Hallucinations

Montelukast’s Underrecognized Adverse Drug Events

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The US Food and Drug Administration (FDA) first alerted healthcare professionals (HCPs) about a possible association between the use of leukotriene inhibitors and neuropsychiatric events in 2008 and added information to product labels in 2009. The reported events included agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor. While the precaution was extended to all agents in this class (montelukast [Singulair®], zafirlukast [Accolate®], and zileuton [Zyflo®]), particular concern has been raised about montelukast due to its widespread use in both adult and pediatric patients for multiple indications. Montelukast is approved for the chronic treatment of asthma, acute prevention of exercise-induced bronchial constriction, and relief of both perennial and seasonal allergic rhinitis symptoms. Singulair is approved in adults and children 6 months of age and older. Continued concerns about suicidality and neuropsychiatric events with montelukast were again raised at a recent FDA Pediatric Advisory Committee (PAC) meeting in September 2014. Medscape spoke with Sally Seymour, MD, and Erika Torjusen, MD, MHS, both at the Center for Drug Evaluation and Research in the Division of Pulmonary, Allergy, and Rheumatology at the FDA, about the advisory committee meeting, concerns with these agents, and the implications for HCPs.

Medscape: Can you briefly review the concerns presented at the advisory committee meeting about these agents?

Dr Seymour: On September 23, 2014, montelukast [Singulair] was discussed at the PAC meeting as part of a routine pediatric safety review conducted after a drug has new pediatric labeling.

During the open public hearing, a parent who represented numerous groups wanted to raise awareness of the potential for neuropsychiatric events with montelukast. The speaker stated that, despite the FDA’s communication efforts and information in the product label, many physicians are not aware or do not communicate the risk for neuropsychiatric events to patients.

As part of the discussion, the committee reviewed the current montelukast labeling regarding the risk for neuropsychiatric events. Members wanted HCPs to be cognizant of the association with neuropsychiatric events and consider discontinuing montelukast if they occur. The PAC recommended a communication directed at HCPs to raise awareness of the association of neuropsychiatric events. This Medscape interview is a result of the committee’s recommendations.

Medscape: In addition, the committee heard about the available objective data regarding montelukast and neuropsychiatric events. Could you summarize those data? What do we know about these adverse events, what they look like, how acutely they occur, and the populations in which they occur?

Dr Seymour: At the PAC meeting, we briefly summarized the FDA’s previous review of this safety issue. In 2008-2009, we reviewed available data (postmarketing and clinical trial data) to evaluate the risk for neuropsychiatric events with leukotriene modifiers: montelukast, zileuton, and zafirlukast. During this review of spontaneous postmarketing reports, we noted a variety of neurologic or psychiatric adverse events associated with use of these products. Reports included: agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor. Some of these reports appeared to be consistent with a drug-induced effect. Events were noted in both adults and children, and the onset of events varied.

Based upon these data, the FDA required the manufacturers to add information to the product labels. All of these labels now have a warning/precaution about the risk for neuropsychiatric events.

Medscape: This was a pediatric advisory committee meeting. Were all of these events reported in children, or are adults also experiencing these adverse events?

Dr Seymour: We have reports of children and adults experiencing these types of events. We especially want to reach out to HCPs taking care of children because montelukast is approved for children down to 6 months of age, and detecting these events in children may be more challenging. Small children can’t report side effects, and young children or teenagers may experience changes in behavior or mood that can be mistakenly attributed to a normal phase of development. Therefore, parents and practitioners need an increased level of awareness about the risks of montelukast in these age groups.

Medscape: Are these adverse events reversible with drug discontinuation, and is there a time frame in which they are likely to occur?

Dr Torjusen: The most common adverse events are typically not serious. These events are generally reversible with cessation of therapy. In terms of timing, we have reports following initiation of montelukast and after chronic use.

