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Many medications that have legitimate and essential medical uses carry a risk of physical dependence, which can occur even when a medication is taken as prescribed. Certain types of medications are more likely to cause dependence, including opioids, benzodiazepines, barbiturates, and stimulants commonly used to treat ADHD. [1][2]
Guidelines exist to help ensure the safe and appropriate prescribing of these medications.
Understanding dependence potential
Dependence potential describes the risk that a medication or drug may cause a person to develop physical dependence. Dependence occurs when the brain and body adapt to repeated exposure to a drug, resulting in withdrawal symptoms when the person lowers their dose or stops taking the medication.
The specific symptoms and severity of withdrawal can vary depending on several factors, including the type of medication, dose, frequency of use, and length of time they were taking it. [1][3]
Certain prescription medications (like stimulants, opioids, benzodiazepines, and barbiturates) have a higher potential for causing dependence. With these medications, physical dependence may develop more easily, particularly with prolonged, frequent, or repeated use.
Many medications with significant dependence or misuse potential are classified as controlled substances and are more closely regulated because of their potential for misuse, abuse, and addiction. [1][2]
Dependence vs addiction
While physical dependence and addiction often co-occur, they can also occur separately. Physical dependence is a process of biological adaptation to a certain substance that triggers withdrawal symptoms if a person abruptly cuts back their dose or stops using.
Addiction, on the other hand, involves the compulsive, uncontrolled, and problematic use of a substance, despite experiencing significant problems or impairment as a result. [1][2]
Why dependence can occur even when taking a medication as prescribed
Physical dependence is largely the consequence of a natural process called neuroadaptation, which is when the body and brain adjust to the presence of a substance taken regularly. When the drug is removed or reduced too quickly, a person can experience withdrawal, which describes another process of neuroadaptation as the body adjusts again to being without the substance.
How often this may happen and the length of time it takes for this neuroadaptation process to occur each vary depending on the individual, the type of substance, and the typical dose, but can occur quickly with certain types of medications.
In some instances, physical dependence can occur over the course of a few weeks of regular use, even when a person takes the medication exactly as prescribed. [3][4]
Prescription medications with a high dependence potential
Certain types of medication carry a high risk for dependence, meaning physical dependence occurs more quickly and easily. Often, these include controlled substances also known to carry a high risk for abuse, misuse, or addiction, including opioids, benzodiazepines, stimulants, and barbiturates. [1][2][3]
Opioid pain relievers
Prescription opioids (like oxycodone, morphine, and codeine) are commonly prescribed as painkillers. Opioids are known to carry a high risk for misuse, dependence, overdose, and withdrawal and are classified by the DEA as controlled substances because of these risks.
While opioids are often medically necessary for controlling moderate to severe pain, dependence can form quickly, even when used as prescribed. [2][3]
Benzodiazepines
Benzodiazepines are prescription sedatives that are commonly prescribed for anxiety or sleep problems, and include medications like alprazolam, clonazepam, lorazepam, and diazepam.
Because of the high risk for abuse, misuse, addiction, dependence, and withdrawal, these medications are controlled substances with boxed warnings from the FDA. According to some research, benzodiazepine dependence can occur after only 3 weeks of regular use, even when taken as prescribed. [2][4]
Prescription stimulants
Prescription stimulants (like Adderall, Ritalin, and Vyvanse) are commonly prescribed for the treatment of attention-deficit hyperactivity disorder (ADHD), but they are known to carry a high risk for abuse and dependence.
In some instances, there have been reports of people developing dependence quickly, especially when the medication is being abused. During withdrawal, reports of fatigue, low concentration, mood swings, irritability, and psychosis are common. [3]
Barbiturates
Barbiturates are sedatives that work by depressing the activity of the central nervous system, and include medications like phenobarbital, amobarbital and pentobarbital.
Barbiturates are much less commonly prescribed, but they are sometimes used in the treatment of seizure disorders, migraines, and sleep conditions. [2][4]
Safety and prescribing considerations
The specific safety concerns and risk management considerations vary depending on the type of medication being prescribed. [1][2][3]
| Medication Class | Common Uses | Dependence Potential | Major Concerns | Key Prescribing Considerations |
|---|---|---|---|---|
Best prescribing practices explained
There are a number of guidelines and best practices that have been developed to help lower the risk when the use of controlled medications is medically indicated. Ensuring that the medication is clinically indicated and that the potential benefits outweigh the risks is foundational to best practice guidelines.[1]
Considering the medical and psychiatric history of the individual patient is also necessary, including the consideration of pre-existing conditions and diagnoses, current medications, past and current substance use patterns.
