Overall, individuals with past-month prescription amphetamine use had a greater likelihood of new-onset psychosis or mania than individuals without past-month use. The risk was highest in those taking 30 mg or more of dextroamphetamine (which corresponds to 40 mg of Adderall), according to the study.

Previous studies have linked stimulants to psychosis and mania risk; however, information had been lacking on whether dosing impacted risk.

“Stimulant medications don’t have an upper dose limit on their labels, and our results show that it is clear that dose is a factor in psychosis risk and should be a chief consideration when prescribing stimulants,” said lead study author Lauren Moran, MD, a pharmacoepidemiology researcher at McLean Hospital. “This is a rare but serious side effect that should be monitored by both patients and their doctors whenever these medications are prescribed.”

Moran said the study was born out of her past clinical observations as an inpatient psychiatrist. She and her McLean colleagues would regularly see patients coming in experiencing first episodes of psychosis, and their medical records would reveal they were prescribed high doses of stimulants by their doctors.

Researchers reviewed electronic health records of Mass General Brigham patient encounters between 2005 and 2019, focusing on adults aged 16 to 35, the typical age of onset for psychosis and schizophrenia. All patients were admitted to McLean Hospital following referrals from other hospitals in the Mass General Brigham healthcare system. The researchers identified 1,374 cases of individuals presenting with first-episode psychosis or mania, compared to 2,748 control patients with a psychiatric hospitalization for other conditions like depression or anxiety. They conducted a comparison analysis of stimulant use over the preceding month and accounted for other factors, including substance use, in order to isolate the effects of stimulants.

They found the attributable risk percentage among those exposed to any prescription amphetamine was nearly 63% and for high dose amphetamine was 81%. These findings suggest that among people who take prescription amphetamine, 81% of cases of psychosis or mania could have been eliminated if they were not on the high dose. While a significant dose-related risk increase was seen in patients taking high doses of amphetamine, no significant risk increase was seen with methylphenidate (Ritalin) use, which is consistent with previous research, including a 2019 study led by Moran.

While the study does not prove causality, the researchers note there is a plausible biological mechanism in neurobiological changes that include a release of higher levels of the neurotransmitter dopamine from amphetamines, that parallel dopaminergic changes observed in psychosis.

Limitations of the study include inconsistencies with how electronic health records are kept. Additionally, with the research taking place in a psychiatric hospital in the Boston area that sees many patients with psychosis, it may make these findings less generalizable to other parts of the country.

Moran said the findings need not create alarm but should lead to extra caution when these medications are prescribed, especially for those who have risk factors for psychosis and mania.

“There’s limited evidence that prescription amphetamines are more effective in high doses,” said Moran. “Physicians should consider other medications our study found to be less risky, especially if a patient is at high risk for psychosis or mania.”

Authorship: In addition to Moran, Mass General Brigham co-authors included Joseph P. Skinner, BA (BWH), Ann K. Shinn MD, MPH (McLean), Kathryn Nielsen (McLean), Vinod Rao, MD, PhD (MGH), Trevor Taylor, MD, MPH (MGH), Talia R. Cohen (McLean), Cemre Erkol, MD (McLean), Jaisal Merchant, MA (McLean), Christin A. Mujica, MA (McLean), Roy H. Perlis, MD, MSc, (MGH) and Dost Ongur, MD, PhD (McLean).

Funding: This work was funded by a grant from the National Institute of Mental Health (NIMH), R01 MH122427.

Disclosures: Perlis received personal fees from Genomind, Burrage Capital, Psy Therapeutics Inc, Circular Genomics Inc, and Vault Health unrelated to the submitted work. Dr. Ongur received honorariums for scientific presentations to Neumora Inc. and Guggenheim LLC unrelated to the submitted work. Dr. Moran is employed by Sage Therapeutics (unrelated to this work and after study completed and submitted for publication). All other authors report no financial relationships with commercial interests.

Paper cited: Moran, LV et al. “Risk of Incident Psychosis and Mania with Prescription Amphetamines,” American Journal of Psychiatry. DOI: 10.1176/appi.ajp.20230329

The post High doses of some prescription stimulants tied to increased psychosis risk appeared first on Pharmacy Update Online.

By understanding the intricacies of feelings, attitudes, and experiences which are interlinked with delusions, clinicians will be better able to build trust and genuine engagement with patients.

In a new study, published today (4 May 2022) in The Lancet Psychiatry, researchers collated and reviewed first-hand accounts of the experience of delusions from patients with psychosis in mental health settings. In their review, the team used a new methodological approach informed by philosophy to combine and synthesis all the available qualitative evidence. The team then developed a new model to better understand how delusions emerge and are shaped by different contexts from multiple levels of explanation.

The authors examined the experiences of more than 370 patients, described in 24 different scientific studies and found a number of themes that were common across all the studies.

For most participants, for example, delusions were not just a symptom of illness or an irrational belief. Delusions often were the most compelling way that the person could make sense of their life, in the context of a radical alteration of reality and intense emotions. While the experience could be hostile, sparking fear or panic, individuals could also experience awe or wonder, or deep meaning in their delusions.

When reality is altered in this way, individuals can struggle to make sense of their own identity, experiencing self-doubt or a loss of control or, conversely, the feeling that they are someone special, or with a unique purpose. In the latter case, the delusional experience seemed to provide a sense of coherence, purpose and belonging at a time of intense life stress and can therefore be interpreted as temporarily adaptive or beneficial.