Medscape: You noted that the committee made a determination that more outreach and strengthening of prescriber warnings was warranted. Were there any other committee recommendations? For example, will there be any requirement to manufacturers to conduct any further studies?

Dr Torjusen: Based on the testimony provided during the open public hearing, the PAC recommended potential strategies for increasing awareness of the neuropsychiatric events that may occur with montelukast. Possibilities raised by the committee included labeling changes, education of providers, and consideration for further studies. The PAC recommendations can be found on our website.

Dr Seymour: When the FDA completed its initial review in 2009 and required the companies to update the product labeling, we did not require clinical trials to further evaluate this issue. Because this is a known safety issue, the FDA does not think that changes to the prescriber information or clinical studies are warranted at this time. The PAC noted that the patient labeling was clear.

Medscape: Given that this is a class-wide concern, should all leukotriene inhibitors be avoided in patients who experience these symptoms in response to one agent? Or is it worth a clinician trying another drug in the same class if it was felt it was really indicated?

Dr Torjusen: Based on the data available, this does appear to be a class effect and is the reason the labeling change was applied to all of the drugs in the class of leukotriene inhibitors. Therefore, if a patient experiences neuropsychiatric symptoms while on one leukotriene inhibitor, we would recommend that they avoid other drugs in the class.

Medscape: Why do you think this now 5-year-old safety issue is not well known by prescribers?

Dr Torjusen: That is a good question. It is possible that awareness of the association between montelukast and neuropsychiatric events has faded. HCPs are inundated with new products and new safety information, and keeping up with all of this can be a challenge. In addition, the types of events experienced are highly variable. Detecting these events in children and young adults can be particularly challenging. Young children may be less able to articulate these experiences, and parents may unknowingly attribute symptoms to be part of developmental changes. Therefore, reminders of important safety concerns may be necessary at times for both patients and providers.

Medscape: What are the key take-home messages for clinicians who are prescribing this class of drugs?

Dr Torjusen: The key take-home message is for HCPs to be aware of the risk for neuropsychiatric events with the use of montelukast. Providers should inform their patients and families that these types of side effects are a possibility with these medications, and they should follow up with their patients after initiation of therapy.

Patients should also notify their HCPs if side effects occur, and HCPs should consider discontinuing therapy if patients develop neuropsychiatric symptoms.

Medscape: Are there resources for patient education that clinicians can and should use?

Dr Torjusen: Certainly, clinicians can always refer to the product label for montelukast [Singulair], which provides safety information for the product. In addition, the patient prescribing information provides useful information on the product, including side effects.

Information about the FDA’s review of the safety issue can be found on the FDA website.

Serious adverse events should also be reported to the FDA MedWatch or by calling the FDA at 1-800-FDA-1088. Patients and HCPs who want more information about specific products can go to the FDA website or contact the FDA [1-888-INFO-FDA].

Hallucinations Are Far More Common Than We’ve Been Led to Believe, Study Suggests

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If you’ve experienced hallucinations, you’re not alone.

New research has found that hallucinations are far more common among the general population than most people realise – and they aren’t limited to disorders commonly associated with psychosis, such as schizophrenia or borderline personality disorder.

A study looking at more than 7,400 people in the UK found that 4.3 percent of participants had experienced either visual or auditory hallucinations in the past year – this included people with and without mental health issues, and showed that the phenomenon wasn’t limited to those with psychosis.

“There is a general idea in psychiatry that hallucinations are a feature of psychosis,” lead researcher Ian Kelleher from the Royal College of Surgeons in Ireland told Léa Surugue at the International Business Times.

“But when we looked at a whole range of mental health diseases we found that hallucinations are symptoms that occur in a wide range of mental health disorders such as depression or anxiety.”

Generally, when we talk about mental health issues, there’s a divide between the psychotic disorders, such as borderline personality disorder and schizophrenia, and non-psychotic disorders, including depression and anxiety.

For this study, the researchers used borderline personality disorder as an example of a psychotic disorder.

