Trazodone Dosages by Use

What is Trazodone?

Trazodone (Desyrel) is an atypical antidepressant medication. It belongs to a class of drugs called serotonin antagonists and reuptake inhibitors (SARIs).^1,2,3

Trazodone is FDA-approved for treating major depressive disorder. It has gained recognition as an off-label treatment for various conditions like:^1,2,3,4,5

• Sleep disorders
• Anxiety
• Dementia
• Substance abuse
• Bulimia
• Fibromyalgia

In this post, let’s look at trazodone, its side effects, and how it’s used for off-label applications like sleep, anxiety, and sundowning.

How Trazodone Works

The exact mechanism of action of trazodone has yet to be fully understood. The drug works in multiple ways, which explains some of its off-label uses. Some known mechanisms of trazodone involve blocking the following:^4,6

• Serotonin transporter (SERT or 5-HTT): SERT’s primary function is to reabsorb serotonin from the tiny gap between neurons. When trazodone blocks SERT, the action increases the concentration of serotonin in the brain, alleviating depressive symptoms.
• Serotonin type 2 (5-HT2) receptors: Blocking these receptors explains some of trazodone’s anxiolytic (anti-anxiety) and antidepressant effects. 
• Histamine receptors: Histamine promotes wakefulness and alertness. By blocking H1 histamine receptors, trazodone can cause sedation and drowsiness. 
• Alpha-1-adrenergic receptors: These receptors are involved in regulating arousal and wakefulness. By blocking these receptors, trazodone can promote sedation and drowsiness.

Trazodone’s effect on serotonin reuptake (reabsorption) and its blocking of serotonin, histamine, and alpha-1-adrenergic receptors contribute to the drug’s therapeutic actions. 

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Trazodone and Sleep

Trazodone in low doses is generally safe and effective for treating insomnia, although this is an off-label use. Over the years, this medication has become more popular as a sleep aid rather than an antidepressant. 

Is Trazodone a Strong Sleeping Pill or an Antidepressant?

While trazodone can effectively promote sleep, other more potent sleeping pills, like zolpidem (Ambien), are available.⁶ Trazodone’s use as a sleep aid is generally reserved for individuals with comorbid depression, anxiety, or dementia.⁷ 

Recommended Trazodone Dosage for Sleep?

Trazodone is not FDA-approved for insomnia. A common prescribed dosage for insomnia is often 25-50 mg daily at night.⁸

Studies have shown varying dosages, ranging from 25 to 150 mg. These dosages are still lower than those given for depression, where the usual starting dose is 150 mg daily. ^{4,6,7,9,10,11,12} 

Doctors usually start their patients on the lowest dose and gradually increase it if necessary. Some factors can affect the dosage, such as: 

• Age
• Overall health
• Presence of other medical conditions

People should take trazodone shortly before bedtime. Taking it too early may lead to excessive drowsiness during the day; taking it too late may cause difficulty waking up in the morning. 

How Many Hours Does Trazodone Last?

It varies. Trazodone has a relatively short half-life, ranging from 3 to 6 hours. But its sedating effects may continue for several hours after administration. Factors such as dosage, individual metabolism, and overall health will also affect the duration.^7,11

Trazodone and Anxiety

Trazodone is not FDA-approved to treat anxiety. Doctors prescribe it as an off-label medication and reserve it for cases where other drugs have not been effective or suitable. Moreover, not everyone can tolerate trazodone, and side effects may occur. 

Does Trazodone Decrease Anxiety?

Trazodone has been shown to have anxiolytic (anti-anxiety) properties. Based on some studies, trazodone is: 

• Comparable to diazepam (Valium) in treating people with generalized anxiety disorder (GAD)¹³
• Effective in some people with panic disorder or agoraphobia with panic attacks¹⁴
• Helpful against nightmares and insomnia associated with post-traumatic stress disorder (PTSD)¹⁵

Recommended Trazodone Dosage for Anxiety?

