Topical Imipramine + Amitriptyline for Rosacea

Overseen By Manager Clinical Research Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wright State University

Must not be taking: Tricyclic antidepressants, Anti-inflammatories

Disqualifiers: Large tattoos, Tanning bed use, Photodynamic therapy, Pregnant or nursing, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

48 Participants Needed

Trial Summary

What is the purpose of this trial?

Rosacea is a common skin condition associated with easy blushing and red face; many patients with rosacea react to sunlight with increased redness. The purpose of this study is to determine if the use of a topical medication will help reduce sunlight induced redness and irritation in patients with rosacea.

Will I have to stop taking my current medications?

The trial requires you to stop using imipramine, amitriptyline, or any other tricyclic antidepressants, as well as topical anti-inflammatory medications within 1 week before starting. If you are a control subject, you cannot take medications that make you more sensitive to sunlight.

What evidence supports the effectiveness of the drug combination of topical Imipramine and Amitriptyline for treating rosacea?

Research shows that tricyclic antidepressants like amitriptyline have antihistaminic properties, which can help reduce itching when applied topically. Additionally, amitriptyline and imipramine have been effective in relieving pain in conditions like diabetic neuropathy, suggesting they may help with symptoms of rosacea. ^{1 2 3 4 5}

Is the combination of topical Imipramine and Amitriptyline safe for use in humans?

Amitriptyline, a tricyclic antidepressant, can cause skin reactions like rashes and hypersensitivity (allergic) reactions, which usually go away after stopping the drug. In a study comparing amitriptyline to another antidepressant, it was found to have a higher rate of adverse events, but these were not statistically significant. Imipramine, another tricyclic antidepressant, showed similar efficacy to another drug but had more anticholinergic side effects (like dry mouth and constipation). ^{3 6 7 8 9}

How does the drug combination of topical Imipramine and Amitriptyline for rosacea differ from other treatments?

This drug combination is unique because it uses tricyclic antidepressants topically, which have antihistaminic and local anesthetic properties, potentially reducing itching and providing pain relief, unlike standard rosacea treatments that typically focus on reducing inflammation and redness. ^{3 5 8 10 11}

Eligibility Criteria

This trial is for individuals with rosacea, a skin condition that causes blushing and redness. Participants should react to sunlight with increased redness. Specific inclusion and exclusion criteria are not provided, but typically these would detail the age range, health status, and any other conditions or medications that might affect participation.

Inclusion Criteria

Fitzpatrick Skin Type I - IIII

I identify myself as having rosacea or I have never experienced flushing or blushing.

I can share my medical history and current medications, and I'm not on any photosensitizing drugs.

Exclusion Criteria

I am currently taking a tricyclic antidepressant.

I have used anti-inflammatory skin creams or medications like prednisone recently.

I haven't had photodynamic or UCB treatments in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive topical application of 4% imipramine or 4% amitriptyline on the cheek to assess reduction in UVB-induced redness

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in erythema and tolerability of the treatment

24 hours post-treatment

Treatment Details

Interventions

• Amitriptyline
• Imipramine

Trial Overview The study is testing whether applying Imipramine or Amitriptyline creams can reduce sun-induced redness in rosacea patients compared to a control cream (Vehicle). It's likely participants will be randomly assigned to one of the treatments.

Participant Groups

Group I: Imipramine and Vehicle Experimental Treatment 2 Interventions

4% imipramine and vehicle are applied on a 2x2cm2 area of the subject's cheek. The imipramine is applied on one side of the subject's face (cheek) and vehicle is applied on the other side.

Group II: Amitriptyline and Vehicle Experimental Treatment 2 Interventions

4% amitriptyline and vehicle are applied on a 2x2cm2 area of the subject's cheek. The amitriptyline is applied on side of the subject's face (cheek) and vehicle is applied on the other side.

Amitriptyline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Elavil for:

• Depression
• Anxiety and Stress
• Chronic Pain
• Fibromyalgia
• Headache
• Migraine Prevention
• Neuropathic Pain

Approved in European Union as Amitriptyline for:

• Depression
• Anxiety disorders
• Chronic pain
• Fibromyalgia
• Headache
• Migraine prevention
• Neuropathic pain

Approved in Canada as Elavil for:

• Depression
• Anxiety and stress
• Chronic pain
• Fibromyalgia
• Headache
• Migraine prevention
• Neuropathic pain

Who Is Running the Clinical Trial?

Wright State University

Lead Sponsor

Trials

47

Recruited

55,300+

Findings from Research

In a study involving 405 severely depressed patients, both mirtazapine and amitriptyline showed significant reductions in depression scores, indicating their effectiveness in treating severe depression.

There were no significant differences in efficacy between mirtazapine and amitriptyline, suggesting that both medications are equally effective in improving symptoms of depression, including mood, anxiety, and sleep disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of severely depressed patients: a meta-analysis comparing efficacy of mirtazapine and amitriptyline. Kasper, S., Zivkov, M., Roes, KC., et al.[2019]

In a 6-week double-blind crossover trial with 20 patients, desipramine provided statistically significant pain relief for those suffering from painful diabetic neuropathy, especially in weeks 5 and 6.

