Background: A common neurodevelopmental disorder referred to as Attention Deficit Hyperactivity Disorder (ADHD) has a first line treatment of stimulant medications in school-aged children and adolescents . A common comorbidity found in children and adolescents with ADHD is schizophrenia. Because ADHD patients are 4.3 times more likely to develop schizophrenia , comorbid conditions should be taken into account when prescribing stimulant medications. The presented case suggests that amphetamine use in adolescents with ADHD and early-onset schizophrenia can exacerbate the symptoms of psychosis.
Case Report: A 16-year-old male with a six-year history of ADHD presented to the Emergency Department with altered mental status and bizarre behavior first day. The patient presented with an acute onset of negative (eg, apathy, poverty of speech, latent response, flat effect) and positive (paranoia and response to internal stimuli) symptoms of schizophrenia while taking Vyvanse 60 mg daily for ADHD. During his stay, Vyvanse was discontinued and he was given 0.5 mg of Risperdal twice daily and 10 mg of Zyprexa as needed. Over the remains of hospital stay, the patient became more cooperative, able to follow commands, and able to complete activities of daily living with direction. On follow-up with the patient over a six-month period, he became withdrawn from his peers and family and had continued to have symptoms of paranoia. He also continued to respond to internal stimuli and at times exhibited aggressive behavior. The acute onset of hallucinations, paranoia, and negative symptoms with the use of Vyvanse and the improvement of symptoms with the discontinuation of Vyvanse suggest that the stimulant medication contributed to the exacerbation of the psychotic symptoms observed in this case.
Conclusion: The significant factors that must be noted in this case are the symptom variation with and without the use of stimulant medication, the acute onset of symptoms and the lack of history of psychiatric disorders other than ADHD. These factors suggest that the stimulant medication played a role in the acute-onset of schizophrenic symptoms. We believe that further studies are needed to determine an algorithm for treating children and adolescents with less invasive methods prior to considering stimulant medication.
Two neurodevelopmental disorders that can profoundly interfere with or reduce the quality of and individual’s life are Attention Deficit Hyperactivity Disorder (ADHD) and schizophrenia. In recent studies, these two conditions have been thought to have a possible link, which will be discussed in this document. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) states that “people with ADHD show a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.’ ADHD can be classified as three different types: hyperactive/impulsive, inattentive, and combined. Each classification has its own definition and characteristics. Characteristics that make up the hyperactive/impulsive subtype are restlessness, fidgeting, excessive talking, difficulty remaining seated, and inability to inhibit behavior. These symptoms typically peak at seven to eight years old and by adolescence they may give more mild symptoms including feelings of restlessness and inability to settle down. The inattentive subtype of ADHD is characterized by: difficulty maintaining attention, distractibility, organization difficulties, forgetfulness, and avoidance of tasks requiring constant mental effort. These symptoms are apparent by age eight to nine and persist throughout life. ADHD and schizophrenia can share similar characteristics and risk factors. Schizophrenia is a mental health condition with symptoms categorized as positive symptoms (hallucinations, delusions, disorganized thoughts and behavior, paranoia, and agitation), negative symptoms (social withdrawal, poor hygiene, flat affect, avolition, anhedonia, alogia), and cognitive symptoms (deficits in working memory, attention, processing speed, and intellectual functioning). Various literature and studies have shown overlapping symptoms occurring in both ADHD and schizophrenia, which include: inattention, thought disorders, and psychosis (occurring in about 10% of patients with ADHD). “Youth with early-onset schizophrenia frequently show greater premorbid deficits in attention, learning, and socialization” against those who develop schizophrenia as adults . Comorbidities are very common and create a risk in certain populations, for example, schizophrenia is found in the ADHD population 4.3 times more frequently than the regular population . A genetic component of the pathogenesis between schizophrenia and ADHD has been shown due to the likelihood of first-degree relatives of patients with ADHD to receive a diagnosis of schizophrenia more commonly than second-degree relatives of patients with ADHD .
