Desvenlafaxine


Article Author:
Raheel Naseeruddin


Article Editor:
Raman Marwaha


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James Hughes
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Phillip Hynes
Tehmina Warsi


Updated:
11/28/2018 4:13:37 PM

Indications

Desvenlafaxine is an antidepressant that is FDA-approved drug to treat major depressive disorder in adults.[1] For healthy women who have contraindications to estrogen, desvenlafaxine can be used off-label to treat hot flashes during menopause.[2]

Although not FDA approved in adolescents, the TORDIA studies have shown that serotonin and norepinephrine reuptake inhibitors like venlafaxine have efficacy in treating major depressive disorder in treatment-resistant depression in adolescents.

Mechanism of Action

Desvenlafaxine is an antidepressant medication that belongs to a category of drugs that inhibits the reuptake of both serotonin and norepinephrine known as SNRIs. Desvenlafaxine is the major active metabolite of venlafaxine. Therefore, the 2 agents are structurally similar in that they both contain 2 chemical rings that are not next to each other.[3] In vitro studies have shown that desvenlafaxine is 10 times more selective for serotonin than it is for norepinephrine which makes it similar to the drug duloxetine.[3] Surprisingly, the drug that desvenlafaxine is derived from, venlafaxine, has an affinity to serotonin 30-times more than it does to norepinephrine. Currently, the time to inhibit reuptake in serotonin and norepinephrine is known for duloxetine, milnacipran, and venlafaxine. However, no such data is available for desvenlafaxine. Like the other SNRIs, there is a weak effect on the dopamine and its reuptake.[3]

Metabolism

The half-life of desvenlafaxine is 11 hours, and it is metabolized through the liver with a small amount broken down via the cytochrome P450 system. Since CYP enzymes are not involved in its metabolism, there is not as large of a concern for drug-drug interaction as compared to its counterparts. Renal excretion is a major route of desvenlafaxine elimination. Nearly 45% of the medication is unchanged when eliminated in the urine. It is important to consider treating with a lower dose when dealing with patients with moderate to severe renal impairment or end-stage renal disease.[3]

Administration

Desvenlafaxine is taken orally. The medication can be taken with or without food. The dosage should be changed based on the patient’s symptoms and their ability to tolerate the drug. The starting therapeutic dose is 50 mg. It comes in a 25-mg, 50-mg, and 100-mg tablet available only as an extended-release. The 25-mg dose is commonly used when tapering off of the medication. The maximum dose of desvenlafaxine is 400 mg.

Adverse Effects

There is a broad range of general adverse effects that can be experienced with the usage of desvenlafaxine. A study done comparing desvenlafaxine to a placebo in treating major depressive disorder in adolescents noted the most common side effects to be abdominal pain, decreased appetite, headache, and nausea. Less commonly noted were diarrhea, dizziness, and cough. As with most selective serotonin reuptake inhibitors (SSRIs), a close eye should be kept on increased suicidal ideation. Abruptly stopping the use of desvenlafaxine can cause irritability, nausea, and headaches. Gradually tapering the medication is recommended to avoid such side effects.[4]

Contraindications

Prescribing this medication is contraindicated if a patient has a hypersensitivity to the drug or any components in its formulation.

Although rare, serotonin syndrome is a very serious condition that carries a high mortality rate. Taking a thorough history and doing a proper medication reconciliation can help prevent this serious condition. Signs of serotonin syndrome include tachycardia, sialorrhea, hyperactive bowel sounds, mydriasis, hyperthermia, and diaphoresis. If unsure whether a patient is suffering from serotonin syndrome the Sternbach and Hunter criteria can be used to help arrive at a definitive diagnosis. It can be caused by combining monoamine oxidase inhibitors, tricyclic antidepressants, triptans, additional serotonin receptor modulators, and over-the-counter drugs such as St. Johns Wart. Desvenlafaxine should not be started until the previous class of medications listed has been discontinued for at least 2 weeks. If serotonin syndrome is suspected, prompt discontinuation of the offending agent should be done along with supportive measures. If necessary cyproheptadine can be administered.[5]

There is conflicting data on gastrointestinal bleeding being caused by SNRI use. Desvenlafaxine is not specifically documented; however, its combined use with non-steroidal anti-inflammatory drugs may add to the risk.[6]

If a bipolar disorder is being considered in the differential diagnosis, it is important to add a mood stabilizer along with a serotonin receptor modulator to not trigger a manic episode.

There have been documented instances where neonates exposed to SNRIs late in the third trimester who have gone on to develop difficulties with feeding and breathing, which have required prolonged hospitalization. Desvenlafaxine is a category C drug which means that tests done on animals have shown an adverse effect on the fetus and there are no well-controlled studies in humans, but possible benefits may justify the use of the drug in pregnant women despite risks. Desvenlafaxine is excreted into the breast milk with one study reporting that peak levels are 3.3 hours after a dose. When mothers took the sister drug venlafaxine, neonates exposed to the drug via breast milk sometimes experienced poor neonatal adaptation. This reaction could occur in individuals taking desvenlafaxine as well.[7]

Monitoring

A detailed assessment for depression and suicidality should be done, especially at the beginning of therapy or when the dosage is changed. It is necessary to observe patients taking desvenlafaxine for behavior changes such as anxiety, social function, and mania.

