Can minocycline cause anxiety



A Cochrane review assessed 27 randomised trials, involving a total of 3031 patients with acne vulgaris affecting the face or upper trunk, which compared oral minocycline with placebo or other active treatment.2 Although minocycline seemed to be an effective treatment for acne, there was no convincing evidence from good-quality studies that it was superior to other oral antibacterials. These findings were echoed in a pivotal study involving 649 patients with mild to moderate acne randomised to one of the following regimens: oral minocycline, modified release, 100 mg daily; oral oxytetracycline 500mg twice daily; topical benzoyl peroxide 5% twice daily; topical benzoyl peroxide 5% plus topical erythromycin 3% twice daily; and topical erythromycin 2% each morning and topical benzoyl peroxide 5% each evening.3

At 18 weeks, significantly more participants rated themselves at least moderately improved (the primary outcome measure) with benzoyl peroxide plus erythromycin (the regimen with the highest response rate) than with minocycline (which had the lowest response rate) (66% v 54% of patients, odds ratio 1.74 (95% confidence interval 1.04 to 2.90)). Otherwise, there was no significant difference between treatments. The presence of skin colonisation by erythromycin resistant propionibacteria did not affect reported response to erythromycin based treatments, but, crucially, colonisation with tetracycline resistant propionibacteria reduced the effectiveness of both minocycline and oxytetracycline. We can find no published evidence to support claims that minocycline is less likely than other tetracyclines to cause propionibacterial resistance or that switching to minocycline from another tetracycline will improve response.

Further evidence comes from a randomised trial involving 134 patients with moderate to moderately severe acne, which reported mean reductions in the number of inflammatory lesions of around 60% at 12 weeks with either modified release minocycline 100 mg daily or lymecycline 300 mg daily, with no significant difference between the drugs.4

Evidence that oral minocycline might be more effective than other tetracyclines is, at best, weak, being limited to a few, poor quality trials with highly questionable results.2 5 Fundamental flaws in these studies include a lack of blinding, failure to specify the power of the study, reporting of data for only a proportion of participants, only graphical presentation of data, and failure to cite confidence intervals for key results.

Minocycline Side Effects

Medically reviewed by Last updated on Jan 2, 2019.

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In Summary

Commonly reported side effects of minocycline include: headache. Other side effects include: vulvovaginal candidiasis, diarrhea, dizziness, dysphagia, epigastric discomfort, melanoglossia, nausea and vomiting, sore throat, stomatitis, and anorexia. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to minocycline: oral capsule, oral capsule extended release, oral tablet, oral tablet extended release

Other dosage forms:

  • intravenous powder for solution

Along with its needed effects, minocycline may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking minocycline:

Incidence not known

  • Black, tarry stools
  • blistering, peeling, or loosening of the skin
  • blood in the urine or stools
  • blurred or double vision
  • bulging soft spot on the head of an infant
  • chest pain, possibly moving to the left arm, neck, or shoulder
  • confusion
  • diarrhea
  • dizziness or lightheadedness
  • eye pain
  • fast heartbeat
  • general feeling of discomfort or illness
  • general tiredness and weakness
  • hives, itching, or skin rash
  • joint or muscle pain
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • nausea or vomiting
  • red skin lesions, often with a purple center
  • severe headache
  • severe stomach pain
  • sores, ulcers, or white spots on the lips or in the mouth
  • troubled breathing
  • unusual bleeding or bruising
  • upper right abdominal or stomach pain
  • yellow eyes and skin

Some side effects of minocycline may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

  • Continuing ringing or buzzing or other unexplained noise in the ears
  • difficulty with moving
  • hearing loss
  • hives or welts
  • muscle stiffness
  • redness of the skin
  • sleepiness or unusual drowsiness

Incidence not known

  • Bloating
  • discoloration of the tooth
  • increased sensitivity of the skin to sunlight
  • indigestion
  • severe sunburn

For Healthcare Professionals

Applies to minocycline: intravenous powder for injection, oral capsule, oral capsule extended release, oral suspension, oral tablet, oral tablet extended release, oral and topical kit

Nervous system

Headache, dizziness, vertigo. and ataxia have been reported. These side effects were reversible within 3 to 48 hours of stopping therapy and occurred less often with low doses.

