Curated paper 2

Mental health has been overlooked compared to other areas in medicine. It has been overlooked by society as well (Kleinman, 2009). Mental health has been viewed as something that isn’t serious or is easily solved. Most people have heard “suck it up” and  “try not being sad”, when explaining their feelings. In the field of mental health there are brain diseases such as Alzheimer's, Parkinson’s, and schizophrenia which cannot be solved with words. However, possible treatments through medication may be the key to improving these brain diseases.

In the brain, neurons connect and communicate at synapses. At the synapses neurotransmitters carry information from one cell to another. Alzheimer’s disrupts this communication and destroys synapses and kills neurons (Medications for Memory). The death of the neurons can kill someone making Alzheimer's the sixth leading cause of death in the United States (2020 Alzheimer's disease facts and figures). Many may think they are not going to be affected by Alzheimer’s, but it does happen and can happen to anyone with the mutation (Alzheimer's disease and genes).

My grandfather was diagnosed with early onset Alzheimer's at 57. He died at 61 from complications of Alzheimer's. After examining his body after death, University of Utah found that he had rapidly progressive Alzheimer's. I was too young to remember much about my grandfather, but my parents told me my grandpa declined very quickly. One day he couldn’t find his car keys, the next he couldn’t find the car in the garage. My grandfather was a very gentle and kind man, but as his Alzheimer's developed, he became someone our family didn’t know. As his disease worsened, he became more violent which led to him biting and punching nurses. Although it was difficult for the family to see my grandfather decline rapidly, I realized we had it lucky. 

I worked in a nursing facility that specializes in memory loss. I worked there because I felt a calling after hearing of my grandfather's Alzheimer's stories. It was here, I realized that my family had it easier than most families. Although my grandfather's Alzheimer's experience was horrible, it was “rapid” because of his rapidly progressive Alzheimer's. Usually, Alzheimer's is prolonged about 8 years and develops around the mid 60’s (Kane & Marder, 1993). At least my grandfather's decline was quick compared to the residents I cared for. In my experience nearly every family expressed helplessness when witnessing their loved one deteriorate because there is nothing they could do (Treatments).

 Mayo clinic said that the promising leads for Alzheimer's treatments are not going to happen as quickly as they thought (What new Alzheimer's treatments are on the horizon, 2019). Current drug treatments for Alzheimer's disease include donepezil, rivastigmine, and galantamine. These drugs provide symptomatic relief, but poorly affect the progression of the disease. Recent changes in Alzheimer’s treatment have been directed to counteracting the progression of AD. Early detection is crucial to treat other slow progressing diseases, so the same idea is now applied to find better treatments for Alzheimer's. One of those ideas is to use  biomarkers to detect the early signs of  AD (Salomone, Caraci, Leggio, Fedotova, & Drago, 2012). Hopefully biomarkers prove to be promising. 

Parkinson’s disease is the second most common neurodegenerative disorder of aging and the most common movement disorder (Mhyre, Boyd, Hamill, & Maguire-Zeiss, 2012). Parkinson’s Disease (DP) is a progressive, neurodegenerative disorder of aging that affects motor and cognitive functions.(Fröhlich, 2016) Often Parkinson’s is seen as a disease that only affects motor function. However, it is found that people with Parkinson’s report memory loss, trouble finding words, and decreased attention. This is thought to be Parkinson’s disease dementia. The combination of Parkinson’s and dementia creates social and occupational complications because of the motor and cognitive impairment (Fact Sheet: Parkinson's Disease). 

PD was first described in 1827 by Dr. James Parkinson. He was able to identify that PD was different from multiple sclerosis and other disorders characterized by tremors (Goetz, 2011). Dr. Parkinson paved the path for the discovery of PD drug treatments because he was the first to document a clear medical description of the disease. In the early 19th century it was discovered that people suffering from PD had a dopamine deficit. This led to the first human trials of levodopa, an anticholinergic drug, being used to treat dopamine levels (Goetz, 2011). 

Recent treatments for Parkinson’s consists of reasonably understood medications that have proved to be effective in improving motor symptoms. Parkinson’s is also commonly treated with deep brain stimulation; however, the mechanism of how this works is poorly understood (Fröhlich, 2016). In a study, 300 patients were randomly assigned pramipexole or levodopa. They found that initially pramipexole resulted in significantly less on-off motor fluctuations compared to levodopa. However, they concluded that the Levodopa-treated group had a greater improvement in total UPDRS (Unified Parkinson Disease Rating Scale) compared with the pramipexole group. Although Levodopa has been in clinical use for many years, it is still the most effective medication available for treating the motor symptoms of PD (Pramipexole vs Levodopa as Initial Treatment for Parkinson Disease 2000). However, none of these drugs address the cognitive impairment of PD dementia. 

Usually PD dementia is not well known by the public. They think of PD as primarily a motor impairment. However Parkison’s disease also is recognized to have cognitive impairment symptoms as well. Cholinergic deficits, alpha-synuclein, and amyloid-protein contribute to the cognitive impairment in PD. Rivastigmine is the only licensed drug treatment for dementia in Parkinson’s disease (Svenningsson, Westman, Ballard, Aarsland, 2012). Parkinson’s may not have many drug options when it comes to treating cognitive impairment symptoms, but other brain diseases like schizophrenia have many drug options.

Another disease that the science community is trying to treat is schizophrenia. Schizophrenia affects the way someone thinks, feels, and behaves. People with schizophrenia may have lost their touch with reality. If left untreated the disease can disable them. Symptoms are usually diagnosed in the late teen years or the early thirties in male. Psychosis episodes are one of the first symptoms. It is also reported that hallucinations, delusions, and disorganized speech also happen (Schizophrenia). In 2014, 1.1 percent of the population or approximately 2.6 million adults in the United States aged 18 or older were affected by schizophrenia. An estimated 40 percent of individuals with the condition are untreated in any given year (Schizophrenia – Fact Sheet).

