ADHD

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1. A 25-year-old saleswoman recently got promoted to sales manager and oversees 3 other sales reps. She used to excel in the fast-paced world of sales, but has hit a roadblock since her promotion. The additional pressure causes her to be disorganized in the consolidation of her department sales and the write-up of her monthly reports. She gets especially incapacitated when she has to troubleshoot inaccuracies in the books and she has lost three company phones in the last month. What brain area is most likely impaired in this woman?

A. Dorsolateral Prefrontal Cortex

B. Prefrontal Motor Cortex

C. Orbital Frontal Cortex

D. Supplementary Motor Cortex

The correct answer is A.

A - Correct. Sustained attention is hypothetically modulated by the cortico-striatal-thalamic-cortical loop involving the dorsolateral prefrontal cortex (DLPFC). Inefficient activation of the DLPFC can lead to problems following through or finishing tasks, disorganization and trouble sustaining mental effort; the patient exhibits all of these symptoms. The dorsal anterior cingulate cortex is important in regulating behaviors including losing things, being distracted, and making careless mistakes. This area is certainly also inefficient in this patient.

2. It is that time of year again: you are training a psychiatry intern, and taking her along to see your patients. Your last patient of the day is Tom, a 20-year-old pro skateboarder. His impulsive and inattentive symptoms have been stabilized on 25 mg/day of damphetamine (Dexedrine). He has heard that immediate release stimulants can have abuse potential, so he would like to switch to an extended release amphetamine formulation. He asks for more information. Which correct explanation is given to Tom by your intern?

A. All extended release amphetamine formulations lack abuse potential

B. The prodruglisdexamfetamine is the only amphetamine to date that may truly lack abuse potential

C. Only OROS and SODAS formulations lack abuse potential

D. Only the patch lacks abuse potential

- Correct. Long-acting formulations have lower capacity for abuse, and certainly diversion, and the prodrug of amphetamine, lisdexamfetaminedimesylate (Vyvanse), might be the drug that does this best, and might truly reduce chances of experiencing euphoria and thereby reduce abuse potential, although the FDA has not allowed that language in the label. Lisdexamfetamine needs to be ingested, and enzymatically converted in the gut to become effective. Its gradual onset and its chemical structure-which ensures that, no matter how the drug is put into the body, the kinetics replicate those associated with oral administration-prevent an easy way of abusing it.

3. Your neuroscience teacher has just flown through the difference between methylphenidate and amphetamine, and phasic versus tonic stimulation leading to abuse. As you did not catch everything, you are collecting your friends' notes. While your friends' versions explain the difference between methylphenidate and amphetamine similarly, they all differ on the explanation between pulsatile versus tonic stimulation. Which version is correct?

A. Pulsatile stimulation amplifies undesirable phasic DA and NE firing, which can lead to euphoria and abuse

B. Immediate release stimulants lead to tonic firing, which can lead to euphoria and abuse

C. Tonic firing is the result of rapid receptor occupancy and fast onset of action as seen with extended release formulations

D. Extended release stimulants result in phasic stimulation of NE and DA signals, but this does not lead to euphoria and abuse

A
A - Correct. Pulsatile delivery of stimulants can cause a frequent and rapid increase in NE and DA, and this amplifies phasicfiring. Phasic firing is hypothetically associated with reward, feelings of euphoria, and abuse potential.

4. Scarlet, a 25-year-old bar tender, was diagnosed with ADHD at age 10. She has been on and off medication since then; first on immediate-release methylphenidate, then on the patch. She has experimented with illicit drugs during her late adolescence and is still a heavy drinker. After a few years of self-medication with alcohol and cigarettes, she is seeking medical attention again. You decide to put her on 80 mg/day of atomoxetine (Strattera), one of the non-stimulant medications effective in ADHD. Why does atomoxetine lack abuse potential?

A. It decreases norepinephrine levels in the nucleus accumbens, but not in the prefrontal cortex.

B. It increases dopamine levels in the prefrontal cortex but not in the nucleus accumbens.

C. It modulates serotonin levels in the raphe nucleus.

D. It increases dopamine in the striatum and anterior cingulate cortex. B - Correct. The prefrontal cortex lacks high concentrations of DAT, so in this brain region, DA gets inactivated by NET. Therefore, inhibiting NET in the prefrontal cortex increases both DA and NE. As only a few NET exist in the nucleus accumbens,

atomoxetine does not induce an increase in DA and NE in the nucleus accumbens, the reward center of the brain, thus atomoxetine does not have abuse potential.