Trazodone’s usual starting dose for adults with generalized anxiety disorder (GAD) is 150 mg daily. Doctors may adjust the dose to 400 mg, at most, for outpatients and 600 mg for inpatients. For comparison, the usual starting dose for depression is 150mg daily; their maximum allowable doses are similar.¹²

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Trazodone and Dementia

Trazodone is not FDA-approved for treating dementia, but it’s sometimes prescribed off-label to manage certain symptoms associated with the condition. 

Dementia is an umbrella term that describes a group of symptoms characterized by: 

• A decline in cognitive abilities
• Memory loss
• Behavioral changes
• Difficulties with daily functioning

Individuals with dementia often have trouble sleeping and experience sundowning, which can significantly impact their quality of life. 

Dementia and Alzheimer's are closely connected, but they are different. Alzheimer's disease is a specific type or cause of dementia characterized by the accumulation of abnormal protein deposits in the brain.¹⁶

Does Trazodone Cause Dementia or Worsen Cognitive Decline?

No, trazodone is not known to cause dementia or worsen cognitive decline. 

However, its sedating properties may be considered a treatment option in some cases. In Spain, 20.36% of trazodone prescriptions are for Alzheimer’s patients.^6,17

Findings remain inconsistent and inconclusive regarding whether trazodone affects dementia or improves cognition in people with Alzheimer’s.^6,18,19,20 It may promote sleep, though, making it a popular treatment for insomnia in people with dementia. It also appears to have a better safety profile than other sedating drugs.⁶

Nevertheless, it’s important to monitor individuals with pre-existing dementia when using trazodone. This is due to the drug’s side effects that may impact their well-being. 

What Is the Best Medication to Help Dementia Patients Sleep?

None. Sleep medication is apparently not advised for individuals with dementia because they may experience increased confusion and a higher risk of falling the following day.

However, in severe sleep problems and when non-drug treatments have been ineffective, doctors may propose a short-term trial of sleep medication as a potential option.²¹

The choice of medication will depend on various factors, including specific sleep disturbances and the patient’s unique characteristics. The selection must be made in consultation with healthcare professionals, considering each patient's potential benefits and risks.

Here are some medications used to treat sleep problems among people with dementia.

Trazodone

Trazodone has the potential as a treatment for people with dementia and associated sleeping disorders. In one study, it’s the most commonly used sedative drug, with an effectiveness of 65.7%.²²

Melatonin for Insomnia

Melatonin is a hormone involved in regulating sleep-wake cycles. Melatonin supplements are commonly used as a sleep aid as it can promote a more regular sleep pattern. As a natural chemical, it’s generally safe, although its effectiveness can vary from person to person.

Melatonin has been popularly prescribed for people with dementia.^21,23 However, one meta-analysis involving six trials involving melatonin and melatonin-like ramelteon found no clear evidence of sleep improvement.²⁴

Orexin Antagonists

In a meta-analysis involving two trials, orexin antagonists have shown beneficial effects on sleep among people with dementia.²⁴

Orexin antagonists are a class of medications that target and block the activity of orexin receptors in the brain. Orexin, or hypocretin, is a nerve protein that regulates wakefulness, arousal, and sleep-wake cycles. 

By blocking orexin receptors, orexin antagonists can modulate the sleep-wake system and promote sleep. Examples include suvorexant, lemborexant, and daridorexant; all are FDA-approved for insomnia treatment.^25,26

Zolpidem 

Zolpidem (Ambien) belongs to a class of drugs known as sedative-hypnotics, primarily used for the short-term treatment of insomnia. 

In a two-week trial involving zolpidem and trazodone, zolpidem showed benefits across different sleep parameters. It even showed superior results to trazodone, maintaining its sleep benefits over the entire duration.⁶

Other Sleep Medications

Other medications used to treat sleep changes include:²⁶

• Tricyclic antidepressants (TCAs like nortriptyline)
• Benzodiazepines (like lorazepam, oxazepam, and temazepam)
• Sleeping pills (like zaleplon and chloral hydrate)
• Atypical antipsychotics (like risperidone, onlanzapine, and quetiapine)
• Older classical antipsychotics (such as haloperidol)

Note that there are caveats in using antipsychotics and benzodiazepines, mainly because they carry a higher risk of side effects.^23,27

Can Trazodone Help with Sundowning?

