Medication Summary
Several classes of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), bupropion, mirtazapine, and vilazodone, have been used in the treatment of depression, although not all have been studied in the pediatric population. Of these, the types most frequently used in the pediatric population are SSRIs.
SSRIs are greatly preferred over the other classes of antidepressants. Because the adverse-effect profile of SSRIs is less prominent, improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with TCAs. Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when treating a child or adolescent with mood disorder.
Antidepressants, SSRIs
Class Summary
Selective serotonin reuptake inhibitors (SSRIs) are a relatively new group of medicines used to treat emotional and behavioral problems, including depression, panic disorder, obsessive-compulsive disorder, bulimia, and posttraumatic stress disorder in adults. These medications are beginning to be used to treat the same problems in children and adolescents. Serotonin is a neurotransmitter that exists naturally in the brain. The SSRIs increase serotonin signaling in certain brain circuits eventually inducing a change in neurochemical receptors that may help mediate an antidepressant effect. SSRIs include, but are not limited to, the following medications: fluoxetine, paroxetine, sertraline, citalopram, and fluvoxamine. In youth, paroxetine has been associated with increased suicidal thinking and behavior compared to other SSRIs. [55]
Escitalopram and fluoxetine have been approved by the FDA for treatment of pediatric depression. Fluoxetine has been the most studied agent for pediatric depression, and, in the 2022 AACAP clinical practice guidelines, fluoxetine is preferred over other SSRIs for the treatment of pediatric depression. [2]
Fluoxetine (Prozac)
Fluoxetine is an antidepressant agent that is chemically unrelated to the tricyclic, tetracyclic, or other available antidepressants. It selectively inhibits presynaptic serotonin reuptake with minimal or no effect on the reuptake of norepinephrine or dopamine and has been the best studied agent for pediatric depression. It is one of two FDA approved medications for pediatric depression and, in the 2022 AACAP clinical practice guidelines, fluoxetine is preferred over other SSRIs for the treatment of pediatric depression.
Escitalopram (Lexapro)
Escitalopram is an isolated enantiomer of citalopram and shares a similar clinical profile, including risk of QT prolongation at higher doses. It has better evidence for efficacy in child and adolescent depression than other SSRIs except for fluoxetine. It is one of two medications approved by the FDA for the treatment of pediatric depression.
Sertraline (Zoloft)
Sertraline selectively inhibits presynaptic serotonin reuptake. Sertraline is approved by the US Food and Drug Administration (FDA) to treat obsessive-compulsive disorder (OCD) in children. It has also been used off-label to treat depression in children.
Fluvoxamine (Luvox CR)
Fluvoxamine is a potent selective inhibitor of neuronal serotonin reuptake. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and, thus, has fewer adverse effects than tricyclic antidepressants (TCAs). However, fluvoxamine has greater potential for drug-drug interactions than other SSRIs and generally requires twice daily dosing due to its short half-life. Fluvoxamine is approved for treatment of obsessions and compulsions in adults and children aged 8 years and older with OCD.
Citalopram (Celexa)
Citalopram enhances serotonin activity owing to selective reuptake inhibition at the neuronal membrane. Although citalopram is not FDA approved for use in children, various clinical trials have shown efficacy in the treatment of moderate-to-severe major depressive disorder (MDD) in children and adolescents. Citalopram may cause more QT prolongation than other SSRIs in a dose-dependent fashion and has been associated with Torsade de Pointes, ventricular tachycardia, and sudden death at daily doses exceeding 40 mg per day. Citalopram should be avoided in patients with long QT syndrome.
Paroxetine (Paxil, Paxil CR, Pexeva)
Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. It has a weak effect on norepinephrine and dopamine neuronal reuptake. In youth, paroxetine has been associated with increased suicidal thinking and behavior compared to other SSRIs. For maintenance therapy, make dosage adjustments to maintain the patient on the lowest effective dosage, and reassess the patient periodically to determine the need for continued treatment. This medication should not be stopped abruptly due to risk of discontinuation symptoms.