. Patrick, a 15-year-old high school student, has trouble finishing his math tests within the allotted time because he gets easily distracted. In his English literature class, his grades are poor because of careless spelling mistakes. His pediatrician suggests testing his selective attention using the ____________ to see if the ____________ is aberrantly activated on an fMRI*. (*this is a hypothetical question, as imaging techniques, while important research tools, cannot, to this date, be used for diagnostic purposes)

A. Stroop Task; orbital frontal cortex

B. N-back Test; prefrontal motor cortex

C. Stroop Task; anterior cingulate cortex

D. N-back Test; dorsolateral prefrontal cortex

C
C - Correct. The Strooptask is used to test selective attention. In the Stroop task, the participant is shown words that are written in a different color. The goal is to name the color in which the word is written, not read the word itself. For example, if the word "blue" is written in "red," then the correct answer is "red." The anterior cingulate cortex is involved in this type of task, and will activate when the participant does this task. Inefficient activation of the anterior cingulate cortex is related to symptoms such as paying little attention to details, making careless mistakes, not listening, and getting distracted; these are all symptoms that Patrick is experiencing.

. Tammy, whose inattention and hyperactivity responded well to a daily dose of 0.2 mg of clonidine, comes to see you because she has been put in charge of a huge project at work and is afraid of failing to properly manage it. You agree to increase her dose to 0.3 mg/day for the time of this project only. A few weeks later she comes back saying that, after successfully completing her project, she went on vacation to relax with her friends and experienced extreme dizziness and drowsiness when they went to the hotel sauna. Additionally, she had forgotten to pack enough clonidine so she had not been taking any for the last few days. At her yearly physical yesterday, her PCP said that her blood pressure was extremely high. What could have happened?

A. The session in the sauna led to her high blood pressure

B. The rapid discontinuation of the medication led to the high blood pressure

C. The rapid increase in medication dose led to high blood pressure

D. High blood pressure can be experienced on vacation as a rebound effect following a high stress period

The correct answer is B.

The most common side effects of clonidine include sedation, dizziness, dry mouth, constipation, fatigue and weakness. These can be exacerbated at doses higher than 0.2mg/day. A - Incorrect. Extreme heat, such as saunas, can exacerbate the common side effects of clonidine. The common side effects include: sedation, dizziness, dry mouth, constipation, fatigue, and weakness. B - Correct. Tammy is experiencing high blood pressure due to rapid discontinuation of the drug. When clonidine is stopped, it should be tapered to avoid rebound effects, including nervousness and increased blood pressure. C - Incorrect. High blood pressure is not normally a side effect of clonidine. D - Incorrect.

7. A mother brings her 17-year-old daughter, Clarice, to see you. Clarice has been successfully treated with 40 mg/day of sustained release d,l-methylphenidate (Ritalin SR) for 3 years. However, she has recently become irritable and secretive, and comes home late with no explanation. Her mother has noticed that she has been stealing money from her purse. Her performance in school is sliding and the teacher has brought up her lack of attention. What do you do next?

A. Raise the dose of methylphenidate to 60 mg/day to deal with break-through symptoms

B. Switch Clarice to 40 mg/day of immediate release d,l-methylphenidate (Ritalin) and suggest psychoeducation

C. Switch Clarice to 60 mg/day of atomoxetine (Strattera) and screen for substance use disorder

D. Stop pharmacotherapy and monitor progression of symptoms

The correct answer is D.

Clarice could potentially show signs of non-adherence, due to the reemergence of some of her symptoms (inattention). This could be a sign of her diverting or abusing her medication. The mood issues mentioned by her mother, in conjunction with her stealing money, are warning signs of a potential substance use disorder. A - Incorrect. A dose of 40 mg/day of sustained release d,l-methylphenidate is already at the high end of the dosage range, so it would probably be wise not to raise the dose in this patient. B - Incorrect. It would not be recommended to switch this patient to an immediate release stimulant in light of her potential substance use disorder. Psychoeducation might be advisable, in terms of teaching her about comorbidities in ADHD and the need of treatment. C - Incorrect. Once it has been determined whether Clarice is diverting/abusing her current medication, she could be switched to atomoxetine, as it is approved in children, adolescents, and adults, and it lacks abuse potential.Screening her for substance use disorder could be wise. D - Correct. However, the best thing might be to stop the medication altogether in this patient, establish a new baseline, and make sure she is both compliant and not abusing drugs. Then, a stimulant can be reinstituted with more confidence.

