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JtT

Jane,

I just need a discussion response to each of these 2 posts. I will post their case studies as well. Thanks!

Post

a response to the following:

· Provide the case number in the subject line of the Discussion.

· List three questions you might ask the patient if he or she were in your office. Provide a rationale for why you might ask these questions.

· Identify people in the patient’s life you would need to speak to or get feedback from to further assess the patient’s situation. Include specific questions you might ask these people and why.

· Explain what physical exams and diagnostic tests would be appropriate for the patient and how the results would be used.

· List three differential diagnoses for the patient. Identify the one that you think is most likely and explain why.

· List two pharmacologic agents and their dosing that would be appropriate for the patient’s ADHD therapy based on pharmacokinetics and pharmacodynamics. From a mechanism of action perspective, provide a rationale for why you might choose one agent over the other.

· If your assigned case includes “check points” (i.e., follow-up data at week 4, 8, 12, etc.), indicate any therapeutic changes that you might make based on the data provided.

· Explain “lessons learned” from this case study, including how you might apply this case to your own practice when providing care to patients with similar clinical presentations.

peninah

Volume 2 Case 21: Hindsight is always 20/20 or Attention Deficient Hyperactive Disorders

COLLAPSE

Top of Form

Hindsight is always 20/20, or attention deficit hyperactivity disorder

31-year-old man with a chief complaint of anxiety of “different types” • Patient states that he “has been successful in graduate school, has financial worries, but states that he worries and is tense most of the time”.

Questions/Rationale for Patient

· What triggers your anxiety?

Rationale: This question helps gather baseline information to determine if the patient recognizes the factors that triggers his anxiety. Knowing the triggers can help the patient foresee and combat the anxiety before it gets worse.

· What decreases the anxiety?

Rationale: The patient’s knowledge of how to reduce the feeling of anxiety by having the coping skills, would be a tool for a better quality of life. Determining how to reduce the condition helps the patient participate in his own treatment, to achieve better outcomes.

· What is your current anxiety level on a scale of 0 – 10?

Rationale: This is an important question to determine the condition that the patient is currently in when this interview is taking place. This helps the provider know the level of anxiety that the patient considers to be high and low, and if they took any medication or used any coping skills prior to the visit.

Questions to ask the Family

Patient’s wife

1. What changes do you notice when your husband is at the peak of his anxiety?

Rationale: Getting the wife’s take is important to get a history of changes in behavior that may be affected during periods of anxiety. The patient may not be aware of these changes himself, so a close associate would be the best resource for this.

2. Has your husband been fully compliant with his medication regimen?

Rationale: This is a very important question to determine compliance of the patient’s regimen. Knowing whether the the patient is taking his medication as ordered would determine if the provider needs to educate of importance of compliance or review and revise the medication (Hamed et al., 2015).

3. When did this disorder start and what triggered it?

Rationale: The patient’s spouse would be a good historian when the husband started to experience anxiety and what caused it. It is important for the provider to understand the source of his anxiety, in order to treat the patient holistically.

Physical Exams and Diagnostic Testing

It is important to begin the interview by gathering good data regarding the history of his condition, is it chronic, intermittent, triggers, initial attack. Determining whether the medication regimen is working is essential to his treatment; has he engaged in any non-pharmacological treatments like Cognitive Behavioral Therapy? (Danielson et al., 2018).

Tests that can be done include:

Thyroid Stimulating Hormone test- This test is important because hyperthyroidism may have similar symptoms as anxiety and should be ruled out (Ströhle et al., 2018).

The Vanderbilt Assessment Scale – A 55 question assessment to check for ADHD and other disorders such as oppositional-defiant disorder, anxiety, and depression.

Differential Diagnosis

1. Generalized Anxiety Disorder

With the display of symptoms including restlessness, financial worries, difficulty concentrating that effect daily functioning, it is possible that GAD is a possible diagnosis. Chronic anxiety symptoms for a long time get in the way of activity of daily living and can affect the patient’s health outcome

1. Trauma

Trauma can cause many similar symptoms that are exhibited in ADHD. Such symptoms include difficulty concentrating, difficulty sleeping, disorganization, hyperactivity, and can be seen in both conditions

1. Post-Traumatic Stress Disorder (PTSD)

Both PTSD and ADHD are accompanied by symptoms such as increased worry that does not wade, agitation and irritability, lack of concentration.

1. Panic Disorder

The patient displays symptoms of anxiety and panic disorder with difficulty breathing, nausea, diaphoresis.

Medications

Stimulants such as methylphenidate (Ritalin 2.5–5 mg/dose twice daily), and amphetamine (Adderall 5 mg BID), are best for ADHD, and work to increase norepinephrine and dopamine neurotransmission in the brain. Methylphenidate works by stopping the presynaptic dopamine transporters of central adrenergic neurons and the Amphetamines increases the release of catecholamine to increase the release of dopamine, which helps the patient have a better environmental response (Martinez-Raga et al., 2017).

Lessons Learned

As an advanced nurse practitioner, it is important to base treatment on comprehensive data from the patient and other contacts close to him. To treat the patient, it is important to consider all possible diagnoses before prescribing medication and recommending non-pharmacological treatments such as CBT and DBT (Coghill & Seth, 2015).

References

Coghill, D., & Seth, S. (2015, November 19). Effective management of attention-deficit/hyperactivity disorder (ADHD) through structured re-assessment: the Dundee ADHD Clinical Care Pathway. Child and adolescent psychiatry and mental health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652349/.

Danielson, M. L., Bitsko, R. H., Ghandour, R. M., Holbrook, J. R., Kogan, M. D., & Blumberg, S. J. (2018). Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016. Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834391/.

Hamed, A. M., Kauer, A. J., & Stevens, H. E. (2015, November 26). Why the Diagnosis of Attention Deficit Hyperactivity Disorder Matters. Frontiers in psychiatry. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659921/.

Martinez-Raga, J., Ferreros, A., Knecht, C., de Alvaro, R., & Carabal, E. (2017, March). Attention-deficit hyperactivity disorder medication use: factors involved in prescribing, safety aspects and outcomes. Therapeutic advances in drug safety. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367662/.

Ströhle, A., Gensichen, J., & Domschke, K. (2018, September 14). The Diagnosis and Treatment of Anxiety Disorders. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206399/.

Bottom of Form

Hung

Case #14 The scatter-brained mother

COLLAPSE

Top of Form

Case #14 The scatter-brained mother whose daughter has ADHD, like mother, like daughter.

List 3 questions you might ask the patient if he or she were in your office. Provide a rationale for why you might ask these questions.

1. Have you ever been diagnosed with any mental disorders?

According to Pehlivanidis et al, (2020) ADHD mostly start in childhood. Asking this question will enable me to understand the patient’s history and help in identifying any underlying conditions that may occur alongside her ADHD.

1. Are your parents involved in your life?

It is important to know if the client’s parents are part of her life. She is a single parent and having a good support system (parents, friend, co-workers) will help to improve her outcome. The more support she has the more likely she will be able to maintain therapy.

1. Have you ever thought of killing yourself?

There is a strong comorbidity between mood and anxiety disorders. Among patient with major depressive disorder (MDD) anxiety disorders such as social phobia, panic disorder and GAD. GAD is thought to being related to MDD (Maes, et al. 2018).

Identify people in the patient’s life you would need to speak to or get feedback from to further assess the patient’s situation. Include specific questions you might ask these people and why.

· The first people I would like to talk to would be the client’s adoptive parents. I would ask them if the client had any social, physical, or emotional issues growing up.

It would be important to speak to the client’s adoptive parents to understand how she was growing up and how she did in school. It the parents did notice any behavioral disorders then did they seek treatment. If so, what kind of treatments were done.

· If possible I would like to speak with the client’s biological parents or siblings. I would ask them specifically if they suffered from any mental disorders.