“These experiences are complex and nuanced,” said lead author Dr Rosa Ritunnano, consultant psychiatrist and researcher at the University of Birmingham’s Institute for Mental Health and the University of Melbourne. “When we train clinicians in treating psychosis, we need to ensure they are going beyond ‘correcting’ a dysfunction or ‘curing’ a symptom. Instead, by trying to understand how the delusion is shaped by the patient’s emotions, life experiences and socio-cultural contexts, we can devise treatment and support that is more relevant to the individual.”

The approach has particular resonance for situations in which a patient may be detained without their consent with the aim of protecting themselves from harm. The number of patients detained in this way has been steadily rising for several years, with particular ethnic groups and those with learning disabilities being particularly impacted in this process.

“One of the main issues is that all too often, the patient’s voice is lost within the process of trying to help them,” says Dr Clara Humpston, one of the senior authors on the paper. “Carers, clinicians and family members all have a challenging task in learning how to listen. That means accepting that there may not be a shared view of reality, but the patient’s experience is still true and valid, and ought not to be silenced.”

DOI – 10.1016/S2215-0366(22)00104-3 

The post How can mental health professionals open their minds to psychosis? appeared first on Pharmacy Update Online.

One person in 2000 suffers from a microdeletion of chromosome 22 that can lead to the development of psychotic disorders, such as schizophrenia, in adolescence. In addition to symptoms such as hallucinations or delusions, psychotic disorders also comes with a progressive decline in intelligence quotient (IQ). If current drug treatments are successful in containing psychotic symptoms, nothing can be done to prevent the deterioration of intellectual skills that leads to loss of autonomy. Researchers at the University of Geneva (UNIGE), Switzerland, have discovered that prescription of selective serotonin reuptake inhibitors (SSRIs) — a class of drugs used to treat anxiety and depression -in late childhood can reduce the deterioration of intellectual abilities, and have a neuroprotective effect on some of the brain regions affected by the psychotic illness. This study, to be read in the journal Translational Psychiatry, opens up a new field of research and new hope for people affected by the microdeletion of chromosome 22.

The average IQ is around 100 points. However, for people who may develop a psychotic illness, such as those with a microdeletion of chromosome 22, the average drops to 70-80 points. “The problem is that when a psychotic disorder occurs, such as schizophrenia, the brain frontal lobe and the hippocampus are particularly affected, which leads to the gradual deterioration of already below-average intellectual capacities,” explains Valentina Mancini, a researcher in the Department of Psychiatry at UNIGE Faculty of Medicine and first author of the study. From then on, the average IQ drops to around 65-70 points, leading to a loss of autonomy that requires a protected environment. “At present, drug treatments manage to contain psychotic symptoms, such as hallucinations, anxiety or distortion of reality, but there is no treatment that can reduce the deterioration of affected people’s intellectual capacities,” notes the Geneva researcher.

200 patients followed over a 20 years period reveal a possible solution

The team of Stéphan Eliez, professor in the Department of Psychiatry at UNIGE Faculty of Medicine, has been following 200 patients affected by the microdeletion of chromosome 22 for the past 20 years. “30 to 40% of them developed schizophrenia psychotic disorder,” he explains. “Thanks to this cohort, we found that people suffering from this syndrome lost 7 to 8 IQ points from childhood to adulthood. This figure rises to 15 IQ points for those who developed psychotic disorders.”

Yet the physicians noted that two to three teenagers a year are exceptions, and even gained IQ points. Why? “We made a comprehensive analysis of these patients’ medical data to find out any common feature in the treatments prescribed to them by their GP,” explains Valentina Mancini. Two observations caught their attention.

The first is the prescription of small, regular doses of SSRIs — a drug that increases the levels of serotonin, a neurotransmitter involved in the regulation of behaviour — in late childhood and throughout adolescence. “These drugs increase neurogenesis and act on synaptic plasticity. They are prescribed today to reduce anxiety and depressive symptoms,” explains the Geneva researcher. And the younger the patients received this treatment, at around 10-12 years of age, the more the frontal lobe and the hippocampus — and therefore the intellectual capacities — were preserved from deterioration caused by the psychotic illness. The second observation is that a neuroleptic drug — prescribed in small doses to control psychotic symptoms such as hallucinations or delusions — also seems to have a positive effect if added to SSRIs during adolescence. “These two medications, especially when combined, have thus preserved the anatomical structure of the brain affected by the degradation responsible for the decline in intellectual capacity,” remarks Stéphan Eliez.

A promising discovery for the future of people at risk of psychosis

This study provides for the first time an indication of a neuroprotective preventive treatment for the development and preservation of IQ. “It should be stressed that too great a deterioration of intellectual skills progressively leads to a very problematic psychosocial dependence. Here, we could succeed in protecting this population,” notes Stéphan Eliez.

Once the results of this study are confirmed, the effect of SSRIs could be tested on other types of patients and possibly prescribed preventively to people at risk of intellectual deterioration, such as individuals with other genetic syndromes like Fragile X or Down’s syndrome, or children of schizophrenic parents. “We also want to investigate whether the 3% to 4% of adolescents in the general population who develop psychotic symptoms would see this risk reduced by taking this drug,” continues Valentina Mancini.

The Geneva team will now compare the results obtained from their research cohort with international databases in order to confirm the neuroprotective role induced by these treatments prescribed at the end of childhood, adolescence being the critical phase for the onset of psychotic diseases.

Journal Reference:

1. Valentina Mancini, Johanna Maeder, Karin Bortolin, Maude Schneider, Marie Schaer, Stephan Eliez. Long-term effects of early treatment with SSRIs on cognition and brain development in individuals with 22q11.2 deletion syndrome. Translational Psychiatry, 2021; 11 (1) DOI: 1038/s41398-021-01456-x

The post Protecting the intellectual abilities of people at risk for psychosis appeared first on Pharmacy Update Online.