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What Happens When You Mix Trazodone and Gabapentin?

What Happens When You Mix Trazodone and Gabapentin?

Drugs are a lot like people. Everyone has their own preferences with who they choose to mingle with. Mixing two drugs that work in harmony can result in a life-changing treatment. On the opposite end, there are substances that don’t subscribe to cross-collaboration. Or do they?

Mixing drugs is always dangerous, but combining trazodone with gabapentin could result in depressive effects that may cause negative health consequences.

What is Trazodone? 

Trazodone hydrochloride is a non-addictive antidepressant drug. Its makeup resembles antidepressants known as selective serotonin reuptake inhibitors (SSRIs).

SSRIs work to keep your brain stocked with serotonin (the “happy” chemical). They prevent the “messengers” to the brain, called neurons, from taking back what’s already been released. This increases the amount of serotonin in the brain, which improves your mood.

Trazodone is different. It is part of another drug group, serotonin receptor antagonist reuptake inhibitors (SARIs). This mouthful to say means that trazodone plays double duty to restore the balance of serotonin in your brain. SARIs not only stop the reabsorption of serotonin (like SSRIs do) but also block certain receptors, called neurotransmitters in the brain. This is what serotonin attaches to. The effects of trazodone block these receptors. This allows the body to increase the total amount of serotonin in the central nervous system (CNS). This reaction reduces anxiety and sleep issues that depression causes.

Trazodone has many “off-label” purposes, not FDA-approved (Food and Drug Administration). The most common conditions prescribed off-label are insomnia, anxiety, and schizophrenia. It’s also prescribed in addiction recovery. In 2017, people named trazodone as one of the most popular sleeping meds. The FDA has never approved trazodone as a sleep aid.

The long-term use of trazodone leads to dependence and withdrawal when stopped. Taking trazodone in high doses or with other drugs that make you drowsy has adverse effects. It amplifies sleep into heavy sedation. Medications like sleeping pills, muscle relaxers, and anxiety medications warn against combining with trazodone.

Reviewing drug interactions paints a general image of how a drug plays with other drugs. There’s a lot to cover and not enough room. For instance, two “alternative” medications may seem like an odd couple — at first. This pairing is a mixing of trazodone and gabapentin. Sounds harmless, right?

What is Gabapentin?

Gabapentin (Neurontin, Gralise, Horizant) is a non-narcotic anticonvulsant medication. known as gamma-aminobutyric acid (GABA). It comes in tablet or liquid form and has two purposes. It treats seizures caused by epilepsy and nerve pain from various conditions.

Gabapentin mimics the effects of GABA, a natural chemical in the brain. GABA is gamma-aminobutyric acid. It calms excited neurons that induce seizures and pain signals. This makes it a worthwhile anticonvulsant medication to control and prevent seizures. It is a non-opioid prescribed off-label as an analgesic. It gives nerves pain relief like from problems from diabetes or shingles.

Doctors are more relaxed in prescribing the non-controlled drug. This can lead to an “anything goes” mindset. Without restrictions, it can become an experimental treatment.

Gabapentin shares ample side effects with trazodone. Dizziness, mood changes, and sleepiness top the list. The FDA warns about breathing problems and other serious side effects it can cause. Like trazodone, not taking the drug produces withdrawal symptoms. These present as more severe forms of its side effects.

So which is it? Are gabapentin and trazodone friends or enemies? 

Synergistic Effects

Synergistic effects mean that two (or more) drugs cooperate. Some medications need their other half to work. It’s easy to assume similar side effects will combine into one super-strength treatment.

There is interest in using trazodone and gabapentin together to treat pain. One of these conditions is diabetic peripheral neuropathic pain. Diabetic neuropathy (DN) is a type of chronic pain. This painful diabetic neuropathy is from nerve damage caused by diabetes. It is not altogether understood yet. This impacts individuals’ quality of life and can even turn fatal. 

The current options to manage this condition don’t work so well. A better pain relief answer is on the research radar. The disorder has led to digging deeper into a dual-treatment approach to decrease pain. Both treat and decrease adverse effects to give pain relief.

Medical guidelines suggest using antidepressants is a direct treatment for DN pain relief. Studies in a clinical setting indicate the potential of low doses of trazodone with gabapentin to help diabetic patients. DN doesn’t respond very well to typical opioids.

