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Parkinson’s Disease and Rehabilitation
Published in K. Rao Poduri, Geriatric Rehabilitation, 2017
Biemiller Rachel A., Irene Hegeman Richard
Psychosis in PD presents another treatment challenge. Frequently seen later in the disease and associated with cognitive impairment, psychosis can be induced by PD medications. In the early stages of the disease, PD medications can be decreased in an effort to improve hallucinations; however, there is a risk of worsening the motor symptoms. Unfortunately, many antipsychotic medications (even those considered “atypical”) may worsen PD motor function. Clozapine has been shown to be effective for the treatment of psychosis in PD [74]. However, its potential to cause agranulocytosis makes its use difficult due to required long-term blood draws. Quetiapine has not been shown to definitively treat psychosis in PD, but due to its lower risk of extrapyramidal side effects and scant need for monitoring, it has been the primary medication used for psychosis in clinical practice. A recent study demonstrates the efficacy of pimavanserin, making it a promising treatment for the future [75,76].
Degenerative Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James A. Mastrianni, Elizabeth A. Harris
While many antipsychotics are labeled as atypical, only two have more consistently been demonstrated not to worsen parkinsonism significantly: Clozapine: given in smaller doses than needed for psychosis (starting at 12.5 mg daily and seldom increasing above 100 mg daily), may help to control the psychotic features and permit higher doses of levodopa–carbidopa to be used. Disadvantages are that weekly blood counts are required because of the risk of agranulocytosis, and it also causes sedation, hypotension, or rarely myocarditis.Quetiapine: while appearing clinically efficacious, three randomized, controlled trials do not support its efficacy over placebo. Regardless, it is commonly used as first-line therapy in low doses (12.5–150 mg daily), preferably at night as it may also cause sedation and therefore improve any coexistent insomnia. Note that long-term use of atypical antipsychotics in elderly patients are associated with sudden risk of cardiac death.Pimavanserin: selective serotonin 5-HT2A inverse agonist is approved for treatment of PD psychosis (34 mg daily, or 10 mg daily if taking CYP3A4 inhibitor). It was efficacious in treating psychosis over a 6-week study period. Side effect includes QT prolongation, edema, and fatigue.Acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) were developed as symptomatic treatment of cognition and behavior in mild to moderate dementia of Alzheimer's type, but have been extended to use in PD dementia. They inhibit acetylcholinesterase and thus decrease acetylcholine breakdown in the synaptic cleft. All have broadly similar efficacy, although only rivastigmine has been demonstrated to show improvement in a randomized, controlled trial.Memantine: Two randomized, double-blind trials suggest that memantine (an NMDA receptor antagonist) may lead to global improvement of cognitive function or at least in some cognitive subdomains, such as speed on attention tasks. Nonpharmacologic therapies (e.g. transcranial magnetic stimulation, cognitive rehabilitation) are under investigation.
Current and emerging pharmacotherapeutic strategies for Tourette syndrome
Published in Expert Opinion on Pharmacotherapy, 2022
There are a few recent studies on emerging treatments for TS that modulate histaminergic, noradrenergic, and serotonergic pathways [33]. A trial investigating atomoxetine, a noradrenaline reuptake inhibitor which might improve response inhibition parameters in patients with TS, has been registered. An H3-receptor antagonist called AZD5213 has been assessed for safety and tolerability in patients with TS, however it has not shown any significant difference compared to placebo. Pimavanserin is a serotonin receptor inverse agonist (without dopamine receptor antagonist properties) which is approved for the treatment of Parkinson’s disease psychosis. The results of a recent open-label phase 1 pilot study to evaluate pimavanserin in the treatment of motor and behavioral symptoms in adults with TS were encouraging and warranted further research by larger, placebo-controlled, trials [92]. Of note, the adverse effects of pimavanserin were reported to be common but not severe (headache, bloating, dizziness, drowsiness, nausea, and dysgeusia. A significant degree of tic reduction was demonstrated when D-cycloserine, an antibiotic with learning enhancing properties, was administered to patients with TS undergoing habit reversal training (as compared to patients treated with habit reversal training and placebo) [93]. A follow-up study of D-cycloserine augmented habit reversal training for youth with tic disorders has been registered.
Hallucinations and delusions associated with Parkinson’s disease psychosis: safety of current treatments and future directions
Published in Expert Opinion on Drug Safety, 2022
Stuart H Isaacson, Leslie Citrome
Pimavanserin is the only drug approved in the US for treating PDP. The efficacy of pimavanserin 34 mg/d for PDP was principally demonstrated in a randomized, placebo-controlled clinical study [30]. An open-label extension study of >400 patients with PDP found a durable response after a total of 10 weeks treatment [32]. A long-term, open-label study of patients previously enrolled in randomized controlled studies found that patients had mostly mild or moderate adverse events with pimavanserin during a median of 454 days of treatment [33]. No evidence for adverse effects on motor function, daytime or nighttime sleep or cognitive function has been demonstrated from clinical studies with pimavanserin [30,59–61]. On the basis of these findings, treatment guidelines from the International Parkinson and Movement Disorder Society recommend pimavanserin as clinically useful for the treatment of PDP.
Treating hallucinations in Parkinson’s disease
Published in Expert Review of Neurotherapeutics, 2022
Alice Powell, Elie Matar, Simon J. G. Lewis
Where treatment is needed, cholinesterase inhibitors have a reasonable safety profile but only rivastigmine has good evidence for reducing visual hallucinations. Clearly, pimavanserin offers significant potential for the management of these patients but its limited availability has restricted the significant accumulation of ‘real world’ experience among treating clinicians. Where hallucinations form part of a more pervasive psychosis with associated delusions, patients will typically require management with atypical antipsychotics, ideally for the shortest period possible given the increased mortality that has been reported with this class of drugs. Whilst the strongest evidence base would support the use of clozapine, the need for intensive monitoring often leads clinicians toward the use of quetiapine. In these scenarios, patients often already have advanced disease, limited life expectancy and poor quality of life. As such, an open discussion of the risks and benefits of therapy is recommended with patients and families. Regular review of the need for ongoing therapy is recommended and for both cholinesterase inhibitors and antipsychotics, gradual withdrawal is advised to avoid withdrawal syndromes and rebound psychosis.