Trazodone alternatives: What can I take instead of trazodone?

Compare trazodone alternatives | Mirtazapine | Doxepin | Amitriptyline | Paroxetine | Bupropion | Natural alternatives | How to switch meds

Trazodone hydrochloride (brand names Desyrel and Oleptro) is a commonly used medication to treat major depressive disorder (MDD). It can help improve mood, increase energy level, decrease anxiety, and reduce insomnia associated with depression. Trazodone is a unique antidepressant as it is both a serotonin antagonist and reuptake inhibitor and a 5HT2 receptor antagonist.

As a drug that doesn’t belong to any of the main classes of antidepressants, trazodone may be referred to as a serotonin modulator. It works to increase the amount of serotonin, which is an important neurotransmitter (chemical messenger). Increased serotonin in the central nervous system (CNS) can stabilize mood, happiness, and overall well-being. Additionally, trazodone blocks histamine H1 receptors (similar to an antihistamine), which can be associated with enhanced sleep and potential for daytime drowsiness. These unique properties have led to many off-label uses of trazodone including sleep disorders, anxiety, Alzheimer disease, substance abuse, bulimia, and fibromyalgia. 

Although clinical trial data is limited, trazodone is often used at lower doses as a sedative to help with sleep in people with depression either alone or in combination with other antidepressants. Trazodone is available as a tablet and is typically taken one to three times daily for depression. Clinical studies have shown trazodone to be comparable in treating depression to other antidepressant medications including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). Trazodone avoids the issue of sexual dysfunction, insomnia, and anxiety that can be common with SSRI and SNRI therapy.

While an effective treatment for some people, trazodone may not be the best or safest option for all people managing depression. Common side effects of trazodone include sedation, dizziness, dry mouth, and nausea. Serious side effects of trazodone include priapism (painful, prolonged erection), orthostatic hypotension (sudden drop in blood pressure), heart arrhythmias, serotonin syndrome, and suicidal thoughts. Trazodone has a black box warning (highest FDA safety-related warning for serious or life-threatening adverse effects) for an increased risk of suicidal thoughts and behaviors in children and young adults. 

Due to the way the liver and kidney break down trazodone, special care is necessary for people with severe liver problems and severe kidney impairment. Published literature on trazodone use in pregnant women has not found any associated risks of miscarriage, major congenital disabilities, and adverse maternal or fetal outcomes. Healthcare providers should consider the risk of untreated depression if planning to discontinue or change antidepressant treatment while a person is pregnant. In breastfeeding, caution should be used as small amounts of trazodone have been found in breast milk.

What can I take in place of trazodone?

There are other options available to treat depression that do not improve with trazodone and other options for those who have both depression and sleep problems. These alternative prescription medications include other serotonin modulators, atypical antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). These options may be more suitable for certain individuals due to their different uses, side effect profiles, and dosages. If pricing is a factor in finding an alternative to trazodone, a SingleCare prescription discount card may help reduce prescription costs of up to 80% at participating pharmacies. Switching from one antidepressant to another can be common in order to find the best fit for the person. A study of a claims database analysis involving 134,287 patients treated with antidepressants determined 23.2% had a treatment change including 9.5% with a switch in antidepressants and 9.1% with an addition of combination therapy. 

RELATED: What you should know before switching antidepressants

Other alternatives to trazodone:

• Desipramine
• Desvenlafaxine
• Deuloxetine
• Fluoxetine
• Fluvoxamine
• Imipramine
• Levomilnacipran
• Nortriptyline
• Phenelzine
• Tranylcypromine

RELATED: Depression Treatments and Medications

Top 5 trazodone alternatives

The following are some of the most common alternatives to trazodone.

1. Mirtazapine

Mirtazapine is an atypical antidepressant and has a unique way of working. Mirtazapine is an alpha-2 adrenergic antagonist and serotonin 5-HT2 receptor antagonist. Like trazodone, mirtazapine is used to treat major depressive disorder and can cause sedation. Due to mirtazapine’s sleep-promoting effects, it may be an alternative to trazodone for people managing both depression and sleep problems. A literature search that analyzed studies involving mirtazapine in depressed patients that specifically assessed sleep found mirtazapine produced significant improvement in sleep efficiency, total sleep time, and sleep quality. Along with sedation, common side effects of mirtazapine include increased appetite, weight gain, and dizziness. Mirtazapine has a starting dose of 15 to 45 mg tablet by mouth at bedtime.

2. Doxepin

Doxepin belongs to a group of antidepressants called tricyclic antidepressants (TCAs). Doxepin can be used for depression, anxiety, and insomnia. Due to sedating effects, TCAs like doxepin can be used in people with depression who have insomnia. However, TCAs have more side effects to be aware of including dry mouth, orthostatic hypotension, constipation, sexual dysfunction, nausea, dizziness, blurred vision, increased appetite, and weight gain. For depression or anxiety, doxepin is dosed as a 150 to 300 mg capsule by mouth at bedtime.

