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What are the treatment options for severe acne?

Updated: May 19, 2023


Disclaimer: The information in this article is not meant as specific individual medical advice. Please consult your dermatologist or other medical professional about your skin or medical condition.


Acne affects as many as 85% of teenagers and 12% of adult women. [1]

When acne is severe, it can cause permanent scarring, poor self-image and sometimes depression and anxiety.

What is acne?

Acne is a chronic skin problem that affects the pores (hair follicles) and oil glands (sebaceous glands) of the skin.

It is characterized by having blackheads, whiteheads and red painful pimples, usually on the face and sometimes over the upper body.

When acne is severe, a person can have multiple large painful nodules and cysts on the face, shoulders, chest and back.

Sometimes these large acne lesions can cause thick and raised scars, called keloid scars.

What type of acne do you have?

The severity of acne is considered to be moderate when a person is regularly breaking out in many blackheads and whiteheads (comedones) and red bumps, zits, pus bumps or pimples (inflammatory lesions) and some scarring.

Acne is considered to be severe when a person has large nodules and cysts. This type of acne is also called nodulocystic acne.

Some women may also have hormonal acne, where acne lesions are related to her body’s androgen (testosterone, DHEA) levels.

What causes acne?

Acne is caused by plugging of pores by thickening of the skin, debris and oil production. This causes blackheads and whiteheads (comedones).

In addition, a bacterium, called Proprioniacterium acnes (P acne), grows in acne lesions and causes inflammation. This causes red bumps, zits, pimples or pus bumps (inflammatory lesions).

There are also genetic factors that determines the number and size of the acne lesions and the amount of inflammation that happens.

There is increasing evidence that suggest that food rich in carbohydrates (high glycemic index diets) may be associated with acne. In some small studies, people who follow a diet with low carbohydrate load experienced improvement in acne severity.

There are also some studies that show that consuming cow’s milk, especially skim milk, may increase the risk of developing acne.

Certain hormonal treatments and replacements including testosterone and progesterone, which are androgens, also drive acne lesions to form.

What are the treatments for moderate and severe acne?

There are several treatment options for moderate and severe acne for both men and women. These include:

  • Combined use of topical treatments

  • Oral antibiotics

  • Oral isotretinoin

For women with hormonal acne that is moderate or severe, there are also the options of using:

  • Combined oral contraceptives

  • Oral spironolactone

We will review each of these in further detail.

Combined use of topical treatments

The most commonly used topical treatments for acne are

  • Benzoyl peroxide

  • Topical antibiotics such as clindamycin

  • Topical retinoids such as adapalene and tretinoin

  • Topical dapsone

Read more about these topical treatments on my post about topical acne treatments for mild acne.

These topical treatments can be used individually, but are more effective when used in combination for moderate or severe acne.

For more details on the individual topical treatments and how their work, please refer to “Topical acne treatments for mild to moderate acne”.

Briefly, benzoyl peroxide[2] and topical antibiotics[3] are anti-bacterial and anti-inflammatory, which means they reduce P Acne in the skin, and reduce inflammation.

Topical retinoids, such as adapalene (Differin®), tretinoin (Retin-A®) and tazarotene (Tazorac®), are treatments derived from vitamin A and is helpful in breaking up whiteheads and blackheads, and overall reduces the number of new acne lesions.

Topical benzoyl peroxide in combination with topical antibiotic, and a topical retinoid are helpful, together because they act on different parts of a person’s acne.

Topical dapsone (Aczone®) is also helpful in reducing inflammation in acne, especially in adult women. As such, it is sometimes use in place of benzoyl peroxide and topical antibiotics, especially if this combination is causing skin irritation or is not effective.

However, in people with severe acne, sometimes topical treatments alone are not strong enough to be effective.

Oral antibiotics

There are several oral antibiotics that may be prescribed to treat moderate and severe acne.

Oral antibiotics are also useful for treating acne that has not responded to topical treatments alone.

There is a concern about bacterial resistance with the use of oral antibiotics.

As such, oral antibiotics are used only when acne is moderate or severe.

In addition, the use of oral antibiotics is ideally limited to 3 to 4 months. Sometimes these antibiotics are used for longer durations because a patient needs it for acne control.

