What is the recommended use of imipramine (tricyclic antidepressant) pamoate for treating depression in adolescents?

Imipramine Pamoate Should Not Be Used for Adolescent Depression

Imipramine pamoate (and all tricyclic antidepressants) should not be prescribed to adolescents with depression due to lack of proven efficacy, high lethality in overdose, and availability of safer, more effective alternatives. 1, 2

Why Tricyclics Are Contraindicated in Adolescent Depression

Lack of Efficacy

• Tricyclic antidepressants have not been proven effective in treating depression in children or adolescents in controlled trials 1
• Research demonstrates that only 44% of adolescents improved with imipramine treatment (mean dose 246 mg/day), despite good compliance and adequate plasma levels 3
• SSRIs demonstrate clear, statistically significant efficacy in adolescent depression, while tricyclics do not 2

Dangerous Safety Profile

• Tricyclics should never be prescribed as first-line treatment for suicidal children or adolescents because the difference between therapeutic and toxic levels is small, making them potentially lethal in overdose 1, 2
• The American Academy of Child and Adolescent Psychiatry explicitly states that tricyclics carry greater lethal potential and should be avoided in this population 2
• Cardiac arrhythmia risk exists even at therapeutic doses, with one reported death of a 10-year-old on combined desipramine and dextroamphetamine 1

Poor Tolerability

• Imipramine and other tricyclics are less well tolerated than SSRIs in adolescents with depression 4
• Venlafaxine (an SNRI) and duloxetine showed poor tolerability, but SSRIs generally have acceptable side effect profiles 4

Recommended First-Line Treatment Instead

SSRIs Are the Standard of Care

• Fluoxetine has the most robust evidence for safety and efficacy in adolescents aged 12 years and older, with FDA approval for depression in children as young as 8 years 1, 2
• Escitalopram is FDA-approved for adolescents aged 12-17 years with depression 2
• In the Treatment of Adolescent Depression Study (n=439), fluoxetine showed significantly greater improvement compared to placebo, with response rates of 61% for fluoxetine alone and 71% for fluoxetine plus CBT 1

Combination Therapy Is Most Effective

• Combination treatment with fluoxetine plus cognitive-behavioral therapy (CBT) provides superior outcomes compared to either treatment alone 1
• This combination also produces more rapid initial response than psychotherapy alone 1

The Only Appropriate Use of Imipramine in Adolescents

Nocturnal Enuresis (Not Depression)

• Imipramine is indicated for childhood enuresis in children aged 6 and older at doses of 25-50 mg at bedtime (higher dose for children over 9 years) 1, 5, 6
• Even for enuresis, imipramine should only be used as third-line therapy after enuresis alarms and desmopressin have failed 5
• For enuresis, the dose is 1.0-2.5 mg/kg at bedtime, which is lower than antidepressant dosing 1
• A pretreatment ECG may be obtained to detect underlying rhythm disorders before starting imipramine for enuresis 1

Critical Safety Monitoring If Imipramine Is Inappropriately Prescribed

If a clinician encounters an adolescent already on imipramine for depression (which should not have been started):

• Immediate assessment within 1 week evaluating depressive symptoms, suicide risk, adverse effects, adherence, and environmental stressors 2
• ECG monitoring before treatment and periodically thereafter due to cardiac conduction risks 1, 5
• Secure medication storage to prevent access by the patient or siblings, given fatal overdose potential 5
• Plan transition to an SSRI (preferably fluoxetine) with gradual taper of imipramine to avoid withdrawal symptoms 2

Imipramine Pamoate Formulation Specifics

• Imipramine pamoate is therapeutically equivalent to imipramine hydrochloride when comparing single daily dosing (pamoate) to divided dosing (hydrochloride) 7
• The FDA label for imipramine recommends 30-40 mg/day initially for adolescents, generally not exceeding 100 mg/day 6
• However, this dosing recommendation is outdated and should not be followed given current evidence against using tricyclics for adolescent depression 1, 2