May mental disorder have a genetic component. Knowing if her biological parent or siblings had any mental disorders could help with diagnosing any comorbid disorders the client might have.

· I would like to talk to the client’s daughter. I would ask the daughter what her mother is like at home.

Talking to the daughter will give me insight into what behaviors the client presents at home and how she deals with stress. ADHD patient are usually disorganized, distracted, make careless mistakes, and stressed (Asherson, Buitelaar, Faraone, & Rohde, 2016).

Explain what physical exams and diagnostic tests would be appropriate for the patient and how the results would be used.

It would be important to perform a physical exam that would include mental status exam and neurological exams. Blood work such as a CBC and CMP to ensure that she is healthy before she is prescribed medications. TSH would be important to rule out any thyroid issues. Vitamin B (thiamine) deficiency can cause cognitive, psychiatric, mood, and neurologic symptoms (Gibson, et al, 2016).

List three differential diagnosis for the patient. Identify the one that you think is most likely and explain why.

· ADHD

· GAD

· BIPOLAR

I believe that the client has ADHD with GAD. For a person to be diagnosed with ADD they have to have six or more symptoms, which the clients have met. She is disorganized, misses appointments, feels overwhelmed, hard time keeping a regular schedule and loses things. Her GAD is characterized by her excessive worrying, sleep disturbances, and irritability (Stahl, 2013).

List two pharmacological agents and their dosing that would be appropriate for the patient’s ADHD therapy based on pharmacokinetics and pharmacodynamics. From a mechanism of action perspective, provide a rationale for why you might choose one agent over the other.

· Quillivant XR 20mg daily in the morning and increase weekly by 10-20mg (max 60mg/day). I believe that this medicine is best suited to help the client. She has shown in the past that she is tolerant to Methylphenidate. This formulation is an extended release which has a 12-hour duration rather than the 4-6-hour action of older formulations (Stahl, 2014b). By blocking norepinephrine and dopamine’s reuptake it increases the quantity of those neurotransmitters to enhance the dorsolateral prefrontal cortex and improves concentration and attention (Stahl, 2013). The effects can be immediate and optimum therapeutic level may take several weeks to achieve remission (Stahl, 2014b).

· Benzodiazepines (alprazolam) is prescribed for GAD, panic disorder, and anxiety associated with depression. Alprazolam XR can be started at 0.5-1 mg/day in the morning and increased by 1mg/day every 3-4 days until desired effect (Stahl, 2014b). Alprazolam XR may be less sedating than immediate-release formulations. It is a very useful adjunct to SSRI and SNRIs in treating anxiety disorders (Stahl, 2014b).

Lesson learned

Family history is an important determinant in ADHD, and can occur in adults which can lead to other mental health conditions such as GAD. Not all medications will work the same on all patients. It is important to allow time for medication to work and reach therapeutic levels before changing medications. Adjunctive medications may be a good alternative if applied appropriately.

References:

Asherson, P., Buitellaar, J., Faraone, S. V., & Rohde, L. A. (2016). Adult attention-deficit hyperactivity disorder: key conceptual issues. The Lancet Psychiatry, 3(6), 568-578.

Gibson, G. E., Hirsch, J. A., Fonzetti, P., Jordan, B. D., Cirio, R. T., & Elder, J. (2016). Vitamin B1 (thiamine) and dementia. Annals of the New York Academy of Sciences, 1367(1), 21-30.

Maes, M., Bonifacio, K. L., Morelli, N., R., Vargas, H. O., Moreira, E. G., St. Stoyanov, D., Barbosa, D. S., Carvalho, A. F., & Nunes, S. O. (2018). Generalized anxiety disorder (GAD) and comorbid major depression with GAD are characterized by enhanced Nitro-oxidative stress, increased lipid peroxidation, and lowered lipid-associated antioxidant defenses. Neurotoxicity Research, 34(3), 489-510.

Pehlivanidis, A., Papanikolaou, K., Mantas, V., Kalantzi, E., Korobili, K., Xanaki, L, Vassiliou, G., & Papageorgiou, C. (2020). Lifetime co-occurring psychiatric disorders in newly diagnosed adults with attention deficit hyperactivity disorder (ADHD) or/and autism spectrum disorder (ASD). BMC Psychiatry, 20(1), 1-12.

Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press.

Stahl, S. M. (2014b). The prescriber’s guide (5th ed.). New York, NY: Cambridge University Press.

Bottom of Form

PATIENT FILE

The Case: Hindsight is always 20/20, or attention deficit hyperactivity
disorder

The Question: What to do when a primary anxiety disorder is fully treated
and inattention remains

The Dilemma: Residual inattention may be difficult to treat

Pretest self-assessment question (answer at the end of the case)

How does an alpha-2a receptor agonist really improve attention?

A. It lowers brainstem NE output similar to its antihypertensive effects
B. It promotes DA activity in the DLPFC secondarily
C. It lowers GABA activity, which allows greater glutamate activity in the

thalamus
D. It allows fine tuning of cortical pyramidal glutamate neurons to improve

signal to noise ratios in frontocortical information processing

Patient evaluation on intake

• 31-year-old man with a chief complaint of anxiety of “different types”
• Patient states that he “has been successful in graduate school, has

financial worries, but states that he worries and is tense most of the time”

Psychiatric history

• Has been anxious for many years, mostly since college and now
graduate school

• Working part-time and going to school part-time and feels “torn in many
directions”

• Generally is tense, restless, irritable, and worries about things even
outside school and work
– When legitimate stressors diminish, the anxiety lowers, but is still

present and discouraging
• This causes him to be argumentative and temperamental most of the

time
• He says he is active and likes to stay busy all of the time, but he wonders if

“he is doing too much, as he has no time for all of the things” he wants to do

Social and personal history

• Graduated high school, college, and is enrolled in a graduate-level
training program for family counseling

• Gainfully employed now in a clinical setting
• Married and without children
• Does not use drugs or alcohol

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PATIENT FILE

Medical history

• There are no medical issues but is allergic to penicillin

Family history

• Father has AUD
• Distant family members have probable bipolar disorder

Medication history

• There was serendipitous anxiety relief when his PCP placed him on
hydroxyzine (Vistaril) 50 mg/d for an allergic skin reaction
– This helped to “calm him down” but was only temporary

• Has taken the SSRI paroxetine (Paxil) 40 mg/d but had a difficult time
balancing its anxiolytic effects and its sexual

side effects

– Felt that he was less anxious at these higher doses of this SSRI, but

this was too problematic from a tolerability point of view
– Next changed to the slow-release preparation at a lower dose

(paroxetine-CR 25 mg/d), which better balanced efficacy and
tolerability

• Next, he responded to a radio advertisement for an anxiety research
study and he was placed on an SGRI antiepileptic, tiagabine (Gabitril), as
an augmentation strategy, which he found moderately beneficial at a
dose of 12 mg/d

Psychotherapy history

• Patient has seen a few psychotherapists for both supportive
psychotherapy and PD

• He reports having psychological issues regarding his father, who was
abusive and an alcoholic
– Psychotherapy has been very helpful
– There is no DSM-5 evidence of PTSD despite this history

Patient evaluation on initial visit
• Patient suffers from chronic GAD symptoms that fluctuate over time
• Clear stress-based, adjustment disorder-driven causes of anxiety are

superimposed over a baseline of persistent GAD symptoms
• Despite these symptoms, he is coping fairly well at work and in

relationships
• Has been compliant with medication management, but has somewhat

fragmented care in that he was seeing different providers who were
monitoring his individual medications separately

• Does not appear to be at risk for any suicidal attempts
• Experiences minor sexual side effects and fatigue from his current

medications

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PATIENT FILE

Current medications

• Hydroxyzine (Vistaril) 50 mg/d (antihistamine anxiolytic)
• Paroxetine (Paxil-CR) 25 mg/d (SSRI)
• Tiagabine (Gabitril) 12 mg/d (SGRI)

Question

In your opinion, does this combination of medications make clinical sense?

