#51: Start Low, Go Slow, Get High. Pediatric Anxiety Pt 2: All About Meds

May 18, 2022 | By Sam Masur

Summary

Does just thinking about SSRIs make you anxious? In the second part of a two episode series, Dr. Beth Brannan, a Triple Board Trained Physician, will talk with us about pharmacotherapy for anxiety disorders, including how she decides between medications, how to titrate, and which side effects to look out for.

Credits

• Producer and Writer: Sally Elliott MD and Becca Raymond-Kolker MD
• Showrunner: Sam Masur MD
• Infographic: Sally Elliott MD
• Cover Art: Chris Chiu MD
• Hosts: Justin Berk MD, Chris Chiu MD, Becca Raymond-Kolker MD
• Editor: Justin Berk MD; Clair Morgan of nodderly.com
• Guest: Beth Brannan, MD

Pediatric Anxiety Pharmacology Pearls

1. Pharmacology for anxiety is ideally done along with CBT (Cognitive Behavioral Therapy).
2. SSRIs (selective serotonin reuptake inhibitors) are the first line, evidence-based medications for anxiety disorders in children. While they are evidence based, the majority of pharmacology for anxiety disorders and OCD in children is off-label.
3. Consider fluoxetine if there is concern for adherence as it has a longer half life.
4. Start low, titrate slowly, and get high (anxiety and OCD tend to respond to higher levels of SSRIs compared with mood disorders).
5. Black box warning for increase in suicidal thinking however, untreated serious psychiatric illness confers a greater risk of suicide.
6. After starting a patient on an SSRI, it is important to have regular follow up and supervision.
7. Keep anxiety on the differential when seeing a child with externalizing behavior. Internalizing disorders like anxiety and depression are underdiagnosed and externalizing disorders like ODD and conduct disorder are overdiagnosed disproportionately in children from racially and ethnically minoritized backgrounds.

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Pediatric Anxiety Notes

Identifying Candidates for Pharmacotherapy 

Expert opinion: Patients with anxiety disorders who are good candidates for pharmacotherapy include: 

• those who have a high level of functional impairment
• are struggling with exposure therapy due to high levels of distress
• those with anxiety who lack access to an exposure therapist

Medications for OCD and anxiety are tools in the toolbox. A medication can help reduce the baseline level of anxiety to bring it down to a level where the child is able to engage in the exposures, but it is highly unlikely that a medication will completely eliminate all the anxiety.

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are the pharmacological first line, evidence-based medications in children with anxiety disorders. While they are evidence-based, there is little FDA approval for SSRIs in children.  The majority of pharmacotherapy for anxiety disorders and OCD in children is off-label (CAMS, POTS and Kodish 2011).

Deciding between SSRIs

Expert opinion: Dr. Brannan typically decides between fluoxetine, sertraline and escitalopram. When deciding between which of these three to start, she considers:

• Family history – ask about any relatives who have had good or bad responses to any of these medications.
• Adherence – if there is a concern for imperfect adherence, consider fluoxetine as it has the longest half life
• GI symptoms at baseline – if the child has GI symptoms at baseline, consider starting with a medication other than sertraline, as sertraline can have a larger effect on the GI tract.

Start low, go slow, and get high 

Expert opinion: For anxiety disorders, typically start at low doses and titrate slowly. In order to effectively treat anxiety, the dose of the SSRIs is often higher than for mood disorders. 

Side Effects

Common side effects include:

• GI symptoms – most of the serotonin receptors are in our GI tract (Ponti and Camilleri) This is usually a transient side effect that goes away within weeks. Taking with food can improve the symptoms.
• Feeling restless or having difficulty sleeping. Therefore, Dr. Brannan typically recommends that children take the medication in the morning.
• Feeling tired. This is less common, but if this is the case, can recommend that the child takes the medication at night.
• Easy bruising – there are serotonin receptors on platelets; this does not have an impact on the number of platelets (Rieder 2021). Kids can also get more severe nosebleeds if they are prone to nosebleeds. 