Antidepressants, SNRIs
Class Summary
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are generally considered second-line therapies for depressive disorders, after patient’s have not tolerated or not responded to two SSRI trials. These medications generally have more side effects than SSRIs, but less serious side effects than TCAs. Blood pressure should be monitored while initiating and continuing on SNRI therapy due to rare, but significant increases in blood pressure. In pediatrics, these medications are thought to be associated with a slightly higher risk of suicidal ideation and behaviors compared to SSRIs.
SNRIs have been noted to have significant discontinuation syndromes including mood fluctuations, headache, nausea, imbalance, irritability, general malaise, and flu-like symptoms. For this reason, these medications should be weaned off over a matter of weeks and not abruptly discontinued.
Venlafaxine (Effexor (DSC), Effexor XR, Venbysi XR)
Inhibits serotonin and norepinephrine reuptake to exert an antidepressant effect. May rarely cause significant increases in blood pressure. Efficacy in adults has been shown to be similar to SSRIs, however results in child and adolescent studies remain mixed.
Desvenlafaxine (Khedezla (DSC), Pristiq)
Desvenlafaxine is the primary active metabolite of venlafaxine, this drug was designed to be a more potent and refined form of venlafaxine. In adult studies, desvenlafaxine has been shown to be as effective as venlafaxine and SSRIs. Pediatric data for this medication, however, has been largely equivocal in placebo-controlled trials.
Duloxetine (Cymbalta, Irenka)
Duloxetine inhibits serotonin and norepinephrine reuptake at presynaptic membranes. It is commonly used not only as an antidepressant, but also for neuropathic pain and in chronic pain syndromes. Studies done in pediatrics show a small, but significant efficacy in treating depressive symptoms, comparable to fluoxetine, sertraline, and escitalopram.
Antidepressants, TCAs
Class Summary
From the 1960s to the late 1980s, tricyclic antidepressants (TCAs) represented the primary pharmacologic treatment for depression in the United States. Therapeutic effects of TCAs are thought to be caused by their ability to block the reuptake of the neurotransmitters serotonin and norepinephrine in nerve terminals, which results in alterations in the sensitivity of various neuroreceptors.
TCAs are not currently recommended as a first-line treatment for depression in children and adolescents, but may be indicated for other disorders including migraine disorders or obsessive-compulsive disorder. TCAs commonly used in children and adolescents are imipramine (Tofranil), nortriptyline (Pamelor), clomipramine, and amitriptyline.
TCAs should be initiated at low doses to minimize adverse effects; in adolescents, TCAs are usually prescribed in once-daily bedtime doses. Because children metabolize medications more quickly than adults, prepubertal children usually require twice-daily dosing.
Imipramine (Tofranil)
Imipramine inhibits the reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at the presynaptic neuron. Use parenteral administration for starting therapy only in patients unable or unwilling to use oral medication.
Nortriptyline (Pamelor)
Nortriptyline works by inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, thus increasing the synaptic concentration of these neurotransmitters in the central nervous system (CNS). Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action.
Desipramine (Norpramin)
Desipramine may increase the synaptic concentration of norepinephrine in the central nervous system (CNS) by inhibiting reuptake by the presynaptic neuronal membrane. It may have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation of serotonin receptors. Extreme caution should be used when desipramine is prescribed to patients with a family history of sudden death, conduction abnormalities, or cardiac dysrhythmias. In addition, in certain patients, seizures may precede dysrhythmias and death.
Amitriptyline
Amitriptyline inhibits the reuptake of serotonin and/or norepinephrine at the presynaptic neuronal membrane, thus increasing the concentration of these neurotransmitters in the CNS.
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Psychotherapy
- General Considerations in Antidepressant Pharmacotherapy
- Selective Serotonin Reuptake Inhibitors
- Serotonin and Norepinephrine Reuptake Inhibitors
- Tricyclic Antidepressants
- Other Antidepressant Pharmacotherapy
- Non-pharmacologic medical treatments
- Indications for Hospitalization
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