Case example
A 16-year-old comes in for a well child check. She has a history of anxiety and depression and is on 20mg of escitalopram daily. She goes to therapy weekly and finds it helpful. The medication has helped her depression but she is still pretty anxious at school most days. The anxiety distracts her from focusing on school work and she avoids going places on the weekend because of it. Her psychiatrist just retired and she has not been able to find a new one yet. She has already tried and didn’t respond to fluoxetine and had side effects sertraline. She wants to change her medication. What are your options?
FDA Approvals since 1997
| Medication | FDA approval | formulation | dosing | notes |
| Prozac/fluoxetine | MDD: 8 years oldOCD: 7 years old | Capsules 10-40mgTablets 10-60mg
Liquid 20mg/5ml |
Start at 10mgMax approved dose 60mg | Long half lifeP450 interaction (2D6, 2C19 inhibitor) |
| Zoloft/sertraline | OCD: 6 years old | Tablets 25-100mgLiquid 20mg/1ml | Start 25mgMax dose 200mg | GI side effects possibly more common |
| Lexapro/escitalopram | MDD: 12 years oldGAD: 7 years old | Tablets 5-20mgLiquid 5mg/5ml | Start 5mgMax dose 20mg | Side effects possibly less common |
| Luvox/fluvoxamine | OCD: 8 years old | Tablets 20-100mg | Start 25mg BIDMax dose 200mg 8- 11 y.o.
300mg > 11 y.o. |
Short half lifeP450 interactions
Only used in OCD Discontinuation symptoms common |
| Cymbalta/duloxetine | GAD: 7 years old | Capsules 20-60mg | Start 30mgMax dose 120mg | Can be BID dosingModerate P450 interaction |
SSRIs
Although selective serotonin reuptake inhibitors (SSRIs) are commonly used in children to treat mood, anxiety and other symptoms, there are limitations on what has been formally FDA approved in children. Sertraline is approved only for Obsessive Compulsive Disorder (OCD) in children as young as 6 years old, fluoxetine is approved for Obsessive OCD in children age 7 and up and Major Depressive Disorder (MDD) for age 8 and up. Fluvoxamine is approved for OCD in children as young as 8. Escitalopram is approved for MDD in ages 12 and up and as of May 2023 for Generalized Anxiety Disorder (GAD) for children age 7 and up. These SSRIs and others are used in other diagnoses, age groups and beyond FDA approved dosages. There is some study data to support such use.
Anxiety disorders, especially OCD is known by psychiatrists to often require a high dose of medication beyond the usual dose that can treat depression. Although studies in children are limited there have been a number of trials showing benefit in adults when treating OCD with high doses of SSRI medications. Sertraline has been studied up to 400mg daily while the FDA approved maximum dose is 200mg. Escitalopram has been studied and found to have benefit in doses up to 50mg daily while the FDA approved maximum dose is 20mg. In patients who did not respond to a 20mg daily dose, 80% had treatment response at a higher dose. The average dose in higher dose trials was 33.8mg per day.
A meta review from 2020 of SSRIs in children and adolescents found fluoxetine was more efficacious in MDD compared to other antidepressant medications. Fluvoxamine and paroxetine were more effective in the treatment of anxiety disorders. Fluoxetine and sertraline were more efficacious in the treatment of OCD. Bupropion and desipramine showed improvement in ADHD symptoms. Because all antidepressants include a black box warning for increased risk of suicidal thoughts, this should always be discussed with children and their parents when prescribing these medications. The warning was based on a meta-analysis of many studies that suggested suicidal thoughts or behavior was present in 4% of young people prescribed antidepressants and 2% of those prescribed placebo. After the black box warning was fist instituted in 2004, antidepressant prescribing went down and adolescent suicide attempts by overdose increased. Further studies of suicide risk with antidepressants since 2004 have shown a potential increased risk for suicidality with paroxetine and venlafaxine. Sertraline actually reduced suicidality risk in youth with anxiety.
Other Medications
Duloxetine (Cymbalta), a selective serotonin and norepinephrine reuptake inhibitor, is approved for Generalized Anxiety Disorder (GAD) for age 7 and older. Lurasidone (Latuda) which is an atypical antipsychotic medication is approved for bipolar depression in children age 10 and older. There are a number of Tricyclic Antidepressants approved for use in children and teens but their use is limited by significant side effects as well as the risk of toxicity and overdose. Clomipramine is approved for OCD in children age 10 and up. Amitriptyline, desipramine, protriptyline, and trimipramine are all approved for MDD in age 12 and up. Imipramine is approved for enuresis in children age 6 and older.
Although not FDA approved in children or adolescents, there have been studies on mirtazapine which show benefit for depression and anxiety in children age 12 and up. It also can help with sleep and can increase appetite. Mirtazapine has been shown to be helpful for adolescents with ADHD and anxiety or depression who are also on stimulants for their ADHD. It can cause weight gain, so that is important to monitor, but if they have had appetite suppression from the stimulant, this could be helpful to counteract the effect.
Case Example Continued
Luckily you have a number of options that are likely to be safe and effective. Switching medications is an option and prescribing above the FDA approved maximum dosing is also reasonable. Increase this teenager’s dose above 20mg daily could prove useful to help her anxiety symptoms. Switching to or adding on duloxetine which is approved in GAD could also be an alternative. If she had ADHD symptoms instead of anxiety symptoms with her depression, bupropion could be a useful addition. Or if she had ADHD and were on a stimulant already, especially if she were struggling with appetite or low weight, mirtazapine could be helpful.
References
www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-Education/Pharmacy-Education-Materials/Downloads/ad-pediatric-factsheet11-14.pdf
Antidepressant Medications: Use in Pediatric Patients
pmc.ncbi.nlm.nih.gov/articles/PMC6738970/
Antidepressants for Pediatric Patients – PMC
Chris Paxos; Moving beyond first-line treatment options for OCD. Ment Health Clin. 2022 Nov 3;12(5):300–308. doi: 10.9740/mhc.2022.10.300
Moving beyond first-line treatment options for OCD – PMC
Katharine Boaden, Anneka Tomlinson, Samuele Cortese, Andrea Cipriani. Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment. Front Psychiatry. 2020 Sep 2;11:717. doi: 10.3389/fpsyt.2020.00717
Use of mirtazapine in children and adolescents
onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pnp.493?msockid=2ee0e151ec6a6d521801f719edf86c0c
AUTHOR:
Dr. Melissa Lorang, MD
Child, Adolescent and Adult Psychiatrist
Vista Hill Foundation