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Newer Atypical Antidepressants

Written byDesiree Smith

Major depressive disorder (MDD)

Is an illness that has an influence on the way people feel, think, and act. Some individuals suffer a single episode of depression, while others have multiple episodes during their lifetime. The Diagnostic and Statistical Manual of Mental Health Disorders, 5th Edition (DSM-5) is used to diagnose depression. The symptoms to diagnose a person with MDD must persist for at least two weeks and include five or more of the following. The symptoms are depressed mood or irritability; decreased pleasure or interest; notable changes in weight and appetite; change in sleep; change in activity; fatigue or loss of energy; feelings of guilt or worthlessness; problems with concentration; or thoughts of death or suicide (American Psychiatric Association, 2013).

Treating depression successfully with medications depends on how effective the medication is, treatment resistance, and the patient’s ability to tolerate the medication. Until recently, medications directed specifically at treating depression worked only by encouraging monoamine activity. This was done mostly by blocking reuptake of the monoamines themselves. Monoamines include serotonin (5-HT), norepinephrine or dopamine (Pierz &Thase, 2014).

There are currently numerous medications to treat unipolar depression including: selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA), monoamine oxidase inhibitors (MAOIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist/reuptake inhibitors, second-generation antipsychotics, alpha2 antagonists, norepinephrine reuptake inhibitors, and tetracyclics (D'Agostino, English & Rey, 2015)

Viibryd (vilazodone) and Trintellix (vortioxetine) are two newer medications on the market that are indicated to treat depression.These two new medications use additional mechanisms to treat depression, because they act as SSRI and modify the influence of various serotonin receptors.

Viibryd is a SSRI and a5-HT1A partial agonist. This dual mechanism action has earned Viibryd the name serotonin partial agonist/reuptake inhibitor (SPARI). ASSRI increases serotonin accumulation in the synapse by blocking serotonin reuptake by the serotonin transporter (Pierz &Thase, 2014). Blocking serotonin reuptake causes a nonspecific 5-HT receptor activation. 5-HT1A partial agonism activates 5-HT1A auto receptors and postsynaptic heteroreceptors. It is possible that Viibryd also increases the desensitization of the 5-HT1A auto receptors, which in theory may be the cause of the rapid onset of therapeutic effectiveness (Pierz &Thase, 2014).

Buspar (Buspirone) is a 5-HT1A partial agonist and has been used for a long time by clinicians to treat anxiety/depression. By combining these two mechanisms into one medication, SSRI and 5-HT1A partial agonism, Viibryd has a similar effect of combining a traditional SSRI (Lexapro, Zoloft, Prozac, etc.) and Buspar (Pierz &Thase, 2014).

Trintellix is a SSRI, 5-HT1A partial agonist, 5-HT3 antagonist, 5-HT1D antagonist, 5-HT7 antagonist, and a 5-HT1B partial agonist (D'Agostino, English & Rey, 2015). This medication is the first and only compound with these characteristics. Trintellix binds with high affinity to the serotonin transporter. Affinity refers to the degree that one substance combines with another.The higher the affinity means the more it combines. Affinity refers to the measure of how tightly a medication binds to a receptor.The antidepressant effects that are offered by Trintellix are thought to be secondary to increasing serotonin in the central nervous system through inhibiting reuptake. Trintellix’s binding affinity is proportional depending on the dose. This means that increasing the dose will cause more binding to the receptors that are being targeted. Every time the dose is raised by 5 mg the affinity increases by 15 %. What makes Trintellix different from Viibryd and other more traditional antidepressants is that it has complex receptor binding affinities. It promotes the reuptake blockade of the serotonin transporter, agonist activity at the 5-HT1A receptor, partial agonist activity at the 5-HT1B receptor, and antagonism at the 5-HT1D, 5-HT7, and 5-HT3 receptors (D'Agostino et al., 2015).

Research suggests Trintellix has fewer sexual side effects as compared to SSRI (Stahl, 2017).Numerous studies reveal greater cognitive effects when compared to other antidepressants. Patients who have treatment resistant depression or who do not respond to other antidepressants may respond to Trintellix (Stahl, 2017).

Generic name: Vilazodone, Brand name: Viibryd

Often prescribed for: Major depressive disorder (MDD),Obsessive compulsive disorder (OCD) or Anxiety (Stahl, 2017). Onset: may be faster than with other typical antidepressants. Research suggests onset of efficacy as early as week 1, but with standard titration the full therapeutic dose of 40 mg will reveal the most efficacious results after the third week. Notable side effects: Nausea, diarrhea, vomiting, insomnia, dizziness, bruising and rare bleeding, rare hyponatremia (most often in elderly patients), sexual dysfunction, SIADH (syndrome of inappropriate antidiuretic hormone secretion). Serious side effects: Rare seizures and/or induced mania and activation of thoughts of suicide. Dosing: usual dose range is 20 – 40 mg/ day. Dosage forms are 10mg, 20mg, and 40mg tablets. Initially 10mg/day; increase dose to 20mg/day after the first week; can increase to 40mg/day after one more week; should be taken with food (Stahl, 2017).

Generic name: Vortioxetine, Brand name: Trintellix

Often prescribed for: Major depressive disorder (MDD), Generalized anxiety disorder (GAD), cognitive symptoms associated with depression, geriatric depression (Stahl et al., 2017). Onset: therapeutic action is not commonly immediate, but often is delayed 2 – 4 weeks. Notable side effects: Nausea, vomiting, constipation, sexual dysfunction.Serious side effects: Rare seizures and/or induced mania and activation of thoughts of suicide. Dosing: usual dose range is 5 - 20mg/ day. Dosage forms are 5mg, 10mg,15mg, and 20mg tablets. Initially 10mg/day; can decrease to 5 mg/day or increase to 20mg/day depending on patient response; maximum dose is 20mg/day; can take with or without food; tablet should not be divided, crushed or dissolved (Stahl, 2017).


American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.

D'Agostino, A., English, C. D., & Rey, J. A. (2015). Vortioxetine (brintellix): a new serotonergic antidepressant. P &T: a peer-reviewed journal for formulary management, 40(1), 36–40.

Pierz, K. A., & Thase, M. E. (2014). A review of vilazodone, serotonin, and major depressive disorder. The primary care companion for CNS disorders, 16(1), PCC.13r01554. doi:10.4088/PCC.13r01554

Schwartz, T. L., Siddiqui, U. A., & Stahl, S. M. (2011). Vilazodone: a brief pharmacological and clinical review of the novel serotonin partial agonist and reuptake inhibitor. Therapeutic advances in psychopharmacology, 1(3), 81–87. doi:10.1177/2045125311409486

Stahl, S. (2017). Stahls essential psychopharmacology: Prescribers guide (6th ed.). Cambridge, United Kingdom: Cambridge University Press.

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