Protriptyline for ADHD

Protriptyline is a tricyclic antidepressant that is less sedating than other TCADs. It is approved in the USA for the treatment of ADHD, as well as for depression, narcolepsy and headaches.¹ It also has an anxiolytic effect and helps with chronic pain.

• Noradrenaline reuptake inhibitors
  • also causes an increase in dopamine in the PFC, as NETs in the PFC reabsorb slightly more dopamine than noradrenaline
• increases serotonin neurotransmission at high doses
• can cause calcium-dependent cell death
• acts as a FIASMA (functional inhibitor of acid sphingomyelinase).

Protriptyline shows initial clinical effects within the first week of taking it. It therefore has the fastest onset of action among the tricyclic antidepressants.
Protriptyline is a secondary tricyclic amine and is structurally similar to nortriptyline.
Protriptyline is subject to limited hepatic first-pass metabolism.
Protriptyline can cross the blood-brain barrier.
The half-life of protriptyline is about 74 hours (more than three days). With long-term use, protriptyline has a long half-life of 80 to 200 hours and therefore takes up to a month to reach a steady state.

Due to the higher side effects, TZADs are not the first choice compared to other antidepressants.