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Trazodone is an FDA-approved treatment for depression as well as 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.
NOTE: Selfhacked does not support taking or not taking this or any drug. We think drugs should only be tried as a last resort if needed and/or your doctor recommends it. Do not take this post as promoting the use of this medication. It’s for informational purposes alone. It’s a popular drug and people should know what it’s used for, the scientific evidence behind it, and its drawbacks.
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 reabsorbed, which will allow more available serotonin in the brain [R].
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 also works rapidly, and the effects are evident within the first week of treatment [R].
Not only is trazodone effective but also it is relatively safe when compared to other available drugs. It also shows more advantages over other antidepressants regarding therapeutic efficacy due to its multifunctional properties [R, R].
It seems safe while maintaining its effectiveness in long-term use. Data suggests that trazodone has less potential for abuse than other drugs like triazolam and zolpidem [R].
Trazodone Mechanisms 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 [R].
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 [R, R].
- Blocks α-adrenergic receptors decreasing the arousing effect of noradrenaline [R, R].
- Blocks histamine H1 receptors decreasing the arousing effect of histamine [R].
At high doses it:
- Blocks the serotonin transporter (SERT), which increases serotonin that stimulates 5-HT1A receptors exerting its antidepressant effects [R, R].
- 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 [R, R].
Uses of Trazodone
1) Trazodone 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 [R, R].
In a double-blind 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 [R].
Another 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 [R, R].
In a 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 [R].
2) Trazodone Improves Insomnia
Due to its sedative properties, it is the second most commonly prescribed medication for the treatment of insomnia [R].
Patients with Alzheimer’s disease also suffer from sleep disorders. In a study (DB-RCT), Alzheimer’s patients received either trazodone or placebo, and the results showed that trazodone improved their sleep [R].
In a double-blind study of 6 men between 18-32 years old, trazodone significantly enhanced deep sleep [R].
Imipramine, hydroxyzine, and thioridazine were unsuccessful in treating a 7-year-old girl with a severe sleeping disorder. Trazodone was the only treatment that provided significant relief of her symptoms [R].
3) Trazodone 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 [R].
Due to its hypnotic and sedative effects, trazodone has been used to treat various anxiety disorders [R].
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 [R].
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 [R].
4) Trazodone Helps Treat Alcoholism
When treating alcohol addiction with oral medication, the treatment primarily focuses on alleviating the withdrawal symptoms [R].
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 [R].
Trazodone was effective in treating 17 alcoholic patients’ withdrawal symptoms by blocking norepinephrine receptors [R].
A study (DB-RCT) of 16 patients with alcoholism suggested that trazodone is an option to treat post-withdrawal symptoms and prevent alcohol relapses [R].
In a study where researchers and patients knew what medication was administered, trazodone reduced relapse rate and maintained abstinence in 60% of the patients [R].
5) Trazodone Can Treat Bulimia Nervosa
In a study (DB-RCT) of 42 women with bulimia nervosa, trazodone proved to significantly decrease the frequency of binge eating and vomiting [R].
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 [R].
6) Trazodone 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 [R, R].
A study reported that after 56 days of trazodone therapy, 34 out of 52 patients improved symptoms of anxiety, self-esteem, insomnia, and aggressive behaviors [R].
A 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) [R].
7) Trazodone 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 [R].
Aggressive behaviors are thought to be caused by a deficiency of serotonin. By blocking serotonin reuptake, trazodone increases the amount of serotonin reducing aggression [R].
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 [R].
Aggressive and impulsive behaviors significantly improved in 13 out of 22 hospitalized children who were unresponsive to other antidepressants [R].
Trazodone has long-term effects and is used to control behavioral disturbances in children [R].
8) Trazodone Improves Sexual Dysfunction
Selective serotonin reuptake inhibitors may cause sexual dysfunctions in up to 70% of the users. However, when used with trazodone, patients reported improvements in overall sexual functions [R].
9) Trazodone 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 [R].
In a study (RCT) of 26 dementia patients, trazodone significantly decreased irritability, agitation, depressive symptoms, and eating disorders in 10 patients [R].
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 [R].
Trazodone 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 [R].
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 [R, R].