First-generation antipsychotics were developed in the 1950s while second-generation antipsychotics emerged in the 1980s (Abou-Setta). In the second-generation came rise to Clozapine, a medication that works in the brain to treat schizophrenia. Clozapine rebalances dopamine and serotonin to improve thinking, mood, and behavior. Clozapine is a long term medication and requires long term treatment when used for schizophrenia. Missing dosages can increase the risk of relapse in symptoms. Common side effects increased heart rate, low blood pressure, high blood pressure, drowsiness, sedation, dizziness, insomnia, vertigo, increased salivation, weight gain, constipation, nausea, vomiting, indigestion, and fever (Clozapine (Clozaril and FazaClo).

A study was done to evaluate the effects of long-term treatment with clozapine in 96 schizophrenic patients. All patients have taken other neuroleptics which were ineffective or caused side effects. A significant improvement in 43% and moderate improve in 38% of the patients was found. Common side effects were sedation, hypersalivation, weight gain, and obstipation. The paper concluded that clozapine is an effective antipsychotic drug that offers many advantages for schizophrenic patients. However, it stated that the risk to benefit ratio should be re-evaluated in long term studies (Lindström, 1988). 

After discussing brain diseases and the medications that can treat them, it’s clear to see we still have a long way to go. Although we have made progress in discovering new medications, improving upon these medications to treat these horrible brain diseases should continue to improve. Drugs like clozapine stimulated new ideas in medication development for schizophrenia (Kane & Marder, 1993). Hopefully, we continue to see improvements towards finding the most effective and least toxic drugs not only for schizophrenia, but for all brain diseases.

Work Cited

2020 Alzheimer's disease facts and figures. (2020). Alzheimer's & Dementia, 16(3), 391-460. doi:10.1002/alz.12068

Abou-Setta, A. M. (n.d.). First-generation versus second-generation antipsychotics in adults: Comparative effectiveness. Rockville, MD: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.

Alzheimer's disease and genes. (n.d.). Retrieved October 25, 2020, from https://www.alzheimers.org.uk/about-dementia/risk-factors-and-prevention/alzheimers-disease-and-genes

Clozapine (Clozaril and FazaClo). (n.d.). Retrieved October 25, 2020, from https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Clozapine-(Clozaril-and-FazaClo)

Fact Sheet: Parkinson's Disease. (n.d.). Retrieved from https://www.parkinson.org/sites/default/files/PD%20Dementia.pdf

Fröhlich, F. (2016). Parkinson's Disease. Network Neuroscience, 291-296. doi:10.1016/b978-0-12-801560-5.00023-9

Goetz, C. G. (2011). The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies. Cold Spring Harbor Perspectives in Medicine, 1(1). doi:10.1101/cshperspect.a008862

Kane, J. M., & Marder, S. R. (1993). Psychopharmacologic Treatment of Schizophrenia. Schizophrenia Bulletin, 19(2), 287-302. doi:10.1093/schbul/19.2.287

Kane, J. M., & Marder, S. R. (1993). Psychopharmacologic Treatment of Schizophrenia. Schizophrenia Bulletin, 19(2), 287-302. doi:10.1093/schbul/19.2.287

Kleinman, A. (2009). Global mental health: A failure of humanity. The Lancet, 374(9690), 603-604. doi:10.1016/s0140-6736(09)61510-5

Lindström, L. H. (1988). The effect of long-term treatment with clozapine in schizophrenia: A retrospective study in 96 patients treated with clozapine for up to 13 years. Acta Psychiatrica Scandinavica, 77(5), 524-529. doi:10.1111/j.1600-0447.1988.tb05164.x

Medications for Memory. (n.d.). Retrieved October 25, 2020, from https://www.alz.org/alzheimers-dementia/treatments/medications-for-memory

Mhyre, T. R., Boyd, J. T., Hamill, R. W., & Maguire-Zeiss, K. A. (2012). Parkinson’s Disease. Protein Aggregation and Fibrillogenesis in Cerebral and Systemic Amyloid Disease Subcellular Biochemistry, 389-455. doi:10.1007/978-94-007-5416-4_16

Pramipexole vs Levodopa as Initial Treatment for Parkinson Disease. (2000). Jama, 284(15), 1931. doi:10.1001/jama.284.15.1931

Salomone, S., Caraci, F., Leggio, G. M., Fedotova, J., & Drago, F. (2012). New pharmacological strategies for treatment of Alzheimer's disease: Focus on disease modifying drugs. British Journal of Clinical Pharmacology, 73(4), 504-517. doi:10.1111/j.1365-2125.2011.04134.x

Schizophrenia – Fact Sheet. (n.d.). Retrieved October 25, 2020, from https://www.treatmentadvocacycenter.org/evidence-and-research/learn-more-about/25-schizophrenia-fact-sheet

Schizophrenia. (n.d.). Retrieved October 25, 2020, from https://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml

Svenningsson, P., Westman, E., Ballard, C., & Aarsland, D. (2012). Cognitive impairment in patients with Parkinson's disease: Diagnosis, biomarkers, and treatment. The Lancet Neurology, 11(8), 697-707. doi:10.1016/s1474-4422(12)70152-7

Treatments. (n.d.). Retrieved October 25, 2020, from https://www.alz.org/alzheimers-dementia/treatments

What new Alzheimer's treatments are on the horizon? (2019, April 19). Retrieved October 25, 2020, from https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-treatments/art-20047780