• Yes
• No

Attending physician’s mental notes: initial evaluation

• This patient has chronic GAD without many comorbidities
• His GAD exacerbations are often triggered by social stressors
• He is motivated, bright, and compliant
• His medication regimen is interesting, and even though it was provided

by three different clinicians, it makes rational sense
– First, the paroxetine-CR was causing side effects at higher doses,

thus augmenting with other agents while keeping paroxetine-CR at a
low therapeutic dose makes clinical sense

– Second, hydroxyzine (Vistaril/Atarax) was being used as an anti-
allergy medication, but it is approved as an antihistaminergic
anxiolytic

– Third, tiagabine (Gabitril) is an anti-epilepsy medication that has
failed monotherapy trials in GAD and PTSD, but has some supportive
data as an augmentation strategy for TRA when combined with
SSRIs
◦ It is a GAT1 GABA reuptake inhibitor that functions to increase

endogenous synaptic GABA levels
◦ Idiosyncratically, this may cause seizures in non-epileptics who

are prescribed this medication in off-label situations
– Fourth, this regimen facilitates serotonin by blocking the SERT, or

reuptake pump, antagonizes histamine activity at the H1 receptor,
and facilitates GABA by blocking GAT1 transporters
◦ All of these mechanisms are complementary, do not overlap in

pharmacodynamic redundancy, and look to manipulate neural
pathways involved in the etiology of anxiety

Question

Which of the following would be your next step?

• Increase the paroxetine (Paxil-CR)
• Increase the tiagabine (Gabitril)
• Increase the hydroxyzine (Vistaril)

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PATIENT FILE

• Augment the current medications with a fourth agent such as an NRI, a 5-
HT1A receptor partial agonist, or a BZ anxiolytic

• Consider him a partial responder on this regimen, which is unacceptable,
and streamline and convert him to a less complicated regimen with an
SNRI, TCA, or MAOI monotherapy

Attending physician’s mental notes: initial evaluation (continued)
• The combination the patient presents with is a good one, covering many

mechanisms of action that are individual, yet complementary
• There is a significant family history of addiction, so avoiding BZs makes

sense
• He has room to increase any one of his three current medications, but

this will likely exacerbate his sexual and fatigue-based side effects
further, which the patient will not appreciate

Further investigation

Is there anything else you would especially like to know about this

patient?

• What about details concerning his past trauma history?
– Grew up in less than ideal circumstances with an alcoholic and

verbally abusive father
– Denies overt reliving symptoms but clearly has hyperarousal (worry,

muscle tension) thought currently to be from GAD
– Denies avoidant or phobic behavior
– Feels psychotherapy has been very helpful

• What about details regarding personality style and coping skills?
– The patient is socially engaging, hard working, and very active
– If he is not working, he is exercising and being active
– Never seems to sit still as he has always been a busy person
– Keeping busy and exercising allows him to remain calm and more

focused
– Feels he would be distracted and less attentive if he did not have time

to exercise

Case outcome: first interim follow-up visit four weeks later

• Declines escalating the SSRI due to sexual side effects
• Felt tiagabine (Gabitril) dosing is reasonable but mildly fatiguing
• As hydroxyzine (Vistaril/Atarax) is the lowest therapeutically dosed of the

three, he opts to increase this up to 100 mg/d at the risk of daytime sedation
– Returns acknowledging the same symptoms as his first appointment
– States that he is too tired on the increased hydroxyzine dose to

continue it

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PATIENT FILE
Question

Do you find hydroxyzine a reasonable anxiolytic?

• Yes, for short-term, adjustment-based anxiety symptoms
• Yes, for longitudinal anxiety treatment
• Yes, especially for use in patients who cannot risk taking a BZ anxiolytic,

i.e., addictive patients
• Yes, for treating GAD and agitation but not for PD or OCD
• No

Attending physician’s mental notes: second interim follow-up visit
at two months

• This was easy in that escalating the SSRI seems to be helping
gradually

• He is now about 50% better with global improvement in his GAD
symptoms and agrees to continue the SSRI and off-label SGRI

• Will need to discuss with him long-term maintenance on the SSRI and
also some pharmacologic antidotes if his sexual side effects become
intolerable or threaten poor medication adherence in the future

• Tiagabine (Gabitril) has a limited evidence base where switching from an
SSRI to tiagabine monotherapy may maintain efficacy while alleviating
SSRI sexual dysfunction

Case outcome: second interim follow-up visit at two months

• The patient is tapered off hydroxyzine altogether and begrudgingly
agreed to try a higher dose of paroxetine (Paxil-CR) at 37.5 mg /d while
continuing the tiagabine (Gabitril) 12 mg/d
– A moderate reduction in anxiety symptoms occurs
– There were greater sexual side effects noted
– Can see the benefit of the increased SSRI dosing

• Felt to be 20%–30% better compared to the last appointment

Question

If he continues toward full symptom remission, but develops major sexual

side effects, what would you do?

• Just switch to tiagabine (Gabitril) monotherapy
• Lower the SSRI and try a less sexual side effect-prone drug, such as

bupropion-XL (Wellbutrin-XL), trazodone-ER (Oleptro), mirtazapine
(Remeron), vilazodone (Viibryd)

• Add bupropion-XL (Wellbutrin-XL) at doses of 300 mg/d or more to the
SSRI/SGRI combination to alleviate his sexual dysfunction

• Add buspirone (BuSpar) to alleviate his sexual dysfunction

317

PATIENT FILE

• Add sildenafil (Viagra) to alleviate his sexual dysfunction
• Lower the SSRI and switch to a BZ as they have lower incidence of sexual

side effects

Case outcome: interim follow-up visits through five years
• The patient completes graduate school and finds a permanent job in his

field of choice
• Reports much new performance anxiety and hyperarousal around this
• There is now stress in other areas of his life as well, but these create

more dysphoria and despondency suggesting possible onset of
depressive illness

• Tolerates the same medication regimen with good effects until late in his
fifth year of treatment when the adjustment issues and his GAD
symptoms begin to escalate

• Begins seeing his psychotherapist again, and is unwilling to increase his
SSRI any further

Question

What would you do next?

• Nothing, as the psychotherapy should address his adjustment disorder
issues

• Augment the current tiagabine plus paroxetine-CR combination with a
third agent

• Switch his currently failing combination to an SNRI

Attending physician’s mental notes: interim follow-up visits
through five years

• Patient has received a fair amount of anxiety stabilizing treatment from
his current two medications (SSRI plus SGRI) for many years

• While there are certainly adjustment disorder issues here, he does
genuinely have increased GAD symptoms

• His therapist provides PDP, thus giving him a course of CBT for his
performance anxiety is unlikely to help now, as disturbing transference
issues should be avoided

• As he is comfortable on his current medications, adding a third agent to
re-establish his remission makes sense

Case outcome: interim follow-up visits through six years

• The patient considers much of his newer stress and dysphoria to arise
from performance anxiety in his new work

• Starts propranolol (Inderal) up to 30 mg/d as needed, to use specifically
for performance anxiety symptoms, and he does well

318

PATIENT FILE

• For the baseline GAD symptoms, he continues on tiagabine (Gabitril) and
paroxetine-CR (Paxil-CR) but is augmented next with L-methylfolate
(Deplin) 7.5 mg/d
– Ideally this can boost the anxiolytic effects of his SSRI and help avoid

the need to increase the SSRI further, thus avoiding sexual side effects

Note: L-methylfolate (Deplin) is an approved medical food that may boost

the effectiveness of antidepressants in treating depression. Why might this

work in anxiety disorders?