A study conducted in 2013 showed that when geneticists analyzed ADHD patients that were children and schizophrenic patients that were adults there was a statistically significant genetic component that led to the susceptibility of a comorbid condition . Up to 90% of schizophrenia cases and between 60-80% of ADHD cases may result from inheritances . Environmental factors can affect a person, before birth or during childhood and adolescence in both conditions. Due to the facts presented above, comorbid conditions should be taken into account when prescribing stimulant medications. Treatment given in ADHD aids in balancing brain chemical levels that are originally altered by having the condition. These first line medications include stimulants. The prescribed stimulants increase dopamine levels in the brain. Many studies  have shown that an increasing amphetamine regimen has been used to induce a psychosis-like state in mice. Beside stimulant medications in ADHD, schizophrenia which is a dopamine imbalance is primarily treated by dopamine blocking agents . Former studies have demonstrated that patients with schizophrenia have excess amphetamine-induced dopamine (DA) release in the striatum compared to controls . This excess release gives insight into how the stimulants used to treat ADHD could trigger psychosis in patients with comorbid schizophrenia. A recent study found that patients treated with amphetamines (eg, Vyvanse, Adderall) for ADHD have double the risk of developing a psychotic episode when compared to treatment with methylphenidate . The presented case suggests that amphetamine use in adolescents with ADHD and early-onset schizophrenia can lead to emergence or exacerbation of psychotic symptoms.
A 16-year-old male with a six-year history of ADHD presented to the Emergency Department (ED) with altered mental status and bizarre behavior first day. The patient had unintelligible and nonsensical speech along with inappropriate disrobing and agitation. At times, he would continuously repeat the phrase: “red light, green light, blue light, ABC.’ The patient denied auditory and visual hallucinations. He has no past medical history of psychotic episodes. The patient had never been diagnosed with autism or developmental delay, however the parents noted that he began to walk by 18 months, speak at 30 months, and toilet trained at 3 years old. His mother also stated that the patient had delays in emotional and social development. His parents denied any psychiatric disease or illness in the family or any history of suicide attempts. The family denied any prior medication or drug use except for Vyvanse (60 mg daily). Vyvanse was prescribed for the treatment of ADHD, which was diagnosed at 10 years old. The patient denied seizures, loss of consciousness, and traumatic brain injury. There was no additional family history or diagnostic history provided by the patient or his parents. His highest level of education is three years of high school is above average academic achievement. In the ED, he received 1 mg of Ativan and 5 mg of Haldol for agitation. The patient’s, vitals showed: normal temperature at 36.9 C, tachycardia at 108 bpm, and hypertension at 154/97 mmHg.
The patient’s abnormal labs are highlighted as follows: BUN/Creatinine ratio 11.5 (Low), and direct bilirubin 0.3 mg/dL (High). All other labs (CMP, BNP, PT/PTT, LFT, renal function test) were normal including his neutrophil count at 69.5%, lymphocyte count at 22.0% and absolute lymphocyte count at 1.52. Following medication administration in the ED, the patient’s toxicology screen was positive for amphetamines and benzodiazepines. Cocaine, cannabinoids, barbiturates, opiates, and PCP screenings were all negative. A brain CT without contrast was performed; there were no abnormal findings. The patient was medically cleared and admitted to the psychiatric unit for further evaluation. Upon admission to the psychiatry unit the next day, laboratory abnormalities were noted: neutrophil count increased to 76.8% (High), lymphocyte count decreased to 13.4% (Low), and absolute lymphocyte count decreased to 0.9. The patient remained in the psychiatry in-patient unit for seven days. On initial evaluation, the patient was able to clearly state: “I feel like I am going crazy” and “I don’t know why I am here.’ The patient was a poor historian due to an inability to effectively communicate in disorganized thoughts and incomprehensible speech. On examination of his mental status on admission, he was alert and oriented to person and place, but not to time. Although tearful, he was attentive and cooperative. His affect was labile and thought disorganized. His speech was pressured and at times incomprehensible with stuttering and inappropriate volume. He denied hallucinations, delusions, paranoia, obsessions, compulsions, and phobias. He also denied suicidal ideation. The following day, he was observed to be withdrawn, grossly disorganized, affectively flattened, and responding to internal stimuli. His speech continued to decline and became incoherent on subsequent evaluation. His Vyvanse was then discontinued and he was given 0.5 mg of Risperdal twice daily and 10 mg of Zyprexa as needed. The patient continued to have bizarre behaviors such as: inappropriate disrobing, agitation, and response to internal stimuli.
