Desvenlafaxine

Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants in children and teenagers should be dispensed with each prescription. Desvenlafaxine is not FDA approved for use in pediatric patients.

May cause increase in anxiety, nervousness, and insomnia.

May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin or NSAIDs due to ulcerogenic potential. Data are inconclusive regarding extent of bleeding risk of SNRIs in combination with warfarin or other anticoagulants. Bleeding related to SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.

Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.

May cause significant dose-related increases in total cholesterol, LDL, and triglycerides; monitor.

Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda, 2013; Rizzoli, 2012).

Dose-related increases in systolic and diastolic blood pressure have been documented. Monitor blood pressure regularly, and if sustained increases noted, consider dose reduction or discontinuation.

May cause mild pupillary dilation, which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors. Avoid use in patients with untreated anatomically narrow angles.

Interstitial lung disease and eosinophilic pneumonia have been rarely reported with venlafaxine (the parent drug of desvenlafaxine). May present as progressive dyspnea, cough, and/or chest pain. Prompt evaluation and possible discontinuation of therapy may be necessary.

Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

May cause or exacerbate sexual dysfunction.

SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium Disease-related concerns:

May cause sustained increase in blood pressure or heart rate. Control preexisting hypertension prior to initiation of desvenlafaxine. Use caution in patients with preexisting hypertension, cardiovascular conditions, or cerebrovascular disease. Hypertensive effect is dose related.

Use caution; clearance is decreased and average AUC is increased; dosage adjustment is recommended in patients with moderate to severe hepatic impairment.

May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Desvenlafaxine is not FDA approved for the treatment of bipolar depression.

Use caution; clearance is decreased and plasma concentrations are increased; dosage reduction recommended in patients with severe renal impairment or end-stage renal disease.

Use caution in patients with a previous seizure disorder. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

The elderly are at increased risk for orthostatic hypotension with therapy compared to younger adults. Other warnings/precautions:

Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).