DESVENLAFAXINE

brands

Class

• Neuroscience-based Nomenclature: serotonin and norepinephrine reuptake inhibitor (SN-RI)
• SNRI (dual serotonin and norepinephrine reuptake inhibitor); often classified as an antidepressant, but it is not just an antidepressant

DESVENLAFAXINE commonly prescribed for

(Bold for FDA approved)

How DESVENLAFAXINE works

• Boosts neurotransmitters serotonin, norepinephrine, and dopamine

• Blocks serotonin reuptake pump (serotonin transporter), presumably increasing serotonergic neurotransmission

• Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission

• Desensitizes both serotonin 1A receptors and beta adrenergic receptors

• Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, desvenlafaxine can increase dopamine neurotransmission in this part of the brain

How long until DESVENLAFAXINE works

• Onset of therapeutic actions usually not immediate, but often delayed 2–4 weeks

• If it is not working within 6 or 8 weeks for depression, it may require a dosage increase or it may not work at all

• May continue to work for many years to prevent relapse of depressive symptoms

• Vasomotor symptoms in perimenopausal women with or without depression may improve within 1 week

Notable Side Effects

• Most side effects increase with higher doses, at least transiently

• Insomnia, sedation, anxiety, dizziness

• Nausea, vomiting, constipation, decreased appetite

• Sexual dysfunction (abnormal ejaculation/ orgasm, impotence)

• Sweating

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

• Hyponatremia

• Increase in blood pressure

Life Threatening Side Effects

Rare seizures

• Rare induction of hypomania

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24)

weight gain

unusual

sedation

not usual

What to do about DESVENLAFAXINE side effects

• Wait

• Wait

• Wait

• Lower the dose

• In a few weeks, switch or add other drugs

usual dosage range

• Depression: 50 mg once daily

Dosage Forms

• Tablet (extended-release) 25 mg, 50 mg, 100 mg

long term use

• See doctor regularly to monitor blood pressure

habit forming

• No

Renal Impairment

• For moderate impairment, recommended dose is 50 mg/day

• For severe impairment, recommended dose is 50 mg every other day

• Patients on dialysis should not receive subsequent dose until dialysis is completed

Hepatic Impairment

• Doses greater than 100 mg/day not recommended

Cardiac Impairment

• Drug should be used with caution

• Hypertension should be controlled prior to initiation of desvenlafaxine and should be monitored regularly during treatment

• Desvenlafaxine has a dose-dependent effect on increasing blood pressure

• Desvenlafaxine is the active metabolite of venlafaxine, which is contraindicated in patients with heart disease in the UK

• Venlafaxine can block cardiac ion channels in vitro and worsens (i.e., reduces) heart rate variability in depression, perhaps due to norepinephrine reuptake inhibition

Elderly

• Some patients may tolerate lower doses better

• Risk of SIADH with SSRIs is higher in the elderly

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Use with caution, observing for activation of known or unknown bipolar disorder and/ or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

Pregnancy

Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• In animal studies, there was no evidence of teratogenicity at plasma exposure up to 19 times (rat) and 0.5 times (rabbit) the exposure at a usual adult dose; however, fetotoxicity and pup deaths occurred in rats at 4.5 times the exposure at a usual adult dose

• Not generally recommended for use during pregnancy, especially during first trimester

• Nonetheless, continuous treatment during pregnancy may be necessary and has not been proven to be harmful to the fetus

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child

• For many patients this may mean continuing treatment during pregnancy

• Exposure to SSRIs late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia

• Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying

Breast Feeding

• Some drug is found in mother’s breast milk

• Trace amounts may be present in nursing children whose mothers are on desvenlafaxine

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

• For many patients, this may mean continuing treatment during breast feeding