Hydrocodone and trazodone are prescription medications with different mechanisms of action that can interact when taken together. Unlike trazodone, hydrocodone is an opioid analgesic. Meanwhile, trazodone is an antidepressant medication. Although they belong to different drug classes, both can produce sedating effects.
While hydrocodone binds to opioid receptors to relieve pain, trazodone increases serotonin, reducing symptoms of depression. When combined, hydrocodone and trazodone can cause serotonin syndrome, opioid overdose, and even death.
This article will discuss the interaction between hydrocodone and trazodone in detail and explain why mixing these medications, even in low doses, can be very dangerous.
What Is Hydrocodone?
Hydrocodone is a prescription opioid used to control moderate-to-severe pain that cannot be managed with non-opioid painkillers. It is derived from codeine or thebaine and classified as a semi-synthetic opioid.
As a single-entity drug, hydrocodone is only available in the extended-release formulation, marketed under Zohydro® ER, Hysingla® ER, and other brand names. It comes as a tablet or capsule.
Hydrocodone is commonly prescribed as a combination drug, usually containing acetaminophen. Acetaminophen/hydrocodone is available as a generic or brand-name drug (Norco®, Lortab®, Vicodin®) in tablets, capsules, and oral solutions.
Hydrocodone relieves pain by attaching to opioid receptors in the central nervous system (CNS) and blocking pain signals. As effective as it is for pain relief, it comes with considerable risks. Due to the high potential for abuse, dependence, and addiction, it is treated as a Schedule II controlled substance and is not recommended for chronic pain treatment.
Hydrocodone Usage in the USA
Here are some statistics on the usage of hydrocodone in the United States:
- Opioid overdose has claimed the lives of over 80,000 Americans in 2023 alone, with more than 10,000 of these overdose deaths involving natural and semi-synthetic opioids like hydrocodone.
- With more than 23.5 million prescriptions issued to nearly 8 million Americans, acetaminophen/hydrocodone was the most frequently prescribed opioid medication in the United States in 2022.
- In 2022, over 45% of drug misusers—or 3.7 million Americans—abused hydrocodone and its products, making it the most commonly misused painkiller that year.
- The number of hydrocodone and other semi-synthetic and natural opioid overdose deaths increased by nearly 170% between 2002 and 2022.
- The United States accounted for nearly all global hydrocodone use in 2021; unlike other opioids, it is almost exclusively used in the US.
Side Effects of Using Hydrocodone
Hydrocodone can cause various side effects, with the most common ones being:
- Fatigue
- Nausea
- Dry mouth
- Drowsiness
- Constipation
- Abdominal pain
- Lightheadedness
- Difficulty urinating
In some cases, hydrocodone can cause hallucinations, allergic reactions, trouble breathing, and other serious side effects that may require immediate medical help. Talk to your doctor if you experience any unwanted reactions after taking hydrocodone, including those not listed above.
While pain relief is the primary effect of hydrocodone, it can also induce a sense of euphoria and deep relaxation by triggering a sudden dopamine rush. Since people are wired to repeat dopamine-inducing activities, this significantly enhances the risk of opioid abuse.
Furthermore, long-term hydrocodone use and abuse may lead to:
- Liver, heart, and other organ damage
- Tolerance and opioid dependence
- Opioid use disorder (OUD)
- Respiratory depression
- Chronic constipation
- Fertility problems
- Opioid overdose
- Coma
- Death
Take hydrocodone strictly as prescribed and for as little time as possible to reduce the risk of adverse effects.
How Long Do Hydrocodone Effects Last?
Hydrocodone effects last between 4 and 24 hours, and their duration mainly depends on the drug’s formulation. Extended-release hydrocodone has a much longer duration of action than immediate-release formulations, which typically relieve pain for about 4–6 hours. Various other factors, such as the dosage taken, may also affect the duration of hydrocodone effects.
What Is Trazodone, and How Does It Work?
Trazodone is a non-opioid medication belonging to the class of serotonin modulators that is commonly prescribed to treat depression. Considered an atypical antidepressant, it falls under the category of serotonin receptor antagonists and reuptake inhibitors (SARIs). It is usually prescribed when other depressants are ineffective or cause side effects.
Trazodone, which comes in the form of 50 mg, 100 mg, 150 mg, or 300 mg tablets, is available as a generic drug and sold under the following brand names:
- Oleptro®
- Desyrel®
- Trazodone D®
- Desyrel Dividose®
Trazodone works by elevating the level of serotonin in the brain, which helps alleviate symptoms of depression. Its effects aren’t immediate; it may take up to two weeks before it starts working. Trazodone can also make you sleepy. While it is sometimes used off-label to combat insomnia, it is currently only FDA-approved for the treatment of major depressive disorder (MDD).
Moreover, trazodone may be habit-forming, especially if misused (e.g., used recreationally for its relaxing effects). Trazodone abuse increases the risk of adverse effects, such as extreme sedation, respiratory arrest, and overdose. For your safety, always take it as prescribed, and do not discontinue it without consulting your doctor.
Now that we’ve covered the basics, it’s time to examine the interactions between hydrocodone and trazodone.
Hydrocodone and Trazodone Interactions: Risks and Dangers
Hydrocodone and trazodone can interact and cause dangerous—and even life-threatening—adverse effects like severe drowsiness, serotonin syndrome, and overdose. Mixing these drugs is a form of polysubstance abuse and should be avoided at all costs; at worst, this drug combination can have fatal consequences.