Pseudotumor cerebri, bulging fontanels (infants), and decreased hearing have also been reported during postmarketing experience.

Very common (10% or more): Headache (up to 23%)

Common (1% to 10%): Dizziness (lightheadedness), somnolence, tinnitus, vertigo

Rare (0.01% to 0.1%): Hypoesthesia, paresthesia, intracranial hypertension, impaired/decreased hearing

Very rare (less than 0.01%): Bulging fontanels (in infants)

Frequency not reported: Convulsions, sedation, ataxia, benign intracranial hypertension (pseudotumor cerebri), vestibular reactions


Hyperpigmentation of various body sites (including the skin, nails, teeth, oral mucosa, bones, thyroid, eyes , breast milk, lacrimal secretions, perspiration) has been reported. This blue/black/grey or muddy-brown discoloration was localized or diffuse. The most common site was the skin. Pigmentation often reversed when the drug was discontinued; however, resolution took several months or persisted in some cases. The generalized muddy-brown skin pigmentation sometimes persisted, especially in areas exposed to sun.

Biopsies of pigmented tissue have shown granules within the cells which stained positive for iron. This pigmentation faded over time after drug discontinuation.

DRESS syndrome (including fatal cases) has been reported. DRESS syndrome with persistent myocarditis has been reported in at least 3 cases.

Fixed drug eruptions, erythema multiforme, Stevens-Johnson syndrome, and photosensitivity have also been reported during postmarketing experience.

Common (1% to 10%): Pruritus, urticaria

Very rare (less than 0.01%): Angioedema, exfoliative dermatitis, hyperpigmentation of nails/nail beds, Stevens-Johnson syndrome, toxic epidermal necrolysis

Frequency not reported: Hyperpigmentation of various body sites (including bones, mucous membranes, teeth, oral mucosa, tongue, thyroid, eyes , breast milk, lacrimal secretions, structures of inner organs), maculopapular rash, erythematous rash, discolored perspiration, Sweet’s syndrome (acute febrile neutrophilic dermatosis)

Postmarketing reports: Anaphylactoid purpura, pigmentation of skin and mucous membranes, angioneurotic edema, drug rash with eosinophilia and systemic symptoms (DRESS)


Pancreatitis has rarely been associated with use of this drug. In 2 case reports, cystic fibrosis patients experienced pancreatitis during treatment with this drug for acute bacterial exacerbations of respiratory disease. The authors suggested that cystic fibrosis patients, as a result of the disease process, may be more susceptible to drug-induced pancreatitis. Additionally, in at least 1 case, multiple concomitant medications were taken; therefore, a temporal relationship between this drug and pancreatitis could not be proven conclusively.

Esophagitis and esophageal ulcerations have been reported in patients taking the capsule or tablet formulations of tetracycline-class antibiotics. Most of these patients took the drug immediately before going to bed.

Enterocolitis, pancreatitis, glossitis, dysphagia, and tooth discoloration have also been reported during postmarketing experience.

Common (1% to 10%): Dry mouth

Rare (0.01% to 0.1%): Diarrhea, nausea, stomatitis, discoloration of teeth, vomiting

Very rare (less than 0.01%): Oral and anogenital candidiasis, dyspepsia, dysphagia, enamel hypoplasia, enterocolitis, esophagitis, esophageal ulcerations, glossitis, pancreatitis, pseudomembranous colitis

Frequency not reported: Antibiotic-associated colitis, oral cavity discoloration (including buccal mucosa, tongue, lip, gum), abdominal cramping, inflammatory lesions (with monilial overgrowth) in the oral and anogenital regions


Common (1% to 10%): Arthralgia, myalgia

Very rare (less than 0.01%): Arthritis, bone discoloration, systemic lupus erythematosus (SLE), exacerbation of SLE, joint stiffness, joint swelling, joint discoloration, myopathy, hypersensitivity-associated rhabdomyolysis

Postmarketing reports: Polyarthralgia, exacerbation of systemic lupus, transient lupus-like syndrome

Lupus-like reactions induced by this drug have commonly presented with arthralgia or arthritis, myalgia or malaise, and positive ANA titer. Patients with highly positive anti-double stranded DNA (anti-dsDNA) antibodies have rarely been reported. All patients recovered after the drug was discontinued; however, several required short courses of corticosteroids.