• SSRIs treat both depression and anxiety, so should L-methylfolate
(Deplin) augmentation

• L-methylfolate theoretically enhances the one-carbon metabolic cycle,
which lends to the ability of neurons to make more monoamines, such
as serotonin

• L-methylfolate’s ability to escalate serotonin levels allows SSRIs to be
more effective in that SERT inhibition now accounts for more synaptic
serotonin availability when compared to those levels prior to
augmentation
– Essentially, the SSRI now has more serotonin to work with
– This mechanism theoretically should enhance serotonin

antidepressant or anxiolytic efficacy in TRD or TRA
• The patient does not respond to the L-methylfolate (Deplin)

augmentation and it is discontinued
• Switches to a combination strategy where the 5-HT1A partial receptor

agonist-approved GAD anxiolytic, buspirone (BuSpar) 30 mg/d, is added
to the SSRI paroxetine-CR (Paxil-CR) while the SGRI tiagabine (Gabitril)
is tapered off and deemed to be ineffective at this point
– Around this time, warnings that tiagabine may induce seizures in

certain non-epilepsy patients also led to the decision to not escalate
it further and to discontinue its use

• The combination of buspirone/paroxetine-CR failed to obtain remission

Question
What would you do next?

• Insist he change to a CBT therapist
• Augment with an alpha-2-delta calcium channel blocking antiepileptic

medication such as gabapentin (Neurontin) or pregabalin (Lyrica)
• Deem that his SSRI is also ineffective and switch to an SNRI
• Deem that his SSRI is also ineffective and switch to a BZ

319

PATIENT FILE

Attending physician’s mental notes: interim visits through year six

• This patient is appearing to have more significant TRA now
• He is being treated by a competent psychotherapist and is compliant

with his medications
• He is very agitated at times, which is interfering with his work
• Would like to use an as-needed BZ while we work out a longer-term

strategy, but worries about addiction given his family history
• Failed an SSRI, a 5-HT1A receptor partial agonist, an antihistamine

anxiolytic, and an SGRI

Case outcome: interim follow-up visits through six years
(continued)

• The patient agrees to taper off paroxetine-CR (Paxil-CR) and is started on
an SNRI, duloxetine (Cymbalta), and is titrated to 60 mg/d
– Its escalation further is limited by side effects of frequent headaches

and lightheadedness that do not dissipate with time
• During this time, he is allowed 0.5 mg as needed and uses the BZ

GABA-A receptor PAM, alprazolam (Xanax), with close monitoring for
misuse
– Misuse does not occur and the anxiolytic is clinically effective while

awaiting the SNRI to become more effective
• At the 60 mg/d monotherapy SNRI dose, the patient states that his GAD

symptoms are well controlled but not in remission
– Still has fluctuating bouts of tenseness, irritability, and worry,

regardless of situational stress
– No longer requires the as-needed alprazolam and it is

discontinued
• In addition, states that one of the main residual complaints is

inattention, inability to focus on longer tasks. This leads to actual and
perceived performance problems at work, raising his anxiety and
dysphoria further
– Interestingly, while physically injured recently and unable to exercise

for a few weeks, he realized he is routinely hyperactive
– Reflects that he has been this way “since he was a kid”

Question
Does this patient have ADHD that was missed in the initial evaluation?

• No, GAD has indecisiveness, inattention, poor concentration,
and psychomotor agitation are key symptoms that can look identical
to ADHD

• No, the ADHD was not diagnosed in his elementary school years and is
not valid as an adult diagnosis as such

320

PATIENT FILE

• Yes, his GAD has likely been treated to remission, his adjustment
disorders have resolved, and these residual symptoms are likely
comorbid ADHD that went undiagnosed for years

• Maybe, but it does not matter as inattention as a residual symptom of
GAD or from comorbid ADHD may be treated by similar medications

Attending physician’s mental notes: interim visits through year
six (continued)

• The patient’s history, in retrospect, makes a good case for long-standing
inattention, which likely predates the GAD onset

• Despite adequate GAD treatment and resolution of social stressors, he is
inattentive and not at his peak of possible wellness

• It would be a win–win situation if an augmentation agent could be utilized
that might lower his remaining anxiety and also treat his inattentive
symptoms

• As his SNRI, duolextine (Cymbalta), has full ability as an NRI, using an
ADHD-approved NRI such as atomoxetine (Strattera) would be
redundant and likely not be helpful

• Owing to intolerability, his current SNRI cannot be increased to gain
better NRI effects

• Adding bupropion-XL (Wellbutrin-XL) might act in a novel manner as a
DRI and redundantly as an NRI, would not risk addiction, but again is
partially redundant given his SNRI use

• Adding a stimulant or wakefulness-promoting agent may work well for
inattention, but escalate his anxiety as a side effect and further risk addiction

• Adding an alpha-2 receptor agonist, such as guanfacine-ER (Intuniv)
(approved for child and adolescent ADHD) might allow for an
improvement in ADHD-driven inattention or dampen anxiety further,
secondarily improving inattention
– There would be little risk of addiction or escalating his anxiety
– This drug is also an antihypertensive, hence low blood pressure may

be a risk

Case debrief
• GAD is one of the most common anxiety disorders
• GAD is one of the highest comorbidities to occur in those suffering with

adult ADHD
• A win–win situation occurs in this comorbidity when the SNRI class of

medications is able to treat the anxiety with its SNRI dual mechanism of
action, and treat the ADHD symptoms specifically with the SNRI’s NRI
mechanism
– In this case, the patient experienced a partial ADHD and GAD clinical

response, but not remission

321

PATIENT FILE

• In order not to escalate this patient’s GAD symptoms or risk addiction,
stimulants were avoided by using the ADHD medication, guanfacine-ER
(Intuniv)

• This was added to his duloxetine (Cymbalta) and titrated to 2 mg/d
• If the patient had comorbid depression (instead of GAD) and ADHD, then

a stimulant augmentation might be ideal as it would be less likely to
aggravate anxiety (which would not be present), and might carry with it
good antidepressant and procognitive effects

• In this patient, low-dose guanfacine-ER improved his attention,
concentration, and anxiety to where he was deemed to be in remission
from both GAD and ADHD

Take-home points

• There are several ways to treat GAD
• Psychotherapy, SSRI, SNRI, 5-HT1A receptor partial agonism, anti-H1

receptor antagonism, and GABA-A receptor PAM are all mechanistic ways
with solid evidence bases with regard to treating GAD symptoms

• Like depression, GAD can become more treatment resistant and the use of
combination and augmentation strategies may be utilized in a method
similar to that of treating depressive disorders, i.e., rational polypharmacy

• When combining/augmenting, clinicians should use drugs with
different mechanisms of action instead of redundant mechanisms, as this
may theoretically increase effectiveness and avoid additive side effects

• Some off-label medications may have limited data to support their use,
but understanding each medication’s mechanism of action gives
theoretical backing and permission to use it as long as the prescriber
documents the rationale behind its use

• In this case, the SGRI mechanism of tiagabine (Gabitril) would be
suggestive for anxiolysis as other medications that facilitate GABA
activity (i.e., BZs) help anxiety as well

Performance in practice: confessions of a psychopharmacologist

• What could have been done better here?

– Instead of using polypharmacy approaches with a limited evidence
base (e.g., SGRI), consider using solid approved monotherapies
earlier for GAD, such as buspirone (BuSpar), Venlafaxine-ER
(Effexor-XR), duloxetine (Cymbalta), etc.