There’s plenty of unnecessary stigma surrounding all of those conditions, but in particular, people with psychotic disorders are usually considered unique in that they see and hear things that aren’t there.

But the new study suggests that this divide might not actually exist.

“There is a general idea in psychiatry that hallucinations are a feature of psychosis,” lead researcher Ian Kelleher from the Royal College of Surgeons in Ireland told Léa Surugue at the International Business Times.

“But when we looked at a whole range of mental health diseases we found that hallucinations are symptoms that occur in a wide range of mental health disorders such as depression or anxiety.”

Generally, when we talk about mental health issues, there’s a divide between the psychotic disorders, such as borderline personality disorder and schizophrenia, and non-psychotic disorders, including depression and anxiety.

For this study, the researchers used borderline personality disorder as an example of a psychotic disorder.

There’s plenty of unnecessary stigma surrounding all of those conditions, but in particular, people with psychotic disorders are usually considered unique in that they see and hear things that aren’t there.

But the new study suggests that this divide might not actually exist.

The team looked at data from the 2007 Adult Psychiatric Morbidity survey, which included surveys over the space of a year on the mental health of 7,403 people in England aged over 16.

As you’d expect, many of these participants had been diagnosed with a mental health condition – in England, it’s estimated that one in six people suffer from mental health problems in any given week.

But the team wanted to narrow down whether hallucinations were any more common among people with psychotic disorders compared to those with non-psychotic ones.

To do this, the researchers looked at how many people with borderline personality disorder (which is associated with psychosis) reported seeing or hearing things that other people couldn’t in the past year, compared with the number of participants with non-psychotic depression or anxiety.

The results showed that hallucinations weren’t significantly more prevalent in individuals with borderline personality disorder (13.7 percent) than those with a non-psychotic mental disorder (12.6 percent).

Not only that, but more than 4 percent of all respondents reported hearing or seeing things that others couldn’t – including those who’d never been diagnosed with mental health issues.

Based on the results, the team suggests that hallucinations aren’t exclusively symptoms of psychosis, and shouldn’t be stigmatised.

“Hallucinations are more common than people realise. They can be frightening experiences, and few people openly talk about it,” Kelleher told Surugue.

“Our research is valuable because it can show them they are not alone and that having these symptoms is not necessarily associated with having a mental health disorder. It breaks the taboo.”

But this is just one study and it has its limitations – for starters, the team relied on participants to self-report whether or not they’d experienced hallucinations, which isn’t the most accurate technique.

And although it was a decent sample size, the researchers only looked at people in England, which is not a diverse enough demographic to draw any far-reaching conclusions about hallucinations in general.

But the findings echo the results of a much larger study published in 2015, which looked at data on more than 31,000 people from 19 countries.

Similar to these latest results, that paper found that around 5 percent of the general population reported experiencing hallucinations, whether or not they were diagnosed with a mental illness.

“We used to think that only people with psychosis heard voices or had delusions, but now we know that otherwise healthy, high-functioning people also report these experiences,” said lead researcher John McGrath, from the Queensland Brain Institute in Australia, when the study came out.

As research into hallucinations continue, it’s becoming apparent that many of the symptoms we once associated with mental health disorders are actually more common than we once thought.

In fact, a separate study that came out last week showed that people who go through life without experiencing any mental health problems are more unusual than those who do.

By further investigating who does and doesn’t experience visual or auditory hallucinations and how they occur, researchers will hopefully get a better idea of who’s at risk of developing serious mental health conditions in future.

The research has been published in the British Journal of Psychiatry.

The Link Between LSD and Music

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LSD and music are always linked, and it is now known that music alters the experience of taking the drug. Imperial College neuroscience student Mendel Kaelen has been studying music and the drug, and a big challenge is the type of music.

It has been Mendel Kaelens job to set the ideal playlist for a trip, and as it must fulfill research regulations, it has not been easy. The intent is to find a therapeutic use for the drug, and the initial attempt is to find a way to treat depression. As all therapy trials use music now it is vital the right tunes are used.