Severe acute myopathy associated with this drug (100 mg orally per day) occurred in a 17-year-old male after strenuous exercise. His laboratory values were as follows: ESR 33 mm/hr, CRP 0.84 mg/dL, creatine kinase 87,297 units/L, AST 1307 units/L, ALT 311 units/L, LDH 4935 units/L, aldolase 12.6 units/L, alkaline phosphatase 145 units/L, GGT 66 units/L. Muscle enzyme levels normalized and his symptoms resolved 1 month after this drug was discontinued.

IV minocycline plus quinupristin-dalfopristin were associated with myalgia and arthralgia in 36% of neutropenic cancer patients (n=56).


Common (1% to 10%): Fatigue, malaise

Uncommon (0.1% to 1%): Fever

Very rare (less than 0.01%): Discoloration of secretions


-Frequency not reported: Magnesium intoxication (including flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and CNS depression, respiratory paralysis)


Common (1% to 10%): Mood alteration


Death has been reported in some cases involving hypersensitivity syndrome, serum sickness-like syndrome, and lupus-like syndrome.

Pulmonary infiltrates, night sweats, fever, and eosinophilia have developed in several patients receiving this drug. These effects were thought to be due to drug hypersensitivity.

Case reports have described a severe CNS -pulmonary hypersensitivity syndrome requiring high-dose corticosteroid therapy. Signs and symptoms have included dry cough, fever, ataxia, muscle weakness, numbness, visual abnormalities, abnormal brain MRI, seizures, pulmonary infiltrates, elevated serum IgE, elevated erythrocyte sedimentation rate (ESR), and eosinophilia.

Eosinophilic pneumonia with relapsing acute respiratory failure requiring mechanical ventilation and corticosteroids has been reported in a 54-year-old woman. Initial symptoms included dry cough, low-grade fever, fatigue, and dyspnea. Eosinophilia, elevated leukocytes, and C-reactive protein (CRP) were noted. At 14 days after being discharged and resuming this drug, the patient developed rapidly progressive respiratory failure again requiring mechanical ventilation.

Late-onset drug fever (associated with fever, sore throat, abdominal pain, weakness, loose bloody stools, fatigue, 40-pound weight loss, ESR 99 mm/hr, CRP 5 mg/dL, and mild increases in liver enzymes) has been reported in a 15-year-old boy after using this drug for 24 months for acne. After 1 year of therapy, at least 1 other case of late-onset drug fever occurred. Other reported cases of drug fever generally occurred after 2 to 4 weeks of drug exposure.

Rare (0.01% to 0.1%): Anaphylaxis/anaphylactoid reaction (including shock, fatalities)

Frequency not reported: Hypersensitivity, hypersensitivity syndrome (consisting of cutaneous reaction , eosinophilia, and at least 1 of the following: hepatitis, pneumonitis, nephritis, myocarditis, pericarditis; with or without fever, lymphadenopathy), serum sickness-like syndrome (consisting of fever, urticaria/rash, arthralgia, arthritis, joint stiffness/swelling, lymphadenopathy; with or without eosinophilia), autoimmune vasculitis, drug fever, eosinophilic pneumonitis, drug hypersensitivity (e.g., pulmonary infiltrates, night sweats, fever, eosinophilia), serum sickness, serum sickness-like reactions, severe central nervous system (CNS)-pulmonary hypersensitivity syndrome

Postmarketing reports: Hypersensitivity reactions, anaphylaxis


Frequency not reported: Positive antineutrophil cytoplasmic antibody (ANCA) titers, polyarteritis nodosa, ANCA-positive crescentic glomerulonephritis, ANCA-positive vasculitis, autoimmune hepatitis, necrotizing vasculitis and systemic reactions

Rare cases of necrotizing vasculitis and systemic reactions have been reported, characterized by lymphadenopathy, eosinophilia, increased liver function enzyme levels, and dermatologic involvement. In each case, this drug was discontinued and in some cases, corticosteroid therapy was necessary to assist in the resolution of symptoms.


