For many people with ADHD, stimulant medications like amphetamines can feel like a game-changer, bringing focus and stability to everyday life. But there’s a serious side to consider: recent research shows that high doses of these medications could come with unexpected risks. 

In fact, young adults on higher doses of amphetamines may face over five times the risk of developing psychosis or mania compared to non-users. With amphetamine prescriptions steadily rising, it’s more important than ever to understand the potential mental health impacts of higher doses — so we can make informed, balanced choices in managing ADHD.

How Do ADHD Medications Affect Mental Health?

ADHD medications, specifically stimulants like amphetamines and methylphenidate, are commonly prescribed to manage symptoms of ADHD. These medications work by altering neurotransmitter levels in the brain — primarily dopamine and norepinephrine. Here’s how they impact mental health:

• Increased Dopamine and Norepinephrine Levels: Stimulants boost dopamine and norepinephrine activity in the prefrontal cortex, the area responsible for focus, impulse control, and executive functioning. This increase helps reduce inattention and impulsivity, two core symptoms of ADHD.
• Potential for Enhanced Mood Stability: At appropriate doses, ADHD medications can improve mood stability and reduce frustration or anger. This is often linked to their ability to help individuals control impulsive reactions. In addition, they may handle daily stressors better. But, misuse or higher-than-prescribed doses can produce the opposite effect.
• Risk of Mood Changes at Higher Doses: High doses may over-stimulate the brain, resulting in heightened anxiety, irritability, or even mood swings. Misuse or high-dose prescriptions may amplify risks of adverse mental health outcomes, such as increased anxiety and paranoia. An estimated 5 million Americans misused prescription stimulants, emphasizing the importance of monitoring dosage carefully.
• Sleep Disruptions and Mental Health Impact: Stimulants can disrupt sleep, which is crucial for emotional regulation and mental health. Inadequate sleep can exacerbate ADHD symptoms, leading to a cycle of increased irritability, anxiety, and impaired focus. Studies indicate that around 50% of adults with ADHD also experience sleep disturbances, underlining the need for balanced dosing and effective sleep hygiene.
• Depression and Anxiety Symptoms: Some studies suggest a possible correlation between stimulant use and anxiety symptoms. Low to moderate doses often don’t trigger these symptoms. But higher doses can overstimulate the brain, potentially leading to an increase in anxiety or depression for some individuals. People with ADHD are more prone to co-existing anxiety and depressive disorders. And stimulants may exacerbate these conditions in susceptible individuals.
• Physical Health Effects with Mental Health Implications: Side effects like elevated heart rate or increased blood pressure can create physical sensations associated with anxiety. These effects are often mild. However, they can worsen if stimulant doses are too high or not well-monitored. 

How Does the Study Examine the Link Between High-Dose Amphetamines and Mental Health?

A study explored a pressing concern in mental health: whether high doses of amphetamines used to treat ADHD and related conditions can increase the risk of psychosis and mania. Conducted as a case-control study, the research focuses on young adults with significant mental health needs. Examining whether higher doses of amphetamines contribute to severe mental health side effects. 

Why Focus on High-Dose Amphetamines?

Amphetamines, commonly prescribed for ADHD, help manage symptoms by directly affecting dopamine levels in the brain. This medication has shown effectiveness in reducing ADHD-related challenges.

Higher doses of stimulants can overstimulate the brain, leading to symptoms of psychosis and mania. In recent years, amphetamine prescriptions have risen sharply across the United States. This increase raises significant questions about the safety of high-dose usage. Researchers are now examining the potential risks tied to these growing prescription rates.

• Primary Objective: The study primarily aimed to assess how high doses of prescription amphetamines relate to the risk of developing new-onset psychosis or mania. Researchers focused on understanding this potential link to inform safer medication practices.
• Past Research: Previous studies indicated that amphetamines could increase psychosis risk, particularly among those using these medications long-term or in high doses. This research attempts to add precision to this risk by examining the specific impact of dose levels.

What Methodology Did the Study Use?

To provide reliable findings, the study implemented a case-control design using electronic health records. The researchers carefully selected and categorized participants to compare outcomes in amphetamine users and non-users.

1. Case-Control Design: This type of study compares patients who developed the condition of interest (cases) to those who did not (controls). This allow the researchers to assess potential risk factors.
2. Participant Selection: Participants were individuals aged 16–35 admitted to McLean Hospital between 2005 and 2019 with either psychosis or mania. Case subjects with these conditions were matched with control subjects. Controls were primarily hospitalized for anxiety or depression.
3. Focus on Recent Amphetamine Use: The study focused on amphetamine use within the past month. Capturing only recent exposure to these medications. This method supports a clearer link between drug use and mental health outcomes. Limiting the timeframe helps highlight the immediate effects on mental health.

How Did the Study Categorize Amphetamine Dosage?

One of the study’s core strengths is its detailed categorization of amphetamine dosages, which allows for a nuanced understanding of dose-response relationships. Doses were converted to a standardized measure called “dextroamphetamine equivalents” and divided into terciles to simplify analysis.