– Instead of considering adult ADHD as a diagnosis of exclusion,
evaluate this symptom complex earlier in care
◦ Perhaps use of a rating scale, such as the ASRS would help

• Possible action items for improvement in practice

– Research typical comorbidities and presentations for adult ADHD
patients

322

PATIENT FILE

– Research diagnostic rating scales and instruments that may aid in
diagnosing ADHD in adults

Tips and pearls
• Antihypertensives are often used in psychopharmacology practice
• Prazosin, an andrenergic alpha-1 receptor antagonist, is gaining

popularity for use in treating nightmares associated with PTSD
• Propranolol, a beta-adrenergic receptor antagonist, has been a standard

approach in treating performance-type SAD for many years
– It may also aid in treating and preventing PTSD if used quickly after

exposure to traumatic events
• Clonidine and guanfacine, both adrenergic alpha-2 receptor agonists,

have been used for treating childhood ADHD, off-label, for many years
– Clonidine, especially, has been used in an off-label manner to treat

agitation and insomnia associated with anxiety disorders as well
– Slow-release preparations of clonidine and guanfacine are approved

for childhood ADHD now (Kapvay and Intuniv)

Mechanism of action moment

Why does adrenergic alpha-2 receptor agonism treat ADHD

symptoms?

• Stimulating presynaptic alpha-2 receptors in the LC, with the use of
approved antihypertensive medications within this pharmacological
family of medicines (e.g., guanfacine [Tenex] and clonidine [Catapres]),
dampens adrenergic tone by reducing NE release, and thus causes a
lowering of blood pressure

• Dampening of peripheral sympathetic, noradrenergic tone makes sense
from an anxiolytic point of view in that palpitations, diaphoresis,
tremulousness are driven by the sympathetic nervous system and
diminished by certain antihypertensives
– However, this mechanism may not explain how these drugs treat

ADHD, where good cortical noradrenergic tone is actually needed to
treat ADHD symptoms

• The slow-release preparations of these medications are now approved
for childhood ADHD (e.g., guanfacine-ER [Intuniv] and clonidine-ER
[Kapvay])
– When prescribed for ADHD, they hypothetically stimulate

postsynaptic alpha-2 receptors on cortical glutamate pyramidal
neurons, instead of those located presynaptically in brainstem
regulatory centers that control blood pressure

– Centrally in the DLPFC, these noradrenergic agonist drugs
hypothetically affect postsynaptic cortical heteroreceptors in that they
bind to alpha-2 NE heteroreceptors located upon glutamate neurons

323

PATIENT FILE

Mechanism of Action of Alpha-2a Agonists Guanfacine-ER and Clonidine

prefrontal cortex

nucleus accumbens – no action

DAT

D1 D2

NE
neuron

imidazoline
receptor

sedation
hypotension

clonidine

∝2B
∝2C ∝2A

NET

guanfacine
ER

D1 D2

DA
neuron

Figure 21.1. Mechanism of action of alpha-2a agonists guanfacine and
clonidine.

• Alpha-2 adrenergic receptors
– Are present throughout the CNS, including the prefrontal cortex, but

do not have high concentrations in the nucleus accumbens
– In particular, are believed to mediate the inattentive, hyperactive, and

impulsive symptoms of ADHD, while other alpha-2 adrenergic
receptors may have other functions

324

PATIENT FILE

• Clonidine is an alpha-2 adrenergic receptor agonist that is non-selective,
and binds to alpha-2a, -2b, and -2c receptors
– It also binds to imidazoline receptors, which contribute to its more

sedating and hypotensive effects as well
– Although clonidine’s actions at alpha-2a receptors make it a

therapeutic option for ADHD, its actions at other receptors may
increase side effects

– The slower-release preparation of clonidine (Kapvay) is approved for
ADHD, keeping drug plasma levels lower and helping mitigate these
side effects

• Guanfacine-ER (Intuniv) is a more selective alpha-2a receptor agonist,
and thus has therapeutic efficacy with a reduced side-effect profile as it
does not stimulate the alpha-2b and -2c receptors as much as clonidine
products do

• In Figure 21.2A, a DLPFC glutamate pyramidal neuron is depicted
• Situated on this neuron’s spine is an alpha-2a adrenergic heteroreceptor

and a D1 dopaminergic receptor
• These are both connected via cAMP to cation channels called HCN

channels
• If DA and NE act in concert and are in balance, binding their respective

receptors, then the HCN channels are opened to the appropriate size
allowing the pyramidal glutamate neuron to fire efficiently – not too much
and not too little

• If millions of these cortical neurons fire efficiently and in synchrony,
adequate attention and concentration theoretically occur

• In ADHD, patients may have an imbalance in this cortical system, which
allows inefficient processing with subsequent inattention

• In situations such as those with inattention due to ADHD, or even anxiety,
these HCN channels may be out of balance

• In Figure 21.2B, endogenous NE may bind to an alpha-2a heteroreceptor
and this will in turn close down its associated HCN channel
– This allows the glutamate pyramidal neuron to retain some of its

internal electrical signal (it maintains or improves its signal to noise
ratio) and to become focused on its own firing

– If this occurs, in millions of these neurons, the DLPFC may become
more efficient and allow for better focus and concentration
symptomatically

• It is at these alpha-2a receptor sites where ADHD medications such as
clonidine-ER and guanfacine-ER may exert their anti-ADHD mechanism
of action

325

PATIENT FILE

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326

PATIENT FILE

Two-minute tutorial

Using antihypertensives in psychiatric practice

• Clinicians have to be aware and competent in their use
– This may be achieved by reading each drug’s approved package

insert or by reviewing relative prescribing textbooks
• All antihypertensives are antihypertensive; therefore, a key therapeutic

effect in patients with elevated blood pressure includes a lowering of the
problematic blood pressure
– However, in psychiatric care, many of our patients treated with

antihypertensives are actually normotensive, so that lowering their
blood pressure may not be desired

• A standard of care likely should involve routine blood pressure
monitoring in the office setting of the psychopharmacologist because
– Many of our antidepressant medications that elevate NE may

increase blood pressure
– Many of our medications that increase weight gain may increase

blood pressure
– Many of our medications that antagonize alpha-2a or alpha-1

receptors may lower blood pressure
• These three things likely encompass most prescribing practices, and

therefore, should drive better use of blood pressure monitoring

Clinical pearls should include

• In those patients who are normotensive, provide adequate informed
consent and start at low doses of the antihypertensive drug being
used

• Warn of common side effects: lightheadedness, dizziness,
orthostasis, and syncope

• Suggest patients start treatment on a day where they can afford to lie
down and not drive, if they need to combat fatigue or hypotensive side
effects

• Initially suggest patients also increase fluids and salts if these side
effects occur

• Start at a lower than normal dose when compared to patients
suffering from essential HTN, and titrate more slowly to avoid side
effects

• Consider teaching the patient to self-monitor at home with a
commercially available automated blood pressure cuff/system

• A win–win scenario may occur if the patient is hypertensive from an
idiopathic or iatrogenic point of view
– For example, if the patient becomes hypertensive on an SNRI

(iatrogenic) or comes to your practice with essential HTN

327

PATIENT FILE

(idiopathic), then use of an antihypertensive becomes warranted
for the HTN and for their ADHD, insomnia, or anxiety

– Clinicians, in these cases, may treat HTN and psychiatric
symptoms simultaneously

Posttest self-assessment question and answer

How does an alpha-2a receptor agonist really improve attention?

A. It lowers NE output similar to its antihypertensive effects
B. It promotes DA activity in the DLPFC secondarily
C. It lowers GABA activity, which allows greater glutamate activity in the

thalamus
D. It allows fine tuning of cortical pyramidal glutamate neurons to improve

signal to noise ratios in cortical information processing
Answer: D
As depicted in the figures in this case, specifically for inattention symptoms,
these antihypertensive, alpha-2 noradrenergic receptor agonists act upon
heteroreceptors. They modulate glutamate pyramidal neurons originating in the
frontal cortex. In synchrony with other pyramidal neurons, alpha-2 receptor
agonists improve signal to noise ratios and may fine tune neuronal firing, thus
improving attention and concentration. Lowering NE tone for HTN reasons
would not help attention. This is a separate mechanism of action. Alpha-2
agonists do not promote DA activity; rather they act in concert with endogenous
DA activity, which occurs at the D1 receptor also situated on glutamate neurons.
The alpha-2 agonists do not manipulate GABA in order to modulate glutamate
neurons.

