Vilazodone: A Novel Antidepressant

Vilazodone was approved by the Food and Drug Administration in the U.S. earlier this year, but is just now becoming available in pharmacies for prescription use.  The drug is marketed in the U.S. under the trade name Viibyd.  It is novel in that it the only antidepressant that combines two mechanisms that can increase serotonin in the brain cortex: selective serotonin reuptake inhibition and partial agonism of the 5HT1A receptor.  There are multiple selective serotonin reuptake inhibitors, i.e. fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro).  

There are also compounds that have an agonistic effect on the 5HT1A receptor.  These include:
Antidepressants: trazodone, nefazodone
Antianxiety drugs: buspirone
Atypical antipsyhotics: aripiprazole, ziprasidone, clozapine, asenapine
Illicit drugs/compounds: MDMA (ecstasy), LSD, psylocybin, cannabidiol (cannabis)
Antimigraine compounds: ergotamine
Other compounds: yohimbine

The combination of SSRI and 5HT1A agonist effect may synergistically increase serotonergic transmission.  

Two published clinical trials on vilazodone are available on PubMed.  The table below summarizes some of the key findings from the two published trials.

The dose of vilazodone studied was 40 mg in both studies.  Because of the common occurrence of gastrointestinal side effects, doses are typically initiated at a smaller level and increased to 40 mg over the first week or so.  The pattern and prevalence of gastrointestinal side effects with vilazodone appears similar to levels seen in previous SSRI trials.  Although headache was commonly reported with vilazodone, the rate did not differ from the rate endorsed by placebo.  Dizziness, dry mouth, insomnia and abnormal dreaming were endorsed at a higher level with vilazodone but by less than 10% of the subjects.

Although vilazodone was statistically superior to placebo on almost all depression measures, it was not statistically superior in remission rates in the Kahn study.  This finding along with the relatively low absolute response rate of 27.3% in the vilazodone group is a little disappointing.

The response and remission rates found in these two studies were similar to SSRIs.  Head to head comparison with an SSRI would be informative to see if vilazdone has any effectiveness or adverse event superiority.  Sexual side effects are common with the SSRIs and the two randomized vilazodone studies reported no difference in sexual side effects between vilazodone and placebo.  Additionally, the Rickels study showed some evidence for anxiety symptom reduction.  Clinical trials examining the effectiveness of vilazodone for anxiety disorders will likely be soon completed.

Disclosure:  The author has no stock in the parent company of vilazodone (Forest Labs).  Additionally no honoraria or research grant support has been received related to this drug.  The author received no reimbursement for writing this post and the comments are entirely those of the author.

Information on the agonists for the 5HT1A receptor obtained from Wikipedia.

Chemical molecular structure of vilazodone from Creative Commons file at Wikepedia by author Meodipt.

Rickels K, Athanasiou M, Robinson DS, Gibertini M, Whalen H, & Reed CR (2009). Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. The Journal of clinical psychiatry, 70 (3), 326-33 PMID: 19284933


Khan A, Cutler AJ, Kajdasz DK, Gallipoli S, Athanasiou M, Robinson DS, Whalen H, & Reed CR (2011). A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. The Journal of clinical psychiatry, 72 (4), 441-7 PMID: 21527122

Bupropion for the Treatment of Sexual Dysfunction

3D Model of Chemical Structure for Bupropion

Bupropion is a drug approved in the United States for the treatment of depression (Wellbutrin) and for smoking cessation (Zyban).  In contrast to the selective serotonin reuptake inhibitor (SSRI) class of drugs, i.e. Prozac, bupropion appears to have a predominant effect on blocking the reuptake of dopamine.  It appears to also be a nicotinic acetylcholine receptor antagonist possibly contributing to it’s effect on nicotine withdrawal symptoms.

Sexual dysfunction commonly presents as an adverse effect of the SSRIs and can be the reason for drug continuation in a significant minority of patients.  Some clinicians have used bupropion augmentation in an effort to reduce the sexual dysfunction associated with the SSRI drugs.  Many clinicians feel this is an effective approach despite limited research to support the strategy.   Now two randomized controlled clinical trials published from a research team in Iran provide more support for bupropion and it’s effects on sexual function in both men and women.

Safarinejad and colleagues conducted two independent studies.  In the first study, a series of women reporting distressing reduced sexual desire and activity were identified.   Three hundred and twenty three subjects were randomized to receive either bupropion SR 150 mg or placebo.   The study sample was limited to pre-menopausal women with regular menstrual cycles and no evidence of major depressive disorder.  The women on bupropion noted improvement in sexual function across a variety of psychometric domains.  Over 70% reported being definitely satisfied with treatment compared to less than 10% of those on placebo.   Bupropion was typically well-tolerated although rates of headache, insomnia, dry mouth, nausea and muscle aches were noted in between 5 and 10% of the bupropion group (statistically higher than the placebo group).

In the second study, 234 men being treated with an SSRI drug-related sexual dysfunction problem participated in a twelve week trial of bupropion SR 300 mg per day.  The types of sexual dysfunction included erectile dysfunction (73%), low sexual desire (66%), orgasm dysfunction (51%) and dissatisfaction with intercourse performance (50%).

Men assigned to the active bupropion treatment had significant reductions in the psychometric severity ratings in several domains.   Subjects reported reduced erectile dysfunction along with an increase their sexual desire.  The number of intercourse attempts increased from one to slightly more than two per week with bupropion while there was essentially no change in the placebo group.  Similar to the women’s study, men in the bupropion group had some increased endorsement of adverse effects including headache (8.5%), insomnia (6.8%), dry mouth (6.0%), nausea (5.1%), muscle aches (5.1%) and dizziness (5.1%).

The author notes that SSRI related sexual dysfunction is common in men and often not queried during medical visits.  Sildenafil (Viagra) also appears to be helpful for SSRI erectile dysfunction.  Given the research support for bupropion and sildenafil in ED associated with SSRIs, more clinicians should search for the problem and consider treatment options.  Neither drug has FDA approval for these indications, but clinical trials for these indications should be considered by their manufacturers.

3D model of the chemical structure of bupropion provided by the user:Sbrools under the Creative Commons Attribution-Share Alike 3.0 Unported license.

Safarinejad MR, Hosseini SY, Asgari MA, Dadkhah F, & Taghva A (2010). A randomized, double-blind, placebo-controlled study of the efficacy and safety of bupropion for treating hypoactive sexual desire disorder in ovulating women. BJU international, 106 (6), 832-9 PMID: 20151970


Safarinejad MR (2010). The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study. BJU international, 106 (6), 840-7 PMID: 20067456