The Acne Medication Playbook: From Drugstore Staples to the Nuclear Option Doctors Save for Last

By: Dr. Caitlin Colvard | MD

Acne Is Common, Confusing, and Treatable

Acne is not just a teenage problem—it’s a global condition that affects people well into adulthood. In fact, up to 15% of adult women and 5% of adult men continue to struggle with breakouts beyond their twenties. For many, acne is more than a cosmetic nuisance; it can cause scarring, dark spots, and deep psychological stress that affects confidence, relationships, and even career opportunities. To help save money on acne prescriptions, try SaveHealth, the prescription discount website.

The frustrating part? There are hundreds of creams, gels, cleansers, and pills advertised as solutions, but knowing what actually works is daunting. Walk down the skincare aisle at any drugstore, and you’ll see rows of products claiming to “zap zits,” “clear skin fast,” or “fight breakouts.” Online, influencers promote everything from natural oils to light therapy masks. Meanwhile, doctors talk about prescription options with names that sound intimidating, like “isotretinoin” or “spironolactone.”

The good news is that dermatologists today have a clearer roadmap than ever before. The American Academy of Dermatology (AAD) recently updated its acne guidelines to emphasize combination therapy (treating acne from multiple angles at once), short-term antibiotic use (to avoid resistance), and powerful but safe escalation strategies for severe cases. What this means for patients: there’s a proven stepwise way to move from mild to stubborn acne without feeling lost.

This article is your playbook. We’ll start with the over-the-counter heroes, move into prescription topical therapies, step up to oral medications, and finally discuss the “nuclear option” dermatologists save for the toughest cases. By the end, you’ll understand what works, why it works, and where each option fits into the bigger picture.

Over-the-Counter Staples: Where Most People Should Start

Benzoyl Peroxide: The Unsung Hero

When dermatologists are asked what single drug they’d keep if forced to choose, many point to benzoyl peroxide (BPO). Why? Because it is one of the few acne treatments that directly kills Cutibacterium acnes, the bacteria that fuels inflammation, without ever leading to resistance. That’s a critical distinction. Antibiotics may work temporarily, but bacteria can adapt and stop responding. BPO remains effective decade after decade.

It’s available in strengths from 2.5% to 10%, in cleansers, gels, and creams. Interestingly, studies show that lower strengths (2.5–5%) are often just as effective as higher strengths, but less irritating. That means patients don’t need to suffer unnecessary redness or peeling to see results.

BPO works best for inflammatory pimples (the red, sore kind) but also prevents resistance when combined with antibiotics—so much so that dermatologists almost never prescribe antibiotics without recommending BPO alongside them. The downside? It can bleach fabrics, so that favorite pillowcase or shirt might not survive contact.

Salicylic Acid: The Pore Cleaner

If BPO is the bacteria killer, salicylic acid is the pore janitor. Belonging to the beta-hydroxy acid (BHA) family, it penetrates oily pores and dissolves dead skin cells that clog them. This makes it especially helpful for blackheads and whiteheads.

It’s less potent than prescription retinoids but is a good entry-level option for people dipping their toes into active skincare. You’ll find it in cleansers, toners, spot treatments, and even medicated makeup. Dermatologists often recommend it as an adjunct, not a mainstay—something to layer in alongside retinoids or BPO for extra comedone control.

Adapalene: The First Over-the-Counter Retinoid

When the FDA approved adapalene 0.1% gel (Differin) for OTC use, it was a game-changer. For the first time, a true retinoid—a class of vitamin A derivatives considered the backbone of acne therapy—was available without a prescription.

Retinoids work by normalizing how skin cells shed, preventing clogged pores at the root. They also reduce inflammation and improve skin texture over time. Unlike BPO or salicylic acid, adapalene is not just a surface treatment—it helps reset the skin’s biological rhythm.

The catch? Patience is required. Retinoids often take 8–12 weeks before real results appear, and the “purge” phase (temporary worsening) can discourage beginners. But dermatologists emphasize sticking it out; for many, retinoids become a lifelong ally not just against acne but also against fine lines and uneven tone.

Prescription Topical Therapies: Raising the Stakes

When OTC products aren’t enough, dermatologists often prescribe stronger topicals. These target acne at multiple levels: unclogging pores, calming inflammation, fighting bacteria, and even modulating hormones.

Retinoids: The Cornerstone of Modern Acne Care

While adapalene is available OTC, stronger retinoids like tretinoin, tazarotene, and trifarotene remain prescription-only. These are more potent, sometimes more irritating, but also more effective. They don’t just prevent breakouts—they improve skin quality overall, fading hyperpigmentation and smoothing texture.

The newest retinoid, trifarotene (Aklief), was designed to treat both facial and truncal acne. For patients struggling with chest and back breakouts, this represents the first retinoid specifically studied and approved for body use. That’s a big step, since truncal acne has historically been under-treated.

