Protriptyline hydrochloride is a tricyclic antidepressant that is used to improve mood in people with depression. It is also used for anxiety. Protriptyline was first patented in 1962, and it is sold under many brand names. It is an amine with the empirical formula of CHN. It is a more potent antidepressant and has fewer sedative and tranquilizing effects than other TCAs.
Results of one study of 25 women who were treated with 20 mg of Protriptyline each morning for 12 weeks showed 86% fewer headaches each month with an average dropping from 28.2 to 11.7 days. More than two-thirds had a 50% reduction in the number of headaches per month. The study also showed an average of 1 pound per month weight loss.
One study reported that Protriptyline can be helpful in brain-injured adults with attention and behavioral difficulties. . It has been shown to also improve the drowsiness, apneic episodes, snoring, and cataplexy related to narcolepsy. 
When it comes to mood, the two important chemicals in the brain are serotonin and norepinephrine. These are often decreased in people who are depressed and are the main targets of antidepressants. Protriptyline has the fastest onset of action among other tricyclic antidepressants, and thus clinical effects can occur within the first week of use. It is a secondary tricyclic amine and structurally similar to nortriptyline. It undergoes limited first-pass hepatic metabolism and is able to cross the blood-brain barrier. Protriptyline has a long half-life of 80 to 200 hours when used long-term, requiring up to a month to reach steady state. The half-life of protriptyline is approximately 74 hours (greater than 3 days).
Unlike other tricyclic or tetracyclic antidepressants which can be given from 75 to 300 mg/day, Protriptyline is given at much lower doses and increased as necessary. Unlike other tricyclic and tetracyclic which are often dosed once a day, dosage for protriptyline is divided into 3 or 4 times a day. When the drug must be stopped, taper to avoid effects of withdrawal.
The maximum dose is 60 mg a day, if necessary, beginning at a lower level and increasing gradually while looking for the patient’s response and any side effects as the dosage increase.
Protriptyline like all TCAs has multiple adverse effects. Although as effective as SSRIs and SNRIs, TCAs, and MAOs are not used as first-line treatment due to their side effects. Among the TCAs, protriptyline is the most likely to cause tachycardia, hypotension, anxiety, and agitation, and for this reason, some European countries have discontinued protriptyline use
Adverse Effects (like all TCAs)
Most Common Adverse Effects
Rare, More Serious Adverse Effects
Tricyclic antidepressants have many side effects, some of which are life-threatening. Among the tricyclic antidepressants, protriptyline is the most potent and most likely to cause hypotension, agitation, and cardiac effects. For this reason, protriptyline has multiple contraindications, including people with the following:
Protriptyline’s initial dose is 15 mg per day divided into 3 or 4 doses per day, with a max dose of 60 mg per day. However, taking more than recommended or taking the daily dose at one time can have significant consequences which can manifest in cardiac arrhythmias or EKG changes, especially QRS-widening hypotension, confusion, visual hallucinations, delusions, ataxia, tremors, syndrome of inappropriate ADH, tinnitus, hyperactive reflexes, muscle rigidity stupor, convulsions, coma, and even death.
ECG is recommended and close monitoring for patients over the age of 50, especially in those taking more than 20 mg per day, due to sensitivity to anticholinergic, cardiovascular, hypotensive, and sedative effects.
Like other antidepressants, protriptyline increases suicidal ideation and attempts in children, adolescents, and young adults and is not recommended in patients under the age of 12 or intended for those under the age of 6.
Tricyclic antidepressants, like all antidepressants, are used in a group of patients that are already at increased risk of attempted suicide. Thus, overdose with such drugs is something that needs to have a plan at hand. Furthermore, TCAs are often used in drug-resistant depression, which makes them even more of a risk than the first-line SSRIs and SNRIs. thus protriptyline is a very potent TCA and a dangerous drug for overdose.
Treatment of protriptyline toxicity includes gastrointestinal decontamination with gastric lavage and activated charcoal l and treating the symptoms that arise due to the overdose as necessary; for example, norepinephrine and IV fluids for hypotension, IV sodium bicarbonate for prolonged QRS duration, and benzodiazepines for anxiety, agitation, or seizures.
Protriptyline is an older tricyclic antidepressant which has little use today. Healthcare workers including the pharmacist and prescribing nurse should be familiar with newer antidepressants which are much safer. Patients already on protriptyline should be gradually weaned off and started on the newer antidepressants if there are no contraindications.
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