Some hepatic reactions had an autoimmune basis and occurred after several months of therapy.

In 1 case, a patient developed rapidly progressing liver failure after using this drug for 4 weeks for acne. The patient had stopped this drug 2 weeks prior to onset of malaise. Liver transplantation was considered, but the patient slowly recovered without significant intervention.

Other reports of immunologically-mediated progressive liver dysfunction have rarely occurred. In 1 case, a patient received a liver transplant after fulminant hepatic failure which was thought to be related to a 3-year history of daily therapy to treat acne. The dose of this drug ranged from 50 to 200 mg/day. A second patient had been using this drug to treat acne for 1 year just prior to seeking medical attention for an “influenza-like” syndrome. Upon hospitalization, it was determined that the patient was experiencing an autoimmune-mediated hepatitis, most probably related to this drug. Resolution of symptoms occurred in both of these cases after therapy was discontinued and each patient had received appropriate supportive medical care.

Hepatitis and liver failure have also been reported during postmarketing experience.

Rare (0.01% to 0.1%): Increased liver enzymes, hepatitis, autoimmune hepatitis/hepatotoxicity

Very rare (less than 0.01%): Hepatic cholestasis, hepatic failure (including fatalities), hyperbilirubinemia, jaundice

Frequency not reported: Autoimmune hepatitis with lupus-like symptoms, increased liver function test values, acute hepatic failure, liver injury, acute hypersensitivity hepatitis associated with eosinophilia and dermatitis


Rare (0.01% to 0.1%): Increased BUN/serum urea, interstitial nephritis, acute renal failure

Postmarketing reports: Reversible acute renal failure


-Frequency not reported: Aggravation of preexisting renal failure, azotemia/uremia, nephrotoxicity (associated with acute fatty liver), renal tubular damage, Fanconi-like syndrome

Nephrotoxicity associated with acute fatty liver has been reported with high tetracycline doses. High serum levels of tetracyclines have been associated with azotemia, hyperphosphatemia, and acidosis in patients with renal dysfunction.

Degraded tetracycline may cause renal tubular damage and a Fanconi-like syndrome.


Rare (0.01% to 0.1%): Eosinophilia, leukopenia, neutropenia, thrombocytopenia

Very rare (less than 0.01%): Hemolytic anemia, pancytopenia

Frequency not reported: Agranulocytosis, antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis

Hemolytic anemia, thrombocytopenia, and eosinophilia have also been reported during postmarketing experience.


Rare (0.01% to 0.1%): Cough, dyspnea, pulmonary infiltration

Very rare (less than 0.01%): Bronchospasm, exacerbation of asthma, pulmonary eosinophilia

Frequency not reported: Pneumonitis, hypersensitivity pneumonitis, pulmonary lupus, eosinophilic pneumonia, pleural effusions, relapsing acute respiratory failure

Postmarketing reports: Pulmonary infiltrates with eosinophilia


Rare (0.01% to 0.1%): Myocarditis, pericarditis


High serum levels of tetracyclines have been associated with azotemia, hyperphosphatemia, and acidosis in patients with renal dysfunction.

Rare (0.01% to 0.1%): Anorexia


-Frequency not reported: Hyperphosphatemia, acidosis


Very rare (less than 0.01%): Abnormal thyroid function, brown-black microscopic thyroid discoloration

Frequency not reported: Discolored breast secretions

A condition characterized by dark pigmentation (brown-black microscopic discoloration) of the thyroid gland has been reported; however, there was no clinical or laboratory evidence of thyroid dysfunction (unknown clinical implications).

Brown-black microscopic thyroid discoloration and abnormal thyroid function have also been reported during postmarketing experience.


Very rare (less than 0.01%): Balanitis (due to lesions on the glans penis), vulvovaginitis

Postmarketing reports: Deleterious effects on spermatogenesis

Balanitis has also been reported during postmarketing experience.


