Trazodone Increases Motor Symptoms in Idiopathic Parkinson’s: A Case Report

“There are three constants in life… change, choice and principles.” Stephen Covey

“The night is the hardest time to be alive and 4 AM knows all my secrets.” Poppy Z. Brite

ABSTRACT
Trazadone is a widely used antidepressant drug that has been approved for many years; trazodone has been used to treat major depression. In a different scenario, trazodone has been used for treating insomnia due to its sedative effect. Unfortunately, trazadone occasionally has been shown to induce parkinsonism in patients previously undiagnosed with Parkinson’s. What is described here is a case study, of yours truly, where my motor symptoms were made worse following a short course of trazodone therapy (50 mg tablet/evening) that was prescribed for insomnia. New symptoms that became apparent during this treatment included:

• A shuffling gait with freezing.
• Dystonia in both lower and upper limbs.
• Muscle cramps in both calves.

In contrast to these new symptoms, the only symptoms I have ever experienced to date with Parkinson’s have been occasional lower right leg cramps, stiffness on my right side, and a right arm tremor. Stopping the trazodone led to a reversal of symptoms over the last 2-3 weeks, with some remaining shuffling of gait/freezing, which is reversed soon after taking my first-morning dose of carbidopa/levodopa. Thus, the main conclusion is that people(person)-with-Parkinson’s (PwP) should be aware of this potential side-effect of trazodone. This blog post is to spread awareness of the possible adverse effects of trazodone in PwP when using this well-known drug for insomnia. Please note that this case study of n=1 may not reflect how other PwP might react while taking trazodone. I still thought it was important to at least describe it in a blog post.

INTRODUCTION
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the older adult population. Approximately 90,000 new PD cases are diagnosed each year in the United States, adding to the 1.5 million people who presently are living in the USA with PD. Currently, there are a total of approximately 10 million people worldwide living with the disease. The symptoms of PD begin due to the progressive loss of dopamine-producing neurons in the brain’s substantia nigra pars compacta region. PD primarily presents as a movement disorder (symptoms including rigidity, slowness of movement, postural instability, and resting tremor); however, numerous co-morbid non-motor symptoms frequently also occur, and some examples include depression, psychosis, sleep disorders, dementia, lower gastrointestinal tract disturbances, urinary disturbances, and apathy. 

An especially troubling non-motor issue for many people (person)-with-Parkinson’s (PwP) is a sleep disorder. Sleep disorders in PD include the following: rapid eye movement (REM) sleep behavior disorder (RBD), insomnia/sleep fragmentation, excessive daytime sleepiness, restless leg syndrome, and obstructive sleep apnea. As one might expect, sleep disorders dramatically lessen the quality of life in PwP.  Although there is a growing appreciation for understanding sleep disorders in PD, we still lack, to some extent, the best-case scenario for treating the various sleep disorders in PD.

Trazadone is a trizolopyridine compound that was approved in 1981 by the Food and Drug Administration for managing major depressive disorders.  As with many older drugs, they have often been used and prescribed off-label for various uses. Trazodone has been widely used for its combined antidepressant and tranquilizing properties. Furthermore, trazodone has recently been used as a sleep aid without further testing. Trazadone has generally been found to be safe; however, the drug has been found to inhibit midbrain dopaminergic neurotransmitter activity. This short note is to describe my experiences with trazodone when prescribed for insomnia.

PATIENT DESCRIPTION
I saw a movement disorder specialist in early 2014 at the age of 59 and received a diagnosis of idiopathic PD. My presenting symptoms included a stiff right-side neck, a stiff right hand, and slowness of movement. I had a swallowing defect, and the volume of my voice was lessened. My right leg would drag when overly tired. My tremor was not like the typical PD tremor. I left the neurologist’s office with a prescription for a dopamine agonist, whereby I was provided substantial symptom relief.

By 2017, due to PD progression, the traditional therapy of carbidopa/levodopa was added to my regimen, along with a NeuPro dopamine agonist patch. Along this journey path, I dosed down and off of the dopamine agonist ropinirole, which has been described here in detail. Along with an increase in exercise, and a change in work to phased retirement and then to being retired, my daily regimen has remained steady for the last 4-5 years, which includes 2.5 tablets of carbidopa/levodopa (25 mg/100 mg) every 4 hours for four doses, and then two tablets at the end of the evening, and a daily 6 mg NeuPro patch. As has been previewed here on many occasions, I do take several supplements in an attempt to slow down the progression of the disorder.  

From 2014-present, I have only taken 1 step backward when challenged by the Neurologist in the pullback test. My cognitive level is still good, although remembering names is becoming more challenging. As my neurologist always asks, I do not get lost when driving my car around and coming back home, and I still dress myself every day. The most significant component to making my symptoms worse has been stress, which was the primary reason for my retirement (the expected roles in academic life can be very stressful).

RESULTS
Although there are slight hints of the progression of my PD, the biggest issue for me currently is trying to get more sleep. I have tried all sorts of treatment strategies, which also have been reviewed over the years in this blog. My new Family Practice physician and I talked it over recently, and she prescribed trazodone (50 mg tablet/evening) to treat my insomnia. I naively started taking it without first thinking I should look on the internet about this drug. My bad!

