Imipramine for ADHD

Trade name of Imipramine: Tofranil, also available as a generic

Imipramine is the oldest tricyclic antidepressant and has been used since the 1940s.
Among the tricyclic antidepressants, desipramine is said to have a better effect on ADHD than imipramine, nortriptyline and amitriptyline ¹

Active ingredient: imipramine, is converted to desipramine in the body
Dosage for ADHD:

• 5 to 10 mg/day
• 10 to 50 mg / day, divided into 2 doses / day²
• 4 x 10 mg/day up to a total of max. 150 mg/day³
  (Dosage instructions of the attending physician alone are decisive!)

Imipramine works

• Serotonerg⁴
  • As a serotonin reuptake inhibitor, whereby this effect predominates⁵⁶
• Noradrenergic⁴
  • As a noradrenaline reuptake inhibitor (quite strong)⁵
    Tricyclic antidepressants generally have this effect.⁷
• Adrenerg
  • As an antagonist of the alpha-adrenoreceptor⁵
• Dopaminergic
  • As a dopamine reuptake inhibitor⁵
    Tricyclic antidepressants generally have this effect.⁷
• Anticholinergic⁴
  • As an antagonist of the MAChR acetylcholine receptor⁵
• Histaminergic
  • As an antagonist of the H1 histamine receptor⁵
    Antidepressants that have an H1-antihistaminergic effect (e.g. imipramine, doxepin, mianserin, desipramine and amitryptiline) significantly inhibit histamine-induced ACTH secretion in rats. ⁸ This could also apply to mirtazapine.⁹
• Weak interaction with sigma-1 receptor⁵
  • Nevertheless reduces the sigma-1 receptor density.¹⁰
• Inhibition of the enzyme acid sphingomyelinase (ASM) = FIASMA = Functional Inhibitor of Acid SphingeMyelinAse = Functional Inhibitor of Acid Sphingomyelinase⁵¹¹

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

With imipramine, it can take 3 to 10 days (reduction in hyperactivity at 75 mg/day)¹ or 8 to 10 weeks³ for the full effect to be felt.

Imipramine is converted into desimipramine in the body. Desimipramine has an activating effect and is said to be slightly more effective than imipramine when taken as medication¹
At low doses, imipramine does not usually cause drowsiness. However, if a fatiguing effect occurs, it is recommended to take imipramine in the evening. The drowsiness is then sleep-promoting and the conversion of the imipramine active ingredient to desimipramine takes place 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 in combating emotional outbursts (outbursts of anger, stress “explosions”).

Imipramine is recommended for comorbid enuresis.¹²

When used to treat ADHD, a much lower dosage is required than would be usual when used as an antidepressant.
In some people with ADHD, imipramine is effective from the first tablet - i.e. without the usually required flooding phase of 2 (to 3) weeks. This could be related to the immediate effect of serotonin on the inhibition of impulsivity.
In rare cases, imipramine can trigger depression as a side effect.

Huessey reported an effect of imipramine in ADHD at 10 to 50 mg/day, divided into 2 doses/day, with an effect over 24 hours and an improvement in sleep.² 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 non-responders.¹³

We do not know of any person with ADHD for whom imipramine has been effective, although a neurologist known to us often 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, whereby these drugs reinforce each other, as both have a dopamine reuptake inhibiting effect. A cumulative overdose could result:

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

Side effects

Tricyclic antidepressants are associated with numerous side effects in adults, such as:³

• Drowsiness
• orthostatic hypertension
• Constipation
• Urinary retention
• Cardiac arrhythmia
• Toxicity in case of overdose