Does trazodone affect the central nervous system? (+3)

In this article, we will discuss whether trazodone affects the central nervous system. We will also discuss how it affects the central nervous system, the effects of its dose and long-term use on the central nervous system, and other related information. 

Does trazodone affect the central nervous system? 

Yes, trazodone does affect the central nervous system (CNS). It is an antidepressant and changes the concentration of certain neurotransmitters in the brain. This influences different functions that the CNS regulates. 

Trazodone belongs to the class of serotonin antagonists and reuptake inhibitors (SARIs) and is FDA-approved to treat major depressive disorders (1). Its CNS effects make it beneficial for different CNS disorders. 

Trazodone also has some side effects on the CNS due to its mechanism of action. Trazodone’s CNS effects are associated with its dosage. Duration of treatment may also have an impact on the CNS effects of trazodone. 

How does trazodone affect the CNS? 

Your CNS is composed of the brain and spinal cord. Neurotransmitters are chemical messengers in the brain that help the brain to communicate with the body. Trazodone affects the CNS in the following ways:

Neurotransmitter modulation: 

Trazodone works on different neurotransmitters to produce its CNS effects. It blocks the reuptake of serotonin which increases serotonin concentration in the brain. It blocks some serotonin receptors like 5-HT2A and 5-HT2C (1). 

Trazodone also acts as an antagonist of histamine and alpha-1 adrenergic receptors. Its interaction with different neurotransmitters results in its therapeutic effects and makes it beneficial for different disorders (1). 

Antidepressant effect: 

Trazodone is primarily used as an antidepressant. This CNS effect is mainly due to the modulation of serotonin concentration in the brain. A dysfunction in serotonin synthesis, transport, and concentration is involved in depression (2).

Serotonin deficiency is associated with depression, negative emotions, and other side effects (2). Thus, trazodone increases serotonin concentration and produces an antidepressant effect. 

Sedative effect: 

The sedative effects of trazodone are widely known and its use in sleep disturbances is well established. Sedation is another CNS effect that is associated with the antagonism of different receptors. 

Trazodone produces its sedative effects by blocking the 5-HT2A receptor, histamine (H1) receptor, and alpha-1 adrenergic receptors. These receptors play a role in alertness and wakefulness (1). 

CNS side effects: 

Trazodone’s effects on neurotransmitters also produce some side effects. Due to sedation, trazodone can result in cognitive and motor impairment. Therefore caution is required while operating heavy machinery (3). 

Some other CNS side effects of trazodone include (3):

  • reduced concentration
  • dizziness
  • confusion 
  • disorientation
  • light-headedness
  • nervousness
  • fatigue
  • drowsiness
  • headache

Trazodone and CNS: What are the therapeutic uses? 

Due to the CNS effects of trazodone, it is used for many disorders. They mainly include psychiatric conditions.  It is FDA-approved for MDD. Non-FDA-approved therapeutic uses of trazodone include (1,4): 

  • insomnia
  • substance abuse
  • obsessive-compulsive disorder
  • anxiety
  • complex regional pain syndrome
  • Alzheimer’s disease
  • schizophrenia
  • bulimia
  • fibromyalgia
  • alcohol withdrawal
  • opioid withdrawal

Are the CNS effects of trazodone dose-dependent?

The CNS effects of trazodone depend on the dose you are taking. Trazodone produces sedative effects in low doses (25-150mg). In these doses, trazodone does not produce its antidepressant effects (5). 

To produce an antidepressant activity, trazodone must saturate serotonin transporters. This is achieved with doses between 150-600 mg (5).

Thus, the CNS effects of trazodone are dose-dependent. Your healthcare provider will prescribe low doses if you are not depressed but struggle with sleep. 

What are the long-term CNS effects of trazodone?

The long-term effects of trazodone on the CNS have been mentioned in different studies (6,7). The studies discuss that long-term use of trazodone can be associated with cognitive improvement and a delay in cognitive decline (6,7). 

Long-term use of trazodone has shown a positive impact on cognition which may be associated with a decrease in insomnia and depression. Insomnia is associated with neurodegenerative diseases and cognitive deterioration (6). 

Studies have shown that long-term use of trazodone enhances slow-wave sleep which delays the long-term cognitive decline. Due to this, it can be a potential intervention in dementia. This, however, needs further research (7). 

How to reduce the CNS side effects of trazodone? 

To reduce the risk of CNS side effects of trazodone, your healthcare provider will initiate the treatment with a low dose. The dose can be increased gradually to reach the recommended dose of 150mg/day (3).

If you are taking a 150mg/day dose of trazodone, it is advised to take it in divided doses. This reduces the risk of drowsiness and sedation which can impair your functioning at work. High doses of trazodone should not be taken in the morning

Taking trazodone at night improves your sleep and prevents you from the struggles of staying awake in the morning while you have to work. Taking trazodone after a meal is recommended for optimum effects (3). 

Take trazodone as advised by your healthcare provider. If you have any concerns about the CNS side effects of trazodone, discuss it with your healthcare provider. 

What are some other side effects of trazodone?

Some other side effects of trazodone include (1,3):

  • blurred vision
  • dry mouth
  • orthostatic hypotension
  • QT prolongation
  • arrhythmias
  • priapism
  • visual hallucinations
  • acid reflux

In my perspective, trazodone affects the central nervous system. It regulates the concentration of neurotransmitters by acting on different receptors. Its antidepressant effect is produced by inhibition of serotonin reuptake. The antagonism of serotonin, histamine, and alpha-1 adrenergic receptors by trazodone causes sedation. Due to its mechanism of action, trazodone also results in some CNS side effects. The CNS effects of trazodone depend on its dose. Long-term use of trazodone is associated with a positive influence on cognition. High doses of trazodone should be taken at night to reduce the CNS side effects. 

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