Frequency not reported: Injection site erythema, injection site pain


Frequency not reported: Papillary thyroid cancer

Postmarketing reports: Thyroid cancer


Frequency not reported: Discoloration of conjunctiva, discoloration of lacrimal secretions, grey scleral pigmentation, macular pigmentation

Cases of grey scleral pigmentation and macular pigmentation have been reported in elderly patients after chronic use of this drug (5 to 12 years).

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Minocycline pills are antibiotics sold as Minocin, Dynacin, Vectrin, Solodyn and generic minocycline. This antibiotic has been in use since the 1970’s and is a great acne therapy. It kills the acne bacteria more effectively than many other acne pills and has a separate “anti-inflammatory” effect. This means it reduces the redness, swelling and tenderness or pimples whether it kills the acne bacteria or not. Because of this effect, minocycline is now also being used for some people with painful, swollen joints.

Of all the antibiotic pills used for acne, minocycline is one of the most effective, easiest to take and has the least side effects. Side effects do occur, but are usually minor. Minocycline rarely causes significant blood or internal problems. A topical acne cream is normally used along with these pills.

Start off taking it only at bedtime for a few days until ones body gets “used to” this medication. During this time dizziness or headaches may occur. These last a few hours and are gone by the morning. After that, the medication can be taken any time and is easiest to remember at meals. Only the generic form must be taken one hour before or two hours after meals. If the side effects continue, the drug can be taken at a lower dose or stopped. One in a hundred people have an allergy to the drug which shows up as outbreaks of hives two or three weeks into the treatment, or feeling sick or unwell.

There are a few significant, but very rare side effects that develop in about 1 in 10:000 people. One is hypersensitivity lupus/hepatitis, which causes severe joint pains. The other is pseudotumor cerebri (an accumulation of fluid around the brain) that causes progressively worsening headaches and vision problems. Stop the medication if these occur. They resolve over time, but very slowly. These also occur with some other antibiotics. A form of lupus seems unique to minocycline. It appears after taking the pill for an average of 3 years. Remember that facial scarring and long lasting psychological harm are very real “side effects” of acne and are much more common than 1 in 10,000.

If acne does not improve after several months of minocycline, a dermatologist will change the acne medicine to a different one. If the acne improves, the dose needs to be lowered or minocycline will build up in the body. As this accumulates, the medication turns dark purple in the body and might show up as a discoloration. This looks like bruises that don’t go away, or dark pigment in acne scars. The pigmentation will clear up as long as it is recognized and the medication is stopped, but it may take a year or more. This is one of the reasons regular exams are needed for people on minocycline. More difficult pigmentation problems occur if the maximum dose is taken for a few years. Recent research has show that the pigment problems may be avoided by taking Vitamin C 500mg twice daily.

Overall, minocycline is safer than ibuprofen or penicillin. Minocycline has been a standard treatment for severe acne for over 20 years and has been proven safe and effective with proper usage.

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The medical information provided in this site is for educational purposes only and is the property of the American Osteopathic College of Dermatology. It is not intended nor implied to be a substitute for professional medical advice and shall not create a physician – patient relationship. If you have a specific question or concern about a skin lesion or disease, please consult a dermatologist. Any use, re-creation, dissemination, forwarding or copying of this information is strictly prohibited unless expressed written permission is given by the American Osteopathic College of Dermatology.

Patient Stories 5/10/17

Acne & Antibiotics: Why I Regret Not Speaking with my Doctor

by: Samantha Relich for Choosing Wisely Canada

Years after being on long-term antibiotics for her acne, a patient regrets not having a conversation with her doctor earlier.

For a long time, when Lauren looked in the mirror all she wanted was her acne gone. By the time she was in the 11th grade she had exhausted all her options for topical over-the-counter treatments.

A little desperate, she visited her family doctor who prescribed her Minocycline, an antibiotic. “I was already on birth control, so the antibiotic was the first thing that my doctor went to,” says Lauren. Her doctor told her that her acne looked like it might be cystic and advised her that an antibiotic was likely the only treatment that would give her clear skin.