Less frequently, trazodone can cause the following severe side effects:
1) Trazodone May Cause Heart Disorders
Several cases showed that trazodone caused heart disorders while treating insomnia patients [R].
2) Trazodone May Cause Priapism
Priapism is a condition where a painful erection lasts for more than 4 hours without sexual stimulation [R].
3) Trazodone 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 [R].
4) Trazodone 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 [R].
5) Trazodone May Cause Withdrawal Symptoms
6) Trazodone Can Cause Weight Changes
In a study (DB-RCT) comparing amitriptyline, trazodone, and placebo, trazodone produced slight weight loss in overweight patients. However, the results were statistically not significant [R].
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 [R, R].
The side effects and warnings may not be comprehensive, so speak to your doctor before taking any drug.
- Drug interactions between trazodone and:
- Fluconazole (for fungal infection) can cause toxicity since they are both metabolized by the cytochrome CYP3A4 [R].
- 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 [R].
- Warfarin (blood thinners) affected the blood clotting effect of warfarin in 3 clinically relevant cases. Warfarin doses should be adjusted if trazodone treatment is initiated or stopped [R].
- Other drug interactions have also been described [R].
- Although the exposure of babies to trazodone via breast milk is minimal, you should tell your doctor if you’re pregnant or breastfeeding before starting the treatment [R, R].
- 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 [R].
“I was taking Xanax for many years to treat my anxiety. New guidelines, however, said I couldn’t continue because of the pain medicines I take and fear of overdose. My doctor prescribed Trazadone. I was hesitant at first but I took it because I wasn’t sleeping. It works great! I can’t believe I like it even better than the Xanax! While on Xanax I still had anxiety but this med has really helped both anxiety and insomnia“.
“Trazodone has worked wonders for my insomnia! I used to have terrible, intractable insomnia at least one night a week. This went on for years. Ambien didn’t put me to sleep, it just made me feel awful. Finally, a doctor prescribed me trazodone, and it is perfect. I fall asleep within minutes. I take anywhere from 12.5 mg (I cut my pills into quarters) to 25 mg a night. I have taken up to 50 mg but higher doses tend to leave me feeling pretty zoned out the next day. I highly recommend giving it a shot”.
“50 mg taken with water directly before bed puts me to sleep within ten minutes or so. I wake up 7-8 hours later (unless forced to get up earlier by my alarm clock) without feeling drugged or groggy. The insomnia being treated was the kind where I was able to fall asleep after about a half hour in bed, but then I would wake up again after a couple of hours and be unable to fall back asleep. This mild, non-addictive drug has successfully addressed insomnia that has affected me since childhood”.
“It did take about a week before this medication worked predictably and reliably. A couple of times during the first week I experienced vivid, though not unpleasant dreams. Since then my ability to get a full night of restful sleep has been consistent. I haven’t developed a tolerance for trazodone nor do I experience any withdrawal symptoms if I miss a day or two of use. I like that” [R].
“I took Trazodone for 2 months for insomnia. Could not wait to get off of the stuff. Valeriana works better with none of the side effects” [R].
Effect on erection:
‘Trazodone appears to give me long lasting and effortless erections from 3 to 5 hours after I take it. It has taken me over a year to notice this however as I am usually in a deep trazodone induced slumber at such times. During the day, while I am awake and the trazodone has largely metabolized, I appear to have the developed the opposite problem. I strongly suspect this issue will abate after I wean myself from the trazodone” [R].
“I was on this for a while as an antidepressant. It works for a short while until the side effects bite you in the ass and you need higher doses. Spent 21 days on a water fast to get off a 15 year run of all sorts of these types of drugs, cold turkey! Never looked back, now use many alternatives that are not pharmaceutical. Can’t see any “health benefits” to this!”.
“I was prescribed 50mg. One pill to take before bed”. “The last time I saw the clock before going to sleep was 10:30 pm. I awoke at 11:30 pm feeling off. I was suddenly wide awake, and I noticed that I couldn’t feel my toes. They had gone completely numb. I had no idea what was happening and became very agitated. My stress shot through the roof and every hour I kept checking my toes to see if they were blue. They weren’t”. “Right as I had finally begun to fall asleep I had a non-epileptic seizure. I did not return to sleep. The numbness did not subside until around 3-4pm the next day”.
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