I'm looking any experience of EPS ( in particular Resting Tremor, Rigidity and Micrographia) developed following long-term treatment with paroxetine
I would not even attempt to answer your question without more information. Why do you suspect symptoms of idiopathic PD would be due to longterm use of paroxetine? What is the age of the patient? What does the patient do for a living (occupation)? Have they ever lived on a farm? Have they ever abused recreational drugs such as methamphetamime? Do they have a positive family history of Parkinson's disease, parkinsonism or any other neurodegenerative disorder? Does the patient respond favorably to dopaminergic therapeutics?
Male, 54 yo, lawyer, no substances abuse , no positive famiiarity for neurodegenerative disorder. He is taking paroxetine 10 mg /die and lorazepam 2.5 mg /die since over 15 years for a cronic GAD. The discontinuation of treatment such as the administration of anticholinergics as well results in improvement of the symptoms of Parkinsonism. 18F-DOPA PET result was not suggestive of PD
The diagnosis of PD remains a clinical diagnosis. 18F-DOPA PET imaging is a very good research tool however, given that the imaging changes seen early in the clinical course of the PD may be less than 10% different from those seen in a healthy control, the results of such studies must be used with caution in a clinical setting. How was it determined that the PET scan in this case was abnormal? Was the patient's data compared with that from a normative control group or just with a single healthy control subject? Has the patient been given a trial of carbidopa levodopa to determine his clinical response to dopaminergic therapeutics?
Of course there is clinical response to dopaminergic therapeutics, but my question is if this Parkinsonism can be determined by long term use of paroxetine or it's just an idiopathic PD
The age at onset is a little younger than average. Based on this aforementioned observation, the only question in my mind would be: Did the use of paroxetine contribute to the subclinical progression of an idiopathic disease process by increasing oxidative stress to thereby result in a younger than expected age at onset? That said, there is some data to suggest paroxetine may actually be neuroprotective at least in animal models of PD (https://www.ncbi.nlm.nih.gov/pubmed/20566832). Adult rats treated with paroxetine showed an upregulation the antioxidant enzymes, carbonyl reductase 3 (CBR3) and aldose reductase (AR), suggesting a possible neuroprotective effect (http://journal.frontiersin.org/article/10.3389/fphar.2013.00086/full). Based own these data and your description of the patient I find it hard to hypothesize that paroxetine contributed to the symptoms seen in this patient. I reserve the right to alter my opinion if you can provide additional data that I am not currently aware of.
I agree with your reasoning at all.
Thank you so much for your contribution, it was really helpful to me.
Francesco
Selective serotonin-reuptake inhibitors (SSRIs) have been reported to induce extrapyramidal signs and symptoms especially in the elderly.
Here is an interesting study about it : Am J Geriatr Psychiatry. 2000 Summer;8(3):226-31.
Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A prospective double-blind study in depressed elderly patients.
Very interesting this study... at last it does strengthen the thesis of the colleague Marcia.
Thank you for your spot Vasileios
I think that Paroxetine rather unmasked the tremor of PD. Anecdotical evidence (unfortunately unpublished): during my stay at a gerontopsychiatrical ward, we saw three patients in a row rehospitalized for recurrence of a depressive episode fulfilling the DSM-criteria. The episodes before that event had reacted fine to tricyclics, but our department head wanted to avoid anticholinergic side effects and put them on paroxetine. All developed parkinsonian tremor within days, which ceased after stopping. Afterwards, depression was well-controlled by L-DOPA-treatment.
Thanks for sharing your experience Dirk, It seems that SSRI in monotherpy would act as a protective factor against Parkinsonism , while in risk subjects such as those taking antipsychotics drugs they seem instead to unmask PD
Another concern might be whether there was a drug-drug interaction with the SSRI. We once reported a patient who developed parkinsonism associated with the combination of fluoxetine and cimetidine (patients can now purchase the latter drug over-the-counter in the US). See J Geriatr Psychiatry Neurol 1995;8:231-233.
Drug-drug interaction is certainly an element to be considered at all times. In fact the outcome of a drug interaction can be harmful to the patient as the interaction may causes toxicity or a decrease in efficacy. Although there are literally thousands of potential drug interactions that have been described in the literature, de facto relatively few are likely to cause serious problems in most patients. In this specific case the patient has been following the same therapy without any modification for many years so I think it is unlikely that the cause of the side effects is to be sought in drug interactions.
Thank you so much for your interest and contribution to this case
According to the title of this thread, this case presented herein resulted after long-term treatment with paroxetine which indicates to me that the clinical manifestations are unlikely to be related to a drug-induced change in neurotransmission per se. Most cases of DIP emerge in close chronological relationship to starting the patient on a drug. The insidious emergence of extrapyramidal symptoms which are not reversible with cessation of exposure following long-term use of paroxetine continues to suggest to me that the symptoms observed in this patient are idiopathic and unlikely to be related to the drug. Furthermore, the clinical response to dopaminergic therapeutics observed in this case suggests there is loss of dopaminergic neurons in the substantia nigra pars compacta.
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