What is a common indication for using Tricyclic Antidepressants (TCA) in children?

From the Guidelines

Tricyclic antidepressants (TCAs) are commonly used in children for the treatment of enuresis, specifically nocturnal enuresis, with imipramine being the most frequently prescribed TCA for this purpose, typically given in doses of 25-50 mg at bedtime for children aged 6-12 years, with adolescents sometimes requiring up to 75 mg 1.

Key Points to Consider

• The effectiveness of imipramine for enuresis is seen in approximately 50% of unselected children, with a significant relapse rate of up to 50% 1.
• The mechanism of action of imipramine in treating enuresis is unknown and not conclusively related to blood level, but it is thought to decrease bladder detrusor muscle contractility and increase sphincter tone, while also potentially affecting sleep architecture 1.
• Due to safety concerns, including cardiovascular side effects and toxicity in overdose, imipramine is generally not considered a first-line treatment for depression in children, but it may be used as a third-line therapy for enuresis in tertiary care facilities 1.
• Before starting TCA therapy for enuresis, children should undergo basic evaluation, including urinalysis and assessment of any underlying conditions, and parents should be educated about keeping the medication secure due to its potential toxicity 1.

Important Considerations

• Imipramine should be used with caution, particularly in children with a history of palpitations or syncope, or any sudden cardiac death or unstable arrhythmia in the family, and a pretreatment electrocardiogram may be necessary to detect an underlying rhythm disorder 1.
• The most serious problem associated with imipramine is ingestion by the patient's younger siblings, leading to serious or fatal consequences, highlighting the need for secure storage of the medication 1.
• Other side effects of imipramine, such as mood changes, nausea, or insomnia, may occur, but they often disappear even if treatment is continued 1.

From the FDA Drug Label

A dose of 2. 5 mg/kg/day of Imipramine Hydrochloride Tablets USP should not be exceeded in childhood. The common indication for using Tricyclic Antidepressants (TCA) in children is not explicitly stated in the provided drug label. However, it can be inferred that imipramine is used in children, likely for depression or other psychiatric disorders, given the discussion of suicidality risk in children and adolescents with MDD, OCD, or other psychiatric disorders.

• Key points to consider when using TCAs in children include:
  • Dosing: A dose of 2.5 mg/kg/day of Imipramine Hydrochloride Tablets USP should not be exceeded in childhood.
  • Cardiovascular monitoring: Extreme caution should be used when giving this drug to patients with cardiovascular disease.
  • Seizure disorder: Patients with a history of seizure disorder require careful consideration, as this drug may lower the seizure threshold.
  • Concomitant medications: Patients receiving certain medications, such as guanethidine, clonidine, or methylphenidate hydrochloride, may require downward dosage adjustment of Imipramine Hydrochloride. 2

From the Research

Indications for Tricyclic Antidepressants (TCA) in Children

• A common indication for using Tricyclic Antidepressants (TCA) in children is for the treatment of nocturnal enuresis (bedwetting) 3, 4, 5, 6.
• TCAs have proven efficacy in the treatment of enuresis, with imipramine being the most commonly used TCA for this condition 3, 4, 6.
• The use of TCAs in children with enuresis is recommended as a second-line treatment, with careful monitoring by the prescribing clinician due to possible adverse effects 5.
• Other indications for TCAs in children include the treatment of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and anxiety disorders, although the evidence for these indications is less compelling 5.

Treatment Outcomes

• Studies have shown that TCAs, particularly imipramine, are effective in reducing the number of wet nights in children with enuresis, with a reduction of about one wet night per week while on treatment 3, 4.
• However, the effect of TCAs on enuresis is not sustained after treatment is stopped, with most children relapsing 3, 4.
• Comparison of TCAs with other treatments, such as desmopressin and alarm therapy, has shown that TCAs are less effective than alarm therapy in achieving long-term dryness 4.
• The addition of a TCA to other treatments, such as anticholinergics, may be more effective than TCA monotherapy, but the evidence is limited 4.