Viibryd vs Zoloft: A Comparison Of Antidepressants

Antidepressants belong to the most commonly prescribed medications. With the number of antidepressants available, it is difficult to choose which one will be best for you. Viibryd is a relatively novel antidepressant with promisingly lower side effects compared to traditional antidepressants like Zoloft. What are Viibryd and Zoloft, and how do they compare? This blog discusses the scientific literature of Viibryd vs Zoloft, helping you make an informed suggestion to your healthcare provider.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

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Viibryd vs Zoloft

Viibryd is a newly approved antidepressant with potentially lower side effects and comparable efficacy to Zoloft.

How Does Zoloft Work?

Zoloft, is a prescription antidepressant primarily used to treat depression and anxiety [1]. It was among the first approved SSRIs in the 1990s [2].

Specifically, Zoloft belongs to a group of antidepressants called selective serotonin reuptake inhibitors (SSRIs). This means it blocks the re-uptake of released serotonin into the neuron that has just released it. This increases the availability of serotonin in the synapses, enhancing the chances of serotonin binding to the post-synaptic receptor.

Serotonin is a critical neuromodulator in the nervous system that can alter the tendency of neurons to fire. Serotonin receptors are highly heterogeneous, and therefore, the effect of reducing serotonin reuptake depends on the receptors it activates. Overall, however, serotonin modulates mood, appetite, and anxiety, making SSRIs a first-line treatment choice for depression [1].

It's worth noting that Zoloft doesn't cure the conditions it's used to treat, but it can help manage the symptoms.

Zoloft is most frequently used to treat: [3, 4]

Together with many other indications. This is because sertraline has relatively few side effects and lower abuse potential in comparison to other antidepressants, such as Prozac and Wellbutrin or amytriptyline. In a direct comparison, however, Lexapro was found to have better efficacy and specificity in reducing serotonin reuptake [5].

What Is Viibryd?

Viibryd, also known in its generic form, vilazodone, is a prescription medication used to treat major depressive disorder in adults. Like Zoloft, Viibryd is classified as an SSRI but also a partial serotonin receptor agonist, which makes it a multimodal antidepressant [6, 7]. It is one of the most recently approved drugs; vilazodone gained approval only in 2011, and Viibryd, as the brand formulation, was authorised in 2015 [8].

Viibryd works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance. This helps to correct the chemical imbalance associated with major depressive disorder, reducing patients’ symptoms [9].

Viibryd comes in tablet form and is usually taken once daily. Your doctor will start you on the 10mg dose and can increase this to 20mg and then 40mg dose if your symptoms don’t get better after seven days. If you have an exceptionally high metabolism of drugs, your dose can, in rare cases, be increased up to 80mg. It is best to take Viibryd with food [8, 7].

It's important to note that Viibryd is not approved by the FDA for use in anyone younger than 18 years [10]. This is because it has a red box warning for increasing the risk of suicide in children and young adults up to 24 years. A red box warning is the highest warning level the FDA can issue and must, therefore, be prioritised by clinicians.

As with any medication, Viibryd can interact with other substances, including alcohol, other medications, and some supplements, which can affect how the drug works in the body [11].

Viibryd vs Zoloft

Vilazodone, brand name Viibryd, and sertraline, brand name Zoloft, are both SSRIs that were primarily designed to treat depression. However, they have slightly different mechanisms of action, side effects and target patient populations.

Mechanism of Action: Viibryd vs Zoloft

Viibryd is an SSRI and a partial agonist at serotonin 1A receptors. The serotonin 1A receptor can autoregulate the release of serotonin, thereby fine-tuning the response to increased serotonin availability facilitated by the SSRI effect [12, 13].

On the other hand, sertraline is a traditional SSRI. It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance. However, sertraline has been associated with side effects such as weight gain and sexual dysfunction, or rarely, tinnitus [14].

Efficacy and Side Effects: Viibryd vs Zoloft

In terms of efficacy, there have been a couple of comparisons with inconclusive results. One study comparing vilazodone and sertraline found that both medications have equal efficacy in terms of reducing depressive symptoms as measured by the Hamilton Depression Rating Scale (HDRS) [14]. An earlier study compared the number of patients you would need to treat before one of them gets better, called the Number Needed to Treat (NNT). This study found that the NNT was marginally lower in vilazodone, although only one study looked at NNT in sertraline. Critically, the NNT for escitalopram (Lexapro) was much lower than Viibryd and Sertraline, indicating Lexapro is more likely to be effective [15].

Viibryd, however, is associated with fewer side effects, including reduced risks of weight gain and sexual dysfunction. This may be due to its interaction with the serotonin 1a receptor, making it a better option for patients who struggle to experience these side effects [14].

The cited study has several methodological flaws, which were highlighted in a follow-up commentary [16]. The commentary mentioned that the study's authors dismissed people who did not complete the study and only included married couples, making the study population unrepresentative. Therefore, further evidence is needed to replicate whether the sexual dysfunction and weight gain side effects in Viibryd are indeed lower than with Zoloft.

Indications: Viibryd vs Zoloft

Both Viibryd and Zoloft have a red box warning for suicide in children and young people under 24 years old. This means they should be used cautiously in these populations, and patients should be closely monitored [1, 9].

The conditions that Viibryd has approved are significantly narrower than those of Zoloft. These include depression, anxiety and OCD primarily. On top of this, Zoloft is also prescribed for bipolar disorder, body dysmorphic disorder, and premenstrual dysphoric disorder, to name a few [3].

Viibryd vs Zoloft: Pros and Cons

Viibryd and Zoloft are both comparatively effective in treating depression, but they differ in the mechanisms of action, which impacts their side effect profiles. Viibryd, a formulation approved in 2015, is less likely to cause sexual side effects, which are common in Zoloft, approved since the 1990s. Both Viibryd and Zoloft have a red box warning for suicidal ideation and anxiety in young patients, making them suited to similar age ranges. However, Zoloft has a broader range of indications.

Always discuss your treatment choice with your healthcare provider, communicating all side effects that would impact your well-being.

For other comparisons, read our blogs about Strattera vs Celexa or Strattera vs Wellbutrin.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.