Using oral antibiotics in combination with topical treatments can shorten how long a person uses oral antibiotics and decrease antibiotic resistance.[4]

Upon completing oral antibiotic treatment, the topical treatments are usually continued for maintaining clear skin.

Doxycycline and Minocycline

Oral doxycycline and oral minocycline, which belong to the tetracycline class of antibiotics, are considered the first line treatment for moderate and severe acne.

In addition to killing acne bacteria, these antibiotics have an additional action of decreasing inflammation in acne.

Doxycycline is also available at a sub anti-bacterial dose of 40mg daily.

Doxycycline can cause sun sensitivity and stomach upset.

Minocycline may sometimes cause ringing in the ears, dizziness and discoloration of the skin and teeth.

Rarely, autoimmune symptoms and increased brain pressure may occur with these antibiotics.

There may also be a potential association of tetracycline use and the development of inflammatory bowel disease.[5]

Both doxycycline and minocycline should not be used during pregnancy or in children younger than 8 years old.


Oral erythromycin and azithromycin can also be used to treat acne, but is used less often due to risk of antibiotic resistance.

Erythromycin is most commonly used in pregnant women and children younger than 8 years, when oral doxycycline and minocycline cannot be used.

Erythromycin can cause stomach upset, nausea or diarrhea.

Other oral antibiotics

Oral sulfamethoxazole-trimethoprim (Bactrim) is another common antibiotic used when acne does not respond to doxycycline or minocycline or there are side effects.

Bactrim may also cause sun sensitivity and stomach upset. Rarely, severe allergic reaction and decreased blood cell counts may occur.

Oral amoxicillin may also be used to treat acne during pregnancy or when there are no other options available due to side effects or allergies.

Oral antibiotics are usually used in combination with a topical retinoid and benzoyl peroxide.

Acne treatments for hormonal acne in women

Some women experience moderate to severe acne that is related to how their body may be producing androgens (testosterone, DHEA).

Some women may have an underlying condition called polycystic ovarian syndrome which can cause raised androgen levels.

Hormonal treatments in general work through modulating androgens in a woman’s body.

These treatments are typically used for several months, and sometimes years, to control acne.

These treatments should not be used during pregnancy.

Combined oral contraceptives

Combined oral contraceptives, containing both estrogen and progesterone, are effective in treating inflammatory acne in women who also desire contraception.

These work by decreasing the production of androgens (like testosterone and DHEA) and their effect on causing acne lesions to form.

In the United States, there are currently 4 oral contraceptives that are approved by the FDA for treatment of acne. These are Orthro Tri-Cyclen®, Estrostep Fe®, Beyaz® and Yaz®.

The improvement in acne may not be appreciated for the first few months of treatment.

There are side effects associated with combined oral contraceptive use that you want to be aware of.

Combined oral contraceptive use is associated with an increased risk of heart disease, stroke, blood clots and breast cancer.

Hence, contraceptives are not recommended in women who are pregnant or breastfeeding, who have or are at risk of developing breast cancer, heart disease, stroke, liver disease or blood clots.

Combined oral contraceptives should be used under the direction of a provider who specializes in women’s health, such as a gynecologist.


Spironolactone is another prescription medication that is useful for treating women with hormonal acne.[6]

It decreases the production and activity of testosterone, which decreases acne severity and oil (sebum) production in women.

Spironolactone is an overall well tolerated treatment.

Some common side effects are increase urine production because it is a mild diuretic, irregular menstrual cycles, breast tenderness and headache.

Spironolactone should not be used during pregnancy.

It can be used in combination with an oral contraceptive to regulate menses and prevent pregnancy.

Rarely, spironolactone can raise potassium levels in the body (hyperkalemia), usually in people with kidney disease, or taking certain other medications. Processed foods or supplements rich in potassium is not recommended for use when taking spironolactone.

Oral Isotretinoin

Oral isotretinoin is a treatment derived from vitamin A. It is widely known by its brand name Accutane®.

It is mainly used to treat people with severe acne, especially nodulocystic acne.

It decreases oil (sebum) production, acne lesions and scarring.

It also has the benefit of decreasing the relapse rate of acne.

Oral isotretinoin is also useful for treatment of moderate acne that is resistant to other forms of treatment or moderate acne that relapses quickly after stopping oral.

