Duloxetine

# Duloxetine ## Overview - **Classification**: Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) - **Mechanism**: Potently inhibits neuronal reuptake of serotonin and norepinephrine, and weakly inhibits dopamine reuptake. This increases neurotransmitter levels in the CNS. ## Primary Indications 1. **Major Depressive Disorder (MDD)** - Treatment of symptoms. 2. **Generalized Anxiety Disorder (GAD)** - Management of anxiety symptoms. 3. **Diabetic Peripheral Neuropathic Pain (DPNP)** - Management of neuropathic pain. 4. **Chronic Musculoskeletal Pain** - Including chronic low back pain and chronic osteoarthritis pain. 5. **Fibromyalgia (FM)** - Management of pain and other symptoms. ## Adult Dosing ### Standard Dosing **Major Depressive Disorder (MDD)** - **Dose**: Start **20-30 mg** once daily (QD) for 1 week. - **Frequency**: Increase to **60 mg QD**. - **Route**: Oral - **Maximum**: **120 mg QD**, but doses >60 mg QD do not show increased efficacy in MDD. **Generalized Anxiety Disorder (GAD)** - **Dose**: Start **30 mg QD** for 1 week. - **Frequency**: Increase to **60 mg QD**. - **Route**: Oral - **Maximum**: **120 mg QD**, but doses >60 mg QD do not show increased efficacy in GAD. **Diabetic Peripheral Neuropathic Pain (DPNP)** - **Dose**: Start **20-30 mg QD** for 1 week. - **Frequency**: Increase to **60 mg QD**. - **Route**: Oral - **Maximum**: **60 mg QD**. Doses >60 mg QD do not show increased efficacy. **Fibromyalgia (FM), Chronic Musculoskeletal Pain** - **Dose**: Start **30 mg QD** for 1 week. - **Frequency**: Increase to **60 mg QD**. - **Route**: Oral - **Maximum**: **60 mg QD**. Doses >60 mg QD do not show increased efficacy. ### Dose Adjustments - **Renal Impairment**: Not recommended in patients with **CrCl <30 mL/min** (ESRD or severe renal impairment). - **Hepatic Impairment**: Not recommended in patients with **chronic liver disease or cirrhosis**. - **Elderly Patients**: Start with lower doses (e.g., **20 mg QD**) and titrate slowly due to increased risk of orthostatic hypotension and falls. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Safety and efficacy **not established**. - **Special Notes**: Use generally **not recommended**. ### Infants (1-12 months) - **Dose**: Safety and efficacy **not established**. - **Special Notes**: Use generally **not recommended**. ### Children (1-12 years) - **Generalized Anxiety Disorder (GAD) (7-17 years)** - **Dose**: Initiate **20 mg QD** for 2 weeks. - **Frequency**: Then increase to **30 mg QD**. - **Maximum**: **60 mg QD**. - **Special Notes**: Patients should be able to swallow capsules whole. ### Adolescents (13-18 years) - **Major Depressive Disorder (MDD) (13-17 years)** - **Dose**: Initiate **20 mg QD** for 2 weeks, then **30 mg QD**. - **Frequency**: Target dose is usually **30-60 mg QD**. - **Maximum**: **120 mg QD**, but doses >60 mg QD do not show increased efficacy. - **Generalized Anxiety Disorder (GAD) (13-17 years)** - **Dose**: Initiate **20 mg QD** for 2 weeks, then **30 mg QD**. - **Frequency**: Target dose is usually **30-60 mg QD**. - **Maximum**: **120 mg QD**, but doses >60 mg QD do not show increased efficacy. - **Special Notes**: Consider lowest effective dose due to increased risk of suicidality. ## Safety Information ### Contraindications - **Absolute**: Concomitant use with **MAOIs** (or within 14 days of discontinuing). - **Absolute**: Uncontrolled **narrow-angle glaucoma**. - **Absolute**: Severe **renal impairment (CrCl <30 mL/min)**. - **Absolute**: Severe **hepatic impairment/cirrhosis**. - **Relative**: Concomitant use with potent **CYP1A2 inhibitors** (e.g., fluvoxamine, ciprofloxacin, enoxacin). ### Common Adverse Effects - **Very Common (>10%)**: Nausea, dry mouth, headache, constipation, insomnia, dizziness, fatigue. - **Common (1-10%)**: Diarrhea, somnolence, sweating, blurred vision, abdominal pain, decreased appetite. - **Serious but Rare**: Serotonin syndrome, hepatotoxicity, suicidal ideation/behavior, severe skin reactions (e.g., SJS), orthostatic hypotension, falls (especially elderly). ### Key Drug Interactions - **MAOIs**: Risk of **serotonin syndrome** (hyperthermia, rigidity, mental status changes). **Contraindicated**. - **Other Serotonergic Drugs (SSRIs, SNRIs, triptans, TCAs, fentanyl, lithium)**: Increased risk of **serotonin syndrome**. Monitor closely. - **CYP1A2 Inhibitors (fluvoxamine, ciprofloxacin)**: Significantly **increases duloxetine plasma levels**. Avoid concomitant use or reduce duloxetine dose. - **CYP2D6 Substrates (e.g., TCAs, risperidone)**: Duloxetine is a moderate **CYP2D6 inhibitor**, can increase levels of co-administered drugs. - **Alcohol**: May worsen **liver injury** risk. Advise caution. - **NSAIDs/Anticoagulants**: Increased risk of **bleeding** due to effects on platelet aggregation. ## Monitoring & Follow-up - **Before Treatment**: Baseline blood pressure, heart rate, hepatic function tests, renal function (CrCl). - **During Treatment**: Blood pressure, heart rate (periodically), hepatic function (if clinically indicated), mental status for worsening depression or suicidality (especially initially and with dose changes). - **Clinical Signs**: Monitor for signs of serotonin syndrome (agitation, hyperreflexia, fever), liver injury (jaundice, dark urine, abdominal pain), withdrawal symptoms upon discontinuation. ## Clinical Pearls - 💡 **Discontinuation**: **Taper slowly** over at least 2 weeks to avoid withdrawal symptoms (e.g., dizziness, nausea, headache, anxiety). - 💡 **Administration**: Swallow capsules **whole**, do not chew or crush, as it affects the enteric coating. Can be taken with or without food. - 💡 **Suicidality**: Monitor all patients, especially children, adolescents, and young adults, for worsening depression or emergence of suicidal thoughts. - 💡 **Pain Relief**: Pain relief may take **several weeks** to become noticeable. Counsel patients on realistic expectations. - 💡 **Nausea**: Taking with food or at bedtime may help mitigate initial nausea. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.