Psychosis with methylphenidate or amphetamine in patients with ADHD

Moran LV, Ongur D, Hsu J, Castro VM, Perlis RH, Schneeweiss S. Psychosis with Methylphenidate or Amphetamine in Patients with ADHD. N Engl J Med. 2019 Mar 21;380(12):1128-1138.

Abstract

BACKGROUND:

The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied.

METHODS:

We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases.

RESULTS:

We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09).

CONCLUSIONS:

Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.).

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Methods

Researchers assessed patients 13 to 25 years of age who were diagnosed with ADHD and who started taking methylphenidate or amphetamine between January 1, 2004 and September 30, 2015 using data from two commercial insurance claims databases.

A new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis was the assessed outcome.

They estimated hazard ratios for psychosis using propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, comparing psychosis incidence between the two stimulant groups, and then pooling the results across the two databases.

Results

A prescription for a stimulant for ADHD was received by 337,919 adolescents and young adults.

Researchers analyzed 221,846 patients with 143,286 person-years of follow up; they matched 110,923 patients taking methylphenidate with 110,923 patients taking amphetamines.

In the matched populations, 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) were reported (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09).

https://www.mdlinx.com/journal-summaries/psychosis-methylphenidate-amphetamine-adhd/2019/03/22/7561460?spec=neurology