Stimulant-Induced Punding and Stimulant Discontinuation-Induced Manic-Like Symptoms in a Preadolescent Male

Introduction

Punding is a medical term used to describe drug-induced, complex, prolonged, purposeless, and stereotyped behaviors (including sorting, handling, grooming, cleaning, and disorganized tidying up) that resembles stereotyped grooming by animals on a high dose of stimulants. It was initially described in patients who chronically misuse amphetamines and was later also associated with Parkinson's disease patients on dopamine agonists. Punding is generally associated with dopamine dysregulation (Evans et al. 2004; Fasano and Petrovic 2010).

There are also limited data describing similar behaviors in children prescribed stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) although these are usually mild and the term “punding” has not been used. The hypothesis is that the obsessive stereotyped behaviors are part of the spectrum of stimulant-induced abnormal movements such as tics (Borcherding et al. 1990).

Medication-induced mania is a relatively better-studied phenomenon (Viktorin et al. 2017). Antidepressants and rarely stimulants have been implicated in inducing mania in patients diagnosed with bipolar disorder (Perugi et al. 2017). However, mania occurring on medication discontinuation is rare and usually associated with antidepressants. We are unaware of mania induced by discontinuation of a stimulant.

Case Report

We present an interesting case of a 12-year-old boy with long-standing ADHD combined type who appeared to have stimulant-induced punding and stimulant discontinuation-induced manic symptoms. A second opinion was sought when he developed manic-like symptoms after each of three consecutive trials of discontinuing lisdexamfetamine (LDX) for his ADHD. Parents wanted to know if he had bipolar disorder.

History of Present Illness

Toby is the second of five children. He had been an easy baby who fed and slept well. However, when he first started nursery school at age 3 years, his teacher reported that he did not stick with anything and was disorganized in his play. He was so physically active, the Committee on Preschool Special Education gave him sensory-integration therapy and a “shadow” at school for a few hours a day to facilitate participation in group activities. Fortunately, Toby was a good-natured child who often got silly but was not a behavior problem. However, he always had learning problems in reading and math, which required support services.

Work became noticeably harder in fourth grade, but he had two teachers who “loved him” and Toby was willing to work hard as a result. However, because of a decline in academic performance in fifth grade, an increase in distractibility, impulsivity, and disruption in class as well as oppositional behavior at school when more work was demanded, parents decided to switch Toby to a smaller school. He was hyperactive, impulsive, and distractible there as well, which impacted learning and peer relationships.

Psychoeducational testing did not reveal any intellectual reason for his struggles. An abbreviated WISC V revealed a full-scale IQ of 93, verbal comprehension of 81, working memory of 103, and processing speed of 111. Reading, math, and written language achievement standard scores were in the high 80s; language testing was within normal limits with the exception of pragmatic language where it was noted he was sometimes off topic.

Parents consented to a trial of stimulant medication and Toby began taking LDX 30 mg. Focus and activity level improved initially with some associated decline in appetite and ability to fall asleep. However, after a week, he started to appear overly anxious, picked at his lips and bit, and chewed objects. He became hyperfocused, able to do only one activity at a time and perseverated relentlessly on it. His preferred activity was drawing and would draw and redraw the same objects over and over again with reams of paper devoted to this. He could not play with other children because he could not stop what he was doing and transition to playing with peers.

After 3 weeks, with doctor consent, parents stopped the LDX. Within a day, Toby's personality completely changed. He became frenetic and driven, not just hyperactive. He also became markedly irritable and angry. He engaged in previously unwitnessed and inappropriate behaviors, including “mooning people” and using “toilet language.” Parents described it as “ADHD on steroids.” This phase lasted for about 3 days and then abruptly stopped. TOBY returned to his baseline.