Clascoterone (Winlevi): Hormone Blocking Without Pills

Hormonal influence is a huge driver of acne, especially in teens and adult women. Until recently, the only way to counter this was with oral treatments like birth control pills or spironolactone. Then came clascoterone 1% cream (Winlevi), the first topical androgen receptor inhibitor.

Applied directly to the skin, clascoterone reduces sebum production and inflammation without systemic hormone effects. This makes it appealing for patients wary of oral hormones. While still new, dermatologists are excited about its potential as part of combination therapy.

Topical Antibiotics: Still Useful, but Never Alone

Clindamycin and erythromycin are classic topical antibiotics for acne, but their use has changed dramatically. In the past, they were often prescribed solo, leading to widespread resistance. Now, dermatologists insist they must be combined with BPO. Many products conveniently package the two together, ensuring both efficacy and stewardship.

Azelaic Acid: A Multitasker

Azelaic acid is one of dermatology’s most versatile agents. It’s comedolytic (helps unclog pores), antibacterial, anti-inflammatory, and even reduces hyperpigmentation. For patients with skin of color who deal with dark spots after acne, azelaic acid does double duty. It’s also one of the few acne treatments considered safe during pregnancy, making it invaluable for expectant mothers.

Dapsone Gel: A Niche but Valuable Option

Dapsone gel may not be as widely used as other topicals, but it fills an important role for certain patients. It’s particularly effective for inflammatory acne in women and is well-tolerated. One quirky side effect: if layered with benzoyl peroxide, it can cause a temporary orange or yellow discoloration on the skin or facial hair. It’s harmless but startling if you don’t expect it.

Fixed-Dose Combinations: Simplifying Regimens

Adherence is one of the biggest barriers to acne success—patients simply forget or get overwhelmed by multiple steps. Enter fixed-dose combination therapies. Products like adapalene/BPO (Epiduo) gel or Twyneo (tretinoin + BPO) deliver two proven agents in one tube, improving compliance and reducing irritation through clever formulations.

Twyneo, approved in 2021, is particularly innovative because it stabilizes tretinoin (which usually degrades quickly in BPO’s presence) so both can be applied at once.

Oral Medications: When Acne Needs Systemic Firepower

Topicals are the foundation, but for moderate to severe acne, dermatologists often turn to oral medications. These tackle acne at the systemic level, calming widespread inflammation, addressing hormones, and shrinking oil production.

Oral Antibiotics: A Short-Term Boost

Antibiotics like doxycycline and minocycline have long been mainstays of acne therapy. They work by reducing bacterial load and calming inflammation. But because of resistance concerns, the AAD recommends limiting their use to three months or less, always in combination with topical retinoids and BPO.

The newest player, sarecycline, is a narrow-spectrum antibiotic designed to be gentler on the gut and less disruptive to beneficial bacteria. It represents an evolution in how dermatologists think about antibiotics: not just effectiveness, but collateral damage.

Hormonal Therapies: Especially for Women

For women, hormones are often a major acne trigger. Dermatologists leverage this by prescribing combined oral contraceptives (COCs) or spironolactone.

COCs lower androgen activity, reducing oil production. Several formulations have specific FDA approval for acne. They can be transformative for women whose breakouts flare cyclically.

Spironolactone, meanwhile, is technically a blood pressure drug but is used off-label for acne. At doses of 50–100 mg daily, it blocks androgens at the skin level. Many women experience dramatic improvement within a few months. Importantly, recent studies show that routine potassium monitoring may not be necessary in young, healthy women without risk factors, simplifying long-term use.

Isotretinoin: The Nuclear Option

When all else fails—or when acne is severe and scarring—dermatologists reach for isotretinoin (formerly Accutane). This drug fundamentally changes the skin by shrinking oil glands, normalizing cell turnover, and reducing inflammation. For many, it induces long-term remission.

But isotretinoin comes with caveats. It is highly teratogenic—causing severe birth defects if taken during pregnancy. In the U.S., it’s dispensed under the strict iPLEDGE program, which requires enrollment, regular pregnancy testing, and contraception. Side effects include extreme dryness, nosebleeds, photosensitivity, muscle aches, and sometimes elevated lipids or liver enzymes.

Despite these hurdles, isotretinoin remains the most powerful tool in dermatology’s arsenal for acne. For patients whose lives are disrupted by scarring breakouts, it can be life-changing.

Quick Hits: Side Effects & Safety Pearls

• Retinoids: Temporary dryness, peeling, photosensitivity—ease in slowly, moisturize daily.

• Benzoyl Peroxide: May bleach fabrics; crucial partner against antibiotic resistance.

• Topical Antibiotics: Always combine with BPO to avoid resistance.