The dose of Risperdal was then increased the following day to 1 mg twice daily. He continued to give negative symptoms (affective flattening, poverty of speech, apathy, and latent response), however after the increase in Risperdal, he stated that he was feeling better. Over the remains of the hospital stay, the patient became more cooperative, able to follow commands, and able to complete activities of daily living with direction. He was discharged on day eight with a plan to follow up with his psychiatrist and psychologist for further evaluation and therapy. The patient was discharged with Risperdal 1 mg twice daily and Vyvanse 60 mg once daily. One week later, he arrived to the crisis psychiatric unit due to continuous ongoing symptoms of bizarre behaviors such as: agitation, inappropriate disrobing, inability to care for himself, and response to internal stimuli. At the first interview, he was cooperative, but unable to hold meaningful conversations and proceeded to respond with abnormal vocalizations resembling grunts. He appeared to be frustrated by his inability to communicate. The patient was then admitted to the psychiatric in-patient unit due to disorganized speech and behavior that placed him at the risk of harming himself. During the intake interview, he was unable to explain the reason for admission and nonverbal report such as pointing and gesturing was preferred over verbalization. During follow-up interviews, the patient began to use one-word answers (i.e., “good,’ “yes,’ and “no”) besides hand gestures when answering questions. He appeared to understand the stated questions and could reply with one-word answers, however, he was unable to provide further explanations when queried for additional details. He continued to appear frustrated by his inability to communicate.
During his five-day stay, his behavior was disorganized, intrusive on the privacy of others, agitated, and at times sexually preoccupied. He also presented with hallucinations and paranoia. During his stay, Vyvanse was again discontinued. On the final day in the in-patient unit, the patient denied depression, paranoia, and suicidal and homicidal ideation. The patient was then discharged with Risperdal 1 mg twice daily and was informed to discontinue Vyvanse and follow up with his psychiatrist for further evaluation of an early onset of schizophrenia with psychosis exacerbated by amphetamine use. On follow-up with the patient’s psychiatrist over a six-month period, we were told that he began to become withdrawn from his peers and family. He recovered many of his ability to communicate verbally, however he continued to respond to internal stimuli as well as exhibit paranoia. He was taking Risperdal 1 mg but gained over 20 pounds so he was switched to Ability 20 mg PO HS. We were also informed that the patient has only one friend he talks too and has become a loner. The patient is also very paranoid and at times he can get quite aggressive. His current diagnosis is Schizophrenia, while he still has ADHD the psychostimulants could exacerbate his psychosis, so the decision remained to keep the patient off Vyvanse.
In the case example, amphetamine use exacerbated symptoms of psychosis in an adolescent male diagnosed with ADHD and early-onset schizophrenia. Dalsgaard et al. (2014) discovered that there was a correlation between having ADHD as a child and having schizophrenia as an adult leading to a 4.3 times more likely chance when comparing with children without ADHD. This event demonstrates awareness among practitioners regarding the association between ADHD and schizophrenia for the implementation of proper treatment regimens. This case illustrates a patient who presented with an acute onset of negative symptoms (i.e., apathy, poverty of speech, latent response, flat effect) and positive symptoms (i.e., paranoia and response to internal stimuli) of schizophrenia while taking Vyvanse 60 mg once daily for treatment of ADHD. On discontinuation of Vyvanse and administration of antipsychotic medication, the patient’s symptoms improved. He became cooperative and able to complete activities of daily living with assistance.
On follow up over a six-month period, he continued to respond to internal stimuli and to exhibit paranoia and aggressive behavior, solidifying the diagnosis of early-onset schizophrenia. Right example illustrates that stimulant medications exacerbated psychotic symptoms in this patient, as an acute onset of psychosis occurred with the use of Vyvanse, yet these symptoms diminished when Vyvanse was discontinued. The results are congruent with findings from previous research that showed an association between exposure to prescription stimulants and an earlier age of the onset of psychosis . The link between ADHD and schizophrenia requires further research.
Although these conditions differ significantly in presentation, they can occur simultaneously and can also share symptoms. How exactly, they overlap is still unclear. Some patients with ADHD may develop psychosis or symptoms of schizophrenia, while patients with known schizophrenia may develop symptoms of ADHD. Although not typical of ADHD, thought disorder and psychosis can occur in both schizophrenia and ADHD. Because around 10% of people with ADHD experience psychotic phenomena it raises whether or not these phenomena are triggered by stimulants used as ADHD treatment . It is known fact that the striatal dopamine transporter density differs in patients with ADHD who have received stimulant medications in comparison to those with ADHD who have not taken stimulants . This event indicates that stimulant medication can change brain chemistry and therefore opens the door to exploring additional alterations that may be influencing the development of schizophrenia later in life. Even, it has been shown that ADHD patients prescribed stimulant medications have an increased risk of having a psychotic episode . Because stimulants are agents that increase dopaminergic activity, working antagonistically to antipsychotics, clinicians should be cautious when prescribing stimulants to patients with or at risk for schizophrenia.
