Depression is common in patients with Parkinson’s disease (mean prevalence 17% in patients with Parkinson’s). It can be the first sign of the disease. It can be treated with antidepressants. There is little evidence that patients with Parkinson’s disease might benefit more from anyone particular class of antidepressants than any others. The problem with that is side-effects and interactions with the Parkinson medication. ECT is an option for the treatment of depression in Parkinson’s disease. It also helps for the motor symptoms although mostly temporary. As the disease progresses the motor symptoms return or become worse and here is when the Inspire support groups help in all these health issues.
Since Parkinson’s disease is mainly caused by the degeneration of parts of the dopaminergic system, antidepressants working on dopamine, dopamine agonist, might be useful for the treatment of depression in patients with Parkinson’s.
Recently a dopamine agonist was studied as treatment for depression in patients with Parkinson’s disease. Dr Shock favors placebo controlled trials. These are the trials of which we clinicians learn the most. The dopamine agonist studied was pramipexole.
Sustained administration of pramipexole can modify the spontaneous firing of dopamine, norepinephrine, and serotonin neurons in rat brains, suggesting that the therapeutic action of pramipexole might be attributed to increased dopaminergic and serotoninergic neurotransmission in the brain
This study was a 12 week randomized, double-blind, placebo controlled trial. Pramipexole was given in a dose of 0.125-1.0 mg three times per day and compared to placebo in patients with mild to moderate Parkinson’s disease. Patients from 76 centres in 12 European countries and South Africa were included if they were on stable antiparkinsonian therapy without motor fluctuations and had depressive symptoms.
The main outcome criterion was the decrease of the Beck Depression Inventory, a self rating severity scale for depression. BDI scores in the pramipexole group decreased from a mean of 18·7 at baseline to 13·1 at 12 weeks, compared with a decrease from 19·2 to 15·0 in the placebo group. . When adjusted for confounding variables the difference between the two conditions were only 2 points. This difference was significant but is it also clinical relevant?.
The problem with this study is that the focus was on depressive symptoms instead of depression. They used the Beck Depression Inventory and the geriatric depression scale for inclusion. Both screening and severity scales for depression not diagnostic scales. Also the use of their outcome criteria are hard to compare with the usual outcome in depression treatment studies. Mostly in these study diagnostic scales are used for inclusion and response is mostly defined by a 50% decrease in Hamilton Depression Rating Scale score. A better outcome criteria is remission which is mostly defined as a score of 10 or less on the 17 item version of the Hamilton Depression Rating Scale.
Although these results may seem promising as a scientist I really regret the lack of diagnosing depression and using not only self rating scale but also clinician rating scale. What do you think?
Bxarone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, Tolosa E, & Weintraub D (2010). Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet neurology, 9 (6), 573-80 PMID: 20452823
A great step forward, patients don’t have to be awake during the procedure. This video shows a clear description of the old and new procedure for deep brain stimulation (DBS). In the old procedure a frame has to applied after which a brain mapping procedure has to follow, up to 6-8 hours while the patient has to be awake. At the end the patient has to undergo a MRI to see whether the electrodes are in the right place. All very tedious and time consuming. The new procedure takes place in the MRI with anesthesia and takes less time (50%). Have a look at this new procedure in the video.
Is there new hope for Parkinson’s patients? Imaging scientist, Alastair Martin, and neurosurgeon, Dr. Paul Larson, have teamed up to develop a way to perform Deep Brain Stimulation surgery that’s more comfortable for the patients, more accurate and cuts the regular procedure time in half to 3 1/2 hours. The pair, working at the University of California in San Francisco perform DBI surgery while the patient is inside the MRI . The advantage to the procedure is that the patient does not have to be awake, it detects complications on the spot and allows for precise placement of the electrodes in the brain.
More recent news on deep brain stimulation on New Scientist: Smart implants may alleviate neurological conditions
SMART implants in the brains of people with neurological disorders could eventually help develop treatments for people with Parkinson’s disease, depression and obsessive compulsive disorder.
