How long does it take for trazodone to work?

You can thank serotonin if you’ve ever felt pure joy around a puppy or lingering contentment on a quiet night. As the brain’s “feel good” chemical, this neurotransmitter regulates moods, promotes calmness and happiness, and improves deep sleep. People who have depression often have low serotonin levels, but they can correct that imbalance with trazodone, a prescription antidepressant medication that also treats anxiety and sleep disorders. 

For depression, this serotonin modulator may take a few weeks to work, but people struggling with sleep might feel its soothing effects much quicker. Here’s all the information on trazodone’s timeline, effects, and safety. 

Note: Sometimes, veterinarians prescribe trazodone for dogs, and while it’s safe for our canine companions, the information in this article applies solely to humans. 

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How long does it take trazodone to work?

Anyone feeling the weight of depression, the tension of anxiety, or the frustration of insomnia will want their medication to start working as soon as possible. But “the timeframe within which trazodone begins to work varies based on the ailment it’s addressing,” according to Dr. Ryan Sultán, MD, a psychiatrist at Integrated Psych and professor of clinical psychiatry at Columbia University. 

Depression

When taken for depression, trazodone usually takes at least a week to kick in. Results from a 2021 review of clinical trials showed that people with major depressive disorder (MDD) reported significant improvement in as little as one week. However, “typically, it might take a few weeks of treatment, often between two and four, for individuals to start noticing a shift in their mood and energy levels, with the full spectrum of its antidepressant benefits unfolding over a period of up to six to eight weeks,” Dr. Sultán says. 

Doctors typically prescribe trazodone for depression in 50mg–300mg doses, and the specific dosage may also affect how fast it works. 

Anxiety

Unlike depression, anxiety is an off-label use for trazodone. However, its influence on serotonin and calming effects can still help treat people with generalized anxiety disorder. Much like its effect on depression, trazodone can take multiple weeks to work for anxiety. The same 2021 review found that patient improvements weren’t significant after seven days but after 21. 

Insomnia

Trazodone for insomnia is another off-label use, but a fairly common one. That’s because trazodone exhibits sedative effects that make it effective for people with sleep problems. A systematic review from 2017 analyzed various studies where patients taking trazodone for insomnia reported significant improvements. It often takes around 30 minutes to feel the drowsiness associated with trazodone, although it can take up to two hours to reach peak levels in the bloodstream.

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How do I know if trazodone is working?

It’s easy to know whether trazodone works for insomnia—you just feel sleepy. But it’s slightly tougher to assess its efficacy for depression and anxiety. And as we mentioned, it may take a few weeks to experience its full benefits. 

The patient may feel slightly more relaxed in the first couple of weeks. Things that used to cause worry or fear might seem less intimidating, and the patient might feel an improved overall mood. 

However, weeks three and four are where it typically takes off. “If you have depression, you may notice an overall better feeling of wellness. You may start to enjoy the activities you liked doing in the past. You may notice your appetite and sleep patterns becoming more normal.” Dr. Luke Prest, MD, is a physician and author at ChoosingTherapy. “For anxiety, you may feel less anxious in the settings that typically cause problems for you. You may feel a desire to engage more with others.” Completing tasks and interacting with others throughout the day might also feel much easier. If not, the doctor may adjust your dose

Factors that influence how long trazodone takes to work

Every situation is unique, so trazodone works differently, depending on the person. “Your body chemistry plays a big role—some people just naturally respond quicker than others,” says Max Ruvinov, PharmD, MBA, pharmacist, and author at ChoosingTherapy. Sleep levels and stress can affect it, too, he says. But there are also drugs and other substances that can affect its efficiency. They include:

• Alcohol: Both alcohol and trazodone have sedative qualities, which can cause extreme drowsiness, impaired coordination, and slowed reflexes, increasing the risk of accidents. Plus, one study showed more improvements in functioning and well-being in people who drank less alcohol. 
• Cannabis: Marijuana use can worsen trazodone side effects like dizziness, drowsiness, confusion, and difficulty concentrating. 
• Enzyme inhibitors: Trazodone is broken down in the body by an enzyme, so drugs that inhibit that process—specifically azole antifungals like Nizoral (ketoconazole) or Sporanox (itraconazole)—may increase its levels in your body, While this may make trazodone work faster, it can also increase your risk of side effects. 
• Grapefruit: This sour citrus fruit binds to an intestinal enzyme called CYP3A4. Blocking this enzyme can boost the levels of trazodone in your body, increasing your risk of side effects. 

How long should a person be on trazodone?

