Trazodone is an FDA-approved treatment for depression, anxiety, and insomnia. It also has off-label uses for conditions such as bulimia, dementia, and alcoholism. Read on to learn the uses, health effects, and drawbacks of this drug.
Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the clinical and scientific literature. Please discuss your medications with your doctor.
What is Trazodone?
Trazodone is an effective sedative and antidepressant belonging to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). In simpler words, the drug blocks serotonin from binding to its receptors, and it also prevents serotonin from being taken back up into neurons, which allows more serotonin to be available in the brain .
The medication is primarily prescribed to treat depression and insomnia, but it also has numerous off-label uses to treat conditions such as bulimia nervosa, aggressive behaviors, and sexual dysfunctions.
Trazodone works rapidly, and the effects are evident within the first week of treatment .
Data suggests that trazodone has less potential for short-term abuse than other drugs like triazolam and zolpidem .
Trazodone Mechanism Of Action
Trazodone is a dose-dependent multifunctional drug, meaning that it has more than one therapeutic mechanism. At low doses (50-100 mg) it acts as a hypnotic, while at higher doses (150-600 mg) it has antidepressant properties .
At low doses it:
- Blocks serotonin 5HT2 (5-HT2A and 5-HT2C) decreasing the arousing effect of serotonin and leading to an increase in slow-wave sleep/EEG slow-wave activity [1, 7].
- Blocks α-adrenergic receptors decreasing the arousing effect of noradrenaline [8, 9].
- Blocks histamine H1 receptors decreasing the arousing effect of histamine .
At high doses it:
- Blocks the serotonin reuptake transporter (SERT), which increases serotonin that stimulates 5-HT1A receptors exerting its antidepressant effects [11, 12].
- Its active metabolite, methyl-chlorophenylpiperazine (mCPP), also stimulates 5-HT1A receptors leading to wake-promoting effects, which might be variable due to mCPP genetic polymorphisms which occur commonly in the population [9, 13].
Uses of Trazodone
1) Helps Treat Depression
The major depressive disorder is the leading cause of disability affecting approximately 6.7% of the population in the US and over 350 million people worldwide. As an atypical antidepressant, trazodone is frequently used to treat depression [14, 15].
In a double-blind randomized controlled study of 108 patients between 20-28 years old, trazodone was effective in reducing depression symptoms, such as lack of sleep and motivation, and promoting recovery .
Another study (double-blind randomized controlled study) of 127 patients with depression compared trazodone to amitriptyline and placebo. Trazodone outperformed placebo in the treatment of depression and anxiety. Trazodone also produced fewer side effects than amitriptyline [18, 19].
In a study (double-blind randomized controlled study) comparing bupropion and trazodone, 124 patients were randomly assigned to receive either drug. While the overall efficacy of the drugs was similar, the group that received trazodone had a significant improvement on day 7 due to its effects on sleep .
2) Improves Insomnia
Due to its sedative properties, it is the second most commonly prescribed medication for the treatment of insomnia .
Patients with Alzheimer’s disease also suffer from sleep disorders. In a study (double-blind randomized controlled study), Alzheimer’s patients received either trazodone or placebo, and the results showed that trazodone improved their sleep .
In a double-blind study of 6 men between 18-32 years old, trazodone significantly enhanced deep sleep .
3) Improves Anxiety and PTSD Symptoms
Anxiety disorder is characterized by frequent, excessive, and difficult-to-control worry. It is often accompanied by depression and treated in a similar manner .
Due to its hypnotic and sedative effects, trazodone has been used to treat various anxiety disorders .
In a study of 6 patients, trazodone reduced the intensity of PTSD symptoms including agitation, insomnia, severe anxiety, fear, and self-destructive behavior in 4 of the patients .
Trazodone also treats anxiety symptoms in animals and is, therefore, used in various veterinary practices. In a study, trazodone significantly improved anxiety in cats during transportation .
4) Helps Treat Alcoholism
When treating alcohol addiction with oral medication, the treatment primarily focuses on alleviating the withdrawal symptoms .
Trazodone has shown to be effective in decreasing depressive and anxious symptoms as well as cravings for alcohol in patients with alcohol withdrawal symptoms for more than 35 years .
Trazodone was effective in treating 17 alcoholic patients’ withdrawal symptoms by blocking norepinephrine receptors .
A study (double-blind randomized controlled study) of 16 patients with alcoholism suggested that trazodone is an option to treat post-withdrawal symptoms and prevent alcohol relapses .
In a study where researchers and patients knew what medication was administered, trazodone reduced relapse rate and maintained abstinence in 60% of the patients .
5) Can Treat Bulimia Nervosa
In a study (double-blind randomized controlled study) of 42 women with bulimia nervosa, trazodone proved to significantly decrease the frequency of binge eating and vomiting .
In 4 out of 10 patients, episodes of binge eating and vomiting completely diminished, while in 2 of the patients, the episodes were decreased by 55-99%. Trazodone was also the preferred medication due to its low toxicity compared to other drugs .
6) Helps Treat Adjustment Disorders
An adjustment disorder is characterized by stress, sadness, hopelessness, and physical symptoms following an overreaction to a stressful event, probably due to an inability to cope.