Related posts on this blog:
Chocolate is not an antidepressant. Interaction between chocolate and neurotransmitter systems in the brain, such as serotonin, that contribute to appetite, reward and mood regulation were studied but no antidepressant mechanism of chocolate was found.
Most possible psychoactive substances in chocolate are metabolized in the blood by an enzyme (monoamineoxydase A), these substances are unable to pass the blood brain barrier, they are metabolized before they can even reach this barrier. Beta-phenyl-ethylamine is the only possible psychoactive substance in chocolate that passes the blood brain barrier. It is a direct dopamine releasing ingredient. Moreover, cocoa contains caffeine and it’s structural derivatives, these components can have antiparkinsonian effects.
The consumption of chocolate is significantly higher in Parkinson’s Disease patients compared to controls, while consumption of non-chocolate sweets was similar in both groups
The consumption of chocolate was assessed using self questionnaires in patients with Parkinson’s disease (n= 274) and their partners as controls (n=234). Also the consumption of non-chocolate sweets was assessed. Also changes of chocolate and non-chocolate sweet consumption during the disease course was assessed in patients with Parkinson’s disease. All subjects were also asked to fill out the Beck’s depression inventory (BDI) and they were asked for depression in their medical history.
Both depression in medical history and BDI score was higher in the patient group but did not influence the higher chocolate use in patients with Parkinson’s disease. Also medication and other diseases such as diabetes mellitus did not significantly influence chocolate consumption.
A possible explanation for the higher chocolate consumption is patients with Parkinson’s disease might be the high content of biologically active compounds with potential antiparkinsonian effects in cocoa and thus chocolate, such as caffeine and its structural analogous and/or the presence of β-phenylethylamine. This last substance is a direct dopamine releasing ingredient, dopamine is short in Parkinson’s.
Possible limitations of this study:
Only patients from a university based department were included, recall bias or forgetting may play a role with filling out the questionnaire, the two groups were not comparable in age en gender.
Related posts on this blog:
Wolz, M., Kaminsky, A., Löhle, M., Koch, R., Storch, A., & Reichmann, H. (2009). Chocolate consumption is increased in Parkinson’s disease Journal of Neurology, 256 (3), 488-492 DOI: 10.1007/s00415-009-0118-9
Daniel Kraft demos his Marrow Miner — a new device that quickly harvests life-saving bone marrow with minimal pain to the donor. He emphasizes that the adult stem cells found in bone marrow can be used to treat many terminal conditions, from Parkinson’s to heart disease.
The research showed that the cells were able to differentiate into all types of stem cells.
Scientists said the discovery means that a drug that can treat many cancers, such as ovarian and pancreatic cancer, could be developed using embryonic stem cells, much similar to the stem cell therapy in orem ut that’s available to the public.
Remember that you have the option of getting stem cell therapy, which is a non surgical procedure that can help you if you are having difficulties with aging. Again, wanting to use anti-aging procedures is nothing wrong, but if there are cheaper alternatives, why not?
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The scientists were able to make human pluripotent stem cells by mixing stem cells taken from the blood of patients with embryonic stem cells from bone marrow, the journal said.
Stem Cell Therapy Charlotte NC believe that regenerative medicine / cellular therapeutics will play a large role in positively changing the natural history of diseases ultimately, we contend, lessening patient burdens as well as reducing the associated economic impact disease imposes upon modern society.
One of the two key ingredients used to make the pluripotent stem cells were human leukaemia cells.
They injected the human leukaemia cells into the mice which were used as a model for human leukaemia.
The researchers said the mice had the leukaemia cells as well as bone marrow.
One of the mice had a tumour on its head and another had a tumour on its back, but both of the tumours had been treated successfully with chemotherapy.
Terrific improvement especially since it delivers more than 10 times stem cell activity compared to the older method of harvesting bone marrow.
