What are Schedule 3, 4, and 5 controlled substances?

Controlled Substances Schedules III, IV, and V

Schedule III, IV, and V controlled substances are medications with progressively lower abuse potential and accepted medical uses, with Schedule III including hydrocodone combinations and certain anabolic steroids, Schedule IV including benzodiazepines and tramadol, and Schedule V including medications with the lowest abuse potential under federal control.

Schedule III Controlled Substances

Schedule III substances have moderate to low potential for physical and psychological dependence, less than Schedule II but more than Schedule IV 1.

Opioid Medications

• Hydrocodone combination products (≤15 mg hydrocodone) combined with acetaminophen (e.g., Vicodin, Lortab) or ibuprofen (e.g., Vicoprofen) 1
• Codeine combination products (certain formulations with acetaminophen or other non-opioids) 2
• Note: Pure codeine without combination products is Schedule II 2

Non-Opioid Substances

• Anabolic steroids including boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione 3
• Buprenorphine products (partial opioid agonist used for pain and opioid use disorder treatment)

Clinical Considerations for Schedule III

• Equianalgesic doses of Schedule III opioids provide equivalent pain relief to Schedule II opioids—there is no inherent superiority of Schedule II agents 1
• Prescription drug monitoring programs track Schedule III substances to identify diversion and doctor shopping 2
• Schedule III opioids should not be used for chronic pain management in emergency department settings 1

Schedule IV Controlled Substances

Schedule IV substances have low potential for abuse relative to Schedule III and limited risk of physical or psychological dependence 1.

Benzodiazepines and Related Agents

• All benzodiazepine receptor agonists are uniformly classified as Schedule IV 2
• Non-benzodiazepine hypnotics: eszopiclone, zolpidem, zaleplon 2, 4
• Benzodiazepines: alprazolam, estazolam, temazepam, triazolam, flurazepam 2, 5

Opioid Medications

• Tramadol was reclassified to Schedule IV in 2014 by the FDA due to potential for abuse and dependence, despite previous recommendations for use in acute coronary syndrome 1

Weight Management Medications

• Phentermine-topiramate ER is classified as Schedule IV based on concerns for abuse and dependence 1

Withdrawal and Dependence Risks

• Withdrawal symptoms from Schedule IV substances can range from mild dysphoria and insomnia to major syndromes including abdominal cramps, vomiting, sweating, tremors, and convulsions 4, 5
• Abrupt discontinuation should be avoided; gradual tapering under close supervision is mandatory, especially in patients with seizure history 5

Schedule V Controlled Substances

Schedule V substances have the lowest abuse potential among controlled substances with accepted medical use 2.

Characteristics

• Limited quantities of certain narcotics for antitussive and antidiarrheal purposes
• May contain small amounts of codeine or other opioids combined with non-narcotic ingredients
• Some states allow Schedule V medications to be dispensed without a prescription under specific conditions

Prescription Monitoring Requirements

All Schedule III and IV controlled substances are tracked by prescription drug monitoring programs (PDMPs) in most states to identify:

• Diversion patterns 2
• Doctor shopping (variably defined as obtaining prescriptions from ≥2 prescribers within 30 days, >4 during one year, or >5 during one year) 2
• Concurrent prescriptions from multiple providers 2

Critical Prescribing Caveats

Schedule III Opioids

• Long-acting or extended-release formulations are contraindicated for acute pain—they are intended only for opioid-tolerant patients with chronic pain 1
• When prescribing on discharge, use the lowest practical dose for limited duration (e.g., 1 week) and assess patient's risk for misuse, abuse, or diversion 1

Schedule IV Substances

• Patients with history of substance use disorders require careful monitoring when receiving any Schedule IV medication 1
• Physical dependence can develop even with brief therapy at recommended doses 5
• Psychological dependence risk increases with doses above typical therapeutic ranges and longer treatment duration 5

Common Pitfall

Do not assume Schedule II opioids are more effective than Schedule III opioids at equianalgesic doses—this is a misconception not supported by evidence 1. The scheduling reflects abuse potential and regulatory requirements, not analgesic efficacy.