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Levodopa remains the staple for Parkinson's

Clinical Update: Parkinson's Disease - In his latest Clinical Update, Gary Culliton reports on the various treatment options available for patients with Parkinson's disease, and examines the latest research targeting diseased neurons and the potential of stem-cell transplantation

The medication options for Parkinson’s disease are many and varied. The leading agent is levodopa (L-dopa), in the form of Sinemet, Madopar and Stalevo. This directly replaces the dopamine chemical that is lacking in the brain. It is not necessarily used immediately on diagnosis; the stage at which it is introduced depends on the patient.

The traditional view has been that L-dopa medications were of most value if their use was deferred until the patient was in relatively poor condition. There is now a school of thought that believes this medication should be used earlier, so that the patient gets most benefit and the best quality of life.

Held in reserve
L-dopa can sometimes be held in reserve, but not for as lengthy a period as was once the case. “I would use L-dopa as required by the individual and in particular if he or she is falling,” said Dr Tim Lynch, Consultant Neurologist at the Mater Misericordiae University Hospital, Dublin.

L-dopa agents are often very effective initially, but there is a ‘wearing off’ effect in the majority of patients. The pills can also work excessively sometimes. There can be dyskinesias and other complications.

Different formats can lengthen the action of the L-dopa. Preparations include Sinemet (carbidopa-levodopa) and Madopar (levodopa-benserazide). Stalevo is a combination of Sinemet and Comtess (entacapone).

Dopamine agonists stimulate the dopamine D2 receptors in the brain, which are studded around the basal ganglia (automatic centre for movement). These include bromocriptine, pramipexole, ropinirole and rotigotine (which is available via a patch).

Formats include two long-acting, once-per-day pills and three-times-per-day pills. The medication may have to be stopped if there is sudden-onset sleep.

There are three pathways that break down dopamine in the brain, some of which can be blocked. Comtess works by blocking an enzyme called catechol-omethyl transferase (COMT), which breaks down levodopa. This means that more levodopa can enter the brain.

“The data is good that the levodopa remains in the brain for longer,” Dr Lynch added.
There is a debate over whether such pills should be introduced earlier and some trials are ongoing in that area.

A ‘cheese effect’
The monoamine oxidase (MAO) system breaks down dopamine in the brain. The MAO system has both MAO-A and MAO-B as isoforms of this enzyme and blocking both can result in a ‘cheese effect’ – hypertension caused by an interaction of the inhibitor with tyramine.

The old-fashioned antidepressants also blocked the MAO-A system. The MAO-B inhibitors selegiline (Eldepryl) and rasagiline (Azilect) only block one component of the enzyme and do not have this risk.

The aim is to optimise the amount of dopamine present in the brain and the length of time it remains.

In general, Dr Lynch would tend to use MAO-B inhibitors sooner rather than later. They are mild agents and usually well tolerated, he said.

A study (ADAGIO, NEJM) released at the end of last year has prompted debate on whether these inhibitors slow down Parkinson’s.

The study proposes that deterioration was slowed in people who were given rasagiline early. It suggests they needed L-dopa later than might have been expected.

Anti-cholinergics can be particularly effective for tremors, which is the hardest Parkinson’s symptom to treat. Amantadine is a fairly old drug, which was used originally as an anti-viral agent. It can be helpful in some patients who are on L-dopa and who are experiencing dyskinesias. Dr Lynch has a number of patients on a combination of therapies.

Constipation
Constipation has to be treated and low blood-pressure may need to be taken into account. Low doses of benzodiazepines used intermittently can be helpful in stress situations.

Other treatments include deep brain stimulation (DBS) surgery, which can ‘reverse’ the effects of disease progression by up to five years, in correctly chosen patients. DBS can be highly effective in combating tremor among patients who have had a good response to L-dopa, and it is effective in removing dyskinesias.

DBS therapy
Some patients require DBS therapy to block dyskinesias associated with foetal cell transplant. There are clearly issues of ethics and supply, but this data is likely to be used when stem-cell therapy becomes possible.

A Swedish group (Lindval O. et al.) has led the way in this area. There are two trials ongoing in the US, led respectively by Stanley Fahn (Columbia – working with a group from Denver) and Warren Olanow (Mount Sinai).

Both trials found the tissue took well, particularly in younger patients, but it was less effective in older patients.

