Long-Term Duloxetine Withdrawal Syndrome and Management in a Depressed Patient

“Miss B” was a depressed patient (depressed mood, anhedonia, anergia, binge eating, and suicide ideation) with partial remission of symptoms under duloxetine treatment (60 mg/day) for 1 year. However, she disliked the side effects of duloxetine (dizziness and sedation). Therefore, duloxetine was abruptly switched to bupropion 150 mg/day. She started to feel more energy, but with intermittent severe nausea, unexplained fear, and dizziness after quitting duloxetine for 1 day. She still had withdrawal symptoms once-to-twice every week in the following 6 months after the switch. She took duloxetine 30 mg only while feeling withdrawal discomfort in the next 3 months, and then took 15 mg (discarding half the dose of the 30-mg capsule) in the same way for the last month. She took 10 months to recover from long-term and intermittent duloxetine withdrawal syndrome. No residual withdrawal syndrome was noted since that time.

Venlafaxine has a higher selectivity of serotonin receptor (30-fold versus norepinephrine) than duloxetine (10-fold).² Perahia et al. reported that discontinuation-emergent adverse effects of duloxetine happened in around 44.3% of patients, versus 22.9% in a placebo group. They found that duloxetine withdrawal syndrome included dizziness, nausea, headache, paresthesia, vomiting, irritability, and nightmares,³ which were similar to the symptoms of this patient. Duloxetine withdrawal syndrome is similar to that seen in discontinuation of SNRIs and serotoninergic-related antidepressants.³ A 10-fold selectivity for serotonin receptor of duloxetine might explain duloxetine withdrawal syndrome in this patient and why it is not so frequent as with venlafaxine, which has 30-fold higher affinity.² In a current literature search, duloxetine withdrawal syndrome is just mentioned in a few reports.^3,4 Besides, a relatively longer half-life of duloxetine (12 hours)⁵ than the short half-life (5 hours) of venlafaxine,⁶ and possible genotype polymorphism of Asian people,⁶ might explain why the long-term and intermittent duloxetine withdrawal syndrome happened in this patient. A gradual tapering-down of duloxetine dose (not an abrupt switch) or occasional re-use of duloxetine while withdrawing might be helpful for this kind of long-term duloxetine withdrawal syndrome.