WEBMATERIAL for Basic Psychopharmacology Text

WEBMATERIAL for Basic Psychopharmacology Text

Practical Psychopharmacology:

Basic to Advanced Principles

Jungjin Kim, MDandThomas L. Schwartz, MD

Introduction

This online material is meant to be paired with the textbook Practical Psychopharmacology: Basic to Advanced Principles.The written textbook is designed to teach immediate facts needed to make an accurate psychiatric diagnosis and begin entry-level treatment with an appropriate, approved medication.As each chapter progresses, more academic information is shared with the reader (epidemiological, genetic, and neuroanatomical findings) as are more advanced prescribing techniques (off-label and theoretical psychopharmacological applications).In this manner, the written textbook may be used by any clinician as they advance in their knowledge and prescribing techniques.The material on this website provides an opportunity for case-based learning where ideally, textbook readers may see the techniques discussed applied in real-world prescribing situations.Like the textbook, each case covers a DSM diagnosis and advances from relatively simple psychopharmacology decision-making to more complex clinical scenarios.In this manner, the reader may see the information from the textbook utilized in practice vicariously.Ideally, this enhances learning as the online reader is re-exposed to material from the written textbook in a novel and applied manner.The overlying goal is for the reader to take learned information and begin using the skills in psychopharmacological practice in order to improve clinical outcomes for their patients.

CHAPTER 1:ADULT ATTENTION DEFICIT-HYPERACTIVITY DISORDER

Case A

Question

Assuming that you used the DSM-5 criteria, or a rating scale, and you are confident in giving the adult ADHD diagnosis, what approved medication would you choose to start in this particular patient?

A)Amphetamine Slow-Release Stimulant Products

d/l-mixed amphetamine extended release (Adderall XR), lisdexamfetamine dimesylate (Vyvanse)

B)Methylphenidate Slow-Release Stimulant Products

methylphenidate OROS extended release (Concerta), methylphenidate extended release (Focalin XR)

C)Non-Stimulant Products

atomoxetine (Strattera)

Answer

The FDA guidelines would likely suggest choosing (A) or (B) and using a slow-release,adult ADHD-approved stimulant as frontline treatment given their robust efficacy in treating ADHD.All of the above agents are approved and medicolegally make sense, but atomoxetine is not a stimulant.

In clinical practice, adult patients often have more addictive tendencies or ways of misusing the stimulants (e.g., diversion to others for use).It would not be uncommon to insist on a urine drug screen prior to starting a possibly addictive schedule II controlled stimulant.It would make sense to use any of these slow-release products as they should be less intoxicating and euphoric compared to immediate-release stimulants.

Lisdexamfetamine may be the slowest releasing as it is a prodrug and takes time to metablize via the liver into the active drug component.It may last the longest and have less of an abrupt “wearing off” effect.It cannot be snorted or injected to obtain a quicker “high” as it is a prodrug.The methylphenidate products are less aggresive mechanistically in regard to dopamine elevations in the brain’s reward centers and theoretically may have lower risk of addiction in practice.Given this, they may have slightly less activating side effects initially.Therefore, if choosing to follow guidelines and to use a slow-acting, approved stimulant, then choosing the methylphenidate products (B) might make the most sense from guideline, regulatory, and clinical standpoints.(A), amphetamine slow-release stimulants, are very effective but theoretically may predispose patients to greater risk of addiction and initial side effect burden.

One might consider using the atomoxetine (C) product first regardless of guidelines or its tendency toward less robust effectiveness, as it conveys zero chance of addiction.This is a guideline versus real-world clinical dilemma.Guidelines suggest stimulants, but clinicians often feel more comfortable starting with non-addictive medications.If these are ineffective, then the atomoxetine could be switched to a stimulant.

Case A Continued

The patient is started on atomoxetine, as it has the lowest risk of addiction (this patient has distant history of addictive issues).The dose is started at 40mg/day without side effects and is escalated to 80mg/day after a few days of good tolerability.He develops sedation and nausea, and the dose is reduced back to 40mg/day.Once the side effects dissipate, he is titrated back to 80mg/day without issue.After a 6–8 week trial, the patient returns and the clinical interview (or rating scale checklist) suggests he is about 30% better, but he still reports difficulty at work.Atomoxetine is increased to 100mg/day and after a few more weeks there is no further improvement.At this point, atomoxetine is considered to be, at most, partially effective.

Question

This patient likely does not have a great enough effect to warrant staying on atomoextine, and a full therapeutic trial (full dose/duration) was accomplished.The correct action would be to taper off of this medication while titrating onto a new monotherapy.What would you choose next?

A)Amphetamine Slow-Release Stimulant Products

d/l-mixed amphetamine extended release (Adderall XR), lisdexamfetamine dimesylate (Vyvanse)

B)Methylphenidate Slow-Release Stimulant Products

methylphenidate OROS extended release (Concerta), d-methylphenidate extended release (Focalin XR)

Answer

This patient has failed to respond to the only approved, non-addictive adult ADHD medication.Switching to a stimulant is clearly warranted now.As the methylphenidate products (B) have the theoretical potential for less side effects and addiction compared to the amphetamine products (A), starting one of these makes clinical sense given the failure of the non-addictive ADHD medication.

