Reduction of Parkinsonism and Psychosis with Mirtazapine: A Case Report

Godschalx-Dekker, Judith; Siegers, H. P.

doi:10.1055/s-0034-1367014

Cited by 27 publications

(10 citation statements)

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“…Several adrenergic and serotonergic agonists are garnering attention for reducing impulsivity in laboratory rats and humans [50–52], additional experimentation with the current model using receptor-selective compounds will be particularly informative. Nonetheless, given the clinical reports showing the efficacy and tolerability of mirtazapine for treating psychiatric disorders in PD patients [25–30], our results indicate that further investigations into the utility of mirtazapine for treating PPX-induced ICDs are warranted.…”

Section: Discussionmentioning

confidence: 90%

“…Mirtazapine, an atypical antidepressant, reduces behaviors associated with substance use disorders in rats [18–22] and humans [23,24]. Moreover, mirtazapine has been used to treat anxiety, depression, and psychosis in PD patients, and is well-tolerated by PD patients on dopamine agonist therapy with little to no effect on the motor benefits afforded by the agonist [25–30]. This latter feature likely reflects the lack of mirtazapine binding to dopaminergic receptors [31,32].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease

Holtz

Tedford

Persons

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Pramipexole and ropinirole are dopamine agonists that are efficacious in treating motor disturbances of neuropathologies, e.g., Parkinson’s disease and restless legs syndrome. A significant portion of treated patients develop impulsive/compulsive behaviors. Current treatment is dose reduction or switching to an alternative dopamine replacement, both of which can undermine the motor benefits. Needed is a preclinical model that can assist in identifying adjunct treatments to dopamine agonist therapy that reduce impulsive/compulsive behaviors without interfering with motor benefits of the dopamine agonist. Towards that objective, the current study implemented a rat model of Parkinson’s disease to behaviorally profile chronically administered pramipexole. This was accomplished with male Sprague-Dawley rats wherein (i) 6-hydroxydopamine-induced lesions of the dorsolateral striatum produced Parkinson’s disease-like akinesia, measured in the forelimbs, (ii) intracranial self-stimulation–mediated probability discounting indicated impulsivity/risk-taking, and (iii) two doses of pramipexole were continuously administered for 14–28 days via osmotic minipumps to mirror the chronic, stable exposure achieved with extended release formulations. The atypical antidepressant, mirtazapine, is known to reduce behaviors associated with drug addiction in rats, thus, we demonstrated model utility here by determining the effects of mirtazapine, on pramipexole-induced motor improvements versus probability discounting. We observed that forelimb akinesia subsequent to striatal lesions was attenuated by both pramipexole doses tested (0.3 and 1.2mg/kg/day) within 4hr of pump implant dispensing 0.3mg/kg/day and 1h by 1.2mg/kg/day. By contrast, 12–14 days of infusion with 0.3mg/kg/day did not alter discounting, but increases were obtained with 1.2mg/kg/day pramipexole, with 67% of 1.2mg/kg/day-treated rats meeting categorical criteria for ‘high risk-taking’. Insertion of a second minipump delivering mirtazapine did not alter motor function during 14 days of co-administration with pramipexole, but was sufficient to attenuate risk-taking. These outcomes revealed distinct probability discounting and anti-akinesia profiles for pramipexole, indicating that pharmacotherapy, (e.g., mirtazapine treatments), can be developed that reduce risk-taking while leaving motor benefits intact.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease

Holtz

Tedford

Persons

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Although, occasionally, atypical antipsychotics other than clozapine and quetiapine are still being used, the evidence for lack of efficacy and risk of motor worsening has been confirmed further . A single case report by Godschalx‐Dekker and Siegers using the 5HT‐2 A and 5HT‐2C antagonist, mirtazapine, claimed reduction of psychosis in PD without concomitant depression, but there are no trials . Electroconvulsive therapy (ECT) has not been studied in controlled trials, but a recent case series reported improvement in patients with PD and severe psychosis who did not respond to pharmacological treatments .…”

Section: New Treatments and Discoveriesmentioning

confidence: 99%

New clinical trials for nonmotor manifestations of Parkinson's disease

Schrag¹,

Sauerbier

Chaudhuri

2015

Movement Disorders

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Nonmotor manifestations in Parkinson's disease (PD) encompass a range of clinical features, including neuropsychiatric problems, autonomic dysfunction, sleep disorders, fatigue, and pain. Despite their importance for patients' quality of life, the evidence base for their treatment is relatively sparse. Nevertheless, the last few years have seen a number of new trials starting that specifically address nonmotor features as an outcome measure in clinical trials. Large randomized, controlled trials in the last 3 years reported improvement of psychosis with the new selective serotonin 5‐HT2A inverse agonist pimavanserin and of postural hypotension with the oral norepinephrine precursor droxidopa. Smaller new randomized, controlled trials support the effectiveness of Deep Brain Stimulation and opiates for pain, of rivastigmine for apathy and piribedil for apathy post‐DBS, group cognitive behavioral therapy for depression and/or anxiety, continuous positive airway pressure for sleep apnea in PD and doxepin for insomnia, and of solifenacin succinate and transcutaneous tibial nerve stimulation for urinary symptoms. A number of new smaller or open trials as well as post‐hoc analyses of randomized, controlled trials have suggested usefulness of other treatments, and new randomized, controlled trials are currently ongoing. © 2015 International Parkinson and Movement Disorder Society

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“…Mirtazapine (30 mg p.o. hs) was also effective at reducing visual hallucinations in a 67-year-old man with PD previously treated without success with clozapine, quetiapine, and rivastigmine [529]. Similarly, mirtazapine (15 mg p.o.…”

Section: Net Inhibitorsmentioning

confidence: 99%

Monoamine Reuptake Inhibitors in Parkinson’s Disease

Huot

Fox

Brotchie

2015

Parkinson's Disease

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The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia.

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Reduction of Parkinsonism and Psychosis with Mirtazapine: A Case Report

Abstract: Therapeutic effects of medication with strong antagonism for 5HT-2 A and 5HT-2C, like mirtazapine, mianserine, trazodone and nefazodone, in Parkinson-related diseases should be subject for further research. Serotonin might be associated with psychosis in Parkinson-related disease.

Cited by 27 publications

References 10 publications

Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease

Pharmacologically distinct pramipexole-mediated akinesia vs. risk-taking in a rat model of Parkinson's disease

New clinical trials for nonmotor manifestations of Parkinson's disease

Monoamine Reuptake Inhibitors in Parkinson’s Disease

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