References

1. Stahl SM. Novel therapeutics for depression: L-methylfolate as a
trimonoamine modulator and antidepressant-augmenting agent. CNS
Spectr 2007; 12:739–74.

2. Jensen PS, Hinshaw SP, Kraemer HC, et al. Bottom of form ADHD
comorbidity findings from the MTA study: comparing comorbid
subgroups. J Am Acad Child Adolesc Psychiatry 2001; 40:147–58.

3. Schatz DB, Rostain AL. ADHD with comorbid anxiety. A review of the
current literature. J Atten Disord 2006; 10:141–9.

4. Schwartz TL, Nasra G, Ashton A, et al. An open-label study to
evaluate switching from SSRI or SNRI to Tiagabine to alleviate
antidepressant-induced sexual dysfunction in generalized anxiety
disorder. Ann Clin Psychiatry 2007; 19:25–30.

5. Schwartz TL, Nihalani N, Simionescu M, Hopkins G. History repeats
itself: pharmacodynamic trends in the treatment of anxiety. Curr
Pharmaceut Design 2005; 11:255–64.

328

PATIENT FILE

6. Vaiva G, Ducrocq F, Jezequel K, et al. Immediate treatment with
propranolol decreases posttraumatic stress disorder two months after
trauma. Biol Psychiatry 2003; 54:947–9.

7. Hoehn-Saric R, Merchant AF, Keyser ML, Smith VK. Effects of
Clonidine on anxiety disorders. Arch Gen Psychiatry 1981;
38:1278–82.

8. Hollifield M, Mackey A, Davidson J. Integrating therapies for anxiety
disorders. Psychiatr Ann 2006; 36:329–38.

9. Stahl SM. Stahl’s Essential Psychopharmacology, 4th edn. New York,
NY: Cambridge University Press, 2013.

10. Stahl SM. Stahl’s Essential Psychopharmacology: The Prescriber’s
Guide, 5th edn. New York, NY: Cambridge University Press, 2014.

11. Belkin M, Schwartz TL. Alpha-2 receptor agonists for the treatment of
posttraumatic stress disorder. Drugs in Context. 2015; 4:212286.

329

PATIENT FILE

151

PATIENT FILE

The Case: The scatter-brained mother whose daughter has ADHD, like
mother, like daughter

The Question: How often does ADHD run in families?

The Dilemma: When you see a child with ADHD should you also
evaluate the parents and siblings?

Pretest Self Assessment Question (answer at the end of the case)

Patients with comorbid ADHD and anxiety should in general not be

prescribed stimulants

A. True
B. False

Patient Intake
• 26-year-old woman
• Has a daughter with ADHD
• Psychiatrist noted symptoms in the mother and suggested she come

in for her own evaluation
• See the previous Case 13, p 133 for presentation of the daughter’s

case

Psychiatric History
• During interviews with the patient’s daughter (also attended by the

patient) over the past several months, it was not only noted that the
daughter has ADHD with comorbid ODD, but that the mother also
exhibited multiple symptoms consistent with lifelong and undiagnosed
ADHD including

– Mother misses appointments or is late for appointments
– Often appears disorganized
– Did not fi ll out her child’s forms on time
– Did not deliver forms to her child’s teacher, forgot, lost them
– Admits being very disorganized since her second child started

school
– Feels overwhelmed by two children and her life circumstances
– Could also have some signs of depression
– Can’t get organized to take her child to CBT
– Has a hard time keeping a regular schedule and also keeping her

daughter on a regular schedule of going to bed and waking up
– Was unable to remember to remove the daughter’s skin patch

unless she set a cell phone alarm
– All these suggest further evaluation of the mother is indicated

since ADHD commonly runs in families and has a very high
genetic contribution

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PATIENT FILE

152

• Has always done poorly academically
• Has always felt intimidated by any type of testing
• In addition, reports that she has always been worried about the future

and fi nancial stability of her family
• Says she sometimes mentally “freezes when it gets to be too much”
• When her eight year old daughter was diagnosed with ADHD, she

suddenly realized that she had similar problems as a child
• The psychiatrist explained to her that ADHD was highly heritable and

that there was a 75% chance of having a child with ADHD if both
parents have ADHD and thus was asked to fi ll out an Adult ADHD
screening form

Social and Personal History
• High school drop out, age 17 after getting pregnant
• Married age 17, divorced 2 years later
• Two children, ages 8 and 6
• Smoker
• No drug or alcohol abuse
• Single mother works full time in retail
• Father not much involved with his children

Medical History
• None notable
• BP normal
• BMI normal
• Normal lab tests

Family History
• 8-year-old daughter: recently diagnosed with ADHD
• Other family history unknown as the patient was adopted
• See the previous Case 13, p 133 for presentation of the daughter’s

case

Patient Intake
• The last time the patient brought her child to see the psychiatrist, the

mother was asked to fi ll out her own checklist, the Adult ADHD Self
Report Scale Symptom Checklist

– She endorsed many items, mostly inattentive but not really
hyperactive or impulsive such as:

– Having trouble wrapping up the fi nal details of a project once
the challenging parts have been done

– Diffi culty getting things in order
– Diffi culty remembering appointments or obligations

PATIENT FILE

153

– Making careless mistakes on diffi cult projects
– Diffi culty keeping attention on repetitive work
– Misplacing things at home and work
– Distracted by activity around her
– Diffi culty unwinding and relaxing when having time to herself
– Diffi culty focusing/listening during conversations

• Earlier, the mother was also requested to obtain copies of her report
cards from fi rst and second grade

– Her own mother had kept these in storage
– Showed grades that were quite low
– Her teachers had commented on some of the problems endorsed

in the adult ADHD checklist that she continues to experience as an
adult

• Asked how these problems affect her life, she states that:
– They cause great diffi culty managing family matters
– She used to be unable to stay focused in conversations with her

ex-husband, which made him feel she did not care about him
• Additional complaints include:

– Constantly feeling overwhelmed with taking care of the two
children while working fulltime

– Blaming herself for her daughter’s academic diffi culties
– Feeling very emotional and overwhelmed

– “I’m sorry, doctor, but two kids are just too much for this single
mom”

• Having diffi culty sleeping and being irritable with the children at night,
which she regrets later on

• Has many worries, about fi nances, about the future, about her
children’s futures, about getting a better job, about getting her own
education, about fi nding a new partner

Based on just what you have been told so far about this patient’s history

and symptoms, what do you think is her diagnosis?

• Appropriate response to her circumstances with her severe
psychosocial stressors

• Mostly just stress and anxiety
• ADHD
• ADHD and stress
• Generalized anxiety disorder (GAD)
• Major depressive episode
• ADHD and GAD
• Other

PATIENT FILE

154

Attending Physician’s Mental Notes: Initial Psychiatric
Evaluation
• Here is a case that indeed is ADHD, but her symptoms also suggest

that she suffers from GAD
– Constant worry
– Feeling on edge
– Fatigue
– Diffi culty concentrating and her mind going blank
– Irritability
– Trouble sleeping

• Most adults with ADHD are comorbid for a second psychiatric
disorder, and the most common is GAD

• Also, this patient is a smoker which may be related to her ADHD
since a disproportionate number of ADHD patients smoke, perhaps
because of the therapeutic effects of nicotine on ADHD symptoms

How would you treat her?