Case A Continued

The patient is tapered off atomoxetine (Strattera) over a few days and is then started on methylphenidate OROS (Concerta) at 18mg/day.He can increase in increments of 18mg every week if needed.The effect of the stimulants can be noticed within this time frame, and they can be titrated more quickly than the NRI atomoxetine.Typically, the time to increase is related to the next office visit and how often the patient is seen.This patient is gradually titrated to the maximum dose of 72mg/day. He reports a much better effect than the previous atomoxetine trial and is 60–70% improved.He feels that he still has problems sustaining attention late in the day, or on tasks that are more tedious and require greater scrutiny.He still feels impaired at work but is happy with the improvement so far.He denies side effects.

Question

This patient has failed the non-stimulant, atomoxetine, but he is a solid, albeit partial, responder to the stimulant, methylphenidate OROS.You and the patient feel he needs a better response or, ideally, a full remission.What do you offer as the next treatment option?

A)Amphetamine Slow-Release Stimulant Products

d/l-mixed amphetamine extended release (Adderall XR), lisdexamfetamine dimesylate (Vyvanse)

B)Methylphenidate Slow-Release Stimulant Products

methylphenidate extended release (Metadate CD), methylphenidate extended release (Focalin XR)

C)An Off-Label Medication Used for Childhood ADHD

Guanfacine(Tenex), clonidine (Catapres)—the alpha agonists

D)An Off-Label Medication with Known Properties to Improve Attention

Modafinil(Provigil), armodafinil (Nuvigil)—the novel stimulants;or desipramine(Norpramin), nortriptyline(Pamelor)—the TCAs

Answer

This patient is having a fairly good, albeit not perfect, result with a methylphenidate-based stimulant.Knowing that the amphetamine products are more mechanistically robust in regard to enhancing dopamine activity, he is tapered off the methylphenidate product and titrated on to d/l-mixed amphetamine (Adderall XR).It is started at 10mg/dayand increased in 10mg intervals every week and up to a maximum of 60mg/day.

Case A Continued

At a follow-up visit, the patient states he felt 70–80% better on 40mg/day, but seems at the higher dose of 50–60mg/day that he was hyperfocused on tiny details and felt as though he was being “forced to pay attention to little insignificant details.”He also reported some insomnia as a key side effect.

Question:

Given this patient’s side effects of forced vigilance and insomnia, what would you do next?

A)Lower the dose back to 40mg/dayand accept he is 70% better only.

B)Change the d/l-amphetamine product (Adderall XR) to another slow-release product and hope for better tolerability.

C)Add an alpha-2 agonist (clonidine/guanfacine) to the 60mg d/l-amphetamine product to cancel out the side effects.

Answer:

As remission is the goal, reducing the dose and settling for a partial response is not ideal.Sometimes switching to a similar amphetamine product may continue the efficacy while avoiding some side effect.In this case, the patient was tapered off the d/l-amphetamine (Adderall XR) and onto the prodrug product lisdexamfetamine (Vyvanse).This option offers the now-proven successful amphetamine approach (where methylphenidate and atomoxetine failed previously) with a different slow-release mechanism.In this case, the patient was titrated from 30mg to 60mg/day.The full dose range may go to 70mg/dayand the dose increased by 10–20mg every week.At 60mg, the patient reported that he was fully functional at work and even had some success working longer days and focusing better when he arrived home.He feels he is in remission and rating scales confirm this as well.

Case A Continued

Upon further questioning in session, you determine he still has some problems with vigilance on some tasks at work.Long, drawn out, repetitive tasks still are fraught with occasional mistakes, but he is greatly improved.He also admits that it takes him 60–90 minutes to fall asleep at night as he feels he cannot “wind down.”He states he feels groggy in the morning until his stimulant kicks in.

Question:

What would you suggest now?

A)Lower the dose back to 40mg/dayto help his insomnia, but sacrifice a return of some ADHD symptoms and non-remission.

B)Change the amphetamine product (Vyvanse) to another slow-release product and hope again for better tolerability while gaining remission.

C)Add an alpha-2 agonist (clonidine/guanfacine) to the 60mg/daylisdexamfetamine (Vyvanse) product to cancel out the side effects of late night hyperarousal and insomnia and to fine-tune his remaining isolated ADHD symptoms during long, work-related tasks

Answer:

There is now near ADHD symptom remission and great effectiveness with his monotherapy of amphetamine slow-release product.He has mild side effect burden at night.It may make sense to use a low dose alpha-2 agonist as an augmentation at bedtime to dampen his arousal and improve his sleep in an off-label manner and also use it to improve his subtle remaining adult ADHD symptoms.In this case, guanfacine was added, 1mg at bedtime.The patient called stating it was ineffective.Instead of titrating it higher, it was moved to 1–2 hours prior to bedtime.At a follow-up visit, the patient stated this was effective where he gradually was able to wind down and he is back to usual sleeping patterns.He also noted that his mistakes at work were minimal to zero compared to using his stimulant only.His blood pressure and heart rate remained normal throughout.There was no noted misuse or diversion of his stimulants.He had negative urine drug screens.

