Last updated Feb. 2, 2022, by Teresa Carvalho, MS
Fact-checked by Ana de Barros, PhD
Parkinson’s symptoms are recognized by most people as tremors, limb stiffness, impaired balance, and slow movement. However, over the course of this disease, about half of all patients are affected by psychosis, which causes them to see, hear, or experience things that are not real (hallucinations), or believe things that are not true (delusions).
More recently, the FDA approved a sprinkle formulation of the therapy that can be taken more easily by some patients.
How Nuplazid works
Nuplazid is a selective serotonin inverse agonist targeting serotonin receptors called 5HT2A receptors. An inverse agonist is a molecule that binds to the same receptor as an agonist — a molecule that binds to a receptor and initiates a physiological response — but induces the opposite pharmacological response. Serotonin receptors are found throughout the nervous system and mediate the transmission of signals between nerve cells. The 5HT2A receptor has been implicated in mental disorders, but in ways that are still not clearly understood.
Parkinson’s therapies typically work to stimulate dopamine and treat motor symptoms such as tremors, muscle rigidity, and walking. Nuplazid has no binding affinity for dopamine receptors, so it does not interfere with dopaminergic therapy, and it does not bind to other receptors commonly targeted by antipsychotics. That means the therapy will not affect motor skills.
Nuplazid in trials for Parkinson’s disease
Nuplazid’s approval by the FDA was based on data from a six-week Phase 3 placebo-controlled trial (NCT01174004), as well as other supportive studies. In this study, completed in 2012, participants were randomly selected to either receive 40 mg of Nuplazid or a placebo. The results showed that Nuplazid significantly reduced the frequency and severity of psychotic symptoms when compared with a placebo, without impairing motor function.
An open-label extension clinical trial (NCT00550238) was conducted to evaluate the long-term safety and tolerability of Nuplazid, at a dose of 34 mg daily. The trial enrolled participants who had received either once-daily Nuplazid or a placebo during one of three prior six-week Phase 3 studies (NCT00477672, NCT00658567, and NCT01174004).
Data from this open-label study showed that Nuplazid could ease symptoms for up to 10 weeks and was safe and well-tolerated, with no impact on patients’ motor function. A pooled analysis from two of these Phase 3 studies, covering data on 268 patients, also showed a significant lessening in hallucinations and delusions, as well as on secondary psychoses and nighttime sleep.
Another Phase 3 study (NCT03325556) enrolled 392 patients with the most common subtypes of dementia, including Parkinson’s and Alzheimer’s disease. Participants were treated with 34 mg of Nuplazid each day for 12 weeks (about three months) until dementia was stable or with a reduced 20 mg dose if clinically justified within the first four weeks. Patients who responded to treatment were then randomly assigned to continue treatment with Nuplazid (34 mg or 20 mg daily) or placebo for 26 weeks, or six months. Results showed that treatment with Nuplazid significantly delayed time to a psychosis relapse in patients with dementia-related disorders.
Nuplazid is taken orally as two 17 mg tablets, once a day, at any time of the day or at a time recommended by a doctor. The maximum recommended dose is 34 mg per day.
Common side effects include swelling in the legs or arms, nausea, constipation, and changes in normal walking. Other side effects may include hallucinations and feelings of confusion.
There is an increased risk of death in elderly patients with dementia-related psychosis associated with the use of antipsychotic drugs. The causes of death are varied, and include heart failure, sudden death, and pneumonia.
Importantly, Nuplazid is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s psychosis.
Use of Nuplazid is not recommended in people with cardiac arrhythmias, meaning an irregular or slow heartbeat, or for those with severe kidney impairment or liver impairment.
People taking strong CYP3A4 inhibitors (such as ketoconazole) should reduce their Nuplazid dose by one-half. An increase in Nuplazid dosage may be needed in patients who are taking strong CYP3A4 inducers as these therapies may reduce Nuplazid’s efficacy.
More information may be found on the therapy’s label.
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