Trazodone for Treatment of Major Depressive Disorder

This post will attempt to answer following questions regarding role of trazodone in treatment of major depressive disorder (MDD):

  1. How is Trazodone different from SSRIs and SNRIs?

  2. What dose of Trazodone is effective for MDD treatment?

  3. What dose of Trazodone is effective for insomnia treatment (off label)?

  4. Is hypnotic dose of Trazodone effective for MDD treatment?

  5. How to initiate and titrate Trazodone for MDD treatment?

 


(1) How is Trazodone different from SSRIs and SNRIs?

 

Trazodone have following mechanism of action including:

  1. Inhibition of the serotonin transporter.

  2. Serotonin type 2 (5-HT2) receptor antagonism (5-HT2A and 5-HT2C).

  3. α1– and α2-adrenergic receptors antagonism.

  4. Histamine H1 receptors antagonism.

 

SSRIs and SNRIs exert their antidepressant effect through inhibition of the serotonin transporter —-> this results in serotonin increase in synapse —-> agonist effect of serotonin on 5-HT1A , 5-HT2A and 5-HT2C .

 

5-HT1A agonism –> responsible for antidepressant effect.

5-HT2A and 5-HT2C  agonism –> responsible for side effect profile of insomnia, sexual dysfunction and anxiety. 

 

Trazodone by exerting 5-HT1A agonism + 5-HT2A and 5-HT2C  antagonism results in antidepressant response and avoids side effect profile of insomnia, sexual dysfunction and anxiety.

 


(2) What dose of Trazodone is effective for MDD treatment?

 

Trazodone’s is 100 times more potent at 5-HT2A antagonism, compared to inhibition of the serotonin transporter. Hence higher doses are needed for inhibition of the serotonin transporter.

 

DOSE FROM 150-600 MG IS REQUIRED FOR INHIBITION OF SEROTONIN TRANSPORTER –> HENCE IS EFFECTIVE FOR MDD TREATMENT. 

 


(3) What dose of Trazodone is effective for insomnia treatment (off label)?

 

5-HT2A antagonism is known for therapeutic effects on sleep maintenance. 

 

Trazodone at 10 mg dose = acts on 5-HT2A antagonism.

Trazodone at 25- 100 mg dose = causes additional effect on α1– and α2-adrenergic receptors antagonism + Histamine H1 receptors antagonism.

 

DOSE FROM 25-150 MG IS REQUIRED FOR INSOMNIA TREATMENT. 

 


(4) Is hypnotic dose of Trazodone effective for MDD treatment?

 

Hypnotic dose (25- 150 mg) is not sufficient for inhibition of serotonin transporter. Higher doses (> 150 mg) are needed for antidepressant benefit. 

 


(5) How to initiate and titrate Trazodone for MDD treatment?

 

Trazodone’s package insert recommends initiating at 150 mg BID.

Adding Trazodone during day time can result in sedation and can affect compliance, so Initiate at 150 mg HS and increase dose by 50 mg Q3-4 days.

 


SOURCE:
  1. Trazodone package insert.
  2. CNS Spectr. 2009 Oct; 14(10):536-46.
  3. CNS Drugs. 2012 Dec; 26(12): 1033–1049.

Please do post your questions or comments below. 


Dr. Harvinder Singh, M.D. (Admin)


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