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Trazodone vs. Zoloft—Which Drug To Choose for Sleep?

Trazodone vs. Zoloft—Which Drug To Choose for Sleep?

When the night comes, we all hope to catch some sleep and get reenergized for the next day. For approximately 50–70 million adults in the U.S., this isn’t as easy as it sounds.

If you’re in the same situation, you might have tried different methods, from meditation to taking breaks from the screen, with limited success. The best approach is to see a sleep medicine specialist who can recommend effective medications like trazodone and Zoloft.

This trazodone vs. Zoloft comparison will give you a clearer picture of how these drugs work and where to get them.

Zoloft vs. Trazodone—A Concise Overview

Trazodone and Zoloft (sertraline) are both antidepressants—a class of drugs used to alleviate the symptoms of depression and other mood disorders. While they have similar mechanisms of action, these medications have different applications.

Trazodone is sold under various brand names and is primarily prescribed to patients with:

  1. Major depressive disorders
  2. Anxiety disorders
  3. A combination of depressive and anxiety disorders

It’s also used off-label in the short-term treatment of insomnia.

Trazodone works by inhibiting serotonin reuptake by the nerves in the brain, increasing this neurotransmitter’s levels in the nerve synapse. While it’s not a selective serotonin reuptake inhibitor (SSRIs), the drug shares striking similarities with this group of medicines.

Zoloft is a selective serotonin reuptake inhibitor (SSRI) typically prescribed to patients with:

  • Depression
  • Panic disorder
  • Social anxiety disorder
  • Obsessive-compulsive disorder (OCD)
  • Post-traumatic stress disorder (PTSD)
  • Premenstrual dysphoric disorder (PMDD)

The drug blocks the reabsorption of serotonin in the brain, keeping the neurotransmitter in the synaptic gap for an extended period. 

In both cases, the increased serotonin levels in the nerve synapse produce a calming effect while promoting melatonin production and inducing sleep. According to the DEA, trazodone and Zoloft aren’t controlled substances, but you can only get these drugs with your doctor’s prescription.

Check out a side-by-side comparison of these drugs in the table below:




Active component

Trazodone hydrochloride

Sertraline hydrochloride

FDA approval date



Drug form

  • Tablet

  • Capsule 

  • Liquid

  • Tablet

  • Liquid

Available doses

  1. 10 mg

  2. 20 mg

  3. 50 mg

  4. 100 mg

  5. 150 mg

  6. 300 mg

  • 20 mg–oral solution

  • 25 mg

  • 50 mg

  • 100 mg

Suitable for children



Suitable for pregnant women

Consult your healthcare provider

Consult your doctor

Prescription or OTC



Treatment duration

One month maximum

4–6 weeks

Source: Polina Kovaleva

Trazodone vs. Zoloft for Sleep—Dosage Guidelines

Trazodone comes in tablet, capsule, or liquid forms and is available in six doses:

  1. 10 mg
  2. 20 mg
  3. 50 mg
  4. 100 mg
  5. 150 mg
  6. 300 mg

The average starting dose for adults with sleeplessness is 25 mg in tablet form, which may increase depending on your medical history and sleep problems. 

Zoloft comes in four doses:

  1. 20 mg—oral solution
  2. 25 mg
  3. 50 mg
  4. 100 mg

The typical dose for sleeplessness is 50 mg, taken in the evening. Healthcare providers usually prescribe lower doses for patients over 65 or individuals with specific health conditions.

These are average values—your doctor will assess your health status before deciding on the appropriate dose and time to take these medications.

Zoloft and Trazodone—Duration of Effects

Trazodone’s sedative effects typically kick in within 30 minutes. This drug reaches peak concentration within 1–2 hours, and the effects last for about 5–7 hours. 

Zoloft is slow-acting, with peak concentration occurring at 4.5–8 hours

When taking these drugs, you should allocate at least seven hours to sleep. You should also avoid activities that require sharp focus, like driving or operating heavy machinery, for at least one hour after waking up. If you experience persistent fatigue or drowsiness the next day, inform your healthcare provider.

Trazodone Versus Zoloft—Which One Offers Better Sleep?