With teachers begging for help, a few days later, Toby's psychiatrist suggested a change from LDX 30 mg to liquid extended release methylphenidate 40 mg, which continued for a week but did nothing for ADHD symptoms. He was placed back on LDX at 20 mg, augmented with guanfacine 2 mg. However, TOBY once again became significantly anxious and perseverative, spending hours on drawing and doodled excessively in class. He often times got stuck and could not get things out of his head. Nevertheless, he remained on this regimen for almost 2 months. Parents used the next school vacation to give Toby a medication holiday and within 24 hours he again started to display significantly inappropriate and impulsive behaviors. This was more than the return of his ADHD symptoms. He became hypersexual, inappropriate, provocative, verbally assaultive, and extremely hyperactive with inexhaustible energy. This lasted for 10 days and then abruptly stopped in time to return to school at which point his medication regimen was resumed.

Toby's anxious, obsessive, perseverative behaviors returned, and after 2 days, parents decided they wanted medication stopped permanently. Within a day, he became frantic, impulsive, and aggressive. He tried to jump out of the car, threw a bottle at a police officer, set fire in a store, exposed his privates in public, left his house barefooted, fought often with his siblings, and used profane language with strangers—all of which was completely unlike his baseline behaviors. In school, he destroyed other children's papers, stole items of nontrivial value, lied, and provoked other peers. His reckless behaviors and potential danger to himself prompted psychiatric hospitalization.

Over the next month in hospital, Toby's physical aggression and severe irritability required multiple pro re nata (PRN) medications and restraints. He was initially treated with risperidone up to 2 mg for 4 days, which was ineffective, then switched to olanzapine, which was increased from 2 to 20 mg (including the PRNs). Toby was diagnosed with acute mania and lithium was started and increased to 1200 mg with a level of 1.09 meq/L. Metformin was also added for the olanzapine-induced weight gain of 15 lbs. It took 2 weeks before his behavior was calm enough that PRN medication was not needed. By 1 month, he returned to about 90% of baseline and was discharged home. His ADHD symptoms were present but no evidence of anxious perseverative behaviors.

Family History

Dad is a teacher. Mom is a home maker. They are in their late 30s. They have an intact marriage. Although there is a family history of learning issues, there is no real history of either ADHD or any kind of mood or developmental disorder.

Second Opinion

After discharge, parents objected to Toby's sedation and weight gain on olanzapine so it was gradually tapered. They wanted a second opinion about whether he needed to continue taking lithium and felt that his manic episodes were secondary to LDX. At time of his re-evaluation 3 months later, Toby was taking Lithium 900 mg/day (subtherapeutic). As part of the re-evaluation, besides providing the aforementioned history, parents and teachers completed rating scales, including the Swanson, Nolan, and Pelham scale (SNAP-IV) (Swanson et al. 2012; Bussing et al. 2008) and Children's Mania Rating Scale (CMRS) (Pavuluri et al. 2006). The former clearly evidenced ADHD but with little oppositional behavior. The CMRS score was low (5; ≥20 is indicative of mania).

Mental Status Examination

Toby presented as a well-dressed prepubertal male. He was somewhat guarded but cooperative and remarkably distractible, fidgety, and impulsive, getting up and touching various objects around the office. He spoke in a fast monotone that was difficult to understand and also jumped from topic to topic. His speech was not pressured, however, and he was not overly talkative. He described his mood as being “a little happy” but was certainly not elated.

When asked to recall his behavior, Toby said he felt “scared” during the times where he was being reckless. He voiced the family's opinion that the medication made him do “bad things.” He reported that “I went to my cousin's house without shoes, without letting mom know.” (He was only wearing pajamas.) When asked what prompted him to do something like that he reported that he was “angry” but could not recall the reason for being angry. He also reported that he “jumped out of the car and jumped on a truck.” He confessed to stealing from mother's wallet, starting a fire at the dollar store, and throwing a bottle at a policeman. He said he felt guilty about his “dangerous behaviors” but did not feel embarrassed talking about them. He was not able to recall whether he felt euphoric or sad during those times. He admitted he lost his temper often and cursed and swore when he was mad. He felt speeded up, not just hyperactive. “It made me fast. I had tons of energy.” There was no grandiosity, but Toby perceived himself as a likeable, “funny kid who says funny jokes, is talented and who enjoys school.”

With regard to depression, Toby persistently denied feeling sad or crying even once in a while. He scored only 2 out of 27 on the Children's Depression Inventory, noting only “not wanting to be with people many times” and “I have to push myself many times to do my school work.” His score on the Multidimensional Anxiety Scale was also minimal with some endorsement of generalized worrying about death and anxiety related to performing in front of others.

