Does Trazodone lose effectiveness over time? (+3 factors)

In this article, we will discuss whether Trazodone loses its effectiveness over time. We will also discuss the factors which can decrease the effectiveness of Trazodone along with the measures to use Trazodone effectively.

Does Trazodone lose effectiveness over time?

Yes, Trazodone loses its effectiveness over time. It is commonly observed by doctors that their patients stop responding to an antidepressant after some time. Individuals may develop tolerance to the drug, leading to a decreased effectiveness of the drug (1).

Antidepressants work differently for each individual. Some may respond to the medication while some may not. Some people may stop responding to Trazodone much earlier than others. According to researchers, there could be some external factors that may make your Trazodone ineffective or less effective than it once was.

You can say a drug is no longer effective when the symptoms it was treating relapse. If you notice worsening of your depression, anxiety or pain, seek medical attention.

What happens if Trazodone loses effectiveness over time?

Trazodone is an antidepressant which works by increasing the levels of serotonin in the brain by inhibiting its reuptake by the brain cells. An increase in this neurotransmitter helps improve mood, memory attention and other cognitive functions (2).

Trazodone also acts on the neurons of the dorsal horn in the spine, which reduces the pain signals from reaching the brain, treating fibromyalgia and chronic pain (3).

When Trazodone’s effectiveness decreases, it results in the recurrence of fibromyalgia pain and worsens cognitive functioning. If you experience a recurrence of symptoms while taking Trazodone, reach out to your healthcare provider for further management.

Why does Trazodone lose its effectiveness over time?

There are many reasons why trazodone loses its effectiveness and does not work the way it did when you first started taking it. These include:


Some people may build tolerance with time and Trazodone may not work well in such cases. This usually happens when your body gets used to the medication and stops considering it a foreign chemical.

This leads to reduced sensitivity of the receptors and they don’t initiate the expected response when you take the medication.

Low dosage strength

This is common in new users of Trazodone who stick to the initial dose. Most doctors start the treatment with antidepressants with the lowest effective dose. this helps your body adjust to the medication first, before starting to take sufficient doses.

People stick to the initial doses and they soon stop responding to them. This problem is usually resolved by increasing the dose and most people work well with the newly increased dose for a long time.


Not taking Trazodone as prescribed by your physician may reduce its effectiveness by lowering the levels of the drug in the body. A sudden decrease in the level of the drug can cause discontinuation symptoms and worsen your condition.

Drug interactions

The addition of another prescription medication can make Trazodone ineffective. Drug interactions are quite common. Trazodone may interact with other drugs such as antibiotics and steroids etc reducing its effectiveness and increasing the risk of side effects.

Excess levels of stress

Stress can lead to fluctuations in neurotransmitters, which can affect mood and cognitive function. It is important to maintain a stress-free and healthy lifestyle along with drug therapy to treat your illness more effectively.

Underlying health condition

An underlying health condition may make Trazodone ineffective. Any pre-existing medical conditions that affect the kidneys and liver can influence how the body metabolizes and eliminates the drug, which can lead to decreased response.

Treating any undiagnosed or misdiagnosed mental illness with Trazodone can reduce its effectiveness in treating symptoms.

How to use Trazodone safely and effectively?

Trazodone can be used safely and effectively by following a few simple tips:

  • Take Trazodone as prescribed by your doctor.
  • Take your medication at the same time each day to maintain the same concentration of the drug in the blood.
  • Do not miss a dose or discontinue abruptly as it can cause withdrawal symptoms (4). If you missed a dose take it as soon as you remember, but if the next dose is near follow the regular dosing schedule.
  • Store Trazodone in a proper condition. Store in a cool, dry place away from sunlight and moisture as these factors can chemically degrade Trazodone and render it ineffective.
  • Do not crush or chew the tablets or open the capsules before consuming.
  • Do not alter the course of your treatment without a physician’s guidance.
  • Look out for any unwanted side effects, suicidal thoughts and recurrence of symptoms.

What alternatives to consider when Trazodone loses effectiveness?

If Trazodone becomes ineffective in treating your symptoms, consider alternative antidepressants such as:

Selective serotonin reuptake inhibitors (SSRIs)

  • Fluoxetine
  • Sertraline
  • Citalopram
  • Paroxetine

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

  • Venlafaxine
  • Desvenlafaxine
  • Milnacipran

Tricyclic antidepressants (TCAs)

  • Amitriptyline
  • Desipramine
  • Nortriptyline

If you are taking Trazodone to treat fibromyalgia, you can shift to other antidepressants or pregabalin, an anticonvulsant which has shown effectiveness in treating fibromyalgia (5). You can also consider non-pharmacological therapies such as cognitive behavioural therapy and psychotherapy along with medication to help you treat your illness more effectively. 

In my opinion, as a pharmacist, with long-term treatment one can develop tolerance to Trazodone, leading to a reduction in its effectiveness. This can be managed by increasing the dose of Trazodone or changing the drug to another antidepressant.

If your symptoms reappear and you notice any unwanted changes in your behaviour, consult your physician for proper management.

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