Med Check

FDA Committee Votes in Favor of Nuplazid for Psychosis in PD

An Food and Drug Administration (FDA) advisory committee voted 12-2 in March in favor of approving the antipsychotic Nuplazid (pimavanserin) for Parkinson’s disease-associated psychosis (PDP). If approved, the medication would be the first to specifically treat this condition.

The advisory panel vote came after the committee reviewed the results of a phase 3 trial involving 199 patients who were randomly assigned to take pimavanserin or placebo in addition to their standard antiparkinsonian medications for six weeks. The primary outcome was antipsychotic benefit as assessed by the Parkinson’s disease–adapted scale for assessment of positive symptoms (SAPS-PD) in all patients who received at least one dose of a study medication and had a SAPS assessment at baseline and at least one follow-up.

Ninety recipients of placebo and 95 recipients of pimavanserin were included in the primary analysis, which found pimavanserin was associated with a -5.79 decrease in SAPS-PD scores compared with -2.73 for placebo.

Although several reviewers on the FDA advisory committee questioned whether the benefits of pimavanserin in treating PDP symptoms were “clinically meaningful,” the group concluded that even the modest benefit of pimavanserin offered an advantage for PD patients, who have few options for treating symptoms of PDP.

Can Citalopram, Methylphenidate Combination Reduce Symptoms of Severe Mood Dysregulation?

The National Institute of Mental Health (NIMH) is conducting a clinical trial to evaluate the effectiveness of citalopram plus methylphenidate versus methylphenidate plus placebo for decreasing irritability in children with severe mood dysregulation (SMD). SMD is characterized by chronic sadness or irritability, as well hyperarousal (such as insomnia, distractibility, and hyperactivity) and extreme responses to frustration (such as frequent temper tantrums). There are no approved pharmacological treatments for SMD.

For the 12- to 15-week trial, children aged 7 to 17 with SMD will be gradually withdrawn from all current psychotropic medications, followed by a one-week period during which they will take no psychotropic medications. All participants will then be treated once daily with methylphenidate (dose ranging from 5 mg to 80 mg) for two weeks. In the final phase of the trial, participants will be randomly assigned to continue methylphenidate treatment along with daily adjunctive treatment with citalopram (dose ranging from 5 mg to 40 mg) or placebo for eight weeks.

FDA Rejects Cognitive Claim For Brintellix

Takeda Pharmaceutical Company Limited and H. Lundbeck A/S, manufacturers of Brintellix (vortioxetine), announced last month that the FDA has declined their request to expand the antidepressant’s approval to treat cognitive dysfunction in adults with major depressive disorder (MDD). This rejection was somewhat unexpected after the FDA’s Psychopharmacologic Drugs Advisory Committee voted 8-2 to expand Brintellix’s label after clinical trials suggested the medication demonstrated a statistically significant improvement in cognitive performance over placebo and the antidepressant duloxetine.

FDA Issues New Safety Warnings For Opioids

The FDA announced in March that it has issued classwide safety labeling changes—including boxed warnings—for immediate-release (IR) opioid pain medications in an ongoing effort to educate prescribers and patients about the potential risks associated with opioid use. IR opioids are intended to treat pain every four to six hours.

As part of the boxed warning on IR opioids, the FDA will now require a precaution that chronic maternal use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated properly.

In addition, the FDA is requiring updated labeling for all opioids—both IR and extended-release and long-acting (ER/LA) products—to include safety information about potentially harmful drug interactions with other medications that can result in serotonin syndrome.

Modified labeling for all opioids will also include information about opioid effects on the endocrine system, including adrenal insufficiency and androgen deficiency. The labeling changes will make it clear that these negative outcomes can occur whether a patient is taking an opioid to treat pain or if the product is being used for medication-assisted treatment for opioid use disorder.

The FDA is currently reviewing available scientific information about potentially serious outcomes related to interactions between benzodiazepines and opioids. Once this review is completed, the FDA will take necessary actions to ensure prescribers and the public are informed of the risks involved with the use of these medications. ■