FDA Black Box Warning

There were studies done in the early 2000’s that showed an increase in suicidal thinking in youth and young adults through the age of 24 (Friedman 2014). While this important to take seriously, untreated psychiatric illness also confers a greater risk of suicide. Children with severe anxiety disorders or OCD will often have thoughts of life being better off not living as these disorders can be very distressing and impairing and before starting a patient on a psychiatric medication, it is important to assess for suicidal thinking.  The black box warning is one of the many reasons why it is important to monitor and have close follow up once starting a patient on an SSRI.

What do you do if the first SSRI is not effective?

Try another SSRI. Unless the first SSRI switched the patient into a manic or hypomanic episode or there was another major side effect, Dr. Brannan recommends trying a second SSRI before switching classes. If the second SSRI is also ineffective, then consider switching classes. This is also a reasonable time to refer to a psychiatrist.

Other Medications

Clomipramine

Clomipramine is a TCA with some evidence for treating OCD. TCAs can have anticholinergic side effects, cardiovascular side effects, and can be fatal in overdose. For these reasons, Dr. Brannan would only consider starting clomipramine if there was a very compelling reason (i.e. multiple SSRI trials that were not effective, child has imparied functioning due to OCD, no history of cardiac problems, child is not suicidal, etc) (Moraczewski 2021).

SNRIs

Could consider an SNRI if the SSRI is not effective but the patient is tolerating the SSRI well (tolerating the serotonergic load). Duloxetine is the only serotonergic agent with FDA approval for generalized anxiety disorders (Strawn 2018).

Benzodiazepines

Expert opinion: If you are considering short-term augmentation with benzodiazepines, it may be time to refer to a psychiatrist. Benzodiazepines can be used in a short term, scheduled way with a very specific purpose. For example, if the child is too anxious to enter the building to receive their therapy, could consider using a small, scheduled dose of a benzodiazepine so that the patient can access the more durable treatment. 

Hydroxyzine

Expert opinion: Hydroxyzine can be used in a short term, scheduled manner while the child is working on longer term, more durable treatment (i.e. CBT). 

Discontinuation Syndrome

Discontinuation syndrome occurs when stopping an SSRI abruptly. It is not dangerous but it is uncomfortable. Patients may report: headaches, irritability, fatigue, feeling of “tingling” or “zapping” (Gabriel 2017).

Serotonin Syndrome

Serotonin syndrome can occur if a patient is on multiple serotonergic agents. It can be very dangerous. Signs and symptoms  include altered mental status (confusion, agitation), autonomic dysfunction (typically hypertension, tachycardia, hyperthermia) and neuromuscular abnormalities (clonus, tremor, hyperreflexia) . Management includes stopping the serotonergic agents and seeking more intensive medical intervention (Simon 2022).

Diagnostic Inequity

Internalizing disorders like anxiety and depression are underdiagnosed and externalizing disorders like ODD and conduct disorder are overdiagnosed disproportionately in children from racially and ethnically minoritized backgrounds (Williams). If you see a child with externalizing behaviors, it is imperative to keep anxiety on the differential.

Links

CAMS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818613/

POTS: https://pubmed.ncbi.nlm.nih.gov/15507582/

Goal

Listeners will learn about pharmacotherapy for pediatric anxiety in the outpatient setting.

Learning objectives

After listening to this episode listeners will…  

1. Learn about pharmacotherapy for anxiety disorders.
2. Be familiar with common side effects of SSRIs and the Black Box Warning.
3. Learn about steps to take if the first SSRI trial is not effective.
4. Become familiar with discontinuation syndrome and serotonin syndrome.
5. Recognize the importance of keeping anxiety on the differential when seeing a patient with externalizing behaviors.

Disclosures

Dr. Brannan reports no relevant financial disclosures. The Cribsiders report no relevant financial disclosures. 

Citation

Elliott S, Raymond-Kolker R, Brannan E, Masur S, Chiu C, Berk J. “#51: Start Low, Go Slow, Get High. Pediatric Anxiety Pt 2: All About Meds.” The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ May 18, 2022.