Desipramine was effective in relieving pain for many patients, including those who did not experience antidepressant effects, making it a suitable alternative for patients who cannot tolerate amitriptyline due to its side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Max, MB., Kishore-Kumar, R., Schafer, SC., et al.[2022]

Topical applications of doxepin and amitriptyline significantly increased the histamine itch threshold (HIT) in 40 subjects, indicating their effectiveness as antipruritic agents compared to a vehicle control.

Doxepin was particularly effective, with 68% of subjects showing a higher HIT, suggesting that tricyclic antidepressants can be beneficial for treating itching, potentially due to their antihistaminic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of histamine-induced pruritus by topical tricyclic antidepressants. Bernstein, JE., Whitney, DH., Soltani, K.[2019]

In a clinical trial with 40 patients, maprotiline showed a significantly faster improvement in depression symptoms compared to amitriptyline by day 7, although both medications were effective by day 21.

Both maprotiline and amitriptyline led to significant reductions in depression scores, but there was no significant difference in overall effectiveness by the end of the trial, suggesting maprotiline may be a quicker-acting alternative to standard tricyclic antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative speed of onset of the antidepressant effect of maprotiline. Silverstone, T.[2013]

In a study of 80 patients with painful diabetic neuropathy, 60% found relief with imipramine alone, and nearly all patients improved with a stepwise treatment approach, indicating the efficacy of imipramine as a first-line treatment.

The most significant pain relief was observed in patients experiencing the most severe pain, suggesting that imipramine may have a rapid onset of action and a peripheral mechanism, rather than a central one.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain relief in diabetic neuropathy: the effectiveness of imipramine and related drugs. Young, RJ., Clarke, BF.[2019]

Amitriptyline, a tricyclic antidepressant, can cause various skin reactions, including rashes and hypersensitivity reactions, which are among the most common side effects of psychotropic drugs.

The case of a 24-year-old woman illustrates that hypersensitivity syndrome can occur three weeks after starting amitriptyline, leading to serious skin and systemic symptoms, but these typically resolve after stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity syndrome caused by amitriptyline administration. Milionis, HJ., Skopelitou, A., Elisaf, MS.[2019]

In a study of 60 patients with major depressive disorders, both Moclobemide and Amitriptyline showed similar efficacy in improving depression symptoms, with 94% of patients in both groups rated as 'very good to good' by the end of the treatment.

Moclobemide demonstrated a better safety profile, with only 9% of patients experiencing adverse events compared to 19% for Amitriptyline, suggesting it may be a safer alternative for outpatient management of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open comparative randomised study of moclobemide versus amitriptyline in major depressive illness (DSM IIIR) in Nigeria. Ononye, F., Sijuola, OA., Chukwuani, CM., et al.[2022]

A young woman developed a pityriasis rosea-like skin rash after being treated with oral nortriptyline for vulvodynia, indicating a possible drug-induced reaction.

The rash completely resolved after discontinuing nortriptyline, suggesting that while tricyclic antidepressants like nortriptyline are commonly used, they can cause unexpected skin reactions in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pityriasis rosea-like drug eruption due to nortriptyline in a patient with vulvodynia. Bangash, HK., Finch, T., Petronic-Rosic, V., et al.[2021]

In a study involving 100 hospitalized patients with major depressive disorder, milnacipran and imipramine showed similar effectiveness in reducing depressive symptoms over 6 weeks.

Milnacipran had a better safety profile than imipramine, with fewer adverse events, particularly those related to anticholinergic effects, although it did have higher rates of dysuria and shivering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of milnacipran and imipramine in the treatment of major depressive disorder. Lopez-Ibor, JJ., Conesa, A.[2018]

Topical application of amitriptyline at concentrations of 50 mmol/L and 100 mmol/L significantly provided analgesia compared to placebo, indicating its effectiveness in reducing pain when applied to the skin.

The study involved 14 healthy volunteers and found that while higher concentrations of amitriptyline were effective, the only side effect noted was skin redness, suggesting a good safety profile for its topical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical amitriptyline in healthy volunteers. Gerner, P., Kao, G., Srinivasa, V., et al.[2019]

Transdermal application of amitriptyline was found to be more effective than lidocaine in providing cutaneous analgesia in rats, indicating its potential as a topical pain relief option.

Amitriptyline not only produced a stronger analgesic effect but also resulted in a longer-lasting pain relief compared to lidocaine, suggesting it could be beneficial for treating chronic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous analgesia after transdermal application of amitriptyline versus lidocaine in rats. Haderer, A., Gerner, P., Kao, G., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of severely depressed patients: a meta-analysis comparing efficacy of mirtazapine and amitriptyline. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Inhibition of histamine-induced pruritus by topical tricyclic antidepressants. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Relative speed of onset of the antidepressant effect of maprotiline. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Pain relief in diabetic neuropathy: the effectiveness of imipramine and related drugs. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Hypersensitivity syndrome caused by amitriptyline administration. [2019]

7. Nigeria pubmed.ncbi.nlm.nih.gov

Open comparative randomised study of moclobemide versus amitriptyline in major depressive illness (DSM IIIR) in Nigeria. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Pityriasis rosea-like drug eruption due to nortriptyline in a patient with vulvodynia. [2021]

9. England pubmed.ncbi.nlm.nih.gov

A comparative study of milnacipran and imipramine in the treatment of major depressive disorder. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Topical amitriptyline in healthy volunteers. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Cutaneous analgesia after transdermal application of amitriptyline versus lidocaine in rats. [2021]