Both trazodone and Zoloft can be effective for sleep, but none of these is a one-size-fits-all solution. The most effective drug for sleep depends on numerous factors, including your lifestyle, medical history, and the type of insomnia you have. 

Before choosing between these drugs, you should consult a sleep expert who can design a comprehensive treatment plan. The biggest problem is that getting an appointment with a sleep specialist can be challenging due to their limited availability in the U.S.

Thanks to telemedicine platforms like Kick, you can skip the waiting lines and see a sleep doctor almost instantly. Designed by a Stanford sleep expert, Dr. Alex Dimitriu, Kick’s sleep program is highly successful in helping patients overcome sleep problems. Glowing reviews on Trustpilot are a testament to this program’s efficacy.

Transform You Nights With Kick’s Sleep Program

Source: Andrea Piacquadio

Kick’s sleep program combines gentle sleep medications like trazodone with science-backed methods of cognitive behavioral therapy for insomnia (CBT-i), helping you get a comprehensive solution for your sleep issues.

When you join the program, our team will review your medical history and design a safe and effective treatment tailored to your needs. Your doctor will prescribe two trial medications and monitor your condition regularly. If your sleep issues persist after starting treatment, our specialist will adjust your dosage or prescribe a different drug.

Our expert will also offer ongoing guidance and support, including tips on cultivating healthy sleep practices. Kick’s sleep program offers unmatched convenience—you’ll consult your doctor online and have your medications delivered to your doorstep or local pharmacy in a few days.

How To Join Kick

Joining Kick’s sleep program is straightforward:

  1. Go to our signup page to start your 15-minute sleep visit
  2. Complete the intake form to help us understand your medical history and sleep issues
  3. Enter your delivery address and payment information

Our team will review your details and provide feedback within 24 hours, helping you start treatment immediately.

If our doctors decide Kick isn’t the best solution for your sleep issues, you’ll be referred to your primary healthcare provider. In that case, you won’t pay for the initial visit, according to our Doctor Guarantee. Join Kick now to experience the benefits of this risk-free sleep program.

Trazodone vs. Zoloft—Common Side Effects

Source: Marcus Aurelius

Trazodone and Zoloft carry the risk of similar side effects, including:

  • Dry mouth
  • Dizziness
  • Drowsiness
  • Nausea
  • Loss of appetite
  • Sweating
  • Trouble sleeping

Rare but concerning unwanted reactions may include:

  • Fainting
  • Confusion
  • Tremors
  • Irregular heartbeat
  • Swollen face, lips, or tongue

Most patients rarely experience adverse reactions if they follow the instructions on safe use. You should consult your doctor for comprehensive information on these undesirable reactions.

Zoloft vs. Trazodone for Sleep—Who Should and Shouldn’t Use These Drugs?

Trazodone and Zoloft can be taken by adults (18+) grappling with sleep problems, but only under the supervision of a healthcare provider.

Check out the table below for details on who should approach these drugs with caution:

Who Shouldn’t Use Trazodone?

Who Shouldn’t Use Zoloft?

  • Patients allergic to trazodone or its ingredients

  • Individuals who recently had a heart attack or suffer from heart disease

  • People with sleep apnea

  • Patients with a history of substance abuse

  • Users with a history of suicidal thoughts or attempted suicide

  • Persons suffering from schizophrenia or chronic mental health issues

  • People allergic to Zoloft or its components

  • Patients with heart disease

  • Individuals with glaucoma

  • People with a history of seizures

  • Individuals with liver or kidney diseases

You should inform your doctor if you have any preexisting medical conditions or if you’ve recently had a medical procedure that may affect these drugs’ efficacy.

Trazodone vs. Zoloft—Potential Interactions To Consider

Trazodone and Zoloft can interact with other substances, altering their effectiveness or raising the risk of unwanted reactions.

