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Psychosis and Mania Risks in High-Dose Amphetamine Users

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Recent research reveals an 81% higher risk of psychosis in individuals taking high doses of amphetamines for ADHD, urging reconsideration of treatment options and dose limits.

Psychosis and Mania Risks in High-Dose Amphetamine Users
Highlights:
  • High-dose amphetamines increase psychosis risk by 81%
  • No significant risk found in patients taking methylphenidate
  • Experts advise close monitoring and reconsideration of dosage limits
Strong link has been found between high doses of amphetamines, commonly prescribed for Attention Deficit Hyperactivity Disorder (ADHD) and other conditions, and an increased risk of psychosis by recent study (1 Trusted Source
Risk of Incident Psychosis and Mania With Prescription Amphetamines

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). The findings have significant implications for the way doctors prescribe these medications, particularly for individuals who may already be at risk for psychiatric disorders.

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Rise of Amphetamine Prescriptions in ADHD Treatment

Amphetamines are stimulant drugs primarily prescribed for the treatment of ADHD and narcolepsy. They are designed to energize the central nervous system, helping individuals manage conditions such as depression and obesity as well.

However, amphetamine prescriptions have seen a steep increase in recent years. From 2011 to 2021, prescription use of amphetamines surged by 70% in the United States, with a larger spike during the COVID-19 pandemic.

Despite their benefits in managing specific disorders, amphetamines have been increasingly linked to serious psychiatric side effects, especially when used at high doses.


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Increased Psychosis Risk with High Doses of ADHD Drugs

Study conducted by researchers at McLean Hospital in Massachusetts reveals the serious psychiatric risks associated with high doses of amphetamines. The study, recently published in the American Journal of Psychiatry, assessed data from Mass General Brigham patients between 2005 and 2019, focusing on young adults aged 16 to 35.

Researchers analyzed around 1,300 patients experiencing a first episode of psychosis or mania and compared them to a control group of about 2,700 people who were hospitalized for psychiatric conditions like depression and anxiety. The team investigated the patients’ stimulant use and other influencing factors like substance abuse.
  • People taking any prescription amphetamines had a 63% higher risk of developing psychosis or mania.
  • The risk spiked to 81% for individuals on high doses of amphetamines, defined as 30 milligrams (mg) or more.
  • The study suggests that 81% of psychosis or mania cases in high-dose amphetamine users could have been avoided if these patients had not been prescribed high doses.

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Psychosis Risk and Methylphenidate: A Safer Alternative?

Interestingly, the study found no significant increase in psychosis or mania among patients taking methylphenidate. This finding aligns with earlier research from 2019, also led by Dr. Lauren Moran, a pharmacoepidemiology researcher at McLean Hospital.

The study emphasizes the importance of dose management and suggests that physicians should prioritize medications with a lower psychosis risk for patients, particularly those at higher risk of psychiatric disorders.


Reconsidering the Risk-Benefit Balance

Dr. David Merrill, a board-certified geriatric psychiatrist from Providence Saint John’s Health Center, reflected on the significance of the study. According to Merrill, these findings highlight the need for careful patient selection, dose titration, and frequent monitoring when prescribing amphetamines.

He advocates for Starting treatment with the lowest effective dose; Initiating treatment with extended-release formulations to reduce the intensity of drug peaks in the bloodstream and; Considering nonpharmacologic interventions as the first line of treatment whenever possible.

Additionally, Dr. Merrill calls for long-term studies to further explore the relationship between amphetamine use and psychosis, including the potential roles of genetic predispositions and pre-existing mental health conditions.

Dr. Stacy Doumas, chairwoman of Psychiatry at Hackensack Meridian Jersey Shore University Medical Center, noted that while the study’s findings are concerning, they are not entirely surprising. Given the way amphetamines affect neurotransmitters like dopamine, the association with psychosis makes sense from a biological perspective.

Doumas emphasized the importance of exploring whether there is a causal relationship between high-dose amphetamine use and psychosis. She also called for further research, including longitudinal cohort studies and mechanistic studies to investigate the biological mechanisms behind this connection.

Is the Benefit Worth the Risk?


The findings from this study raise crucial questions about the risk-benefit ratio of high-dose amphetamine prescriptions, especially for vulnerable populations. While amphetamines are effective in managing ADHD and other conditions, the psychosis risk cannot be ignored. Doctors are urged to reassess the dosage they prescribe to patients; use methylphenidate as an alternative when appropriate and; continuously monitor patients, particularly those with mental health histories or who are at higher risk of psychosis.

Ultimately, the study reinforces the importance of careful monitoring and the use of lower-risk alternatives where possible, ensuring that patients receive safe and effective treatment.

Reference:
  1. Risk of Incident Psychosis and Mania With Prescription Amphetamines - (https://psychiatryonline.org/doi/10.1176/appi.ajp.20230329)

Source-Medindia


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