Imipramine for ADHD

Trade names of imipramine: Tofranil, also available as a generic drug

Imipramine is the oldest tricyclic antidepressant and has been used since the 1940s.

Active ingredient: imipramine, converted in the body to desipramine
Dosage for ADHD: 5 to 10 mg/day
(Dosage instructions of the attending physician are solely authoritative!)

Imipramine works

• Serotonerg¹
  • As a serotonin reuptake inhibitor, with this effect predominating²³
• Noradrenerg¹
  • As a noradrenaline reuptake inhibitor (quite strong)²
    Tricyclic antidepressants generally have this effect.⁴
• Adrenerg
  • As an antagonist of the alpha-adrenoreceptor²
• Dopaminerg
  • As a dopamine reuptake inhibitor²
    Tricyclic antidepressants generally have this effect.⁴
• Anticholinergic¹
  • As an antagonist of the MAChR acetylcholine receptor²
• Histaminerg
  • As an antagonist of the H1 histamine receptor²
    Antidepressants that are H1 antihistaminergic (e.g., imipramine, doxepin, mianserin, desipramine, and amitryptiline) significantly inhibit histamine-induced ACTH secretion in rats. ⁵ This may also be true for mirtazapine.⁶
• Weak interaction with sigma-1 receptor²
  • Nevertheless reduces the sigma-1 receptor density.⁷
• Inhibition of the enzyme acid sphingomyelinase (ASM) = FIASMA = Functional Inhibitor of Acid SphingeMyelinAse = Functional Inhibitor of Acid Sphingomyelinase²⁸

Imipramine has a rather inhibitory effect overall. It reinforces the inhibitory transmission of information. Imipramine is therefore indicated for ADHD-HI (with hyperactivity) and accordingly less helpful for ADHD-I.

Imipramine is converted into desimipramine in the body. Desimipramine has an activating effect.
At low doses, imipramine does not usually cause fatigue. If a fatiguing effect nevertheless occurs, it is recommended to take imipramine in the evening. The fatigue is then sleep-inducing and the conversion of the imipramine active ingredient to desimipramine occurs during sleep, so that the activating effect of desimipramine is available in the morning. Used in this way, the partially described disadvantages of serotonin reuptake inhibition in sleep problems are probably neutralized.
Imipramine is said to be slightly more effective than nortryptiline against affect breakthroughs (outbursts of anger, stress “explosions”).

Imipramine is recommended for comorbid enuresis.⁹

When used for ADHD, a much lower dosage is required than would be usual when used as an antidepressant.
In some ADHD sufferers, imipramine is effective from the very first tablet - i.e., without the 2 (to 3) week run-on period usually required. This could be related to the immediate effect of serotonin on the inhibition of impulsivity.
Imipramine can cause depression as a side effect in rare cases.

Huessey reported an effect of imipramine in ADHD at 10 to 50 mg/day divided into 2 doses/day, with a 24-hour effect and improvement in sleep.¹⁰ Of 52 children with ADHD-HI or ADHD-C, 67% showed significant improvement with an average daily dose of 50 mg imipramine given once. A laboratory study found no adverse effects in 20 children. Side effects were minimal and occurred mainly in children who were nonresponders.¹¹

We do not know of any ADHD sufferer for whom imipramine would have been effective, although a neurologist we know frequently gave it before prescribing stimulants. This may also be due to a lower dosage (max. 10 mg).

Interaction with methylphenidate:
The German Medical Association points to an interaction between methylphenidate and imipramine, with these drugs reinforcing each other because both have dopamine reuptake inhibitory effects. A cumulative overdose could result:

• Confusion and agitation
• Mood instability
• Irritability and aggressiveness
• Psychotic symptoms