Healthy Living

Antidepressants for Parkinson's Disease

Antidepressants for Parkinson's Disease

Key Takeaways

  • Parkinson's disease is a neurological disorder. The disease affects the movement of muscles, their control, and balance.
  • Depression is a symptom of Parkinson’s disease. Studies have revealed that certain antidepressants help treat this symptom without making other symptoms worse.
  • There is no cure for Parkinson's disease, but there are medications that focus on controlling the symptoms.

Parkinson’s disease affects people of ages 55-75, although it may affect younger people, too. Parkinson's disease is a neurological disorder. This disease affects the movement of muscles, their control, and balance.

Symptoms of Parkinson’s Disease

  • Finding it difficult to walk, balance, and a lack of body coordination
  • Tremors in the hands, fingers, and certain parts of the body
  • Digestion-related problems
  • Slurred speech
  • Memory problems 
  • Difficulty in eating and swallowing food
  • Rigid muscles 

Selegiline

Selegiline belongs to the group of monoamine oxidase type B inhibitors. It is prescribed to control the symptoms of Parkinson’s disease. It is given to people who take a combination of levodopa and carbidopa. Selegiline helps increase the levels of dopamine in the brain.

Selegiline may help in the following ways:

  • Increases the length of time taken by levodopa and carbidopa to control the symptoms.
  • Decreases the needed dose to control the symptoms.
  • Stops the effects of levodopa and carbidopa from wearing off between the doses.

Selegiline comes in the form of capsules and tablets, which are orally taken. Selegiline should be taken twice at breakfast and lunch. It should be taken before breakfast and lunch without any food and drinks. Selegiline does not cure the disease as it only helps control the symptoms of the disease. There are also some side effects associated with the medication. If the side effects are severe or persist for a longer time, then a doctor should be consulted.

The side effects of selegiline are:

Some serious side effects may include:

An overdose may cause:

  • Drowsiness
  • Hyperactivity
  • Chest pain
  • Fast and irregular pulse
  • Seizures
  • Jaw tightness
  • Slow breathing
  • Fever

Rasagiline

This medication is used to treat symptoms of Parkinson’s disease. It can either be taken alone or in combination with other drugs. It can help control the symptoms and help to reduce the amount of “OFF” (decreased mobility and function) time. It belongs to a group of drugs known as monoamine oxidase B or MAO-B inhibitors, which work by increasing the levels of dopamine, norepinephrine, and serotonin in the brain. This medication is orally taken once daily with or without food.

The dosage also depends on the medical condition of the patient, response to the treatment, and other medications the patient is already taking. Some of the drug's side effects are:

Serious side effects may include:

  • Fainting
  • Loss of balance
  • Mental/mood changes
  • Muscle stiffness that may get worse
  • Twitching or uncontrollable movements
  • Swollen ankles or legs
  • Easy bruising or bleeding
  • Unusual strong urges

This medication may cause serotonin syndrome, which occurs when medications that enhance serotonin levels are also taken. Moreover, this drug may rarely cause an extremely high blood pressure or serious allergic reactions. If you experience any serious side effects, try to get medical help immediately.

Why are antidepressants used in Parkinson’s disease?

Depression is a symptom of Parkinson’s disease. Studies have revealed that certain antidepressants help treat this symptom without making other symptoms worse.

Researchers studied two antidepressants and found that both medications led to an improvement in depression. Depression is a major symptom of Parkinson’s disease, which significantly affects the quality of life. Depression is present in almost 50 percent of patients with Parkinson’s disease. Tricyclic antidepressants are older antidepressants, and their use is linked to heart problems and other side effects. 

A study was done on 115 patients with Parkinson’s disease and clinical depression. They were divided into three groups. The patients were given a maximum of 40 mg of paroxetine or 225 mg of venlafaxine daily. Paroxetine is an SSRI (selective serotonin reuptake inhibitor) and is known to increase the serotonin level in the brain, and thus, improve mood. Venlafaxine extended-release is a serotonin and norepinephrine reuptake inhibitor. It helps balance the two hormones and improves mood. The levels of depression of all the three groups were studied and evaluated throughout 12 weeks using the Hamilton Rating Scale for depression. It was found that those on antidepressants showed more improvements than those on placebo. 