Thanks Clinical Cases and Images
- Deep Brain Stimulation (DBS) should only be used when there is a high change that the lives of patients will be improved by its use and when all other possible interventions have been tried
- Patients must be fully informed and informed consent must be obtained
- The whole procedure should be done by teams of appropriate specialists like neurosurgeons, neurologist, psychiatrist and other health professionals that can help the patient before during and after the operation and who will continuously monitor the patient
- The procedure should help restore (but not augment) normal function, should provide relief from pain and distress, and should never be used for law enforcement or for political or social purposes
- It is important to provide follow-up for every patient enrolled in a trial if at all possible and to report the outcomes in scientific journals
These ethical guidelines were recently published in the JAMA and I fully agree with these guidelines. The article starts with a brief description of DBS, it’s complications and a short history of the lessons from past errors of psychosurgery.
Important lessons from the abuses of psychosurgery in the last century make it imperative to have solid hypotheses with strong scientific support and appropriate safeguards (eg, interdisciplinary review boards) before proceeding to treat patients using DBS.
Using these guidelines with the recent technological advances DBS can perhaps help a lot of patients in the near future.
Kringelbach, M., & Aziz, T. (2009). Deep Brain Stimulation: Avoiding the Errors of Psychosurgery JAMA: The Journal of the American Medical Association, 301 (16), 1705-1707 DOI: 10.1001/jama.2009.551
Deep Brain Stimulation (DBS) is mostly used for Parkinson’s Disease. DBS for Obsessive Compulsive Disorder and Depression is just starting to be used. It is unclear how DBS works for Parkinson’s Disease. With DBS an electrical probe is inserted into the brain and it stimulates an area known as the subthalamic nucleus. This can help people with Parkinson’s disease overcome the disorder’s neurological block on movement.
But how does this stimulation work. Some researchers think the technique stimulates neurons that initiate movement. Others say it blocks inhibitory neurons, allowing brain signals to resume. And yet another theory holds that it influences the flow of information along axons — fibers that connect neurons to each other.
A recent study published in Science shows that deep brain stimulation exerts its effect on axons, specifically those that feed into the subthalamic nucleus, rather than on the neurons in the structure.
This is the experiment:
For the Science study, the team genetically engineered mice that have a condition that mimics Parkinson’s disease to produce light-responsive proteins only in certain cells in the brain. Then, the researchers inserted fiber optic threads into the mice’s brains. The team used a pulse of blue laser light to increase activity of the cells, or a burst of yellow laser light to quiet the cells. The scientists also used electrical probes to measure activity of the neurons.
When the researchers turned on the light in cells in the subthalamic nucleus nothing happened. But light stimulation of incoming axons improved the mice’s movements. Quieting activity of the axons made the movement disorder worse.
These findings sugests that to stimulate parts of the brain closer to the surface might be an alternative to deep brain surgery. This is a less invasive procedure than DBS.
In yet another Science publication the stimulation of the spinal cord in mice and rats could restore movement to rats and mice with Parkinson’s–like problems.
It’s good news for patients,” says Feng, who was not involved in either study. “Of course, it is not a cure.”
He says that the light-responsive techniques may help uncover the neural circuitry that leads to other psychiatric diseases, such as depression and obsessive-compulsive disorder, which are also sometimes treated with brain stimulation. And spinal cord stimulation or other minimally invasive therapies may offer psychiatric patients an alternative to deep brain surgery.
This will be continued but it will not stop the use of DBS for Parkinson’s disease and why should it, we don’t know how antidepressants work or ECT for that matter.