• Dapsone: May cause harmless yellow-orange discoloration if layered with BPO.

• Oral Tetracyclines: Can cause GI upset, photosensitivity; avoid in pregnancy and children <8.

• Spironolactone: May cause breast tenderness, irregular periods; must be avoided in pregnancy.

• Isotretinoin: Powerful but tightly regulated; dryness and lab monitoring are part of the package.

The Future of Acne Treatment

The acne landscape is evolving rapidly. New delivery systems like topical minocycline foam allow antibiotics to be used locally rather than systemically. Innovative vehicles like Twyneo reduce irritation by stabilizing harsh actives. And topical hormone blockers like clascoterone open doors for personalized, targeted therapy.

Looking further ahead, research into the skin microbiome may change acne therapy entirely. Instead of simply killing bacteria, future treatments may aim to rebalance microbial communities, promoting beneficial strains while reducing harmful ones.

Acne

Acne treatment doesn’t have to feel like guesswork. Start with over-the-counter staples like adapalene and benzoyl peroxide. If that’s not enough, step into prescription topicals. If acne is more severe or stubborn, move to oral antibiotics, hormonal therapies, or isotretinoin under guidance.

The modern playbook is about targeting multiple causes, avoiding antibiotic overuse, and escalating smartly. With persistence and the right plan, clearer skin is achievable for almost everyone.

Sources:

Core Clinical Guidelines & Reviews

• Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris.

  American Academy of Dermatology (AAD), 2024 update.

• Thiboutot DM, Zaenglein AL, Weiss J, et al. Practical management of acne for clinicians: an international consensus from the Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2018;78(2 Suppl 1):S1–S23.

• Layton AM, Eady EA, Whitehouse H. Recent advances in acne management: focus on topical therapies. Drugs.

  2021;81(10):1115–1130.

Over-the-Counter Treatments

• FDA News Release. FDA approves Differin Gel 0.1% (adapalene) for over-the-counter use.July 2016.

• Leyden JJ. Therapy for acne vulgaris. N Engl J Med. 1997;336(16):1156–1162. (classic but still widely cited for BPO efficacy and resistance prevention).

Prescription Topicals

• FDA Drug Label: Aklief (trifarotene 0.005% cream), approved October 2019.

• FDA Drug Label: Winlevi (clascoterone 1% cream), approved August 2020.

• FDA Drug Label: Twyneo (tretinoin 0.1% + benzoyl peroxide 3% cream), approved July 2021.

• Del Rosso JQ. Clascoterone cream 1% for topical treatment of acne vulgaris: mechanism of action, efficacy, and safety profile. J Clin Aesthet Dermatol. 2021;14(4):S21–S27.

• Thiboutot D, Weiss J, Bucko A, et al. Efficacy and safety of azelaic acid 15% gel in the treatment of acne vulgaris: a randomized trial. J Am Acad Dermatol. 2003;48(5):691–700.

Oral Antibiotics

• FDA Drug Label: Seysara (sarecycline), approved 2018.

• Moore AY, Green LJ, Bruce S, et al. Efficacy and safety of sarecycline, a novel, narrow-spectrum tetracycline, for moderate-to-severe acne vulgaris. J Drugs Dermatol. 2018;17(9):987–996.

• Zaenglein AL, et al. Antibiotic stewardship in acne: limiting duration and combining with benzoyl peroxide.

  AAD guideline summary, 2024.

Hormonal Therapies

• FDA Drug Labels:

  • Ortho Tri-Cyclen (norgestimate/ethinyl estradiol)

  • Estrostep Fe(norethindrone acetate/ethinyl estradiol)

  • Yaz (drospirenone/ethinyl estradiol) — all approved for acne indications.

• Layton AM, Eady EA, Whitehouse H.

  Oral contraceptives and acne: a review of the evidence.

  Br J Dermatol.

  2017;176(1):3–12.

• Plovanich M, Weng QY, Mostaghimi A. Low utility of potassium monitoring among healthy young women taking spironolactone for acne. JAMA Dermatol.

  2015;151(9):941–944.

Isotretinoin

• FDA Drug Label: Accutane/Isotretinoin (multiple generics; REMS program documentation).

• Barbieri JS, et al. Isotretinoin laboratory monitoring in acne patients: A systematic review and meta-analysis. JAMA Dermatol. 2019;155(8):1011–1019.

• Barbieri JS, et al. iPLEDGE program: recent updates and implications for practice.J Am Acad Dermatol. 2022.

Special Considerations

• Draelos ZD. Azelaic acid: a unique topical agent for acne in skin of color and pregnancy. Cutis. 2006;77(6 Suppl):19–24. Thiboutot DM. Hormonal factors in acne: current therapies and future directions. J Clin Invest.2021;131(2):e142811.