• Stimulant for her ADHD
• SSRI/SNRI for her GAD
• Benzodiazepine as need for GAD and insomnia
• Stimulant plus an SSRI/SNRI or benzo for both ADHD and GAD
• CBT for both ADHD and GAD
• Other

Attending Physician’s Mental Notes, Initial Psychiatric
Evaluation, Continued
• It seems as though the primary disorder is ADHD and it will be

simplest if this is treated fi rst, with a single drug, probably a stimulant
• An SSRI/SNRI and/or benzodiazepine can be added at a later time

once the actions of the stimulant are evident
• Even though patients with GAD alone or even normal controls may be

“over stimulated” by a stimulant, in many cases of ADHD comorbid
with GAD, the stimulant is paradoxically calming and well tolerated
and even works for GAD symptoms as well as ADHD symptoms
without having to prescribe a second medication for the GAD

• Any stimulant could be chosen but not all are explicitly approved for
treatment of ADHD in adults

• She was started on mixed salts d,l amphetamine XR (Adderall XR)
• She was referred to a local mental health training program where she

could possibly get CBT for free or for a reduced rate from a trainee
receiving supervision

PATIENT FILE

155

Case Outcome: First, Second, and Third Interim Followup
Visits, Weeks 4, 8 and 12
• Due to scheduling issues, by the time the patient had her fi rst CBT

session, she had already been titrated to 20 mg of mixed salts of d,l –
amphetamine XR

• She thought that the medication had already started to help her and
in fact that she would not have been able to cooperate with the CBT
assignments had she not been on the medication

• Because of lack of side effects but continuing ADHD and GAD
symptoms, the dose of d,l-amphetamine XR increased to 30 mg (off
label since the maximum approved dosage for adults is 20 mg)

• Her BP and pulse were stable on the 30 mg dose but she felt jittery
particularly in the morning and around noon; she also felt very anxious
about her job situation and being able to provide for her family

• Dose lowered to 25 mg, but the jitteriness persisted so the dosage
was further lowerd to 20 mg

• The jitteriness abated but her ADHD symptoms were not well
controlled on the 20 mg dose anymore

• Instructed to stay on 20 mg for two more weeks as she is going on
vacation and not to change the dose until after her vacation and then
retry the 25 mg dose again

• Complained of feeling overwhelmed and irritable
• For most patients, a week between dosing adjustments for a stimulant

being used to treat ADHD is quite adequate
• Weekly intervals give patients and clinicians a chance to see the way

that the dosage is working though the spectrum of challenges that
occur in a typical week

• As vacations do not represent typical activities for a week, special
consideration must be given to the effectiveness of medication
changes that are done while a patient is on vacation

– Many adults with ADHD may relax on vacation and not challenge
themselves with cognitive loads and multitasking so may appear
to be better even without a medication change

– Other adults with ADHD, especially women with young children,
may actually fi nd vacation more challenging

– For example, a parent with ADHD taking a family vacation with
several children in tow may fi nd the planning and organization for
the trip more taxing than anything encountered at work or during
the normal routine at home

– It can also be diffi cult to manage timing the medication
appropriately when traveling to different time zones

PATIENT FILE

156

Case Outcome: Fourth Interim Followup, Week 16
• “Glad to be back from vacation”
• “I don’t think I could have even got through our vacation without my

medication, but I still have a hard time holding things together”
• On at least 20 mg/day dosage of d,l-amphetamine XR combined with

CBT for 12 weeks, including a couple of weeks back from vacation,
the patient still has problems with

– Organizing her day
– Procrastinating
– Following instructions
– Losing items such as her keys which make her late for

appointments/activities
• On the few days that the patient missed, and thus skipped, her

medication inadvertently she realized that the medication was really
helping her concentrate and get through the day even though she
remains symptomatic

• Knowing that she could achieve better functioning on medication she
asked if other medications might accomplish this without the jittery
and anxious feelings

• While other medication options were discussed, the CBT was
continued which was slightly less helpful

How would you treat her now?

• Start lisdexamfetamine 30 mg once in the morning and titrate the
dosage by 20 mg each week until an optimal dosage is achieved

• Start d-methylphenidate XR 10 mg once in the morning and titrate the
dosage by 10 mg each week until an optimal dosage is achieved

• Start OROS methylphenidate 18 mg once in the morning and titrate
the dosage by 18 mg each week until an optimal dose is achieved

• Start atomoxetine 40 mg a day and increase to 80 mg after one week

Attending Physician’s Mental Notes: Fourth Interim Followup,
Week 16
• Lisdexamfetamine, d-methylphenidate XR, OROS methylphenidate,

and atomoxetine are all FDA-approved for the treatment of adults with
ADHD

• On the one hand, the patient found her amphetamine-based stimulant
to be very effective, and thus another long-acting stimulant would be
reasonable

• On the other hand, she had jitteriness with the stimulant, and thus a
non-stimulant would be equally reasonable

• After explaining the options, the patient elected to try another long-
acting stimulant

PATIENT FILE

157

• d-methylphenidate uses a bead-based technology similar to the mixed
salts amphetamine XR in that 50 percent of the beads are immediate-
release and 50 percent delayed-released

• Methylphenidate LA and d-methylphenidate XR employ the same
patented SODAS technology in their delivery systems, but other long-
acting forms of stimulants with beaded delivery systems vary due to
proprietary differences in their manufacturing processes

• For instance, one formulation of methylphenidate utilizes a capsule
that contains a ratio of 30 percent immediate-release beads and 70
percent delayed-released beads

• Although the different technologies used in beaded forms of
stimulants can have clinical implications in individual cases, they all
follow a similar design scheme:

– A bolus of stimulant medication becomes bioavailable rather
quickly as the immediate-release beads dissolve

– Over time, the coating on the delayed-release beads deteriorates,
allowing the stimulant contained within the bead to be released

– The medication within the delayed-release bead becomes
bioavailable about four hours after the patient swallows the
capsule

• Lisdexamfetamine is the only stimulant preparation that is a prodrug:
– In its prodrug form, a lysine molecule is attached to

dextroamphetamine
– Dextroamphetamine will not be active until the lysine is cleaved

from it
– Cleaved lysine is an amino acid that does not contribute to the

clinical effi cacy of this medication
• Lisdexamfetamine could be a good choice for multiple reasons:

– It uses a different delivery system that appears to have a more
consistent interval to maximum concentration (Cmax)

• It is conceivable that the jitteriness this patient was experiencing was
related more to the l-isomer than to the d-isomer

• A nonstimulant such as atomoxetine may be particularly useful in a
patient who has stimulant related side effects, because atomoxetine
does not cause these side effects

• Also, atomoxetine may be particularly useful in patients with
comorbid anxiety

Case Outcome: Fourth Interim Followup, Week 16, Continued
• In the end, the patient and the attending physician agreed upon a trial

of OROS methylphenidate (Concerta)
• Main reasons for this choice:

– To be able to compare the benefi ts the patient experienced on
an amphetamine preparation with those of a methylphenidate

PATIENT FILE

158

preparation since patients may experience differing tolerabilities as
well as effi cacies on methylphenidate versus amphetamine

– To be able to test the uniqueness of the OROS delivery system in
terms of attained effi cacy with better tolerability

• OROS methylphenidate uses a delivery system that is quite different
from beaded delivery systems:

– Coating of OROS methylphenidate contains 32 percent of the
medication

– Remainder of medication is contained within a permeable
membrane that allows water from the gut to enter once the coating
of methylphenidate dissolves away

– Different concentrations of methylphenidate in gel form are
contained in two compartments

– A push compartment absorbs water and expands like a sponge
does, pushing the methylphenidate gel out of the hole at the
opposite end

Case Outcome: Fifth Interim Followup, Week 20
• The patient’s dose was titrated from 18 mg to 72 mg over the course

of four weeks
• Although she did not feel jittery, OROS methylphenidate 72 mg once a

day did not seem to work as well as the mixed salts amphetamine at
30 mg a day

• She voiced concerns that the dosage was more than double that of
the mixed salts amphetamine dosage that was tried

• The psychiatrist explained that methylphenidate compounds are half
as potent as amphetamine ones, and that 72 mg/day is an approved
dose in adults

• She was reminded that her blood pressure and pulse had remained
in the normal range throughout the titration, and she was told that
some of the methylphenidate gel may remain inside the delivery
system and not be bioavailable (inherent proper ties of OROS
technology)

• After documenting that information about off-label use was given
to the patient, the psychiatrist recommended to further increase the
dose of OROS methylphenidate to 90 mg

Case Outcome: Sixth Interim Followup, Week 24
• The patient felt that 90 mg of OROS methylphenidate worked at least as

well as 30 mg of the mixed salts of d,l amphetamine XR
• Her blood pressure and pulse increased a bit from baseline, but they

were still in the middle of the normal range

PATIENT FILE

159

• She still has some problems with organization and losing items, but
she indicates she would continue CBT to address these

• Similar to when she was on the amphetamine compound, once her
ADHD symptoms abated, her anxious feelings became more prominent

– “It’s like now that I can concentrate on my daily tasks, I also feel
much more anxious about the fi nancial security of my children,
and I often feel my throat tighten when I think about the fi nancial
impact of the girls going to college”

– “The thought of losing my job or getting sick frightens me . . .
what would happen to the girls?”