“Trazodone’s flexibility means it can be prescribed for both short bursts and extended periods, depending on the severity and persistence of the symptoms,” Dr. Sultán says. “Short-term usage might span a few weeks to months for immediate issues, while long-term treatment could extend for years, especially for chronic depression—always under the watchful eye of a healthcare professional to mitigate any side effects and adjust trazodone dosages as necessary.”

Dr. Ruvinov agrees. “Trazodone can be taken for quite a while, often several months or even longer, especially if it’s helping,” he says. “But like any medication, using it for a long time comes with some risks. Some people might experience lingering drowsiness, a bit of confusion, or even balance issues.”

Studies like this one from 2023 have suggested that patients with chronic depression can take trazodone long-term with few significant adverse effects. There isn’t much research on long-term trazodone use for sleep, so its effects are still unclear. 

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Who shouldn’t take trazodone?

Trazodone might be a versatile medicine, but as a mood-altering drug with an array of potential side effects, it’s not for everyone. Before beginning treatment, knowing its risks, warnings, and interactions is important. 

Side effects

Not everyone who takes trazodone experiences an adverse reaction, but some do. About one in five people have reported dizziness or high blood pressure. Some other common trazodone side effects include:

• Dry mouth
• Nervousness
• Tiredness
• Nausea or vomiting
• Headache
• Constipation
• Low blood pressure
• Aches and pains
• Problems with coordination
• Abdominal pain
• Blurred vision
• Confusion
• Problems with concentration
• Tremors
• Red, itchy eyes
• Nasal or sinus congestion
• Edema
• Skin reactions
• Disorientation
• Feeling bad
• Fainting
• Muscle pain
• Trouble sleeping
• Sexual dysfunction
• Weight changes

The U.S. Food and Drug Administration (FDA) has issued a black box warning that trazodone may also cause suicidal thoughts, primarily in young adults and children. Some other rare but serious side effects include chest pain, an irregular heartbeat, seizures, fainting, difficulty breathing, unusual bleeding, angle-closure glaucoma, problems with coordination, and worsening depression. Seek medical attention ASAP if you experience any of these while taking trazodone. 

Drug interactions

“Trazodone can interact with other medications and should be used cautiously in these individuals,” Dr. Prest says. The medications that may cause interactions include:

• Drugs that increase serotonin: If levels of serotonin get too high, it can cause a serious medical condition called serotonin syndrome. So avoid monoamine oxidase inhibitors (MAO inhibitors, or MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and other drugs that affect serotonin.
• Blood Thinners: Trazodone may increase the risk of gastrointestinal bleeding, so anyone taking prescription drugs to prevent blood clots—like Coumadin (warfarin) and Eliquis (apixaban)—may need closer monitoring or extra blood tests. 
• Medications that affect heart rhythm: One risk of trazodone is that it can cause an abnormal heartbeat, and a prescription medication like amiodarone (Pacerone) and sotalol (Betapace) could increase that risk. 
• Drugs with sedative properties: Other anxiety medicines, barbiturates, certain antihistamines, muscle relaxants, opioids, and other sleep aids can all depress the central nervous system, compounding trazodone’s sedative effect. 
• Narrow therapeutic index medications: These drugs have a small window between safe and toxic doses like digoxin and phenytoin. Trazodone may increase the amount of these medications in the body, pushing them past that threshold. 
• Certain dietary supplements: OTC natural products like St. John’s Wort and tryptophan can both increase the risk of serotonin syndrome when taken alongside trazodone, according to the Mayo Clinic. 

Other precautions

Since trazodone can affect the heart, people with pre-existing heart disease or a recent heart attack should speak with their doctor before taking it. MedlinePlus says people with a history of psychiatric illnesses, suicidal ideation, cerebrovascular disease, or health conditions like seizures, kidney disease, or liver disease should also get medical advice from their healthcare provider if they’re considering trazodone. 

Certain studies have suggested that trazodone might not increase the risk of miscarriage or birth defects, but there’s not enough evidence yet to say it’s safe for pregnant or breastfeeding mothers. If possible, people who are pregnant or planning on getting pregnant should avoid it. 

Per Dr. Sultán, “Those with a history of substance abuse might face challenges with trazodone, especially given its sedative properties, which could be potentially misused.” Plus, “individuals with bipolar disorder may find trazodone less suitable due to the risk of triggering manic episodes, necessitating careful monitoring.”

A quick look back at the possible side effects above should discourage anyone from driving or operating heavy machinery while taking it until they can see how it affects them. It can induce drowsiness, lightheadedness, confusion, and impaired coordination, putting drivers at a higher risk of causing an accident.