What side effects are associated with this type of intervention?

Nortriptyline, a tricyclic antidepressant used in the treatment of Post-Concussion Syndrome, is associated with several side effects. Common side effects include dry mouth, constipation, urinary retention, blurred vision, weight gain, and sedation. Additionally, tricyclic antidepressants can lower the seizure threshold, necessitating cautious use in patients with central nervous system disease.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved medications for the treatment of Post-Concussion Syndrome (PCS). However, treatments often involve medications that address specific symptoms such as headaches, depression, and cognitive issues. Nortriptyline, a tricyclic antidepressant, is being studied for its potential to alleviate headache symptoms in PCS by modulating neurotransmitters. Similar medications that are sometimes used off-label for PCS symptoms include other tricyclic antidepressants like amitriptyline, as well as SSRIs and SNRIs for mood-related symptoms.

What other types of research exist?

Promising novel alternatives to Nortriptyline for Post-Concussion Syndrome patients include: 1) CGRP antagonists (e.g., Erenumab, Fremanezumab) which have shown efficacy in migraine prevention and may be beneficial for PCS-related headaches. 2) Botulinum toxin injections, which are used for chronic migraine and could be considered for PCS if other treatments fail. 3) Portable neurostimulation devices, which offer a non-pharmacological option for headache management and have shown promise in recent studies.

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Tricyclic Antidepressant

Nortriptyline for Concussion (PeCon Trial)

Q: What is the mechanism of action of this treatment?

Nortriptyline, a tricyclic antidepressant (TCA), works by inhibiting the reuptake of norepinephrine and serotonin, increasing their levels in the brain. This modulation of neurotransmitters helps alleviate headache symptoms, which are common in Post-Concussion Syndrome (PCS) patients. Understanding this mechanism is important for PCS patients as it underscores the potential of TCAs to reduce headache frequency and severity, thereby improving their overall quality of life.

Phase 4

Waitlist Available

Led By Patrick Moreno, MD

Research Sponsored by Lancaster General Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

No loss of consciousness OR loss of consciousness <30 minutes

Not currently receiving pharmacologic treatment for concussion aside from NSAIDs and acetaminophen

Must not have

A personal history of Brugada syndrome

Focal neurological deficits following injury

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 weeks

Awards & highlights

Approved for 5 Other Conditions

All Individual Drugs Already Approved

Pivotal Trial

Drug Has Already Been Approved

Summary

This trial tests whether nortriptyline can help people with headaches after a concussion. Participants will receive nortriptyline along with standard headache treatments. The goal is to see if nortriptyline reduces headache symptoms faster by balancing brain chemicals. Nortriptyline has been tested previously for migraine prevention, but it was not effective when used alone.

Who is the study for?

This trial is for young people aged 13-21 who've had a concussion with headaches lasting over 4 weeks. They must be in good health, able to take pills, and not on other concussion meds except common painkillers. Those with severe brain injuries, uncontrolled mental illness, pregnancy, or known allergies to the drug can't join.

What is being tested?

The study tests if Nortriptyline helps reduce headache symptoms faster than a placebo when added to standard treatments. Participants are randomly assigned to either the drug or placebo group and monitored weekly for symptom changes over four weeks.

What are the potential side effects?

Nortriptyline may cause side effects like mood swings, weight gain, dry mouth, dizziness upon standing up quickly (orthostatic hypotension), and could potentially worsen psychiatric conditions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have not lost consciousness or was unconscious for less than 30 minutes.

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I am only taking NSAIDs or acetaminophen for my concussion.

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My headache, head pressure, and neck pain score is over 3.

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I am between 13 and 21 years old.

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I can take pills and will follow the medication schedule.

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I have had headaches for more than 4 weeks after an injury.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of Brugada syndrome.

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I have specific nerve or brain function issues after an injury.

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I have a history of seizures or a serious brain injury.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Post-Concussive Symptom Inventory (PSCI) score

Side effects data

From 2002 Phase 4 trial • 110 Patients • NCT00000378

orthostatic hypotension

100%

80%

60%

40%

20%

Study treatment Arm

Sertaline

Nortriptyline

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: ExperimentalExperimental Treatment1 Intervention

10mg capsule once daily for 4 weeks of nortriptyline

Group II: ControlPlacebo Group1 Intervention

10mg capsule once daily for 4 weeks of Thick-It filler

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nortriptyline

FDA approved

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Nortriptyline, a tricyclic antidepressant (TCA), works by inhibiting the reuptake of norepinephrine and serotonin, increasing their levels in the brain. This modulation of neurotransmitters helps alleviate headache symptoms, which are common in Post-Concussion Syndrome (PCS) patients. Understanding this mechanism is important for PCS patients as it underscores the potential of TCAs to reduce headache frequency and severity, thereby improving their overall quality of life.

Correlations between serum ami- and nortriptyline concentrations and psychomotor performance.Effect of tricyclic antidepressants and alcohol in psychomotor skills related to driving.