Case B

A 32-year-old male presents admitting to most DSM-5 criteria for ADHD, inattentive type.He gives a clear history of these symptoms dating back to grade school, but also admits he was more hyperactive then as well.He now has a job that requires more scrutiny, vigilance, and sustained attention, and he is getting bad reports as his ADHD seems to be interfering.He has no previous treatments for ADHD.He has borderline hypertension and likely will need to take an antihypertensive.He does not misuse any substances now, but in college admits that he did recreationally use cannabis and sometimes did borrow friends’ stimulants to party with.He states he has not used any of these in at least 10 years.He smokes five cigarettes daily now.He admits to suffering DSM-5 diagnosis of panic disorder (PD).He was treated with cognitive-behavioral therapy (CBT) three years ago and he no longer has full panic attacks.He reports he will have minor attacks of diaphoresis and palpitations several times a year but can dismiss this easily.Additionally, he currently admits to DSM-5 major depressive disorder (MDD) and meets criteria for a moderate single epidode.

Question

Assuming that you used the DSM-5 criteria, or a rating scale, and you are confident in giving the adult ADHD diagnosis that is comorbid with full MDD and subsyndromal PD and a history of substance use disorder (SUD), what approved medication would you choose to start in this particular patient?

A)Amphetamine Slow-Release Stimulant Products

d/l-mixed amphetamine extended release (Adderall XR), lisdexamfetamine dimesylate (Vyvanse)

B)Methylphenidate Slow-Release Stimulant Products

methylphenidate OROS extended release (Concerta), d-methylphenidate extended release (Focalin XR)

C)Non-Stimulant Products

atomoxetine (Strattera)

D)None of the Above

None of the above treat anxiety and may even exacerbate anxiety, none of the above treat depressive disorder, most have addiction risk

Answer

The guidelines would likely suggest choosing (A) or (B) and using a slow-release, FDA-approved adult ADHD stimulant as front line given their robust efficacy in treating ADHD with the caveat that PD and SUD may be exacerbated.Atomoxetine (C) is not a stimulant but has not proven effective in treating MDD or PD and could worsen anxiety as it is an NRI.As it is the least aggressive noradrenergically, it might be least likely to escalate PD or SUD.

The bigger picture might be to attempt to address the ADHD, PD, MDD, and SUD with one unifying agent.The serotonin-norepinephrine reuptake inhibitors (SNRI) might be uniquely qualified as they promote serotonin activity that is well-known to treat MDD and PD and they promote norepinephrine activity that can help ADHD symptoms in a non-addictive manner (similar to the NRI mechanism in atomoxetine).

Venlafaxine ER (Effexor XR) may have the most approvals for treatment of depressive and anxiety disorder withinin the SNRI class.Duloxetine(Cymbalta) and desvenlafaxine (Pristiq) may also theoretically be helpful in a comorbid patient such as this.Levomilnacipran(Fetzima) is a newer SNRI but is much more noradrenergic than the others, theoretically implicating it may be better at ADHD treatment but it is unclear how it would help or even exacerbate anxiety.None of the SNRI are addictive, in light of concern for activating SUD in this patient.

The tricyclic antidepressants (TCAs) often act by using the SNRI mechanism but, unfortunately, carry much more side effect burden (sedation, weight gain, blurred vision, dry mouth, cardiac conduction delays).Imipramine, amitriptyline, and clomipramine are well balanced in regard to increasing both serotonin and norepinephrine activity and can treat MDD and some of the anxiety disorders.The more noradrenergic-specific TCAs (desipramine, nortriptyline, and protriptyline) might be considered more similar to atomoxetine (Strattera) as these have potent NRI properties (albeit with more side effect concerns).If the TCAs are used, sometimes blood plasma levels and EKGs must be monitored.

As an alternative to the SNRI and TCA drugs, the noradrenergic antagonist-selective serotonin antagonist (NaSSA) antidepressant mirtazapine(Remeron) might be considered.It also elevates both serotonin and norepinephrine activity through a non-SNRI mechanism. It manipulates receptors rather than reuptake pumps. It has more associated sedation and weight gain and may increase inattentive symptoms if sedation is marked.It has clear approval for treating MDD and less data for anxiety disorder. Given its sedating effects, it would likely not increase insomnia or anxiety symptoms.It is not addicting.

Bupropion XL (Wellbutrin XL) might be considered.It is a norepinephrine-dopamine reuptake inhibitor (NDRI) antidepressant that is also approved for seasonal affective disorder and for smoking cessation purposes.As it is devoid of serotonin potential, it is not always ideal for treating anxiety disorder, but in this case might address the ADHD and MDD in a non-addictive manner.The patient may also quit smoking cigarettes.It is not addicting.

Finally, all of the agents above have norepinephrine activity promotion as a key mechanism to improve ADHD symptoms.Peripherally, this property may also increase heart rate and blood pressure.Given his borderline hypertensive state, this should be monitored.