Sundowning is when people with dementia experience agitation, confusion, and severe restlessness during the late afternoon or evening hours.^27,28

Trazodone’s sedating properties may promote calmness and reduce behavioral disturbances during this time. However, studies have shown inconsistent findings on trazodone’s effectiveness against sundowning.^6,29

What Medications Are Commonly Used for Sundowning?

Other medications are used to manage sundowning but aren’t much superior to trazodone.

Hypnotics, Benzodiazepines, and Low-potency Antipsychotics

While these drugs are the conventional medications for sundowning, they carry higher risks of side effects. Ironically, they may even cause agitation in people with pre-existing sundowning syndrome.^23,27

Melatonin for Sundowning

This sleep supplement may help with sundowning by promoting a regular sleep pattern. Some studies have shown some behavioral improvement with extended use. But one meta-analysis involving five trials found no evidence of sleep improvement in people with dementia.^23,24

Other Medications for Sundowning

Other medications to treat sundowning include:

• Cannabinoids
• Acetylcholinesterase inhibitors
• N-methyl-d-aspartate (NMDA) receptor antagonists

However, no clear evidence supports their effectiveness. Moreover, cannabinoids are strongly not recommended due to their side effects.^23,28

Similar to insomnia, the choice of medication for sundowning must be based on the individual's specific needs and carefully evaluated in consultation with healthcare professionals.

Trazodone Side Effects

Like any medication, trazodone may cause common side effects like:^{1,2,3,10,12,30}

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Changes in weight or appetite
• Nervousness
• Drowsiness or daytime sleepiness
• Sudden dizziness
• Lightheadedness
• Dry mouth
• Sexual problems in males (like decreased sex drive, inability to get or keep an erection, or delayed or absent ejaculation)
• Sexual problems in females (like decreased sex drive, delayed orgasm, or inability to have an orgasm)
• Stuffy nose
• Red or itchy eyes
• Blurred vision
• Nightmares, vivid dreams, and other dream disturbances

Trazodone may cause some serious side effects that should be immediately brought to a doctor’s attention or emergency medical treatment:^{1,2,3,10,12,30}

• Allergic reactions (like rashes, difficulty breathing, and swelling of face, lips, tongue, or throat)
• Painful or prolonged erection
• Fainting
• Fever
• Migraine headache
• Severe weakness or tiredness
• Sweating
• Confusion
• Chest pain
• Shortness of breath
• Fast or irregular heartbeat
• Severe muscle stiffness or twitching
• Unusual bleeding
• Anxiety
• Agitation
• Hallucinations
• Cognitive and motor impairment
• Serotonin syndrome
• Seizures

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Does Trazodone Cause Memory Loss or Affect the Brain?

Many studies and anecdotes have supported trazodone’s effectiveness against sleeping difficulties. However, regarding cognitive effects, the evidence is inconsistent and inconclusive. 

In one meta-analysis, seven studies showed trazodone does not affect cognition, five showed it reduced cognitive decline, and four showed it caused cognitive impairment.³¹

One study showed trazodone produced small but significant impairments to short-term memory and verbal learning.¹⁹

In a study of patients with CSVD (cerebral small vessel disease), low-dose trazodone appears to be effective in improving concentration and recall abilities.³²

In three cohort studies involving people with dementia, there was no evidence of cognitive benefit from trazodone when compared to other antidepressants.²⁰

What Is the Maximum Dose of Trazodone?

The maximum dose of trazodone will vary depending on the individual taking the medication and the specific condition for treatment. 

Healthcare providers usually initiate trazodone treatment with the lowest amount. If there are no improvements, they gradually increase the next dose until they reach an effective one. 

Taking higher doses can increase the risk of trazodone overdose or side effects. That’s why people should use only the lowest effective dose. Patients should not adjust the dosage or exceed the maximum allowable limit without medical supervision. 

Trazodone Maximum Dose and Depression

Here are the maximum doses for the treatment of major depressive disorder (MDD):^2,12

• Adults: Maximum dose for immediate-release tablets is 400 mg/day for outpatients and 600 mg/day for inpatients. The maximum dose for extended-release tablets is 375 mg/day.

