brands

Class

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

DULOXETINE commonly prescribed for

(Bold for FDA approved)

How DULOXETINE 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

• Presumably desensitizes both serotonin 1A receptors and beta adrenergic receptors

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

• Weakly blocks dopamine reuptake pump (dopamine transporter), and may increase dopamine neurotransmission

How long until DULOXETINE works

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

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

• Can reduce neuropathic pain within a week, but onset can take longer

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

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

Notable Side Effects

• Nausea, diarrhea, decreased appetite, dry mouth, constipation (dose-dependent)

• Insomnia, sedation, dizziness

• Sexual dysfunction (men: abnormal ejaculation/orgasm, impotence, decreased libido; women: abnormal orgasm)

• Sweating

• Increase in blood pressure (up to 2 mmHg)

• Urinary retention

Life Threatening Side Effects

• Rare seizures

• Rare induction of hypomania

• Rare activation of suicidal ideation, suicide attempts, and completed suicide

• 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 DULOXETINE side effects

• Wait

• Wait

• Wait

• Lower the dose

• In a few weeks, switch or add other drugs

usual dosage range

• 40–60 mg/day in 1–2 doses for depression

• 60 mg once daily for diabetic peripheral neuropathic pain and fibromyalgia

• 60 mg once daily for GAD

• 40 mg twice daily for stress urinary incontinence

Dosage Forms

• Capsule 20 mg, 30 mg, 40 mg, 60 mg

long term use

• Blood pressure should be monitored regularly

habit forming

• No

Renal Impairment

• Dose adjustment generally not necessary for mild to moderate impairment

• Not recommended for use in patients with end-stage renal disease (requiring dialysis) or severe renal impairment

Hepatic Impairment

• Not to be administered to patients with any hepatic insufficiency

• Not recommended for use in patients with substantial alcohol use

• Increased risk of elevation of serum transaminase levels

Cardiac Impairment

• Drug should be used with caution

• Duloxetine may raise blood pressure

Elderly

• Some patients may tolerate lower doses better

• 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

• Not studied, but can be used by experts

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

• 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

• 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

• 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