Drowsiness and dizziness are common side effects of hydrocodone and trazodone. Taking these medications together can amplify them, leading to excessive dizziness, drowsiness, and confusion and increasing the risk of accidents and injuries. Although mixing hydrocodone and trazodone at high doses increases these risks, it can be dangerous even at lower doses.
Furthermore, taking hydrocodone and trazodone together or within a short time frame can lead to serotonin syndrome. Although rare, serotonin syndrome usually occurs as a result of polydrug abuse and can be life-threatening.
The main symptoms of serotonin syndrome include:
- Fever
- Tremors
- Seizures
- Confusion
- Blurred vision
- Hallucinations
- Rapid heartbeat
- Muscle stiffness
- Increased sweating
- Nausea and vomiting
- Blood pressure changes
The combination of hydrocodone and trazodone can also dangerously slow down your breathing and lead to respiratory depression. Slowed breathing is often a sign of opioid overdose, a life-threatening emergency that can only be reversed by receiving prompt medical assistance.
If you think you or someone you know may be overdosing or suffering from serotonin syndrome after taking hydrocodone and trazodone, calling 911 is of vital importance.
Effects of Mixing Hydrocodone and Trazodone
Common effects of mixing hydrocodone and trazodone include:
- Confusion
- Severe dizziness
- Enhanced sedation
- Impaired motor skills
- Difficulty concentrating
- Slowed, shallow breathing
Mixing hydrocodone and trazodone can also exacerbate the side effects associated with both drugs, such as nausea and constipation.
Long-Term Effects of Hydrocodone and Trazodone Abuse
Long-term use of hydrocodone and trazodone increases the risk of:
- Health complications. Polysubstance abuse poses significant health risks, and mixing hydrocodone and trazodone is no exception. This drug combination can not only lead to a potentially fatal overdose but also increase the risk of organ damage, respiratory problems, and cardiovascular issues.
- Cognitive impairment. The combination of hydrocodone and trazodone can impair your judgment and thinking. When used over a long time, it may affect your ability to concentrate, recall information, etc.
- Substance use disorders (SUDs). Hydrocodone and trazodone abuse can make you more susceptible to developing a dependence on either of both of these drugs. It also increases the risk of SUDs, especially OUD.
What Does Hydrocodone Dependence Look Like?
Hydrocodone dependence is primarily a physical reliance on this drug; those dependent on hydrocodone have to take it to go about their day as usual. Without it, they experience uncomfortable opioid withdrawal symptoms, ranging from psychological symptoms like cravings and depression to physical ones, such as vomiting, body aches, and diarrhea.
Anyone taking hydrocodone, including those who carefully follow the doctor’s instructions, risks becoming dependent. This is because repeated exposure to hydrocodone affects the brain, causing it to decrease endorphin production and increase that of opioid receptors.
Increased opioid receptor production leads to tolerance. If you take hydrocodone for a prolonged period, it’s only a matter of time before your usual dose will lose its effectiveness. If this happens, do not take more hydrocodone than prescribed, as this is a form of opioid abuse. Instead, consult with your doctor.
If left untreated, hydrocodone dependence can escalate into an addiction. Unlike dependence, opioid addiction is primarily psychological. While those dependent need hydrocodone to feel normal, people addicted to this drug have an uncontrollable urge to take it.
Hydrocodone Addiction
Hydrocodone addiction is characterized by a lack of control over opioid use. If you or a loved one are still taking the drug, even when it’s no longer medically needed or negatively affects your life, it is vital to seek professional opioid addiction treatment.
Some tell-tale signs of hydrocodone addiction include:
- Isolation from family and friends
- Poor performance at school or work
- Loss of interest in previously enjoyed activities
- Multiple failed attempts at quitting hydrocodone
- Failure to meet professional or familial obligations
- Preoccupation with obtaining or using hydrocodone
- Hydrocodone abuse, i.e., taking it in any way other than prescribed
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Key Takeaways
Here are the key things you should keep in mind when it comes to hydrocodone and trazodone:
- Hydrocodone is a highly addictive opioid medication used to manage moderate-to-severe pain.
- Trazodone is an antidepressant medication that works by regulating the amount of serotonin in the brain.
- Hydrocodone and trazodone should never be taken together due to the risk of severe side effects, serotonin syndrome, overdose, and death.
- ANR is an ultra-modern treatment that eradicates opioid dependence by modulating the endorphin-receptor system and restoring normal brain function.
Hydrocodone and Trazodone FAQ
If you have trouble falling asleep but aren’t sure what you can take with trazodone to help you sleep, consult with your doctor to reduce the risk of dangerous trazodone interactions with other drugs. Never take trazodone with any sleep aids—including melatonin—without your doctor’s approval, as this can lead to extreme drowsiness and other adverse events.
Acetaminophen (Tylenol) is a pain reliever you can usually take with trazodone. Although there are no known interactions between acetaminophen and trazodone, it’s best to consult with your doctor before taking any pain reliever while using trazodone.
Never take hydrocodone and a sleeping pill at the same time. Drowsiness is a common side effect of hydrocodone, and mixing it with sleep medications can dangerously amplify its sedative effects, increase the risk of opioid overdose, and lead to other potentially life-threatening adverse effects.
You should never take hydrocodone and tramadol together, as mixing opioids increases the risk of serious side effects like respiratory depression and seizures. It can also cause an opioid overdose, which can be fatal.