Oral isotretinoin can be used in both men and women.

Oral isotretinoin is usually started at a dose of 0.5mg/kg/day and increased to 1.0mg/kg/day.

The treatment continues until a cumulative dose of target dose has been reached, which usually takes about 6 months for most patients to complete.

This dosing regimen has been to found to be associated with a lower acne relapse rate. [7][8]

Oral isotretinoin is best taken with food to improve its absorption.

The main risk of using oral isotretinoin is that it will cause birth defects in pregnancies.

As a result, in the United States, enrollment in iPledge is required by both men and women who take this medication. iPledge is a program that is mandated by the FDA to decrease fetal exposure to isotretinoin. It requires all women to abstain from sex or use 2 contraceptive methods during and until 30 days after completing isotretinoin treatment.

People who take oral isotretinoin can expect to experience severe dryness of their skin, lips and nasal mucosa.

Occasionally, people may experience joint pain, muscle ache, headache or blurred night vision.

Blood tests are usually performed regularly during the treatment period to monitor for raised cholesterol and fat (triglyceride) levels and raised liver enzymes.

There have been situations where people taking isotretinoin experience delayed wound healing and keloid scar formation. As a result, it is recommended that procedures including dermabrasion or laser treatments are delayed for 6 to 12 months.

Changes in mood, including depression, have been reported in people taking oral isotretinoin. According to the American Academy of Dermatology, acne treatment guidelines, “many studies have shown no evidence of depression from isotretinoin”. However, given the prevalence of depression and anxiety in the general population, people who are taking isotretinoin should monitor for these symptoms closely, and inform their prescribing provider if they develop.

There are has been various studies to determine if oral isotretinoin use is associated with or causes inflammatory bowel disease such as Crohn’s disease or ulcerative colitis. The American Academy of Dermatology states that the ‘current evidence is insufficient to provide either an association or causal relationship between isotretinoin use and inflammatory bowel disease.’[9]

Treating individual large zits, nodules or cysts in acne

Injection of triamcinolone acetonide, a corticosteroid, directly into acne lesions is commonly used to treat individual painful larger nodules.[10]

This is usually used to treat a small number of lesions at a time.

Rapid reduction in pain and size of the injected lesions can be expected.

Rare side effects including lightening or thinning of the skin around the injection site may occur.

I hope you have found this article on treatment of moderate to severe acne helpful for making your medical decisions when you meet your dermatologist.

[1] Bhate K. Williams H.C. Epidemiology of acne vulgaris. Br J Dermatol. 2013; 168: 474-485 [2] Fulton Jr., J.E. Farzad-Bakshandeh A. Bradley S. Studies on the mechanism of action to topical benzoyl peroxide and vitamin A acid in acne vulgaris. J Cutan Pathol. 1974; 1: 191-200 [3] Becker L.E. Bergstresser P.R. Whiting D.A. et al. Topical clindamycin therapy for acne vulgaris. A cooperative clinical study. Arch Dermatol. 1981; 117: 482-485 [4] Moon S.H. Roh H.S. Kim Y.H. et al. Antibiotic resistance of microbial strains isolated from Korean acne patients. J Dermatol. 2012; 39: 833-837 [5] Margolis D.J. Fanelli M. Hoffstad O. Lewis J.D. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease. Am J Gastroenterol. 2010; 105: 2610-2616 [6] Goodfellow A. Alaghband-Zadeh J. Carter G. et al. Oral spironolactone improves acne vulgaris and reduces sebum excretion. Br J Dermatol. 1984; 111: 209-214 [7] Strauss J.S. Rapini R.P. Shalita A.R. et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol. 1984; 10: 490-496 [8] Lehucher-Ceyrac La Salmoniere P. Chastang C. Morel P. Predictive factors for failure of isotretinoin treatment in acne patients: results from a cohort of 237 patients. Dermatology. 1999; 198: 278-283 [9] American Academy of Dermatology website. Position statement on isotretinoin. Available at: Accessed January 6, 2016. [10] Levine R.M. Rasmussen J.E. Intralesional corticosteroids in the treatment of nodulocystic acne. Arch Dermatol. 1983; 119: 480-481

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