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Duloxetine

Brands and Forms

  • Cymbalta
    • delayed-release capsule: 20mg, 30mg, 60mg

Uses of Duloxetine

Duloxetine is commonly used for treating Depressive Disorders and Anxiety Disorders.

It is also indicated for the treatment of neuropathic pain, especially in the context of Diabetes Mellitus, and for stress urinary incontinence.

How Duloxetine Works

Duloxetine is a serotonin and norepinephrine reuptake blocker (SNRI). It boosts the actions of serotonin and norepinephrine in the central nervous system, and has similar effects on dopamine.

Cautions when Using Duloxetine

Duloxetine can induce Manic or Mixed Episodes and Rapid Cycling in people with Bipolar Disorder.

Children and adolescents who use antidepressants like Duloxetine may develop self-injurious or suicidal behaviors (for more information, see here).

Use with caution in people with a known seizure disorder, glaucoma, and in those who are taking anticoagulant (blood thinning) medication.

Should not be used by individuals who consume large amounts of alcohol regularly.

Long-term use of Duloxetine may be associated with increased risk of osteoporosis and bone fractures in individuals over age 50.

Duloxetine should not be used during or within 14 days following the administration of an MAOI, because a hypertensive crisis may result.

Do not combine with Thioridazine, because life-threatening ventricular arrythmias could occur.

Dosing of Duloxetine

The usual therapeutic range of Duloxetine is 30-60mg/day, but can be used at doses as high as 120mg/day. It is usually given once daily in the morning but can also be given twice a day.

Duloxetine is usually started at 30mg/day, and then increased to 60mg after one week. Thereafter, it is common practice to wait 4 weeks for therapeutic effects to take place before deciding to increase the dose. Dose increases are usually done in 30mg increments at 2-week intervals to allow time for therapeutic effects to appear.

When wanting to stop this medication, the dose should be decreased gradually over a period of 6-8 weeks. A sudden cessation of the medication can result in a discontinuation syndrome.

Onset of action

Therapeutic effects are not expected before 2-4 weeks at a dose of 30-60mg/day. If no significant effects are seen after 6-8 weeks of use, including at least 2 weeks at a dose of 60mg/day, then the medication may not work at all.

Kidney impairment

Not recommend for patients with end-stage renal disease or severe renal function impairment (CrCl less than 30 mL/min).

Liver impairment

Not to be given to anyone with liver impairment. Not recommended for use in individuals with substantial alcohol use.

Side-effects of Duloxetine

Below is a list of most of the reported side-effects of Duloxetine. Most of these side-effects occur in only a minority of individuals, and many also resolve with time while the medication is continued.

Cardiovascular: hot flushes; palpitations; elevated blood pressure.

Central Nervous System: somnolence; headache; dizziness; insomnia; fatigue; decreased appetite; weakness; decreased libido (see below on managing sexual side-effects); abnormal dreams; migraine; fever; yawning; lethargy; extrapyramidal symptoms (rare); seizures (rare); serotonin syndrome (rare).

Dermatologic: excessive sweating; itchiness; rash; hair loss (rare).

Eyes, Ears, Nose and Throat: nasopharyngitis; pharyngolaryngeal pain; blurred vision; glaucoma; tinnitus.

Gastrointestinal: nausea; dry mouth; constipation; diarrhea; vomiting; dyspepsia; loose stools; flatulence; appetite loss; weight loss or gain.

Genitourinary: ejaculation disorder (see below on managing sexual side-effects); erectile dysfunction; abnormal orgasm; impotence.

Hematologic: increases bleeding time (thins the blood); easy bruising; hemolytic anemia, thrombocytopenia, thrombosis

Muskuloskeletal: joint and muscle pain; risk of osteoporosis and bone fractures with long-term use.

Psychiatric: anxiety; agitation; apathy; worsening depression; suicidal thoughts (overall, Duloxetine use helps to lower risk of suicide); self-injurious behaviors among children and adolescents; can induce Manic or Mixed Episodes and Rapid Cycling in people with Bipolar Disorder; can induce psychosis in people with Psychotic Disorders or Bipolar Disorder.

Respiratory: upper respiratory tract infection; coughing.

Common side-effects of Duloxetine

Somnolence, headache, dizziness, insomnia, fatigue, decreased appetite, excessive sweating, nausea, dry mouth, constipation, diarrhea, sexual dysfunction (about 5%, see below on managing sexual side-effects). Most of these side-effects resolve after a few weeks.

Rare but serious side-effects of note of Duloxetine

  • Children and adolescents who use antidepressants like Duloxetine may develop self-injurious or suicidal behaviors (for more information, see here).
  • Seizures

Duloxetine discontinuation syndrome

Individuals who suddenly stop using Duloxetine after taking the medication at moderate or high doses over a significant period of time are at risk of developing a discontinuation syndrome, which can include the following symptoms: dizziness, electric shock-like sensations, sweating, nausea, insomnia, tremor, anxiety, restlessness, agitation, depressed mood, irritability, confusion, lethargy, and vertigo. These symptoms usually start anywhere from one day to one week after the medication was stopped, and can persists for days or even weeks.

This syndrome can be treated by restarting the medication at its prior dose. It can be prevented by decreasing the dose gradually over a period of 6-8 weeks when wanting to stop the medication. In rare cases, individuals may experience the discontinuation syndrome even when the medication is being tapered gradually; in such cases, an extremely slow and gradual taper will be necessary.

Managing sexual side-effects of Duloxetine

The first step to manage this is to try to lower the dose of the Duloxetine. If this is not possible, or is not an effective solution, then either Bupropion, or Sildenafil (Viagra) or Vardenafil (Levitra), can be added [ref]. (Sildenafil and Vardenafil can be effective for female sexual side-effects as well, including difficulty achieving orgasm [ref, ref]). Caution should be used when combining Duloxetine with Bupropion, as elevations in blood pressure could result.

Bupropion and Mirtazepine are two antidepressants that tend to have very low rates of sexual side-effects.

Duloxetine overdose

Hypertension, hypotension, seizures, serotonin syndrome, somnolence, syncope, tachycardia, vomiting, coma. Can be fatal.

Duloxetine and pregnancy

Category C: some animal studies show adverse effects at very high doses, but no controlled human studies have been done; should only be used in pregnancy if clearly needed and if benefits outweigh potential risks. For further information, see the section on treating Depression in pregnancy.

Medical Monitoring for Duloxetine

Blood pressure should be measured a few weeks after starting the medication and after dose increases.

Drug Interactions with Duloxetine

  • Caution should be used when combining Duloxetine with other medications that can increase bleeding time and reduce blood clotting, including Aspirin, NSAIDs, anti-platelet agents, Heparin and Coumadin.
  • Combination with other serotonergic medications, including SSRI antidepressants, could potentially precipitate a serotonin syndrome.
  • Do not combine with Thioridazine, because life-threatening ventricular arrythmias could occur.
  • Duloxetine blood concentrations can be increased by Fluvoxamine, Paroxetine, Fluoxetine, and Quinidine.
  • Duloxetine can increase blood concentrations of Tricyclic Antidepressants.
  • Duloxetine should not be used during or within 14 days following the administration of an MAOI, because a hypertensive crisis may result.