Genetics may contribute to between 30 per cent and 50 per cent of all Parkinson’s cases. Gene therapy might potentially be applicable to the familial forms of Parkinson’s. The gene deficit needs to be identified and some form of gene therapy may then be employed.

Posted in Mental Health & CNS on 05 February 2010
Tags: Parkinson’s disease

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abortion, accupuncture, ACE inhibitors, acne, ADHD, alcohol, allergies, Alzheimer's, anaemia, anaethesia, anorexia, antibiotics, antidepressants, antihistamine, anxiety, appetite control, arthritis, ASCOT, aspirin, asthma, atherosclerosis, autism, autoantibodies, back pain, beta carotene, beta-blockers, bipolar disorder, birth, bleeding, blindness, blood pressure, body dysmorphic disorder, body mass, breast cancer, breast feeding, bronchitis, Caesarean section, calcium, cancer, carcinogens, carcinoma, cardiac syncope, cardiolgy, cataracts, cervical cancer, chemotherapy, child psychiatry, children, cholesterol, clinical trial, clopidogrel, Clostridium difficile, cognitive behavioural therapy, colectomy, colic, colorectal cancer, complementary and alternative therapies, contraception, COPD, coronary care, coronary stents, Crohn's, cystic fibrosis, defibrillator, dementia, depression, dermatology, diabetes management, diet, disability, DNA, Down's syndrome, eating disorders, echinacea, ECT, eczema, elderly people, endoscopy, epilepsy, erectile dysfunction, euthanasia, exercise, fat, fertility, fitness, flu pandemic, fluoxetine, folic acid, food labelling, fracture, fragile X syndrome, general surgery, genetics, gerontology, GIK infusion therapy, GORD, gout, haemodialysis, hearing, heart attack, heart disease, heart failure, heart health, hepatitis, HIV, hospital care, HPV, HRT, hyperglycaemia, hypertension, hypoglycaemia, IBD, ICU, incontinence, infant, infant mortality, infection, inflammatory bowel disease, influenza, invasive candidiasis, IQ, Irish Heart Foundation, irritable bowel syndrome, keyhole surgery, kidney disease, laser, learning difficulties, leukaemia, liver disease, lumbar disk herniation, lung cancer, lung disease, lymph nodes, macular degeneration, macular oedema, magnetic resonance imaging (MRI), malaria, malnutrition, Marfan syndrome, media, medical ethics, medical research, medication, meningitis, mental illness, metabolic syndrome, migraine, miscarriage, mortality rate, MRSA, multiple sclerosis (MS), NCHDs, nephrology, neurology, OAB, obesity, obstetrics, occupational health, ocular medicine, omega-3, opthalmology, oral cancer, organ transplantation, orthopaedics, osteoporosis, otolaryngology, ovarian cancer, paediatrics, pain management, pancreatic cancer, panic, Parkinson’s disease, patient safety, patient-physician communication, personality disorders, physiotherapy, plastic surgery, polio, practice, pre-eclampsia, pregnancy, preventative health care, probiotics, prostate cancer, psoriasis, psychiatric admission, psychiatry, psychotherapy, PTSD, public health, quality of life, radiology, radiotherapy, rectal cancer, reproductive health, research, resuscitation, rheumatoid arthritis, rheumatology, rhinitis, salt, SARS, schizophrenia, screening, seizures, self harm, sexual abuse, sexual health, sexually transmitted infections, SGA, sinusitis, skin cancer, sleep disorders, smoking, smoking ban, spinal injury, sports medicine, statins, stem cells, stress, stroke, substance abuse, suicide, supplement, surgery, syncope, technology, teenagers, testosterone, thoracic surgery, thrombosis, thyroid cancer, tonsillectomy, tonsillitis, Tourette's syndrome, toxicology, travel medicine, tuberculosis, tumour angiogenesis, type 1 diabetes, type 2 diabetes, ulcer, ulcerative colitis, urinary incontinence, vaccine, vitamins, weight, WHO, women's health, World Health Assembly

«Previous article | Next article»

Levodopa remains the staple for Parkinson's

Clinical Update: Parkinson's Disease - In his latest Clinical Update, Gary Culliton reports on the various treatment options available for patients with Parkinson's disease, and examines the latest research targeting diseased neurons and the potential of stem-cell transplantation

The medication options for Parkinson’s disease are many and varied. The leading agent is levodopa (L-dopa), in the form of Sinemet, Madopar and Stalevo. This directly replaces the dopamine chemical that is lacking in the brain. It is not necessarily used immediately on diagnosis; the stage at which it is introduced depends on the patient.