Trazodone and Zoloft—Interaction With Food and Drinks

You can find a roundup of the interactions between trazodone and Zoloft with foods and drinks in the table below:


Interaction With Trazodone

Interaction With Zoloft

Grapefruit and grapefruit juice

Can increase this drug’s concentration in the blood, raising the risk of side effects

Can interfere with the metabolization of Zoloft, potentially enhancing the risk of side effects


Can contribute to side effects like dizziness, drowsiness, and difficulty concentrating

Can enhance drowsiness and dizziness

Zoloft and Trazodone—Interaction With Other Drugs and Substances

Check out the table below for a detailed breakdown of the interaction between trazodone and Zoloft with other drugs and substances:


Interaction With Trazodone

Interaction With Zoloft

Opioids and CNS depressants

Can enhance the sedative effects, contributing to the risk of drowsiness and accidental falls

Can contribute to the risk of serotonin syndrome, characterized by seizures, confusion, hallucinations, and extreme changes in blood pressure

Heart medications

Can raise the risk of irregular heart rhythm

Can contribute to changes in heart rhythm 

Blood pressure medication

Can enhance the risk of low blood pressure

Can contribute to a drop in blood pressure

Anti-seizure medication

Some anti-seizure drugs (e.g., carbamazepine) can reduce trazodone’s intended pharmacological effects

Can enhance the risk of hyponatremia and reduce the potency of anti-seizure medication

Anti-HIV drugs

Some anti-HIV drugs (e.g., lopinavir) can interfere with the metabolization of trazodone, enhancing the risk of side effects

The potential for interactions is low, but risks can’t be ruled out

Infection medications

Can enhance the risk of unwanted reactions

Can enhance the potency of some antibiotics

Sleep or anxiety medications

Can enhance the sedative effects

Can contribute to increased sedation

Muscle relaxants

Can contribute to the risk of drowsiness and accidental falls

Can enhance drowsiness


Can enhance the sedative effects, raising the risk of drowsiness

Can contribute to the risk of sedation

Herbal supplements

Supplements like St. John’s wort and melatonin can enhance drowsiness

Can contribute to drowsiness

Source: cottonbro studio

Trazodone vs. Zoloft—Alternatives To Consider

While trazodone and Zoloft can offer relief from sleeplessness, they’re not a cure-all. If the risks of using these drugs outweigh the potential benefits, your doctor may recommend alternatives.

Check out the table below for more details:


When Your Doctor May Recommend It

Treatment Duration

Side Effects


You have irregular sleep-wake cycles


  • Headache

  • Dizziness

  • Nausea


You have primary insomnia


  • Drowsiness

  • Dizziness

  • Hallucinations


You have sleep-onset or sleep-maintenance insomnia


  • Sleepiness

  • Diarrhea

  • Impaired motor functions


You have sleeplessness caused by muscle spasms and tension


  • Drowsiness

  • Dry mouth

  • Fatigue


You have insomnia caused by the symptoms of allergic reactions


  • Drowsiness

  • Dry mouth

  • Headache


You have sleepless nights due to severe pain


  • Headaches

  • Feeling sleepy the next day

  • Nausea or vomiting


You have occasional sleeplessness exacerbated by the symptoms of allergic reactions


  • Dry mouth

  • Dizziness

  • Drowsiness


You have insomnia due to anxiety disorders or major depressive disorders 

Consult your doctor for specific guidelines

  • Dizziness

  • Dry mouth 

  • Weight gain


You have sleepless nights caused by restless leg syndrome (RLS)

Suitable for long-term treatment but typically used in the short-term for insomnia

  • Dry mouth

  • Dizziness

  • Drowsiness


You have occasional insomnia accompanied by mood conditions

Suitable for both short- and long-term treatment, so you should consult your healthcare provider first

  • Drowsiness

  • Dry mouth

  • Constipation


You have sleeplessness due to anxiety or depression


  • Increased appetite

  • Increased thirst

  • Headache


You have occasional sleeplessness 


  • Blurred vision

  • Constipation

  • Dry mouth


You have severe insomnia caused by anxiety


  • Drowsiness

  • Fatigue

  • Constipation


You have sleep issues due to anxiety


  • Blurred vision

  • Constipation

  • Dizziness


You have sleep problems caused by migraines or anxiety


  • Fatigue

  • Dizziness

  • Reduced exercise tolerance

This information isn’t exhaustive. Your healthcare provider will assess your medical history before prescribing the safest and most effective sleep aid for your case. 

Featured image source: KATRIN BOLOVTSOVA