Psychopharmacology for primary care providers

In her presentation on psychopharmacology for primary care providers at the virtual 2020 American Academy of Pediatrics National Conference & Exhibition, Rebecca Baum, MD, pediatrician at Mission Children’s Hospital in Asheville, North Carolina, reminded practitioners of 3 guiding principles: That medication alone is rarely the solution; that a primary care provider (PCP) must act as a champion against misinformation; and that medication management is a team sport, involving the patient, caregivers, the PCP, and other health care providers (in particular mental health care providers). “For many pediatricians,” Dr Baum observed, “this can be hard. Providing this kind of medication is not necessarily what we learned during training; it may be hard to learn on the fly; or you may be feeling, ‘do I really want to go there?’ Stigma continues to prevent access to mental care,” she warned, something she urged PCPs to continue to fight against when deemed necessary.

Baum broke down the most common illnesses where psychopharmacology comes into play: attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety.

ADHD

Pediatricians should use the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM- 5) assessment criteria, which tracks inattention, hyperactivity and impulsivity; evidence of impairment (how is the child faring in academics, relationships, sports or other activities); and behavioral rating scales (the Vanderbilt, SNAP, and ADHD rating scales). Medication options for ADHD fall into 2 categories: stimulants (which block reuptake of norepinephrine and dopamine) and non-stimulants (selective norepinephrine reuptake inhibitor and alpha-2 agonists).

Questions pediatricians should also consider would be the onset and duration of action, tolerability, and access of medication; potential for diversion; and delivery system. With the latter, Baum notes, medications now come in a range of forms, including liquid, beaded, chewable, and orally disintegrating, which is extremely helpful for those children not able/too young to swallow a whole tablet.

STIMULANTS

“Stimulant medications have the highest efficacy,” notes Baum, “but non-stimulant medications can be useful for patients unable to tolerate stimulant medications, families concerned about stimulant use (perhaps worries about substance use) or as an adjunctive treatment.” An invaluable source for this, Baum notes, is the ADHD Medication Guide developed by Andrew Adesman (www.adhdmedicationguide.com)​

Stimulant medications include methylphenidate products such as Focalin, Daytrana, and Concerta) and amphetamines (Vyvanse and Adderall), all which should be taken in the morning; Baum suggests adding afternoon short-acting doses if longer duration is needed. Adverse effects can include aggression, irritability, appetite suppression, sleep disturbance and others.

NON-STIMULANTS

Well-known non-stimulants include atomoxetine (Strattera) and alpha-agonists such as guanfacine ER (Intuniv) and clonidine ER (Kapvay). Adverse effects with atomoxetine include hypertension, tachycardia, gastrointestinal upset, suicidal ideation and others, whereas in alpha agonists, they can include sedation and hypotension. “Remember, always maximize the use of one medication before moving to another,” Baum advises. “Switch to another stimulant class if the first trial is not effective and exhaust other options (medication plus mental behavioral interventions) before adding a non-stimulant.”

Common problems of course, can always arise during the course of medicating.

Before making a medication change, Baum suggest doing the following first:

• medication side effects (hold medication over the weekend)
• persistent ADHD symptoms (obtain more history and repeat rating scales)
• new onset depression (also obtain more history and do a depression screen)

DEPRESSION

During this assessment, you should look for low, sad mood or irritability; loss of interest; thoughts about dying; persistent pessimism; loss of confidence and self-worth. Assessments for depression include PHQ-9, along with behavioral changes such as sleeping too much or too little; changes in appetite; fatigue; agitation; slowing of movement and speech; trouble with memory and/or concentration. “When medicating for depression in children, one really needs to see significant impairment or distress, recurrent or persistent symbols and an inability to access psychosocial interventions,” says Baum.

Selective serotonin reuptake inhibitors (SSRIs) are what are most recommended, with fluoxetine (Prozac) for children aged 8 years and older, and escitalopram (such as Lexapro) for children aged 12 years and older. Here, Baum says, the guidance is to start low and go slow, increasing dose as needed after 1-2 weeks, noting maximal effectiveness won’t occur until 4-6 weeks in. Fluoxetine has a long half-life and can be more activating, and always “watch for medication interactions,” reminds Baum. With escitalopram, the half-life is shorter, and it is less activating but also fewer medication interactions with a smaller therapeutic window. Here, adverse effects to SSRIs can include nausea, headaches, dizziness, sexual dysfunction, insomnia, and others.