3. Amitriptyline

Amitriptyline belongs to a group of antidepressants called tricyclic antidepressants (TCAs). Amitriptyline can be used to treat depression, and similar to the TCA doxepin, it can be used in people with depression who have insomnia due to sedating effects. Amitriptyline, like most TCAs, produces additional side effects such as dry mouth, orthostatic hypotension, constipation, blurred vision, and nausea to name a few.. Amitriptyline is dosed as a 50 to 150 mg tablet by mouth at bedtime.

4. Paroxetine

Paroxetine belongs to a common group of antidepressants called selective serotonin reuptake inhibitors (SSRIs). Along with treating major depressive disorder, paroxetine can be used for panic disorder, social anxiety disorder, and premenstrual dysphoric disorder. SSRIs tend to have similar side effects, however nausea and sedation may be more likely to occur with paroxetine. Like trazodone, paroxetine may help with sleep along with treating depression. Other side effects of paroxetine include sexual dysfunction, weight gain, dizziness, and headache. For depression, paroxetine is dosed as either a 20 to 50 mg tablet by mouth once daily or a 25 to 62.5 mg extended-release tablet by mouth once daily.

5. Bupropion

Bupropion is an atypical antidepressant and has a unique way of working. Bupropion is an aminoketone antidepressant. A literature review found that bupropion has a unique sleep profile, which may be well-suited for people suffering from depression. The review found that bupropion was not associated with daytime sleepiness and that sleep disturbance occurred at a low rate compared to other modern reuptake inhibitors. Unlike other antidepressants, the review found the sleep profile for bupropion does not suppress REM sleep. Common side effects of bupropion include agitation, dry mouth, constipation, headache/migraine, nausea/vomiting, and dizziness. Bupropion does have an increased seizure risk and should be discontinued if seizures occur. Bupropion is dosed as a 100 mg tablet by mouth three times daily.

Natural alternatives to trazodone

Alternative remedies for trazodone include certain supplements, lifestyle changes, and diet modifications to help improve mood and overall well-being. Some of these remedies include regular exercise, meditation, cognitive behavioral therapy, and the Mediterranean diet.

Both high-intensity exercise and consistent low-intensity exercise can have a positive impact on brain function improving how people feel. High-intensity exercise releases the body’s feel-good chemicals called endorphins, while low-intensity exercise promotes the release of proteins (neurotrophic or growth factors) which cause nerve cells to grow and make new connections.

RELATED: 6 health conditions that exercise prevents

Meditation can influence self-awareness and may ease depression by momentarily stopping the constant worries and fears that can fuel it. For more sudden symptoms such as anxiety, the 3-3-3- rule may be beneficial. This tactic involves looking around and naming three things one sees, naming three sounds one hears, and moving three body parts such as an ankle, finger, or arm. Cognitive behavioral therapy can be used in mental health conditions like depression, anxiety, substance use, and phobias. This form of therapy can help identify the thinking patterns that cause distress to manage overwhelming emotions and unhelpful behaviors.

The Mediterranean diet involves eating plenty of fruits, vegetables, bread and other grains, potatoes, beans, nuts, and seeds. This diet includes olive oil as a primary fat source and low to moderate amounts of dairy products, eggs, fish, and poultry. A study published in 2020 found that eating a Mediterranean diet along with fish oil supplementation in people self-reporting depressive symptoms showed improved mental health after 6 months. In addition, reduced depression was significantly linked with adherence to the Mediterranean diet, more consumption of nuts, and more consumption of vegetables.

Since trazodone is often used to help with sleep problems in people treating depression, over-the-counter sleep aids are available as alternatives. Melatonin is a natural hormone in the body that promotes sleep that is available as a supplement in dosage forms such as tablets, gummies, and liquid.

RELATED: A melatonin dosage guide: How much do I need to sleep?

How to switch to a trazodone alternative

1. Discuss all health conditions with a healthcare provider

Before switching from trazodone to an alternative, it’s important that the prescribing doctor is aware of all medical conditions. Some alternatives should be used with caution or avoided with certain medical conditions. For example, TCAs like amitriptyline and doxepin can potentially cause damage to the heart and should be avoided in people with heart disease. Additionally, the alternative bupropion should not be used in people with seizure disorders. 

2. Do not suddenly stop taking trazodone without medical advice

Only stop taking trazodone if the prescribing doctor has been consulted and decided stopping the medication is safe. If trazodone is stopped suddenly, there may be sudden withdrawal symptoms or worsening depression symptoms. It’s important for a therapy plan to be established prior to stopping trazodone suddenly. The trazodone dose should be gradually reduced rather than stopping abruptly whenever possible.

3. Discuss all prescription and over-the-counter medications with a healthcare provider

Before switching from trazodone to an alternative, it’s important that the prescribing doctor has reviewed a patient’s medication list including prescription drugs and over-the-counter meds. Some alternatives have dangerous drug interactions that must be avoided.

4. Continue to monitor depression symptoms

It’s important for people treating depression to keep track of their symptoms and behavior over time. Self-monitoring can be done with methods such as recording feelings through journaling or smartphone applications. This information can be shared with the prescribing doctor to help support and reinforce positive change in mental health and to counteract negative developments.