8. Peter, a 35-year-old stockbroker, has been advised by his supervisor to come and see you, the company mental health consultant. His supervisor is complaining that he often comes late to appointments, is inappropriately fidgety, interrupts people during meetings, has been offensive towards coworkers, and has been known to party excessively on weeknights. Peter asserts that he is just fine; he has a lot of projects on his mind and is simply standing up for himself when speaking with others. He likes to go out in the evenings to unwind. Recognizing probable ADHD you are interviewing both the patient and his work buddy, who is a longtime friend. How would you start your questions?

A. Compared to his parents, how often does the patient...

B. Compared to other people his age, how often does the patient...

C. Compared to his childhood, how often does the patient...

D. Compared to his children, how often does the patient...

The correct answer is B.

The symptoms of ADHD can present differently in patients at different ages. While hyperactivity is a main symptom in children for example, this will most likely translate into internal restlessness in adults. A and D - Incorrect. While ADHD has a strong genetic component, it is not advised to ask him first to compare himself to either his children or his parents. An accurate family history however would be beneficial. B - Correct. When trying to diagnose this adult patient with ADHD, it is preferable to first ask him to compare his behavior to the one of other adults his age, as this will give a better idea of the severity of his symptoms at this time. C - Incorrect. While it is important to obtain a medical history, the patient might not have the best recollection and might not be the best judge of his behaviors as a child.

9. You have been treating 32-year-old Robert for ADHD for many years. He has been very happy with his response to atomoxetine (100 mg/day). Recently he came to see you, somewhat agitated and aggressive, complaining that he can't eat, feels like his heart is racing, and his sexual performance has dramatically declined. He says nothing has changed in his life, except for the fact that his PCP put him on paroxetine for probable anxiety. You know that paroxetine is an inhibitor of CYP450 2D6. What type of drug interaction could be at play here?

A. Atomoxetine is an inhibitor of CYP450 2D6, therefore the dose of both drugs should be increased

B. Atomoxetine is an inducer of CYP450 2D6, therefore the dose of paroxetine should be increased

C. Atomoxetine is metabolized by CYP450 2D6, therefore the dose of atomoxetine should be decreased

D. His side effects are not from these drug interactions; atomoxetine does not interact with the CYP450 2D6 enzyme

C - Correct. Thus in the presence of paroxetine, the dose of atomoxetine should be decreased. While sexual dysfunction and decreased appetite could be a side effect of paroxetine, increased heart rate and hypertension are most likely caused by increased levels of atomoxetine. Theses side effects can become serious and need attention.

10. Your colleague asks you for advice on how to treat an ADHD patient with severe liver damage caused by many years of heavy drinking. You know that while most medications used for ADHD should be used with caution or not at all in patients with cardiac impairments; there is only one drug that requires special care when prescribing it to a person with liver impairment. Which drug is it?

A. lisdexamfetamine

B. d-methylphenidate

C. d,l-methylphenidate

D. atomoxetine

E. d,l-amphetamine

F. d-amphetamine

D
D - Correct. Atomoxetine needs to be adjusted in patients with hepatic impairment. For patients with moderate liver impairment, the dose should be reduced to 50% of the normal dose. For patients with severe liver damage, the drug should be reduced to 25% of the normal dose. In addition, atomoxetine itself can rarely cause severe liver damage.

1. A 6-year old child has numerously been asked by the teacher to remain seated during class and to pay attention. While these symptoms can be bothersome to the class, the impulsivity of the child to blurt out her thoughts and yell out answers is most distracting. Which brain area is most likely out of tune in this child?

A. DLPFC

B. Dorsal ACC

C. Subgenual ACC

D. OFC

2. Sheila, a 25-year old college student, is very good in her arts classes, which often comprise shorter projects. She struggles in the classes in which she has to stay focused for long periods of time, or when she is asked to find solutions to different types of tasks. Her doctor suggests testing her sustained attention using the ____________ to see if the ____________ is aberrantly activated on an fMRI.

A. Stroop Task; orbital frontal cortex

B. N-back Test; prefrontal motor cortex

C. Stroop Task; anterior cingulate cortex

D. N-back Test; dorsolateral prefrontal cortex

D3. When prescribing an antidepressant to an ADHD patient on atomoxetine,

it is important to remember that

A. atomoxetine is an inhibitor of CYP450 2D6

B. atomoxetine is an indcuer of CYP450 2D6

C. atomoxetine is not metabolized by CYP450 2D6

D. atomoxetine is metabolized by CYP450 2D6