The Link Between LSD and Music
The areas that contributed to vision were more active under LSD, which was linked to hallucinations. 

Before testing on people, the team tested the theory that drugs such as LSD improve the response to music. Volunteers listened to a few musical tracks, once after taking LSD once after taking a placebo. The tracks were largely unknown so as there would not be an immediate attachment and Brian McBride’s and Greg Haines music was used – along with others. Emotional responses were given to the tracks – were they peaceful, was their tension – and emotions were rated higher after taking LSD not the placebo. Power and tenderness were emotions that scored highly.

Kaelen has also researched using a substance found in magic mushrooms to patients who were resistant to treatment for depression, but the results are not yet available. Here the music ad to last for 6 hours and some tracks were taken from the list of Helen Bonney, a music therapist in the 1960’s.

‘Superhuman’ drug makes users dangerous: police

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Confiscated vials of flakka. Photo / AP

A new synthetic drug makes people feel “superhuman” and has led to a series of dangerous incidents, United States police are warning.

Known as flakka, its effects include hallucinations, rage, delirium, paranoia and a sharp rise in body temperature which leads users to take off their clothes.

One naked man tried to kick in the door of the Fort Lauderdale Police Department in Florida because he thought a mob was trying to kill him. Another, experiencing similar hallucinations, tried to climb the police station fence and became impaled on a spike, police said. He was taken to hospital and survived.

Other cases included a man who ran naked through a neighbourhood convinced he was the Norse god Thor, and tried to have sex with a tree.

Last week, Qushanna Doby, 20, was charged with child neglect after her 1-year-old baby was found abandoned in the street. She said she had blacked out after taking the drug and couldn’t remember where she left the child.

Flakka is mostly made in China and Pakistan and smuggled to the US through the post. It is usually sold in crystal form and can be smoked, injected or swallowed.

Don Maines, a drug treatment expert in Fort Lauderdale, said: “They feel stronger and more sensitive to touch. But then the paranoia sets in. It seems to be universal that they think someone is chasing them. It’s just a dangerous, dangerous drug.”

Scientists Induce Hallucinations Of Past Memories Via Brain Zapping Procedure.

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Is it live? Or is it Memorex memory manipulating mind control technology soon to appear in “safe houses” and black sites around the United States?

Via New Scientist:

A 22-year-old man has been instantaneously transported to his family’s pizzeria and his local railway station – by having his brain zapped. These fleeting visual hallucinations have helped researchers pinpoint places where the brain stores visual location information.

Pierre Mégevand at the Feinstein Institute for Medical Research in Manhasset, New York, and his colleagues wanted to discover just where in the brain we store and retrieve information about locations and places. They sought the help of a 22-year-old man being treated for epilepsy, because the treatment involved implanting electrodes into his brain that would record his neural activity.

Mégevand and his colleagues scanned the volunteer’s brain using functional MRI while he looked at pictures of different objects and scenes. They then recorded activity from the implanted electrodes as he looked at a similar set of pictures.

In both situations, a specific area of the cortex around the hippocampus responded to images of places, but not to images of other kinds of objects, such as body parts or tools. “There are these little spots of tissues that seem to care about houses and places more than any other class of object,” says research team member Ashesh Mehta, also at the Feinstein Institute.
Teleported home

Next, the team used the implanted electrodes to stimulate the brain in this area – a move that the volunteer said triggered a series complex visual hallucinations. First he described seeing a railway station in the neighbourhood where he lives. Stimulation of a nearby area elicited another hallucination, this time of a staircase and a blue closet in his home. When stimulation of these areas was repeated, the same scenes arose.

There were no smells or sounds associated with the hallucinations, he just saw each place, says Mehta. “He got a kick out of it, though. He thought it was sort of trippy and funny. He laughed when he saw it.”