Adults who use high doses of amphetamine-based ADHD medications, such as Adderall, have a five-fold increased risk of developing psychosis or mania. This risk is particularly high among those who use 30 mg or more of dextroamphetamine, and up to 81% of cases of psychosis or mania could be prevented by reducing the dose.
During the COVID-19 pandemic, significant concerns have arisen about people’s mental and emotional health, including increased behavioral problems and difficulties in accessing mental health services.
In addition to the direct impacts of the virus, the stress caused by social isolation, remote learning, financial hardship, and movement restrictions have exacerbated the need for psychological and psychiatric support.
The pandemic has increased global rates of depression and anxiety by 28% and 26%, respectively. Suicide rates have increased to a multi-year high, with 13.5 deaths per 100,000 population in 2020 and rising to 14.1 in 2021. There has also been an increase in symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents.
Additionally, overdose deaths involving opioids rose from 49,860 in 2019 to 80,411 in 2021. During the pandemic, disruptions in opioid addiction treatments and limited access to medications for opioid use disorder (MOUD) have been sources of concern, as many patients rely on such care.
To ensure access to medications, the use of telemedicine increased during the early part of the pandemic. Exceptional measures allowed healthcare professionals to remotely prescribe controlled substances, including ADHD and opioid medications, without the need for an in-person visit and even to patients in other states. Thus, substances such as buprenorphine, benzodiazepines, and stimulants were more easily accessed.
Previous research on the impact of the pandemic on medication prescribing has generally been limited to small, targeted samples.
This study, in contrast, analyzed comprehensive national prescription data from the United States covering the period April 2018 to March 2022.
Medications were observed for five main classes: antidepressants, benzodiazepines, class II (C-II) stimulants, non-stimulant ADHD medications, and buprenorphine MOUD.
This study focused on “incidental” prescriptions, i.e., new treatments initiated for patients who had not used the same class of medication in the previous 12 months.
The goal was to understand how the pandemic affected treatment initiation for different mental health needs, rather than counting total use, to capture the immediate effect of the pandemic on prescribing patterns.
Between April 2018 and March 2022, incidental prescriptions for these drug classes increased from approximately 51.5 million to 54 million.
There was a significant increase in nurse practitioner prescriptions for all drug classes, with the highest demand for C-II stimulants and ADHD medications among young adults aged 20 to 39 and women.
On average, prescriptions for C-II stimulants and non-stimulant ADHD medications grew more rapidly during the pandemic, surpassing pre-pandemic trends after a small decline early in the pandemic period.
However, prescriptions for buprenorphine MOUD temporarily declined, although without a significant change in the overall trend. Prescriptions for antidepressants and benzodiazepines also remained relatively stable.
The sharp increase in the use of C-II stimulants and ADHD medications suggests a possible response to growing demand but also raises concerns about the appropriateness and control of prescribing for these medications. Taking a high dose of ADHD medications is linked to a fivefold increased risk of developing psychosis or mania.
This research is among the first to find a link between increasing doses of the medications—amphetamines in particular—and an increased likelihood of psychotic symptoms. The medications include Adderall, Vyvanse, and generic amphetamines such as dextroamphetamine.
The link between amphetamines and psychosis is not new. Amphetamines increase levels of dopamine in the brain. The neurotransmitter plays several roles in the body, including memory, motivation, and mood, but it is also implicated in psychosis.
Medications can flood the brain with dopamine, and when you flood the brain with dopamine, you can potentially cause psychosis. What had not been established was that the risk of psychosis increased with higher doses, a phenomenon is known as the “dose-response relationship”.
A case-control study using electronic health records was conducted to compare the odds of incident psychosis or mania with the previous month’s exposure to prescription amphetamines.
Case participants were patients aged 16 to 35 who were hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. Control participants were patients with an initial psychiatric hospitalization for other reasons, most commonly depression and/or anxiety.
A) Prescription of Methylphenidate or Amphetamine and B) Number of Psychotic Episodes by Age at Cohort Entry and Year of Cohort Entry. The bars in Panel B represent the number of patients who started taking a stimulant, by year of cohort entry; the dotted and solid lines represent the number of psychotic episodes by year of cohort entry. A psychotic episode was defined as a new diagnostic code for psychosis and a prescription for an antipsychotic medication.
Amphetamine doses were converted to dextroamphetamine equivalents and divided into tertiles. Secondary analyses assessed the odds of psychosis or mania with methylphenidate use.
Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for subjects with past-month prescription amphetamine use compared with no use.
A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with a 5-fold increased odds of psychosis or mania. Use of methylphenidate in the past month was not associated with increased odds of psychosis or mania compared with no use.
Although the use of hospitalized controls excludes individuals with less severe illness, leading to selection bias, the study results suggest that caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania.
Therefore, future studies are needed to distinguish between legitimate increased demand and overprescribing, as well as to develop more specific guidelines for prescribing ADHD medications.
READ MORE:
Risk of Incident Psychosis and Mania With Prescription Amphetamines
Lauren VM, Joseph PS, Ann KS, Kathryn N, Vinod R, Trevor T,
Talia RC, Cemre E, Jaisal M, Christin AM, Roy HP, and Dost O
American Journal of Psychiatry, Volume 181, Number 10
Abstract:
Amphetamine prescribing has increased in the United States in recent years. Previous research identified an increased risk of incident psychosis with prescription amphetamines. The purpose of this study was to examine the impact of dose levels of prescription amphetamines on the risk of this rare but serious adverse outcome. A case-control study using electronic health records was conducted to compare the odds of incident psychosis or mania with past-month exposure to prescription amphetamines. Case subjects were patients ages 16–35 hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. Control subjects were patients with an initial psychiatric hospitalization for other reasons, most commonly depression and/or anxiety. Amphetamine doses were converted to dextroamphetamine equivalents and divided into terciles. Secondary analyses evaluated the odds of psychosis or mania with methylphenidate use. Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for individuals with past-month prescription amphetamine use compared with no use (adjusted odds ratio=2.68, 95% CI=1.90–3.77). A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with 5.28-fold increased odds of psychosis or mania. Past-month methylphenidate use was not associated with increased odds of psychosis or mania compared with no use (adjusted odds ratio=0.91, 95% CI=0.54–1.55). Although the use of hospitalized control subjects excludes individuals with less severe disease, leading to selection bias, the study results suggest that caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania.
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