. Dyskinesias are extra dance-like movements. Earlier, it was feared that levodopa worsens dyskinesias. However, this does not seem to be the case. Other side-effects: Since this book cannot be comprehensive, it is impossible to cover all side effects here. However, some patients report disturbed sleep etc. with levodopa – if you have any of these relatively rare side-effects you should make sure to talk about them with your doctor. Bottom-line: Since it is a potent, safe medication with minimal side-effects, levodopa is the most frequently prescribed medication for Parkinson’s disease. Caution: This information is not a substitute for professional care. Do not change your medications/treatment without your doctor’s permission.