ANXIETY

Medications best known for treating anxiety are sertraline (for children aged 6 years or older, especially for obsessive-compulsive disorder (OCD); and fluoxetine (for children aged 7 years or older, also for OCD).

And, although the US Food and Drug Administration (FDA) indicates duloxetine (Cymbalta) for children aged 7 years and older for generalized anxiety disorder (GAD), it does have a less favorable side effect profile. Baum suggests this medication as “a second line choice” (after 2 failed SSRI trials, and with a mental health consultation).

But at which point should a PCP refer to a mental health specialist? Baum advises here:

• longer duration or recurrent episodes
• lack of response to first line treatment
• significant impairment
• environmental stressors
• increasing number of comorbidities
• use of drugs and alcohol

Finally, Baum says “always remember the ‘buddy system;’ your child psychiatry access lines, integrated behavioral health, a trusted colleague who is more familiar with treating these conditions, the school system and your ‘friendly neighborhood psychiatrist or developmental behavioral pediatrician.’ Remember, treating for mental health is a team sport!”

COMMENTARY

Baum points out the complexity and multidisciplinary needs for managing childhood psychological conditions that often require pharmacotherapy as only part of the solution. Despite favorable efficacy data supporting ADHD and antianxiety medications to their respective childhood disorders,^1-2 high quality evidence for antidepressant use in children is lacking.³ Antidepressant efficacy rates have been recently reported to have only a 10% advantage over placebo with rising placebo efficacy rates in recent comparative antidepressant clinical trials.⁴

The clinical pharmacology profile of psychotropic medications must be considered along with basic prescribing and monitoring instructions, as it is important to recognize the pharmacodynamics profile (eg, onset and duration of action) for specific medications and their dosage forms, as seen with the evolving ADHD stimulant dosage forms and extended release formulations. Precision medicine or pharmacogenomics recommendations are currently limited to dosage adjustment for atomoxetine, and certain SSRI antidepressants, tricyclic antidepressants and antipsychotics for individuals who are polymorphic to their respective drug metabolizing cytochrome P450 2D6 or 2C19 isoenzymes.^5,6 Pharmacogenomics testing and medication prescribing remains to be seen with the absence of positive clinical outcome and cost effectiveness data.

Detailed FDA approved prescribing information including clinical pharmacology information is found in the National Institutes of Health US National Library of Medicine DailyMed database (dailymed.nlm.nih.gov). It is essential to work with psychiatric experts of all disciplines who are experienced with the use of pharmacological as well as non-pharmacological interventions.

—Dr Carlton KK Lee, Pediatric Clinical Pharmacy Specialist, Department of Pharmacy, and associate professor, Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland.

References

1. Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018; 5:727-38.

2. Uthman OA, Abdulmalik J. Comparative efficacy and acceptability of pharmacotherapeutic agents for anxiety disorders in children and adolescents: a mixed treatment comparison meta-analysis. Curr Med Res Opin. 2010 Jan;26(1):53-9.

3. Zhou X, Teng T, Zhang Y, et.al. Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis. Lancet Psychiatry. 2020; 7: 581–601.

4. Khan A, Mar KF, Faucett J, Schilling SK, et.al. Has the rising placebo response impacted antidepressant clinical trial outcome? Data from the US Food and Drug Administration 1987-2013. World Psychiatry. 2017; 16(2):181-92.

5. Clinical Pharmacogenetics Implementation Consortium (CPIC) Genes-Drugs Guidelines. cpicpgx.org/genes-drugs.

6. Green DJ, Mummaneni P, Kim IW, Oh JW, Pacanowski M and Burckart GJ. Pharmacogenomic Information in FDA-Approved Drug Labels: Application to Pediatric Patients. Clinical Pharmacology and Therapeutics. 99(6):622-632.