Psychiatry Research Updates: Stimulants, ADHD and Bipolar Disorder

d-Amphetamine studySTIMULANTS

Misuse of d-Amphetamine

Kathryn G. Fort, MD
Fellow, Child and Adolescent Psychiatry
NYU Child Study Center
Bellevue Hospital Center

Dr Fort has disclosed that she has no relevant relationships or financial interests in any commercial company pertaining to this educational activity

Ample evidence exists to support the notion that drugs are used to enhance social situations, with different effects depending on the specific drug consumed. Based on the extent of rewarding interactions while on a drug, one is more or less apt to repeat use.

In a recent study, 36 normal, healthy adults (aged 18 to 35), with no current Axis I diagnosis but history of light to moderate recreational drug use, were engaged in a three session, double-blind study comparing placebo, 10 mg, and 20 mg strengths of d-amphetamine. Participants completed three tasks in counterbalanced order (“counterbalanced” means the tests were presented in every sequence possible).

In the first task, called the visual probe task (VPL), subjects were shown pictures of actor’s faces posing one specific emotion next to that of a neutral emotion. Data was gained from whether the subject initially gazed toward the emotional or the neutral face (called “initial attentional bias”) and the time looking at the emotional face versus the neutral face. Both were measured (resulting in “total attentional bias”) with electrooculography.

In the second task, called the dynamic emotion identification task (DEIT), subjects were shown a procession of pictures of posed emotions and were asked to push a button when they had identified the emotion. During this timed task, the subjects’ facial responses in the zygomatic and corrugator muscles were measured by electromyography (EMG).

In the third task, called the talking task, subjects conversed with the research assistant about an important person in their life as the number of words spoken was measured.

Amphetamine did not affect initial or total attentional bias during the VPL. The DEIT task showed that amphetamine 20 mg slightly, but significantly, lowered the intensity of emotions in the pictures required for identification of the emotion, with negative emotions (ie, fear, anger, sadness) requiring lower intensities than happiness. Amphetamine also increased the subjects’ facial response to increasingly negative emotions, but not to happy ones. The talking task demonstrated amphetamine’s significant effect on increased talking.

The authors report that although amphetamine did not alter attention, identification, or reactivity to happy emotion, as they had predicted, the increased response to negative emotions was a key finding. They argue that the stimulant medication may increase one’s sensitivity to subtle cues of emotion, which positively effects talkativeness and thus improves social connectedness. They surmise that positive reinforcement from socialization then increases the desire to repeat drug use.

Alternatively, the authors and past research (Dawe et al, Curr Opin Psychiatry (2009) 22:269-273) suggest the increased perception of negative expressions when using amphetamines may contribute to feelings of paranoia.

Despite the limitations of the study—small sample size with light drug use, and inability to systematically vary the drug-taking environment—the main finding that the drug lowered the intensity needed to identify negative emotional expressions is significant, and may lead indirectly to amphetamine’s abuse potential. The increase in socialization acts as a reinforcer, thus promoting further amphetamine use. authors suggest that further research be completed investigating the synergistic effects between drugs and social environments (Wardle MC et al, Psychopharmacology 2012;223:199-210).

CCPR’s Take: This study may not generalize to the younger child psychiatry population because of the targeted small sample of adults without Axis I pathology, but it may shed light on the reasons for abuse and/or diversionary tactics in our more vulnerable population, particularly college-age kids.


ADHD is Persistent and Undertreated

Ruth Gerson, MD
Clinical assistant professor
Department of Child and Adolescent Psychiatry
NYU School of Medicine

Dr. Gerson has disclosed that she has no relevant financial or other interests in any commercial companies pertaining to this educational activity.

The seminal study of preschool ADHD, the Preschool ADHD Treatment Study (PATS), examined the efficacy of stimulant medication (methylphenidate) when added to parent training in preschoolers age three to five years old (Greenhill L et al, JAACAP 2006;45(11):1284-1293). This multicenter, randomized trial has now published its six-year follow-up data, with important findings for anyone treating patients with ADHD.

The initial PATS study took a sample of children aged three to five years old who met criteria for ADHD through interviews and a rigorous battery of scales (including both parent and teacher Connors rating scales). The study enrolled their families in a 10-week parent-training course, and then randomized the children to a double-blind, placebo-controlled trial of methylphenidate. Treatment lasted up to 10 months, and after the completion of the study, children engaged in community treatment at their parents’ discretion.

In this follow-up study, children were assessed again at three years, four years, and six years after the completion of the original study. Sixty-eight percent of children in the original study participated in all three follow-up assessments. Demographic factors did not differ in those who were lost to follow-up compared to those who participated, although baseline symptom severity was not examined as a predictor of attrition.

At six-year follow-up, almost 90% of children (now an average age of 10.4 years old) still met criteria for moderate-to-severe ADHD. While the authors (and clinical wisdom) expected hyperactivity and impulsivity to decline with age, there was no significant decline in any of the symptom categories with age. While the majority of the participants (almost 75%) were boys, girls were rated higher on symptoms of both inattention and hyperactivity/impulsivity. Comorbid ODD or conduct disorder predicted greater ADHD symptoms, and lower IQ was associated with greater inattention.