Unfortunately, there are currently no clear guidelines for clinicians with a treatment regimen for patients with suspected ADHD who also have significant risk factors for the development of schizophrenia. The regimen would need to allow for the risk-benefit ratio of treating ADHD or ADHD like symptoms versus exacerbating possible underlying schizophrenia. This event is especially important because although greater than 50% of adults with schizophrenia meet the criteria for another psychiatric disorder in early adolescence, the most common of these comorbidities is with ADHD. . The presented case demonstrates through an example that discontinuing stimulant medications may aid in decreasing psychotic symptoms in adolescents with similar presentations. This event implies that stimulant medications may not be most appropriate medication for this patient population. Gough and Morrison (2016) make a few suggestions regarding the treatment of ADHD in adolescents who give comorbid schizophrenia. First, it is recommended to treat the psychosis before treating the ADHD. If significant inattention persists, they suggest prescribing non-stimulant medication to prevent exacerbation of psychotic symptoms along with behavioral therapy and counseling so as to improve attention, focus, and impulsiveness. If a step up in treatment is required for ADHD symptom persistence after placement on non-stimulant medications, it is recommended to perform a stimulant trial, however if psychosis worsens, the stimulant should be discontinued.
Due to the atypical presentation of this case, it was difficult to immediately diagnose and treat the patient as the symptoms pointed towards an extensive differential. It was important to re-evaluate the patient at six weeks, three months, and six months following the primary acute psychotic episode so as to exclude certain diagnoses. The significant factors that must be noted here are the symptom variation with and without the use of stimulant medications, the acute onset of symptoms and the lack of history of psychiatric disorders other than ADHD. These factors suggest that the stimulant medication contributed to the acute-onset of schizophrenic symptoms. ADHD, a neurodevelopmental disorder, can present as a solitary condition, or it may also present with schizophrenia. ADHD and schizophrenia share similar characteristics and can be confused with one another due to overlapping symptoms such as inattention, thought disorders, and psychosis. On initial diagnosis, practitioners must take great care to diagnose the correct condition as the treatment options drastically differ. “Symptom history should be supported by collateral information from multiple caregivers and settings and ideally supported by the results of cognitive or psychoeducational assessment” . Stimulant drugs are the first line treatment for ADHD and they work antagonistically to antipsychotics by increasing dopaminergic activity. In some patients, this increase in dopamine levels can induce psychotic phenomena. With the rapidly rising rate of amphetamine prescriptions for the treatment of ADHD, keep in mind the associated risks of psychosis and exacerbation of underlying schizophrenia. Physicians should remember that amphetamines have double the risk of having a psychotic episode in comparison to methylphenidate, which has similar efficacy. This case presents multiple avenues for future studies and potential changes in the timeline of prescribing stimulant medication to those with ADHD. In light of the possible, serious long-term risks that stimulant medications can have on a child and adolescent with ADHD and comorbid schizophrenia, alternative methods for treatment should be considered.
There are numerous studies on non-medicinal treatments and techniques that can be used for ADHD such as cognitive behavioral therapy, regular exercise, and improved sleep hygiene. These treatments should be offered before using stimulant medication that could have long-term risks. In addition to using non-medicinal treatment prior to considering stimulant medications, we also suggest discontinuing the stimulant medication and considering the use of a non-stimulant concerning ADHD with comorbid schizophrenia as to not induce or exacerbate psychosis. Further study is needed to evaluate the link between stimulant medication and psychosis in children and adolescents with ADHD and comorbid schizophrenia. Even, further study is needed to determine an algorithm for treating this subset of children and adolescents with less invasive methods prior to considering stimulant medications. Also, since the effect of stimulant medication on the development of schizophrenia is unknown, studies should be conducted to explore schizophrenia in patients with ADHD and a history of stimulant use in contrast to those without a history of stimulant use.
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