Trazodone worked well for me in inducing sleep. My usual sleeping habit may include 4-5 hours spread out over the evening. Trazodone allowed me anywhere from 6-9 hours of uninterrupted sleep. It was remarkable. However, two weeks into taking trazodone, I woke up one morning barely able to walk. I was only allowed small shuffling steps, and this had never happened before. Additionally, during the days before this happened, I had noticed some dystonia on both hands and feet, and muscle cramps in both legs (remember, I had only ever had problems with my right side). As soon as I was able to take my carbidopa/levodopa and add my NeuPro patch, the symptoms subsided. But I did notice, as I got to the end of the therapeutic phase of each carbidopa/levodopa dose, the shuffling returned.

I immediately did some Med-Line searches and found several papers where trazodone has promoted parkinsonism in patients, and one patient was subsequently diagnosed with idiopathic Parkinson’s. In all cases, upon stopping the drug, the symptoms eventually reversed themselves (usually a couple of weeks to several months). I stopped taking trazodone, and over the next two weeks, my symptoms improved. It should be noted that the worst symptoms, the shuffling and freezing gait, have slowly reversed, and it still melts away following my first carbidopa/levodopa dose. My old Neurologist in Chapel Hill said that all of the symptoms should reverse, but it may take 2-6 months.

DISCUSSION
Chemically induced parkinsonism happens, but it is still not well understood. In one case of trazodone-induced parkinsonism, it took 14 months for the full reversal of effects from the drug in one patient. My hope is that the reversal of my added symptoms continues and it is faster than described for this one particular patient. Clearly, I have some susceptibility factor to trazodone, so it will good for me to stay informed of any new drug that has a trizolopyridine-based structure.

This blog post is meant to warn other PwP who might be prescribed trazodone for their insomnia. Be careful, and I would advise to carefully consider the options of other drugs that can be used to help one sleep (a future blog in the planning stage ).

In conclusion, I took a single 50 mg/night dose of trazodone for insomnia. Trazodone worked well to improve my sleep time substantially. However, trazodone also had extrapyramidal function (a dopamine-receptor blocking agent) to block dopamine’s function, resulting in a substantial appearance of motor-related symptoms (shuffling gait with freezing, dystonia, and muscle cramping, to mention a few symptoms). Upon stopping the trazodone, my exaggerated symptoms have slowly reversed, especially when taking carbidopa/levodopa. On the one hand, we represent a unique patient population, and doing a little research beforehand may save one some difficult drug-induced effects not usually expected of that drug. On the other hand, many of you may already be taking trazodone with no impact on your symptoms. If so, great. Continue on, and do not stop taking trazodone. However, trazodone amplified my motor symptoms, but then again, I am a case of n=1. Regardless, be careful, remain safe, and stay healthy.

REFERENCES
Sarwar, Aliya Iftikhar. “Trazodone and parkinsonism: the link strengthens.” Clinical Neuropharmacology 41, no. 3 (2018): 106-108.

Albanese, Alberto, Paola Rossi, and Maria Concetta Altavista. “Can trazodone induce parkinsonism.” Clin Neuropharmacol 11, no. 2 (1988): 180-182.

Fukunishi, Isao, Tateki Kitaoka, Tetsuo Shirai, Kyoko Kino, Emiko Kanematsu, and Yoshikazu Sato. “A hemodialysis patient with trazodone-induced parkinsonism.” Nephron 90, no. 2 (2002): 222-223.

Fukunishi, Isao, Tateki Kitaoka, Tetsuo Shirai, Kyoko Kino, Emiko Kanematsu, and Yoshikazu Sato. “A hemodialysis patient with trazodone-induced parkinsonism.” Nephron 90, no. 2 (2002): 222-223.

Sharma, Kanishk Deep, Tony Colangelo, and Aaron Mills. “Trazodone-induced parkinsonism: A case report.” International Journal of Clinical Pharmacology and Therapeutics 60, no. 4 (2022): 184.

Hadi, Fatemeh, Elmira Agah, Samaneh Tavanbakhsh, Zahra Mirsepassi, Seyed Vahid Mousavi, Negin Talachi, Abbas Tafakhori, and Vajiheh Aghamollaii. “Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson’s disease and sleep disorders: a randomized, double-blind trial.” Neurological sciences 43, no. 10 (2022): 6141-6148.

“Each of our cells is a living entity, and the main thing that influences them is our blood. If I open my eyes in the morning and my beautiful partner is in front of me, my perception causes a release of oxytocin, dopamine, growth hormones – all of which encourage the growth and health of my cells. But if I see a saber tooth tiger, I’m going to release stress hormones which change the cells to a protection mode. People need to realize that their thoughts are more primary than their genes, because the environment, which is influenced by our thoughts, controls the genes.” Bruce H. Lipton

Cover photo Image by Rudy and Peter Skitterians from Pixabay