What is most striking about this study is that so many children continued to experience moderate-to-severe ADHD symptoms at follow-up despite the fact that a majority of them were on medication (mostly stimulants). The authors struggle to explain this, lacking more detailed data about dosing and compliance with medication. The finding suggests, however, that community providers may be under-treating these children, and if they are not using rating scales like the Connors to assess for efficacy, may not realize that these patients are still quite impaired and in need of additional medication, further parent training and support, or evaluation for comorbid learning disorders or other conditions (Riddle MA et al, JAACAP 2013;52(3):264-278e2).

CCPR’s Take: ADHD in preschoolers is real and persists through school age. We should titrate medication carefully in these cases, and consider monitoring response with rating scales or other objective measures of residual symptoms. Is it possible that stimulants stop working as well over time? There’s no evidence of this, but it certainly hasn’t been well studied, either. More studies— and our own clinical experience keeping track of concrete measures—will tell us if this is a dosing problem, an efficacy problem, or something else.


Early Intervention for Youth at Risk for Bipolar Disorder

Sharon M. Kahler, MD
Clinical Instructor of Child and Adolescent Psychiatry
NYU Child Study Center

Dr. Kahler has disclosed that she has no relevant relationships or financial interests in any commercial company pertaining to this educational activity.

Bipolar I and II disorder (BD I and II) together affect an estimated 2.5% of US adolescents (Merikangas KR et al, Arch Gen Psychiatry 2012; 68(3):241-251), and there is little argument that they result in significant morbidity. Symptoms can often be seen prior to the onset of BD— as early as 10 years beforehand—and many youth who are diagnosed with BD not otherwise specified (BD NOS), Major Depressive Disorder (MDD), and cyclothymia will ultimately go on to develop BD.

Is it possible that early psychosocial interventions, targeted at high risk youth for the development of BD could stabilize mood symptoms and perhaps impede the progression to BD? Recent research suggests that it might be. Family focused therapy (FFT), which, in prior studies has been associated with more rapid and complete remission from depressive episodes in adolescents with BD I and II, may help to do just that.

In a recent randomized trial researchers looked at 40 youth ages nine to 17 at high risk for progression to BD I and II, defined as having BD-NOS, MDD, or cyclothymia with active mood symptoms and at least one first degree relative with BD I or II. Participants were randomly assigned to either FFT-High Risk Version (FFT-HR), which entailed 12 sessions of communication and problem-solving skills training and psychoeducation, or a control group that received one or two family education sessions.

The researchers hypothesized that youth assigned to the FFT-HR group would recover more quickly, spend more time in remission, and have greater improvement in symptoms over a one-year period. A secondary aim was to examine the benefits of FFT-HR for those in families of high expressed emotion (EE) compared to families of low EE. Youth included in the study were also allowed to receive pharmacotherapy, and assignments to FFT-HR vs control were balanced accordingly for medications, age, and initial diagnosis.

As predicted, researchers found that youth assigned to the FFT-HR group recovered more quickly than those in the control group, in 13 weeks compared to 21.25 weeks, a significant difference. Furthermore, those in the FFT-HR group spent a mean of 28.6 weeks in full remission compared with 19.5 weeks in the control group, also a statistically significant difference. Over the one- year period, the youth in the FFT-HR group had a more favorable trajectory of scores on the Young Mania Rating Scale, though not on the child Depression Rating Scale. Overall, youth in high-EE households did significantly worse than those in low-EE households in time to recovery from initial symptoms, and over the follow-up period were more likely to remain symptomatic. Notably, however, FFT-HR had a greater treatment effect on youth from high EE vs low EE households (Milkowitz DJ et al, JAACAP 2013;52(2):121-131).

CCPR’s Take: The small sample size was a limitation to this study. In addition, basic differences in the treatment conditions compared with the control conditions (mean number of contacts 12.43 vs 2.26 respectively) make it unclear if favorable response was due to the content of the contact or frequency and number of hours of contact. Nonetheless, FFT-HR may be a non-pharmacological intervention worth considering for youth who are at high risk for development of bipolar disorder, especially for those who come from high EE households. The favorable effects of FFT-HR found in this study suggest that it may be worthwhile to conduct further research in this area.

Psychiatry Research Updates: Stimulants, ADHD and Bipolar Disorder

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This article was published in print 6 & 7/2013 in Volume:Issue 4:3&4.


APA Reference
Psychiatry Report, T. (2016). Psychiatry Research Updates: Stimulants, ADHD and Bipolar Disorder. Psych Central. Retrieved on April 19, 2019, from


Scientifically Reviewed
Last updated: 25 Jul 2016
Last reviewed: By John M. Grohol, Psy.D. on 25 Jul 2016
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