Pretest self-assessment question (answer at the end of the case)
Which of the following do not appear to have marked weight-loss adverse effects when treating children with ADHD?
A. Guanfacine–ER (Intuniv)
B. Clonidine-ER (Kapvay)
C. Atomoxetine (Strattera)
D. Lisdexamfetamine (Vyvanse)
E. A and B
F. A, B, and C
G. All of the above
Patient evaluation on intake
Nine-year-old presents with his parents who note that they are having a hard time managing him at home and at school
He is “not like their other kids”
Psychiatric history
At age six, they noticed increasing anxiety regarding things such as attending school, death, dying, and incurring illnesses
He would often walk in circles and flap both arms intermittently throughout the day in response
– This increases as his anxiety escalates
– He is “thinking about things” and is restless
– Thoughts may be positive, have a fantasy component, or be daydream-like while walking
– Denies having negative, hostile thoughts
– Does not feel controlled, like he is being forced or told to do this
– Does not have hallucinations or delusions
– Walking in circles does not seem to foster a reduction in anxiety and does not seem repetitive enough where he loses hours of productivity
– He has no other stereotypic movement or functional fixedness issues
– He does have tactile sensitivity with certain food textures and does not like to be hugged or touched, but is amicable and affable
– He does not appear to be rigid or oppositional
Around this age, he developed greater inattention, inability to focus, hyperactivity, and impulsivity, which have gradually escalated over the last two years
– These symptoms now interfere with schooling and have caused him to be held back to repeat one grade
He is a gregarious child who has friends and sustains reciprocal friendships and relationships
There is no evidence of combativeness or violent behavior
Walking in circles occurs at home only now as he is able to control this at school. However, his inattentive and hyperactive symptoms continue and are apparent at home, school, soccer, at the mall, etc., and are pervasive
Recently, the patient is more aware that he is impaired and not moving through school at the same rate as other children
He now finds things to be “difficult,” “boring,” problematic, and his self-esteem is suffering
– At times he is sad, but there is no evidence of MDD, psychotic disorder, or bipolar disorder
Social and personal history
Patient is a third grader
Parents are married and he has three younger siblings
He likes some sports, reads a lot, and plays video games
He was born by normal delivery and reached usual developmental milestones
Medical history
There are no acute medical problems
Used to be roughly at the 50th percentile for height and weight, but since medications were issued by his pediatrician one year ago, he has dropped gradually toward the 10th percentile
The pediatrician is not currently concerned as the family has shorter stature and feels the patient has not lost significant enough weight or “fallen off the growth curve”
There is no personal, nor any family medical history of cardiac issues
The patient does not have any tics or other abnormal involuntary movements
Family history
Mother may suffer from GAD
There is no clear family history of ADHD, intellectual or developmental disorders
Medication history
Started an SSRI, fluoxetine (Prozac), 20 mg/d given by his pediatrician one year ago for the anxious symptoms
Started lisdexamfetamine (Vyvanse) 20mg/d three months ago in addition to the SSRI
– Tolerating this well, but with minimal additional effectiveness
– Previously, D-methylphenidate-XR (Focalin-XR) 10–20mg/d caused him to become sad and emotionally labile
– Methylphenidate transdermal (Daytrana) patch caused heart palpitations and increasing anxiety at 20 mg/d, and was discontinued
– The parents do not attribute his anorexia and gradual weight loss to these stimulant trials as this began earlier with the SSRI monotherapy
Psychotherapy history
Sees a therapist every one to two weeks
Parents have tried many positive reinforcement strategies with little effect
Patient evaluation on initial visit
The patient presents with mild anxious symptoms, but reports his generalized worrying about multiple topics has greatly diminished, as has his walking in circles, since starting the SSRI
The greater clinical problem is inattention, hyperactivity, and impulsivity, which have only minimally responded to an SSRI, low-dose stimulant, and behavioral modification attempts
May now be underweight and short in stature
Current psychiatric medications
Fluoxetine (Prozac) 10 mg/d (SSRI)
Lisdexamfetamine (Vyvanse) 20 mg/d (stimulant)
Question
Is it possible that the SSRI is causing his weight loss instead of the more commonly accused and more often guilty stimulant?