Thanks Science News
Gradinaru, V., Mogri, M., Thompson, K., Henderson, J., & Deisseroth, K. (2009). Optical Deconstruction of Parkinsonian Neural Circuitry Science DOI: 10.1126/science.1167093
Fuentes, R., Petersson, P., Siesser, W., Caron, M., & Nicolelis, M. (2009). Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson’s Disease Science, 323 (5921), 1578-1582 DOI: 10.1126/science.1164901
This is an important question. until now all medication for Parkinson’s disease relieved the symptoms of this disease for a while. The medication couldn’t prevent the progression of the disease resulting in lack of efficacy of the medication. Increasing the dosage until side-effects or adding another therapeutic temporarily resolved the symptoms until the progression again decreased their efficacy.
Hundreds of putative neuroprotective agents have been tested in clinical trials over the past two decades, but none of these agents has been successful at preventing the progression of PD.
In a recent Viewpoint in Nature Clinical Practice Neurology the authors claim that:
We believe that DBS will be the first therapy proven to slow PD progression, and that it must be applied in the earliest stages of the disease to have such an effect.
They base their opinion on the results of animal research. From these animal models it was learned that high frequency deep brain stimulation can be neuroprotective. The animals received DBS during ongoing neurodegeneration, which more accurately represents clinical practice and DBS at high frequency has inhibitory effects on this neurodegeneration.
Results from clinical trials are contradictory. In some trials no significant clinical deterioration during 4 years of DBS therapy could be found, while many trials have noted clinically and statistically significant deterioration of motor symptoms after initiation of DBS therapy.
The authors have stron arguments for these conflicting results:
First, continued functional decline does not eliminate the possibility of positive disease modification—it only eliminates the possibility that DBS might result in a complete halt in progression. Furthermore, none of the studies so far has included a control group that was treated with standard drug therapy, and, thus, progression rates between the two groups have not been compared.
An additional limitation is that all studies to date have been in patients with features of advanced PD, including motor complications of therapy. Currently, patients do not receive DBS therapy until they have developed intractable symptoms and motor complications of therapy; electrode implantation both in clinical trials and in standard of care takes place at an average of 11 years after diagnosis, at which point considerable cell death has occurred, and potentially neuroprotective strategies are unlikely to demonstrate a clear benefit.
The authors have started a pilot clinical trial (ClinicalTrials.gov identifier NCT00282152) to study the neuroprotective effects of DBS in Parkinson’s Disease. They will test the hypothesis that DBS slows the progression of early stage PD.
You can read some more about this trial on Viewpoint in Nature Clinical Practice Neurology.
Hope they will succeed in confirming their hypothesis for such a debilitating disease.
Charles, P., Gill, C., Davis, T., Konrad, P., & Benabid, A. (2008). Is deep brain stimulation neuroprotective if applied early in the course of PD? Nature Clinical Practice Neurology, 4 (8), 424-426 DOI: 10.1038/ncpneuro0848
There is a new blog with the written hands on experience of undergoing deep brain stimulation surgery: Focus on a Cure’s Deep Brain Stimulation (DBS) Journal
This blog is created in the hopes that my experiences will give others inspiration to take a risk and have the courage to face the unknown in order to accomplish the impossible as others have done for me.
Incredible good insight and information about the whole procedure, especially the whole process before deciding to undergo the procedure.
One thing I was surprised about that after all my research and all my conversations with other DBS patients and doctors no one mentioned the steel ball ear plug portion of the halo/frame procedure. During this portion I asked the surgeon why no one ever mentioned this part he told me it was because most people do not remember it. Well let me be truthful I remember ever second of it and I told him I was going blog about it and let the secret out.
On this blog plenty of posts about the use and indications for Deep Brain Stimulation and on Mind Hacks a short list of things that deep brain stimulation has been used to treat.
Thanks Jan at Medblog.nl
In short, we are getting older with many of us. In the next 50 years a lot of inhabitants of the world will be over 65 years. A lot of them will have Alzheimers disease or Parkinsons disease.
How and what to do until then? Watch the video.
Biochemist Gregory Petsko makes a convincing argument that, in the next 50 years, we’ll see an epidemic of neurological diseases, such as Alzheimer’s, as the world population ages. His solution: more research into the brain and its functions.