Out Of The Pipeline

Duloxetine: Dual-action antidepressant

Current Psychiatry. 2004 September;3(9):71-74

References

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2. Fava M. The role of the serotonergic and noradrenergic neurotransmitter systems in the treatment of psychological and physical symptoms of depression. J Clin Psychiatry 2003;64(suppl 13):26-9.

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6. Skinner MH, Kuan HY, Pan A, et al. Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. Clin Pharmacol Ther 2003;73:170-7.

7. Sadock BJ, Sadock VA. Kaplan and Sadock's pocket handbook of psychotropic drug treatment (3rd ed). Baltimore, MD: Lippincott Williams and Wilkins, 2001.

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11. Cymbalta prescribing information Eli Lilly and Co 2004.

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In another study,¹² duloxetine showed worsening only in ASEX item 4 (“How easily can you reach an orgasm?”), indicating some adverse sexual effects in men. No such differences were found in women. Duloxetine’s effect on sexual function needs to be studied further.

Duloxetine is an FDA Use-in-Pregnancy category C medication, meaning that risk to the fetus has not been ruled out. The agent is contraindicated in patients taking monoamine oxidase inhibitors and in those with narrow-angle glaucoma. FDA recommends not using duloxetine in patients with hepatic insufficiency, endstage renal disease, and substantial alcohol use.

DOSING STRATEGIES

Duloxetine, 40 to 120 mg/d, appears to be safe and effective for most adults.^8-10 FDA recommends starting at 40 mg/d (20 mg bid) to 60 mg/d (once-daily or 30 mg bid) with no regard to meals. Dosages >60 mg/d have not shown additional benefit. Age and tolerability should drive initial dosing and titration. Side-effect incidence has not been directly compared at 60, 90, and 120 mg/d.

CLINICAL IMPLICATIONS

In clinical trials, duloxetine has shown a high estimated probability of remission in major depression and has shown efficacy against depression’s physical and emotional symptoms. Based on efficacy and safety data, duloxetine appears to be a first-line treatment option for major depression.

Related resources

Gray GE. Concise guide to evidence-based psychiatry. Washington, DC: American Psychiatric Publishing, 2004.
Schatzberg AF, Nemeroff CB (eds). Textbook of psychopharmacology (3rd ed). Washington, DC: American Psychiatric Publishing, 2004.

Drug brand names

Amitriptyline • Elavil
Cimetidine • Tagamet
Ciprofloxacin • Cipro
Desipramine • Norpramin
Duloxetine • Cymbalta
Enoxacin • Penetrex
Fluoxetine • Prozac
Flecainide • Tambocor
Fluvoxamine • Luvox
Haloperidol • Haldol
Metoprolol • Toprol
Nortriptyline • Pamelor
Paroxetine • Paxil
Propafenone • Rythmol
Propranolol • Inderal
Risperidone • Risperdal
Thioridazine • Mellaril
Timolol • Blocadren, others
Venlafaxine • Effexor

Disclosure

Dr. Rakesh Jain receives research grants from Eli Lilly and Co., Forest Pharmaceuticals, GlaxoSmithKline, Merck and Co., Organon, Pfizer Inc., and Sepracor. He is a consultant to and speaker for Eli Lilly and Co., and is a speaker for GlaxoSmithKline, Pfizer Inc., and Wyeth Pharmaceuticals.

Dr. Shailesh Jain reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of compefting products.

Duloxetine: Dual-action antidepressant

References

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