– She has trouble falling asleep at night, as her mind does not shut
off

ADHD is often comorbid with other psychiatric disorders and one

disorder can mask the symptoms of another. In the present case, this

patient exhibits symptoms of anxiety, probably generalized anxiety

disorder, especially more prominent every time her ADHD symptoms

abate. How would you address the patient’s anxiety at this point?

• Augment with a benzodiazepine
• Augment with buspirone
• Augment with a selective serotonin reuptake inhibitor (SSRI) or SNRI
• Incorporate techniques to resolve anxiety into ongoing CBT

Case Outcome: Seventh and Eighth Interim Followup, Weeks
24 and 36
• Incorporating techniques to resolve anxiety into the patient’s ongoing

CBT would likely be most appropriate, prior to attempting to add a
medication

• A letter was sent suggesting this to the CBT therapist, but after 12
weeks, this led to limited benefi t, and thus medication augmentation
was considered

• Benzodiazepines, buspirone, and SSRIs/SNRIs can all be used to
treat generalized anxiety disorder and are not contraindicated with
stimulants

• After discussion of the options, paroxetine was prescribed to augment
her stimulant and her CTB

Case Outcome: Ninth Interim Followup, Week 48
• After three months on OROS methylphenidate and paroxetine, while

continuing her CBT, at fi rst the patient stated that she “had her life back”
• Then, after thinking back over the past year of treatment, and to how

she had been since childhood she stated, “No, I don’t have my life
back – I fi nally have a life!”

PATIENT FILE

160

Case Debrief
• It took a long time to get both the ADHD and GAD recognized
• It took over a year of trial and error and combination treatment to

attain a remission of symptoms
• Real remission will come when sustained improvement of symptoms

leads to better functional outcomes, not only less subjective distress,
but now perhaps the chance for an education, a better job, and having
enough emotional reserve to develop another relationship

• Stopping smoking might be a goal to tackle in the next year as well

Take-Home Points
• ADHD is highly heritable
• It is not uncommon for adults with previously undiagnosed ADHD to

recognize their own symptoms once their child is diagnosed
• A multigenerational approach should be considered for parents who

have ADHD and who care for children with ADHD
• In the patient’s case, by addressing her own ADHD issues, she also

felt she could be a better parent to her daughter with ADHD

Performance in Practice: Confessions of a
Psychopharmacologist
• What could have been done better here?

– Perhaps ADHD could have been recognized earlier
– Perhaps CBT could have been implemented earlier
– Perhaps she should have been more actively engaged or have had

more serious discussions about smoking cessation already
• Possible action item for improvement in practice

– Make a concerted effort to keep contact with low cost CBT
resources in the community

– Make a more concerted effort to encourage smoking cessation

Tips and Pearls
• Prescribing stimulants to an ADHD patient is very much like tailoring a

“bespoke” treatment, one case at a time
• That is, some patients respond very differently to amphetamine than

they do to methylphenidate
• Many patients respond very differently to one controlled dosage

pattern versus another
• Look for comorbidities in adult ADHD, including both anxiety

disorders and substance dependence/abuse (especially smoking)
• True remission means reduction not just in symptoms of ADHD, but

in the comorbid conditions as well

PATIENT FILE

161

Two-Minute Tute: A brief lesson and psychopharmacology
tutorial (tute) with relevant background material for this case
– ADHD rating scales for adults
– Contributions of genetics to ADHD

Table 1: Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom
Checklist Instructions

162

PATIENT FILE
Downloaded from http://stahlonline.cambridge.org
by IP 100.103.238.216 on Thu Oct 29 01:55:13 UTC 2020
Stahl Online © 2020 Cambridge University Press.
All rights reserved. Not for commercial use or unauthorized distribution.

163

PATIENT FILE

164

Figure 1: Average Genetic Contribution of ADHD Based on Twin Studies

ADHD is one of the most genetically loaded medical or psychiatric
conditions, higher than schizophrenia, asthma or breast cancer.

Posttest Self Assessment Question: Answer

Patients with comorbid ADHD and anxiety should in general not be
prescribed stimulants

A True
B False
Answer: B

References
1. Franke B, Neale BM, and Faraone SV. Genome-wide association

studies in ADHD. Hum Genet 2009; 126(1): 13–50
2. Haberstick BC, Timberlake D, Hopfer CJ et al. Genetic and

environmental contributions to retrospectively reported DSM-IV
childhood attention defi cit hyperactivity disorder. Psychol Med 2008;
38(7): 1057–66

3. McLoughlin G, Ronald A, Kuntsi J et al. Genetic support for the
dual nature of attention defi cit hyperactivity disorder: substantial
genetic overlap between the inattentive and hyperactive-impulsive
components. J Abnorm Child Psychol 2007; 35(6): 999–1008

4. Todd RD, Rasmussen ER, Neuman RJ et al. Familiality and
heritability of subtypes of attention defi cit hyperactivity disorder in
a population sample of adolescent female twins. Am J Psychiatry
2001; 158(11): 1891–8

5. Faraone SV, Advances in the genetics and neurobiology of attention
defi cit hyperactivity disorder, Biol Psychiatry 2006; 60: 1025–7

Twin studies: ADHD is genetic

Hudziak, 2000
Nadder, 1998

Levy, 1997
Sherman, 1997

Silberg, 1996
Gjone, 1996

Thapar, 1995
Schmitz, 1995

Edelbrock, 1992
Gillis, 1992

Goodman, 1989
Willerman, 1973

Breast cancer Asthma Schizophrenia Height

Average genetic contribution of ADHD based on twin studies

ADHD
mean

0 0.2 0.4 0.6 0.8 1

PATIENT FILE

165

6. Stahl SM, Stahl’s Illustrated Attention Defi cit Hyperactivity Disorder,
Cambridge University Press, New York, 2009

7. Stahl SM, Attention Defi cit Hyperactivity Disorder and its Treatment,
in Stahl’s Essential Psychopharmacology, 3rd edition, Cambridge
University Press, New York, 2008, pp 863–98

8. Stahl SM, Atomoxetine, in Stahl’s Essential Psychopharmacology
The Prescriber’s Guide, 3rd edition, Cambridge University Press,
New York, 2009, pp 51–5

9. Stahl SM, d,l methylphenidate, in Stahl’s Essential
Psychopharmacology The Prescriber’s Guide, 3rd edition,
Cambridge University Press, New York, 2009, pp 329–35

10. Stahl SM, Mixed Salts of d,l Amphetamine, in Stahl’s Essential
Psychopharmacology The Prescriber’s Guide, 3rd edition,
Cambridge University Press, New York, 2009, pp 39–44

11. Stahl SM, Paroxetine, in Stahl’s Essential Psychopharmacology The
Prescriber’s Guide, 3rd edition, Cambridge University Press, New
York, 2009, pp 409–15

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