For many medications, best practices recommend starting at a lower dose to assess patient tolerance and response, as well as to find the lowest effective dose.[1][2]
Finally, close patient monitoring and regular follow-up appointments are also essential to best practice guidelines, particularly when prescribing medications with a high dependence potential. In some cases, these follow-up appointments need to include regular labs or drug screens to minimize the risk for abuse or accidental overdose.[1]
Checklist of best prescribing practices
Before prescribing medications with a dependence potential
- Confirm the diagnosis, severity of symptoms, and clinical indication.
- Confirm the patient’s treatment goals and needs.
- Review safer or less invasive alternatives.
- Assess the medication's abuse, dependence, and overdose potential.
- Check the state PDMP database to verify if patient is prescribed other controlled drugs.
- Review the patient's medical, psychiatric, medication, and substance-use history.
- Review specific prescribing guidelines, contraindications, and risks.
- Identify potential drug interactions and verify patient’s current medication list.
- Educate patient about potential benefits and risks and obtain informed consent.
When prescribing medications with a dependence potential
- Educate patient on warning signs or side effects to watch for.
- Select the safest and most effective medication and formulation.
- Start small and use the lowest effective dose.
- Limit to short-term use when clinically appropriate.
- Explain dependence and withdrawal risks.
- Discuss safe storage, disposal, and use.
- Establish expectations for follow-ups, ongoing treatment, and refills.
Patient monitoring during treatment
- Reassess benefits and harms regularly.
- Schedule regular follow-up appointments.
- Encourage patients to reach out with concerns.
- Monitor medication adherence, response, and any side effects.
- Monitor for adverse effects, escalating doses, early refills, and other concerning patterns.
- Utilize labs and urine drug screens when clinically appropriate.
- Reevaluate whether continued treatment remains appropriate.
- Coordinate care with other treatment providers when necessary.
When discontinuing or tapering off medications with a dependence potential
- Collaborate and openly discuss pros and cons with patient.
- Determine whether discontinuation is clinically appropriate or indicated.
- Avoid abrupt cessation when withdrawal could be dangerous.
- Develop an individualized tapering plan when needed.
- Monitor for withdrawal and recurrence of the underlying condition.
- Adjust the taper according to patient response.
- Provide alternative treatment options or referrals when appropriate.
Prescribing guidelines for patients with a history of substance use disorder
Having a prior diagnosis or history of a substance use disorder should be considered an important risk factor, but it is usually not grounds to automatically disqualify a patient from receiving a medication they need.
A number of factors should be considered when a patient discloses a history of substance use, including these: [2]
- Type of substance use disorder and whether it is active or in remission.
- Past or current addiction treatment history.
- Patient’s preference, needs, and stated goals for treatment.
- Severity of symptoms or condition requiring treatment.
- Abuse and addiction potential of the specific medication being considered.
- Whether there are safer alternatives with lower abuse and dependence potentials.
- Individual risk for relapse related to the medication being considered.
- Presence of other important risk or protective factors.
- Ability to safely monitor treatment and adherence.
Specialized treatment and coordination of care
Some patients require involvement from a number of different providers because of the nature or severity of their condition or the presence of one or more co-occurring disorders.
When other providers or specialists are involved, most best practice guidelines indicate the need for coordination of care. Obtaining a signed release of information from the patient will allow you to share information regarding the patient’s care with other involved providers:[1]
- Primary care providers.
- Pain management specialists.
- Addiction treatment providers.
- Mental health or psychiatric providers.
- Neurology providers.
- Pharmacy providers.
- Other medical specialists.
Final thoughts
The goal of responsible prescribing is to balance the expected therapeutic benefits of a medication against any potential risks. This involves selecting the appropriate medication and dose, considering less restrictive and non-controlled alternatives when appropriate, identifying individual risk factors, educating patients about safe use, monitoring treatment through follow-ups, and coordinating care as needed. [1]
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