Due to limited data, trazodone is not considered a first-line agent for adolescents and children. Additionally, trazodone carries a boxed warning regarding an increased risk of suicidal ideation and behaviors in younger patients. 

This cautionary information highlights the potential risks associated with using trazodone in this population. The decision to prescribe trazodone will be made on a case-by-case basis, considering the young patient’s specific needs and circumstances.

Trazodone Maximum Dose and Insomnia

There are no official guidelines from the FDA or manufacturer for the treatment of insomnia. Based on studies, effective doses range from 25 to 150 mg taken during bedtime.^{4,6,7,9,10,11,12} 

Trazodone Maximum Dose and Anxiety

To treat generalized anxiety disorder (GAD), the maximum dose for adults is 400 mg/day for outpatients and 600 mg/day for inpatients.¹²

What Are the Risks of Taking Trazodone for Long Periods?

Under the montiored routine care of a healthcare provider, there appears to be no lasting harmful effect from taking trazodone for a long time. At low doses, trazodone may induce sleep without causing tolerance, mainly because of its short half-life of 3 to 6 hours.^7,11

Doctors must still periodically assess the need for continued use and if symptoms improve with the current dose. They should also monitor patients for withdrawal symptoms that may occur when discontinuing therapy.^2,12

Precautions with Trazodone

It’s essential to be aware of particular precautions to minimize potential risks and maximize the benefits of trazodone therapy. Doing so can enhance the overall treatment experience and reduce the likelihood of adverse effects.

What Foods & Substances Should You Avoid When Taking Trazodone?

There are no specific foods that need to be avoided when taking trazodone. However, patients taking trazodone should avoid:^1,2,33,34

• Alcohol: As a sedative, alcohol can intensify the sedating effects of trazodone (like drowsiness and dizziness). 
• Grapefruit juice: This can increase the concentration of trazodone in the bloodstream, potentially leading to higher levels of the medication than intended. This can result in adverse reactions like QT prolongation. 
• Other drugs that can interact with trazodone: Other antidepressants, blood thinners, sleeping pills, vitamins, and some herbal products (like St. John’s wort) may cause drug interactions.

Who Should Not Take Trazodone?

Trazodone may not be suitable for some people. Don’t take trazodone if you’re one of the following:^1,2 

• Hypersensitive to trazodone or any of its components
• Currently taking or recently discontinuing monoamine oxidase inhibitors (MAOIs)
• Currently taking medications that increase serotonin (like selective serotonin reuptake inhibitors)
• Have a history of priapism (prolonged erection) 
• Pregnant, planning to be pregnant, or breastfeeding
• Other conditions that trazodone may aggravate (like liver failure, kidney disease, or low sodium levels)

Discussion with your healthcare provider allows for a comprehensive assessment and ensures the safe usage of trazodone. Tell your doctor about: 

• Possible drug interactions
• Medical history or existing conditions
• Drug tolerance and worsening depression
• Withdrawal symptoms 

Trazodone carries a boxed warning concerning an elevated risk of suicidal thoughts and behaviors in pediatric patients. This emphasizes the need for careful monitoring and close communication with healthcare professionals when prescribing trazodone to children and adolescents.

Summary

Trazodone is an atypical antidepressant medication that belongs to the serotonin antagonist and reuptake inhibitor (SARI) class of drugs. While the FDA approves it for major depressive disorder, trazodone is also off-label for other conditions such as sleep disorders, anxiety, and dementia.

The exact mechanism of trazodone is not fully understood, but the drug primarily increases serotonin levels in the brain, which helps regulate mood and sleep. 

Trazodone may cause common side effects, including nausea, vomiting, drowsiness, and dizziness. It also can cause serious side effects, such as allergic reactions, prolonged and painful erection (priaprism), and irregular heartbeat. Immediately seek medical attention if you encounter any side effects.

Overall, trazodone is a versatile medication used for various conditions. But its usage, dosage, and potential side effects should be carefully evaluated by healthcare professionals.

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