Lauren jumped at the chance. The first six-month prescription worked so well, that Lauren stayed on the antibiotic for five years. “I just kept taking it,” Lauren says. “You know how it is when you’re in high school and you’re a little vain – once your acne’s gone, you just want it to stay gone.”

In all likelihood, the antibiotic was the solution most likely to clear up Lauren’s acne. However, now off the antibiotic, Lauren worries about the possible long-term side effects of being on an antibiotic so long. She also wishes she had been able to dialogue better with her doctor.

“I just went with it,” she says. As a teenager, it never crossed Lauren’s mind to ask her doctor about the risks associated with long-term antibiotic use. After the initial prescription, renewals became her default response. “It was easy to forget to bring it up when I did see her,” says Lauren.

Lauren took the daily prescription throughout her four years of university. A few times she stopped taking the pill for a month or so, hoping that her skin improved. Each time she stopped taking the pills her acne came back. She finally stopped taking the prescription in 2014.

“I started to realize that being on antibiotics for years couldn’t be good for me,” she says. However, more than that, she was tired of a solution that masked the physical symptoms of the problem but didn’t actually solve it.

“I wanted to figure out the real reason I was getting acne, whether it was hormonal or a food allergy,” Lauren says. She laughs, “I still haven’t really figured it out.” Her skin has improved, though; she has mostly cut out dairy and gluten and describes her new diet as “more on the vegan side.”

“I still really struggled when I came off the antibiotic,” she says. “My skin was the worst it had ever been.” In addition to the dietary changes, Lauren now uses a topical treatment. She explains she wishes she had asked her doctor about alternatives before committing to using the antibiotic for so long. “I probably would have tried lifestyle changes first, if I had known to ask,” she says.

The next time she visits her family doctor, Lauren wants to talk about the possible long-term effects. “I know she gave me the best advice at the time. But I want inquire about the effects that could have come from it,” she says.

Her advice to her high school self is simple she says, “If you’re at the point where you’re being prescribed a pill or another drug, do your research and ask your doctor as many questions as you feel like you need to ask.”

How long can I take an antibiotic to treat my acne?

You can reduce the amount of time you need to take an antibiotic by using all of the medicine in your treatment plan. Acne isn’t an infection, but an antibiotic can provide real relief from deep, painful breakouts.

Certain antibiotics such as doxycycline (dox-ē-cyc-lean) and erythromycin (eh-rith-row-my-cin) can reduce the amount of P. acnes bacteria on your skin and lessen inflammation. When that happens, you may see less acne and sometimes clearing.

Take an antibiotic for the shortest time possible

When including an antibiotic in your acne treatment plan, your dermatologist will prescribe it for the shortest time possible. Because acne takes time to treat, this usually means three to four months. However, some people who have acne need more time on an antibiotic.

Four ways to reduce how long you take an antibiotic

You can shorten the amount of time that you need an antibiotic in your treatment plan by doing the following:

  1. Use all of medicine in your treatment plan.
    When taken alone, an antibiotic can quickly lose its ability to fight acne. When this happens, the bacteria continue to grow and you can develop a condition known as antibiotic resistance. Antibiotic resistance is a global health problem. That’s why your dermatologist prescribes other acne medicine along with an antibiotic. You may need to use benzoyl peroxide or adapalene (ah-dap-ah-lean) gel along with an antibiotic.

  2. Reduce acne flares with gentle skin care.
    To get rid of acne, you may be tempted to scrub your skin clean. Scrubbing can irritate your skin and worsen acne. You can reduce flare-ups by following the skin care tips at, Acne: Tips for Managing.

  3. Keep all follow-up appointments with your dermatologist.
    This will allow your dermatologist to see whether the treatment is working. Some patients need a different antibiotic. Others need a different type of treatment.

  4. Follow your maintenance plan.
    Once your skin clears, you’ll need different acne treatment to prevent new breakouts. Most people can keep their skin clear by using medicine they apply to their skin. Continuing to use the acne treatment in your maintenance plan will help you keep your skin clear and reduce the need for stronger acne medicine like an antibiotic.