Common Medications for Parkinson's Disease

The medications for Parkinson's disease fall under three categories:

1. Medications that increase the levels of dopamine in the brain

  • Dopamine-like Medications - They are available under the brand names Duopa, Parcopa, Rytary, and Sinemet (levodopa and carbidopa). Levodopa can effectively manage tremors as well as other motor symptoms at an early stage, but it can also cause serious side effects.
  • Dopamine Agonists - They include Apokyn (apomorphine), Mirapex (pramipexole), Neupro (rotigotine), Parlodel (bromocriptine), and Requip (ropinirole). These medications mimic the action of dopamine and can be taken either alone or with levodopa.
  • MAO-B Inhibitors - MAO enzyme breaks down dopamine in the brain. Its action is inhibited by MAO-B inhibitors. With their action, the dopamine level in the brain remains intact for use. MAO-B inhibitors include Azilect (rasagiline) and Eldepryl or Zelapar (selegiline).
  • COMT Inhibitors - Catechol-O-methyltransferase (COMT) breaks down dopamine in the brain, and its action is inhibited by COMT inhibitors such as Comtan (entacapone) and Tasmar (tolcapone). These drugs inhibit the action of another enzyme that breaks down dopamine.
  • Symmetrel (amantadine) - This drug may also increase the levels of dopamine in the brain.

2. Medications that control motor symptoms by affecting other neurotransmitters

  • Anticholinergics - They include Artane (trihexyphenidyl), Cogentin (benztropine), and Parsidol (ethopropazine). These drugs reduce the action of acetylcholine and can reduce tremors.

3. Medications that help to control non-motor symptoms

  • Antipsychotics - Psychosis has also been observed in patients with Parkinson's disease. The drug Nuplazid (pimavanserin) was approved in 2016 by the FDA to treat psychosis. This drug blocks serotonin receptors without making the symptoms worse.
  • Antidepressants - Used to treat depression in patients with Parkinson’s disease.
  • Stimulants - In Parkinson's disease, patient stimulants are used to treat excessive daytime sleepiness. 
  • Cholinesterase Inhibitors - Due to aging and Parkinson’s disease, a person may develop memory problems and dementia. Cholinesterase inhibitors are used to treat these conditions. These medications are also used to treat Alzheimer’s disease. They include Aricept (donepezil), Exelon (rivastigmine), Namenda (memantine) and Razadyne (galantamine).
  • Estrogen - Sometimes, post menopausal women with Parkinson’s disease are given this hormone.

Review

Currently, the transmission of monoamines is known to be increased by antidepressants such as serotonin, noradrenaline, or dopamine. But how it is achieved significantly differs among antidepressants.

However, the challenge for all healthcare providers is the effective treatment of the condition and its management. For moderate and severe depression, antidepressants are an appropriate treatment. The first-line agents are SSRIs due to their superior safety profile and better tolerability. However, the choice of medication depends on the interaction potential, adverse reaction profile, patient’s preference, and pharmacological properties.

Many problems may also occur because of antidepressants. The side effects associated with these medications include an increased risk of bleeding, hypernatremia, serotonin syndrome, and discontinuation symptoms. The patient should be closely monitored for these symptoms.

How do medications help?

Levodopa is also called as L-dopa. Carbidopa improves the action of levodopa by helping it get converted into dopamine in the brain. Also, carbidopa reduces the side effects associated with levodopa. Levodopa improves the quality of life and is effective against rigidity and slowness.

An enzyme that degrades dopamine is monoamine oxidase. Selegiline blocks the action of this enzyme.

In the initial stages of treatment, another MAO-B inhibitor called rasagiline is used in combination with L-dopa. It is used for moderate to advanced cases of Parkinson’s disease.

The area of the brain where Parkinson’s disease is thought to originate is the substantia nigra. Dopamine receptors in are stimulated by dopamine agonists in this part of the brain. These drugs also delay motor complications during the initial years of treatment.

Entacapone is a catechol-O-methyl transferase (COMT) inhibitor, which is also known to increase the amount of dopamine in the brain.

In the early stages of the disease, anticholinergic drugs were used to control tremors. They were the first drug used to treat Parkinson’s disease. However, they have been largely replaced by dopamine drugs these days.