Yes, in depression and anxiety studies, the SSRIs have been associated with appetite suppression and weight-loss adverse effects. Anorexia is noted in 7% of adults treated acutely with fluoxetine and 4% with sertraline
No, the SSRIs cause weight gain and appetite increase more often than weight-loss adverse effects
No, the stimulants are well known for their approved use, and off-label use as appetite suppressants in obese patients
No, the stimulants are well known for anorexia and weight-loss adverse effects while treating ADHD
Attending physician’s mental notes: initial evaluation
The patient’s anxiety appears to predominantly contain multifocal worries consistent with GAD, but his repetitive walking behaviors seem to be more in line with OCD
His repetitive movements and arm flapping could be related to mild ASD (formerly Asperger’s disorder in DSM-IVTR), but he has no other ASP symptoms
Regardless, his worries and repetitive behaviors seem controlled; but if history is accurate, his nearly curative SSRI is causing excessive weight loss and enuresis when used at higher therapeutic doses
Does meet ADHD, combined-type diagnostic criteria, and these symptoms are the most problematic for now
Case is complicated by current side effects and previous stimulant trials have been ineffective due to intolerability
Question
Which of the following would be your next step?
Remove the SSRI as his weight loss is problematic
Remove the stimulant as it is the most likely weight-loss agent
Switch to another SSRI in hopes of better tolerability
Switch to another stimulant in hopes of better tolerability
Switch to a novel antidepressant class to continue anxiolysis
Switch to a nonstimulant ADHD-approved medication
Further maximize his current medication regimen
Attending physician’s mental notes: initial evaluation (continued)
Anxiety is so well controlled that removing the SSRI could make things worse
ADHD is poorly controlled so the stimulant should be raised
It is clear that his parents are concerned immensely about his weight and height but it is unclear if the patient is truly at risk or falling off his growth curve, as the pediatrician is non-committal about this finding currently
Case outcome: initial visit
Parents are fully informed and educated about the risks and benefits of both his current medications
After coming for consultation, they are ambivalent about any changes due to the fact:
– That they have had negative effects from previous stimulants and increasing this one worries them
They refuse an increase in his dose, and state they will consider this and call back
– That they have had good effects from the SSRI, and despite current side effects, would not want his anxiety to return
As the patient has been in remission from his anxiety symptoms now for several months, they do reluctantly agree to lower his fluoxetine (Prozac) down to 5 mg/d to lower his side-effect burden and hopefully continue its effectiveness
Further investigation
Is there anything else you would especially like to know about this patient?
What about his collaborating pediatrician and his findings?
– A release of information is obtained
– The pediatrician states that starting the fluoxetine SSRI clearly promoted secondary enuresis at the higher 20 mg per dose
– It is not clear if the weight loss and growth retardation is from the SSRI, the multiple stimulant trials, his genetics, or normal, as he has not fallen off his growth curve yet
– His height and weight trajectories have diminished but are not an imminent problem
– The pediatrician suggests that psychotropics continue to be prescribed as his psychiatric symptoms are the most disruptive and problematic now
– He will consider endocrine and developmental geneticist consultations if these adverse effects worsen and become a clinical dilemma
– He confirms there are no cardiac concerns for this patient and approves use of stimulants. An EKG is not warranted
Is there any reason why he might be vulnerable to side effects from his low-dose psychotropics?
– Fluoxetine (Prozac) is clearly known as a strong inhibitor of the CYP450 2D6 isoenzyme system in the liver
Psychopharmacologists often have to lower doses of other augmentation agents, such as aripiprazole, atomoxetine, desipramine, etc., when fluoxetine is part of the regimen
Amphetamine stimulants are a substrate for CYP450 2D6 and may need to be lowered when combined with fluoxetine in some patients, or they may experience stimulant intoxication or toxicity
Methylphenidate-based stimulants are unlikely to be subject to a drug–drug interaction involving his SSRI via CYP450 isoenzymes
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