The traditional view has been that L-dopa medications were of most value if their use was deferred until the patient was in relatively poor condition. There is now a school of thought that believes this medication should be used earlier, so that the patient gets most benefit and the best quality of life.

Held in reserve
L-dopa can sometimes be held in reserve, but not for as lengthy a period as was once the case. “I would use L-dopa as required by the individual and in particular if he or she is falling,” said Dr Tim Lynch, Consultant Neurologist at the Mater Misericordiae University Hospital, Dublin.

L-dopa agents are often very effective initially, but there is a ‘wearing off’ effect in the majority of patients. The pills can also work excessively sometimes. There can be dyskinesias and other complications.

Different formats can lengthen the action of the L-dopa. Preparations include Sinemet (carbidopa-levodopa) and Madopar (levodopa-benserazide). Stalevo is a combination of Sinemet and Comtess (entacapone).

Dopamine agonists stimulate the dopamine D2 receptors in the brain, which are studded around the basal ganglia (automatic centre for movement). These include bromocriptine, pramipexole, ropinirole and rotigotine (which is available via a patch).

Formats include two long-acting, once-per-day pills and three-times-per-day pills. The medication may have to be stopped if there is sudden-onset sleep.

There are three pathways that break down dopamine in the brain, some of which can be blocked. Comtess works by blocking an enzyme called catechol-omethyl transferase (COMT), which breaks down levodopa. This means that more levodopa can enter the brain.

“The data is good that the levodopa remains in the brain for longer,” Dr Lynch added.
There is a debate over whether such pills should be introduced earlier and some trials are ongoing in that area.

A ‘cheese effect’
The monoamine oxidase (MAO) system breaks down dopamine in the brain. The MAO system has both MAO-A and MAO-B as isoforms of this enzyme and blocking both can result in a ‘cheese effect’ – hypertension caused by an interaction of the inhibitor with tyramine.

The old-fashioned antidepressants also blocked the MAO-A system. The MAO-B inhibitors selegiline (Eldepryl) and rasagiline (Azilect) only block one component of the enzyme and do not have this risk.

The aim is to optimise the amount of dopamine present in the brain and the length of time it remains.

In general, Dr Lynch would tend to use MAO-B inhibitors sooner rather than later. They are mild agents and usually well tolerated, he said.

A study (ADAGIO, NEJM) released at the end of last year has prompted debate on whether these inhibitors slow down Parkinson’s.

The study proposes that deterioration was slowed in people who were given rasagiline early. It suggests they needed L-dopa later than might have been expected.

Anti-cholinergics can be particularly effective for tremors, which is the hardest Parkinson’s symptom to treat. Amantadine is a fairly old drug, which was used originally as an anti-viral agent. It can be helpful in some patients who are on L-dopa and who are experiencing dyskinesias. Dr Lynch has a number of patients on a combination of therapies.

Constipation
Constipation has to be treated and low blood-pressure may need to be taken into account. Low doses of benzodiazepines used intermittently can be helpful in stress situations.

Other treatments include deep brain stimulation (DBS) surgery, which can ‘reverse’ the effects of disease progression by up to five years, in correctly chosen patients. DBS can be highly effective in combating tremor among patients who have had a good response to L-dopa, and it is effective in removing dyskinesias.

DBS therapy
Some patients require DBS therapy to block dyskinesias associated with foetal cell transplant. There are clearly issues of ethics and supply, but this data is likely to be used when stem-cell therapy becomes possible.

A Swedish group (Lindval O. et al.) has led the way in this area. There are two trials ongoing in the US, led respectively by Stanley Fahn (Columbia – working with a group from Denver) and Warren Olanow (Mount Sinai).

Both trials found the tissue took well, particularly in younger patients, but it was less effective in older patients.

Genetics may contribute to between 30 per cent and 50 per cent of all Parkinson’s cases. Gene therapy might potentially be applicable to the familial forms of Parkinson’s. The gene deficit needs to be identified and some form of gene therapy may then be employed.

Posted in Mental Health & CNS on 05 February 2010
Tags: Parkinson’s disease