For patients with early mild symptoms, amantadine can be used and can stimulate the release of dopamine in the brain, and thus, help against muscle rigidity and slowness.

Treating the Onset of Parkinson’s Disease

  • Motor problems can be improved by increasing dopamine concentration with the help of levodopa.
  • Dopamine in the brain can be stimulated by dopamine agonists.
  • Initial therapy may include the use of selegiline and rasagiline, which are MAO-B inhibitors.

Treatment of "OFF" Time

  • Entacapone is a catechol-O-methyl transferase (COMT) inhibitor. The enzyme that blocks dopamine is degraded by this inhibitor, thereby extending the effects of levodopa.
  • The break down of dopamine that is naturally produced in the brain and produced from levodopa is also delayed or slowed down by rasagiline.

Treatment of Other Symptoms

  • Depression - Antidepressants such as tricyclics are used.
  • Psychotic Side Effects - Clozapine and quetiapine are given to treat schizophrenia.
  • Dementia - Donepezil and rivastigmine are in some cases used for Parkinson’s disease.
  • Daytime Sleepiness and Fatigue - Modafinil can be helpful when it comes to treating sleepiness related to Parkinson’s disease.
  • Erectile Dysfunction - Sildenafil, tadalafil, and vardenafil can be beneficial for men who are suffering from erectile dysfunction due to Parkinson’s disease.
  • Drooling - Scopolamine and injections of botulinum toxin into the parotid and submaxillary glands can also be used.

Side Effects

1. Levodopa With or Without Carbidopa 

The toxic effects are considerable. The related physical side effects would include hair loss. Other side effects are:

  • Dyskinesia - It affects the limbs, face, tongue, mouth, and neck. It can cause uncontrolled movements of arms and legs or cause chorea. It is a very distressing side effect.
  • Low Blood Pressure - During the first few weeks, hypotension is common, especially if the initial dose is too high.
  • Gastrointestinal Problems - The common side effects of carbidopa are stomach and intestinal problems. If the drug is taken with food, then it can alleviate nausea. Some doctors also recommend not to eat any proteins until nighttime since this drug can cause interference with the intestinal absorption of levodopa. It may also cause gastrointestinal bleeding.
  • Lung Function Issues - Normal breathing function may get disturbed.

If levodopa is used in combination with other drugs, it may cause psychiatric and mental side effects such as:

  • Vivid dreams and hallucinations
  • Anxiety and sleep attacks
  • Confusion
  • Mixed effects on learning

2. MAO-B Inhibitors

  • Orthostatic hypotension - It causes dizziness and lightheadedness due to a sudden drop in blood pressure.
  • High blood pressure
  • Heartbeat becomes irregular or heart rhythm becomes abnormal

3. Dopamine Agonists

The side effects are very rare but may be severe. They include:

  • Gastrointestinal tract issues
  • Congestion of the nasal passage
  • Orthostatic hypotension
  • Headache that can get severe over time
  • Sudden case of sleep attacks

4. Catechol-O-Methyltransferase (COMT) Inhibitors 

5. Anticholinergic Drugs

  • Nausea
  • Urinary retention
  • Constipation
  • Blurred vision
  • Increased heart rate
  • Severe constipation
  • Mental problems such as memory loss, confusion, and hallucinations

6. Amantadine

  • Swollen ankles 
  • Mottled skin
  • Signs of hallucinations

Rehabilitation Therapies

  • Exercise Programs - Passive exercises are exercises that include stretching and manipulation of the muscles. The main aim of the exercise is to prevent the muscles from shortening. Active exercises include a range of motion, coordination, and speed.
  • Gait Training - Practicing methods of standing, turning, and walking, which will help reduce the risks of falls and help retain balance.
  • Reduce Muscle Freezing - Incidences of muscle freezing can be reduced by practicing certain daily activities.
  • Mental Tasks - This activity can be done by selecting any hobby that requires finger and hand mobility. One should also practice deep breathing techniques and relaxation exercises such as meditation to calm the mind.

Equipment and Assistive Devices

  • Rails can be installed, so that the patient can get up or go down from the bed or bathroom with support.
  • Chairs should have straight backs, armrests, and firm seats.
  • Sliding boards can also be helpful to slide out of the bed.
  • Wheelchairs
  • Electric beds or mattresses