• Dose Terciles: This division created three dose groups: low, moderate, and high. The highest category represented those taking more than 30 mg of dextroamphetamine equivalents, the group most likely to show adverse mental health effects.
• Comparison to Methylphenidate Users: As a secondary analysis, the study looked at methylphenidate (a non-amphetamine stimulant) users. Unlike amphetamines, methylphenidate did not show an association with increased psychosis or mania, suggesting that risks may be unique to amphetamine-based treatments.

What Were the Key Findings?

The study produced several notable findings that reinforce the need for careful monitoring of high-dose amphetamine use, particularly in young adults.

1. Increased Risk with Amphetamine Use: Amphetamine users were found to have a significantly higher risk of developing psychosis or mania than non-users. Amphetamine users face nearly three times the risk of severe mental health issues. Researchers calculated this heightened risk with an odds ratio of 2.68. 
2. High-Dose Effects: The study revealed a clear dose-response relationship. Participants who used high doses (more than 30 mg) experienced a 5.28-fold increase in psychosis or mania risk compared to non-users. High-dose amphetamines carry specific risks, underscoring the need for careful prescribing practices. Responsible monitoring remains essential for patient safety.
3. No Significant Risk with Methylphenidate: For those using methylphenidate, the adjusted odds ratio was 0.91. Meaning, no significant increase in psychosis or mania risk. Methylphenidate could offer a safer option for patients. Particularly to those prone to mental health side effects. It may provide an effective alternative with reduced risk for these individuals.

What Are the Implications of These Findings?

The study’s results highlight the importance of careful use of high-dose amphetamines for prescribers, patients, and policymakers alike.

• Implications for Prescribers: Healthcare providers should prescribe the lowest effective dose of amphetamines, especially for young adults who may be more prone to mental health side effects. Close monitoring for early signs of psychosis or mania is recommended. Adjustments to treatment can be made promptly based on these observations.
• Consideration of Alternatives: Methylphenidate may be a safer option for patients at risk of psychosis or mania. It can also be considered for those needing higher doses of stimulants.
• Future Research Needs: This study offers valuable insights, but more research is needed to clarify how high-dose amphetamines may lead to psychosis and mania. Further investigation will also help identify preventive measures for at-risk populations.

Could TMS Therapy Be an Option for ADHD?

Transcranial Magnetic Stimulation (TMS) offers a promising treatment option for ADHD, especially for those who struggle with traditional medications or experience unwanted side effects. This non-invasive procedure uses magnetic fields to stimulate brain areas linked to attention, focus, and impulse control. 

The TMS Institute of Arizona provides a specialized form of this therapy called Accelerated TMS for ADHD. With shorter and more intensive sessions, Accelerated TMS often brings quicker relief from ADHD symptoms. Our approach aims to support those looking for effective, alternative solutions to managing ADHD.

Studies show that TMS can reduce ADHD symptoms by enhancing brain activity in areas that are often underactive, like the prefrontal cortex. This region is essential for attention, executive functioning, and managing emotions. Targeting these areas may improve core challenges faced by individuals with ADHD.

Here’s why Accelerated TMS stands out:

• Efficiency: Traditional TMS treatments typically require daily sessions over several weeks. Accelerated TMS, however, condenses the treatment into a shorter timeframe, providing intensive sessions within a single week, ideal for those seeking faster results.
• Minimal Side Effects: Unlike stimulant medications, TMS does not cause systemic side effects. Its a safe option for individuals sensitive to medications.
• Long-Lasting Results: Many patients report sustained improvements in focus and reduced impulsivity. There are follow-up sessions available to maintain effectiveness if needed.

While TMS isn’t a cure for ADHD, it can be a valuable tool in a comprehensive treatment plan, enhancing overall well-being and daily functioning.

Why Choose TMS Institute of Arizona for ADHD and Mental Health Support?

We’re more than just a provider. We’re your committed partners in mental health. We understand the unique challenges ADHD can bring and are here to support you with compassionate, expert care. Our team offers Accelerated TMS for ADHD to provide you a faster, effective relief. 

With us, you’ll find the support and guidance you need to make meaningful strides. Let TMS Institute of Arizona help you regain focus, improve impulse control, and enhance your quality of life. You deserve the best in care. Contact us.

References

Chapter 2—How Stimulants Affect the Brain and Behavior. (2021). Nih.gov; Substance Abuse and Mental Health Services Administration (US). https://www.ncbi.nlm.nih.gov/books/NBK576548/

Moran, L. V., Skinner, J. P., Shinn, A. K., Nielsen, K., Rao, V., Taylor, S. T., Cohen, T. R., Cemre Erkol, Merchant, J., Mujica, C. A., Perlis, R. H., & Dost Ongur. (2024). Risk of Incident Psychosis and Mania With Prescription Amphetamines. American Journal of Psychiatry. https://doi.org/10.1176/appi.ajp.20230329

‌ NCDAS. (2024, May 2). NCDAS. https://drugabusestatistics.org/prescription-drug-abuse-statistics/

Dafna Wajszilber, Santisteban, J. A., & Gruber, R. (2018). Sleep disorders in patients with ADHD: impact and management challenges. Nature and Science of Sleep, Volume 10, 453–480. https://doi.org/10.2147/nss.s163074

‌All information in this content is intended for educational purposes only. Please seek professional advice from a healthcare provider for any health-related concerns.