This gap drew attention to alternative drugs like gabapentin for chronic pain relief. Clinical studies focused on these drugs as their actions complemented each other in this case. But why trazodone? Certain antidepressant drugs are a part of pain management. The antidepressant effects of trazodone have been shown to align with decreasing pain. Both drugs given in low doses in clinical studies for DM can reduce pain relief. This doesn’t mean it’s fine to go full speed ahead, however.

Dangers of Pairing

Research shows promise for low doses of antidepressants and CNS drugs in healthcare. This is for very specific conditions like painful diabetic neuropathy. A potential exists this applies to other conditions. This is exciting, aside from a lack of concrete grasp on the workings of both drugs and the disorder.

When dealing with unknowns, precise and low doses are essential. It’s easy to interpret the non-addictive features of the two as safe. The lack of regulations for gabapentin has created the misconception it’s fine to use freely.

A 2016 study revealed 1% of the population abuses gabapentin. For individuals prescribed it, the percentage skyrocketed from 40% to 65%. People who abused opioids also abused gabapentin an estimated 15% to 22%. Drugs can get along well in cases like this. But that isn’t how it works much of the time. 


Using both substances may cause side effects such as:

  • Drowsiness, feeling sleepy
  • Disorientation, dizziness, confusion
  • Inhibition
  • Memory loss, trouble concentrating
  • Weight fluctuations
  • Stuffy nose or fever

You can overdose on either drug. The wrong amount or combining them with other drugs produce trouble breathing and even death. Individuals and doctors don’t always exercise the same carefulness as opioids. Assuming that less oversight makes it harmless is a bad idea.

The sedative and lightheaded properties of gabapentin resemble taking higher doses of trazodone. Both drugs are never advised to mix with over-the-counter drugs. The impairment and sedation in high doses are important. Trazodone and gabapentin’s side effects are lower than other drugs. What they contain is less talked about, but not less crucial.

In higher dosages, both create heavy sedation. Trazodone’s antidepressant abilities aren’t effective when used incorrectly. Evidence-based findings confirm that it is dose-dependent. It makes you sleep and wake up less but doesn’t improve sleep quality. Taking too much can turn into an intoxicated state. This disrupts other body functions. It produces withdrawals or overdoses, like more “dangerous” drugs.

Using trazodone together with gabapentin on your own is not recommended.

Is it Safe to Take Gabapentin and Trazodone in Recovery?


Both drugs have on and off-label usage for people in recovery. This is very relevant for individuals recovering from alcoholism. Post-acute withdrawal symptoms (PAWS) create disruptive and ongoing insomnia. A study tested gabapentin and trazodone (separately) to assess how well they induced sleep.

The sleep quality of both improved greatly over time. But the gabapentin group had stronger improvements faster. A handful of study participants dropped out after the first dose due to morning drowsiness. 

The study had limits though. There was no control group, and no one was blinded to medication. It’s also up in the air if the doses were equal. The comparison did shine a light on possible approved treatments for insomnia rather than off-label. 

Both trazodone and gabapentin cite adverse effects when taken with alcohol. The impairment makes sense. Combining the two on a whim isn’t safe. This differs from clinical studies that take every precaution. Trazodone warns against consuming medications that share similar side effects. Gabapentin falls into this category.

Recovery is not the time to play doctor. There are enough approved treatments for insomnia, depressive disorder, and anxiety. Therapeutic amounts can help, under the close care of medical professionals. High doses are not the way to go. More isn’t always better. The sleepiness from high doses of trazodone is more than a few yawns. It’s a swift downer. It decreases all of your senses. High doses of trazodone have been used to complete suicide.

Both medications are inherently safe if taken as prescribed. They have shown promise to heal that isn’t tapped into yet. Neither have addictive qualities so they can work in a recovery setting. Just not together. Playing it safe in sobriety keeps you alive.

As it stands, neither are sworn enemies that refuse to be in the same place at once. Limiting their interaction with care is the way to get along. If they become too friendly, it might create unpleasant and distressing effects. There are a lot of gaps to fill in first. Gabapentin and trazodone work best as acquaintances for now.

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