An antibiotic can play an important role in helping to clear acne. If you take an antibiotic to treat your acne, be sure to take it seriously. This will allow you to get the most benefit in the shortest time possible.


Centers for Disease Control and Prevention (CDC). “Antibiotic/Antimicrobial resistance.” Last accessed April 19, 2017.

Zaenglein, AL, Pathy AL, et al. “Guidelines of care for the management of acne vulgaris.” J Am Acad Dermatol. 2016;74:945-73.

Minocycline for Acne Changes Skin Microbiota

Antibiotic therapy for acne was linked with variations in the skin microbiota, some of which persisted and weren’t necessarily healthy, a four-patient longitudinal study indicated.

Relative abundance of Cutibacterium acnes decreased 1.4-fold with 4 weeks of minocycline therapy (difference -10.3%, 95% CI −19.9% to −0.7%; P=0.04) in the four participants, women age 25-35. But other bacteria increased, including a transient 5.6-fold rise in the relative abundance of Pseudomonas species, reported Luis A. Garza, MD, PhD, of Johns Hopkins School of Medicine in Baltimore, and colleagues in JAMA Dermatology.

And, in the eight weeks following antibiotic therapy withdrawal, there was a 4.7-fold decline in the relative abundance of Lactobacillus species as well as a 1.7-fold increase in the relative abundance of Streptococcus species, the researchers reported. Abundance of C. acnes partially rebounded as well after minocycline was stopped, such that it was no longer statistically lower than at baseline.

The tetracycline group of antibiotics, including doxycycline and minocycline, often serves as first-line therapy for moderate to severe acne because of these agents’ anti-inflammatory and antimicrobial properties. Recent guidelines suggest restricting systemic antibiotic therapy to 3 to 4 months. However, prior respective studies have shown that the antibiotic treatment period always exceeds the recommended duration, noted Garza’s group.

“Given the widespread use of systemic antibiotics for acne, it is important to understand their effects not only on C. acnes but also on the complete bacterial community of the skin,” they wrote. “Understanding the associations between antibiotics and skin microbiota may help clinicians decrease the likelihood of skin comorbidities related to microbial dysbiosis.”

Recently introduced tools for studying the skin microbiome — including the genome and metabolome — have “invigorated” studies on their relation to disease and human health and “illuminated the diversity of microorganisms inhabiting the skin surface,” noted Tiffany Scharschmidt, MD, of University of California San Francisco, in an accompanying editorial.

Amid so much media attention on these studies, patients have become more interested in the human microbiome as well, noted Scharschmidt.

“In the clinic, this interest manifests as a wide range of patient inquiries regarding the role of microorganisms in skin disease, the influence of prescribed therapies on the microbiome, and strategies or products to ‘optimize’ skin flora for health or cosmesis. Satisfactory answers to these questions are still forthcoming and will likely prove highly nuanced based on the complexity and contextuality of the skin-microbiota relationship,” she wrote.

Clinicians should be enthusiastic about the possibility of microbial-directed or microbial-derived treatments “as future weapons in our therapeutic arsenal while acknowledging that there is much we still do not understand about the influence of current therapies on the delicate symbiosis we maintain with our cutaneous microbiota,” the editorialist emphasized.

“In the context of a growing market of over-the counter products designed to “restore” the skin microbiome, we should further emphasize that there is no universally good or bad skin microbiome,” she continued.

Scharschmidt noted the tiny sample size and other limitations in the study by Garza and colleagues, but nevertheless called the findings “intriguing” and could explain some of the complications often seen from antibiotic therapy in acne.

For their part, Garza and colleagues characterized the study as a pilot investigation. They recruited the four patients in Maryland, who included two white women, one Asian American and one African American. They presented with inflammatory and comedonal acne on the face and reported no recent use of topical or systemic therapy for acne such as retinoids or antibiotics.

Patients were prescribed 100 mg of oral minocycline to take twice daily for 4 weeks. The skin on the forehead, cheek, and chin were sampled for 165 ribosomal RNA gene sequencing at baseline, 4 weeks after starting the antibiotic therapy, and then 1 week and 8 weeks after treatment ended.