Adjustment disorders symptoms are often overlapped with those of major depressive disorder including prolonged feelings of hopelessness, lack of motivation, anxiety, sleep problems, and lack of energy. Due to these overlapped symptoms, antidepressants such as trazodone can effectively treat adjustment disorders [40, 41].
A study (prospective cohort) reported that after 56 days of trazodone therapy, 34 out of 52 patients improved symptoms of anxiety, self-esteem, insomnia, and aggressive behaviors .
A study (double-blind randomized controlled study) of 18 cancer patients diagnosed with adjustment disorder concluded that trazodone was more successful in reducing stress, sleep disorders, and lack of appetite compared to clorazepate (another sedative) .
7) May Improve Aggressive Behaviors
Despite being a normal human behavior when in moderation, excessively emotional or impulsive aggression are often treated with medications such as antidepressants, mood stabilizers, or antipsychotics to prevent self-harm .
Aggressive behaviors are thought to be caused by a deficiency of serotonin. By blocking serotonin reuptake, trazodone increases the amount of serotonin in the brain, reducing aggression .
A study of 3 cases with different levels of aggression proved that trazodone decreases aggressive behavior in children. In each of the cases, aggressive behavior relapsed after treatment discontinuation .
Aggressive and impulsive behaviors significantly improved in 13 out of 22 hospitalized children who were unresponsive to other antidepressants .
Trazodone has long-term effects and is used to control behavioral disturbances in children .
8) Improves Sexual Dysfunction
Selective serotonin reuptake inhibitors (SSRIs) may cause sexual dysfunctions in up to 70% of the users. However, when used with trazodone, patients reported improvements in overall sexual functions .
9) May Treat Symptoms of Dementia
Due to its progressive cognitive and functional decline, dementia is a condition difficult to treat. Hence, dementia symptoms like insomnia and aggression are treated instead .
In a study (randomized controlled trial) of 26 dementia patients, trazodone significantly decreased irritability, agitation, depressive symptoms, and eating disorders in 10 patients .
In another study, 18 out of 22 dementia patients with behavioral complications showed significant improvement with trazodone. This drug may be used as an alternative to neuroleptics or benzodiazepines .
Side Effects of Trazodone
While trazodone is one of the more tolerable antidepressants, some common side effects include drowsiness, dizziness, stomach upsets, vomiting, weakness, decreased alertness, weight loss, tremor, dry mouth, blurred vision, bowel movement disturbances, and delayed urine flow [52, 53].
Less frequently, trazodone can cause the following severe side effects:
1) May Cause Heart Disorders
Several cases showed that trazodone caused heart disorders while treating insomnia patients .
2) May Cause Priapism
Priapism is a condition where a painful erection lasts for more than 4 hours without sexual stimulation .
3) May Cause Auditory Hallucinations
A case reported a female patient experiencing auditory hallucinations after starting taking trazodone. The symptoms decreased dramatically after discontinuing the medication .
4) May Cause Severe Headaches
A patient suffering from a major depressive disorder with no history of severe chronic headache developed the condition after starting trazodone therapy. Headaches didn’t improve when trazodone dosage was decreased but disappeared when the medication was switched to paroxetine .
5) May Cause Withdrawal Symptoms
6) Can Cause Weight Changes
In a study (double-blind randomized controlled study) comparing amitriptyline, trazodone, and placebo, trazodone produced slight weight loss in overweight patients. However, the results were statistically not significant .
Controversially, trazodone was also associated with weight gain (up to 0.5 kg) in a study of 243 patients. In another similar study, however, the drug was associated with slight weight loss, but the results weren’t significant [64, 65].
Contraindications of Trazodone
They include :
- Those taking monoamine oxidase inhibitors (MAOIs) including linezolid and intravenous (IV) methylene blue due to an increased risk of serotonin syndrome.
- Caution should be used in those who have kidney and liver function impairment.
Trazodone Use in Pregnancy and Breastfeeding
Trazodone was shown to be safe in pregnancy and did not increase the normal occurrence of birth defects. Although the exposure of babies to trazodone via breast milk is minimal, you should tell your doctor if you’re breastfeeding before starting the treatment [67, 68].
Drug Interactions of Trazodone
Fluconazole (for fungal infection) can cause prednisone toxicity because both drugs are metabolized by the CYP3A4 enzyme .
Clonidine (for blood pressure) excessively decreased blood pressure in a 12-year-old boy, which caused a syncopal episode associated with hypotension, bradycardia, and sedation .
Warfarin (blood thinners) affected the blood clotting effect of warfarin in 3 clinically relevant cases .
Other drug interactions have also been described .
Alcohol combined with trazodone worsen manual task performance (dexterity) impairment, compared to alcohol alone, which suggests that it isn’t safe for patients receiving antidepressant medication to take alcoholic drinks .
Forms and Dosage of Trazodone
Trazodone is available as immediate- (50, 100, 150, and 300 mg) and extended-release tablets (150 and 300 mg). It is “typically dosed in a range from 200 to 600 mg for the treatment of major depression and from 25 to 150 mg for the “off-label” treatment of insomnia“. It has the potential to lead to sleep onset and maintenance effects and daytime sedation when dosed just before bedtime .
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