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Imipramine for ADHD


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.

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 / day1
  • 4 x 10 mg/day up to a total of max. 150 mg/day2
    (Dosage instructions of the attending physician alone are decisive!)

Imipramine works

  • Serotonerg3
    • As a serotonin reuptake inhibitor, whereby this effect predominates45
  • Noradrenerg3
    • As a noradrenaline reuptake inhibitor (quite strong)4
      Tricyclic antidepressants generally have this effect.6
  • Adrenerg
    • As an antagonist of the alpha-adrenoreceptor4
  • Dopaminergic
    • As a dopamine reuptake inhibitor4
      Tricyclic antidepressants generally have this effect.6
  • Anticholinergic3
    • As an antagonist of the MAChR acetylcholine receptor4
  • Histaminergic
    • As an antagonist of the H1 histamine receptor4
      Antidepressants that have an H1-antihistaminergic effect (e.g. imipramine, doxepin, mianserin, desipramine and amitryptiline) significantly inhibit histamine-induced ACTH secretion in rats. 7 This could also apply to mirtazapine.8
  • Weak interaction with sigma-1 receptor4
    • Nevertheless reduces the sigma-1 receptor density.9
  • Inhibition of the enzyme acid sphingomyelinase (ASM) = FIASMA = Functional Inhibitor of Acid SphingeMyelinAse = Functional Inhibitor of Acid Sphingomyelinase410

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.

Imipramine can take 8 to 10 weeks to take full effect.2

Imipramine is converted into desimipramine in the body. Desimipramine has an activating effect.
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 tiredness 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.11

When used to treat 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 first tablet - i.e. without the usual 2 (to 3) week flooding phase. 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 reports 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.1 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.12

We know of no ADHD sufferer for whom imipramine was effective, although a neurologist we know often prescribed it before 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:2

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

  1. Huessy (1983): Imipramine for attention deficit disorder. Am J Psychiatry. 1983 Feb;140(2):272. doi: 10.1176/ajp.140.2.272b. PMID: 6849467.

  2. Dodson WW (2005): Pharmacotherapy of adult ADHD. J Clin Psychol. 2005 May;61(5):589-606. doi: 10.1002/jclp.20122. PMID: 15723384. REVIEW

  3. Helmchen, Henn, Lauter, Sartorius (2013): Psychiatrie der Gegenwart 1: Grundlagen der Psychiatrie, Springer, Seite 192


  5. Häßler (2009): substanzgebundene Alternativen in der Therapie von ADHS, Seite 174, in: Häßler (Hrsg) das ADHS Kaleidoskop – State of the Art und bisher nicht beachtete Aspekte von hoher Relevanz; medizinisch wissenschaftliche Verlagsgesellschaft

  6. Mang (2018): 05. Monoamine 2: Amphetamin, Ritalin (ADHS), Cocain, Tricyclika, Videovorlesung. ca. bei Minute 40.

  7. Reilly, Sigg (1982): Suppression of histamine-induced adrenocorticotropic hormone release by antihistamines and antidepressants. J Pharmacol Exp Ther. 1982 Sep;222(3):583-8.

  8. Büchs (2009): Einfluss von Mirtazapin auf die Hypothalamus-Hypophysen-Nebennierenrindenachse bei depressiven Patienten; Dissertation, Seite 129

  9. Weber, Wünsch (2017): Sigma-Rezeptor – Das unbekannte Target; Pharmazeutische Zeitung, Ausgabe 05/2017, 30.01.2017


  11. Häßler (2009): substanzgebundene Alternativen in der Therapie von ADHS, Seite 175, in: Häßler (Hrsg) das ADHS Kaleidoskop – State of the Art und bisher nicht beachtete Aspekte von hoher Relevanz; medizinisch wissenschaftliche Verlagsgesellschaft

  12. Huessy, Wright (1970): The use of imipramine in children’s behavior disorders. Acta Paedopsychiatr. 1970 Dec;37(7):194-9. PMID: 4927115.