Garza, speaking to MedPage Today, acknowledged that the study was too small and too short to offer definitive conclusions. “We only looked a short period of time after antibiotics, but people need to look much longer, like even a year, after somebody stops taking antibiotics,” he said.

In their JAMA Dermatology paper, his group also noted that there was no clear, single pattern connecting changes in participants’ skin microbiome to changes in acne lesions, perhaps also a consequence of the small sample size.

“The use of a larger sample size and longer duration of antibiotic treatment would enable better characterization of changes in inflamed lesion count and α diversity, which may respond differently to antibiotic treatment depending on acne severity at baseline,” they wrote. “Longitudinal data of negative control participants receiving no antibiotic treatment, which we did not collect in the present study, would also enable more accurate characterization of the changes in skin microbiota associated with antibiotic treatment.”


This study was supported in part by a Clinical Research Grant from the American Acne and Rosacea Society, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Garza reported no disclosures.

Scharschmidt disclosed relationship with the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Allergy and Infectious Diseases, Burroughs Wellcome Fund, Doris Duke Foundation and Leo Foundation, and Sanofi Regeneron.

Primary Source

JAMA Dermatology

Source Reference: Chien A, et al “Association of systemic antibiotic treatment of acne with skin microbiota characteristics” JAMA Dermatol 2019; DOI: 10.1001/jamadermatol.2018.5221.

Secondary Source

JAMA Dermatology

Source Reference: Scharschmidt TC, “Antibiotics for Acne — A Pilot Study of Collateral Damage to the Skin Microbiome” JAMA Dermatol 2019; DOI: 10.1001/jamadermatol.2018.5146.


Which oral antibiotics are best for acne?


DOXYCYCLINE IS EFFECTIVE (strength of recommendation : B, randomized controlled trial) and the antibiotic of choice (SOR: C, expert opinion) for moderate to severe inflammatory acne requiring oral treatment. Limiting side effects include photosensitivity and gastrointestinal (GI) disturbance.

Other members of the tetracycline family are considered second-line agents because of their side-effect profile and are contraindicated in pregnancy and for children younger than 12 years (SOR: A, meta-analysis, and C, expert opinion). For these patients, erythromycin is effective and better studied than azithromycin (SOR: C, expert opinion). Otherwise, emerging resistance and GI disturbances make erythromycin a third-line treatment.

The use of oral antibiotics should be limited to moderate to severe inflammatory acne unresponsive to topical therapies, including retinoids and antibiotics (SOR: C, expert opinion). Oral antibiotics should be used for at least 6 to 8 weeks and discontinued after 12 to 18 weeks of therapy (SOR: C, expert opinion).

Evidence summary

Acne vulgaris is an extremely common disorder affecting up to 95% of adolescents.1 Doxycycline improves inflammatory lesions and has a tolerable side-effect profile.

The most commonly reported adverse effects of doxycycline are GI disturbance and sensitivity to ultraviolet radiation (sunlight). A recent systematic review found an adverse event rate of 13 per 1 million prescriptions written.3

Minocycline: Probably effective, but not the first choice
A 2003 Cochrane review examined 27 randomized trials that compared oral minocycline with placebo or other active treatments, including topical and systemic antibiotics, in a total of 3031 patients with acne vulgaris on the face or upper trunk.4 The review determined that minocycline is probably an effective treatment for moderate acne vulgaris. However, no reliable evidence from randomized controlled trials (RCTs) justifies its use as a first-line agent, especially given its higher cost relative to other treatments.

Drug resistance weakens macrolides’ “punch”
Macrolide antibiotics, primarily erythromycin, were at one time considered first-line treatment for acne, but have fallen out of favor because of emerging drug resistance. Nevertheless, erythromycin’s price and safety in pregnant women and young children has maintained its standing in acne therapy. A 1986 RCT that compared erythromycin with tetracycline found comparable efficacy: a 65% reduction in papules, from 21 to 12 lesions, for erythromycin and a 62% reduction, from 17 to 10 lesions, for tetracycline (P<.0001).5 The main side effect of macrolide antibiotics is GI disturbance.

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