Toxicity

Desvenlafaxine is rarely lethal when used as a standalone agent. There is a risk of serotonin syndrome when combined with other serotonin augmenting medications, triptans, tricyclic antidepressants, over-the-counter agents, and monoamine oxidase inhibitors. The treatment for overdose is symptomatic and supportive. There is no specific treatment for desvenlafaxine toxicity.

Enhancing Healthcare Team Outcomes

Healthcare professionals such as nurses, physician assistants, and primary care practitioners should keep major depressive disorder in their differential when dealing with patients who may present with depressed mood, anhedonia, feelings of guilt, worthlessness, insomnia, and suicidality. Endocrine abnormalities, along with substance abuse, may also cause these symptoms. Once substance abuse and other factors have been ruled out only then a psychiatric diagnosis of MDD should be made.

It is now common to treat this disease with selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. It is important for providers to assess all the medications being taken by the patient to prevent drug interactions with desvenlafaxine, especially those with decreased glomerular filtration rate (GFR) or hepatic impairment.


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Desvenlafaxine - Questions

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Amitriptyline is to tricyclic antidepressants as desvenlafaxine is to which of the following?



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A 22-year-old female presented to her primary care provider with feelings of worthlessness, decreased sleep, and impaired concentration. She is an avid gardener but told the provider that she does not even want to leave the house. She noticed that her symptoms started roughly 2 months ago and cannot recall a specific trigger. Her provider decided to prescribe desvenlafaxine 50 mg daily. She returns 3 weeks later complaining of recurring thoughts of jumping off a bridge, headaches, decreased appetite, and difficulty achieving an orgasm with her partner of 2 years. Which of the follow-up complaints is the best reason to discontinue treatment?



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A 46-year-old male comes to your clinic stating that he feels he is useless to everyone around him. This feeling has caused him to lose sleep, and now he averages only 2 to 3 hours a night. He is constantly getting scolded by his boss at work for poor performance, which he attributes to difficulty concentrating. A former competitive bodybuilder, he now does not enjoy going to the gym at all. He states that he always feels tired and has no energy. He also states that he has felt this way for 1 month and is “sick of feeling this way.” You decide to prescribe desvenlafaxine to treat his symptoms. Why would the provider recommend this drug to treat this patient?



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A 42-year-old male with a past medical history of migraine headaches, hypertension, gout, and hyperlipidemia presents to the psychiatric outpatient clinic to be evaluated for depression. His current medications include sumatriptan, lisinopril, naproxen, and a multivitamin. After eliciting a thorough history, the provider decides to begin desvenlafaxine to treat depression. Four days later the provider receives a notice that the patient has been admitted to the hospital due to an elevated heart rate, muscular rigidity, sialorrhea, and mydriasis. Ultimately, the diagnosis of serotonin syndrome is made, and he is treated accordingly. Which of the following drugs did desvenlafaxine interact with to cause serotonin syndrome?



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A 45-year-old man presents to the medical office complaining that he is having difficulty sleeping, concentrating at work, having thoughts of hurting himself, and decreased energy. These symptoms started 3 weeks ago and have been getting worse. You decide to start him on desvenlafaxine. Which of the following best explains this drug's mechanism of action?



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Elevated levels of which of the following would cause one to consider using a lower dose of desvenlafaxine?



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Desvenlafaxine - References

References

Low Y,Setia S,Lima G, Drug-drug interactions involving antidepressants: focus on desvenlafaxine. Neuropsychiatric disease and treatment. 2018     [PubMed]
Sansone RA,Sansone LA, Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innovations in clinical neuroscience. 2014 Mar     [PubMed]
Berhan Y,Berhan A, Is desvenlafaxine effective and safe in the treatment of menopausal vasomotor symptoms? A meta-analysis and meta-regression of randomized double-blind controlled studies. Ethiopian journal of health sciences. 2014 Jul     [PubMed]
Atkinson S,Lubaczewski S,Ramaker S,England RD,Wajsbrot DB,Abbas R,Findling RL, Desvenlafaxine Versus Placebo in the Treatment of Children and Adolescents with Major Depressive Disorder. Journal of child and adolescent psychopharmacology. 2018 Feb     [PubMed]
Roweth HG,Yan R,Bedwani NH,Chauhan A,Fowler N,Watson AH,Malcor JD,Sage SO,Jarvis GE, Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport. Scientific reports. 2018 Feb 22     [PubMed]
Desvenlafaxine null. 2006     [PubMed]
Evans RW, The FDA alert on serotonin syndrome with combined use of SSRIs or SNRIs and Triptans: an analysis of the 29 case reports. MedGenMed : Medscape general medicine. 2007 Sep 5     [PubMed]

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