Toby recognized his struggles with attention and concentration. When the examiner pointed out his distractibility he replied “I have too much stuff on my mind. If I want I could concentrate but it makes me tired.” He reported that “When I'm doing something a thought pops up in my mind, so I want to do something else.” He was asked whether his inattention and inability to remain on task interfered with his ability to complete his homework. He said “I do my homework first because I want to go outside and play.”

Parents were advised that Toby's recurrent manic behaviors did sound medication related, but that only follow-up would confirm this. They preferred the risk of recurrence off prophylactic lithium to taking a drug he did not need. They were provided with close psychiatric follow-up.

Formulation and Discussion

How do we explain what appeared to be three manic episodes starting a day after stopping LDX in a child who also exhibited significant levels of obsessive stereotyped behavior on LDX. His ADHD history before starting stimulants was uncomplicated. There was no evidence of mania. His manic symptoms were much worse than a return to baseline after medication had worn off.

Since Toby's manic episodes took place not during but after LDX was stopped, we could not call them stimulant-induced mania (Perugi et al. 2017). Rebound irritability, which begins as stimulant medication levels drop, usually occurs within hours not days after stopping medication (Carlson et al. 2003). It is not accompanied by protracted frantic impulsive hypersexual behavior.

Toby had no immediate or remote family history of a bipolar disorder. The real question is whether these apparent recurrent drug-discontinuation-related manic episodes are a manifestation of toxicity or are prodromal to actual bipolar disorder (Goldstein et al. 1999). Although the answer requires longitudinal follow-up, so far, in the absence of LDX, Toby has shown no recurrence of manic episodes.

One clue suggesting an abnormal drug response is Toby's overly anxious and obsessive behaviors, such as excessive doodling for several hours at a stretch, being stuck and persistent in activities, and being unable to transition to another activity—behaviors that were triggered by taking LDX. Borcherding et al. (1990) described very similar behavior occurring in 23 of 45 stimulant-treated children. This seems to fit the description of punding, which is a phenomenon generally associated with dopamine dysregulation.

Dopamine dysregulation has been studied most in conjunction with Parkinson's disease. Long-term dopamine replacement therapy for Parkinson's disease can cause not only punding but also impulse control disorders such as pathological gambling, hypersexuality, aggressive, and hypomanic behaviors (Evans et al. 2004; Mizushima et al. 2012). It is possible that for Toby, LDX, a long-acting amphetamine, produced not only an excessive amount of dopamine but also more effectively blocked reuptake that led to punding (Cruickshank and Dyer 2009). Relatedly, there is also a condition called dopamine agonist withdrawal syndrome (Pondal et al. 2013), which may occur when otherwise healthy mesocorticolimbic dopamine neurons get overstimulated by dopamine replacement therapy (e.g., l-Dopa in Parkinson's disease). Perhaps LDX stimulation of dopamine production and release acted in that way in Toby. Stopping dopamine replacement therapy leads to a state that resembles methamphetamine salt withdrawal, and symptoms include anxiety, agitation, irritability, dysphoria, and insomnia. Withdrawal is self-limiting but can be protracted. We hypothesize that this may explain Toby's punding and subsequent agitation and manic-like symptoms.

The worsening of behavior with each successive episode suggests a kindling phenomenon. Repetitive stimulant administration may be associated with progressive increases in duration and increasingly pathological behavior (Post and Kopanda 1976).

In conclusion, we tend to agree with Toby's parents that he had a very rare drug response and does not have bipolar disorder at this time. Whether he develops it spontaneously in the future remains unclear. His ADHD symptoms will need to be managed behaviorally or with medication that does not involve the dopamine system.

This case, although seemingly rare, suggests that we need to know more about punding in children taking stimulants. Other than rating scales that ask about anxious/nervous behavior or nail biting, there are no inquiries into some of Toby's symptoms. Furthermore, if the child does have significant symptoms of punding, drug withdrawal should be done very gradually to avoid a dopamine withdrawal syndrome.