Adverse effects[
edit]
Nausea,
somnolence,
insomnia, and
dizziness are the main
side effects, reported by about 10% to 20% of patients.
[34]
In a trial for major depressive disorder (MDD), the most commonly reported treatment-emergent adverse events among duloxetine-treated patients were
nausea (34.7%),
dry mouth (22.7%),
headache (20.0%) and
dizziness (18.7%), and except for
headache, these were reported significantly more often than in the placebo group.
[35] In a long-term study of fibromyalgia patients receiving duloxetine, frequency and type of adverse effects was similar to that reported in the MDD above. Side effects tended to be mild-to-moderate, and tended to decrease in intensity over time.
[36]
Sexual dysfunction is often a side effect of drugs that inhibit serotonin reuptake. Specifically, common side effects include difficulty becoming aroused, lack of interest in sex, and
anorgasmia (trouble achieving orgasm). Loss of or decreased response to sexual stimuli and ejaculatory
anhedonia are also possible. Frequency of treatment-emergent sexual dysfunction in long-term treatment has been found to be similar for duloxetine and SSRIs when compared in clinical trials,
[37][38] while there is some evidence that duloxetine is associated with less sexual dysfunction than escitalopram when measured at 4 and 8 weeks of treatment.
[38]
Postmarketing spontaneous reports[
edit]
Reported adverse events which were temporally correlated to duloxetine therapy include rash, reported rarely, and the following adverse events, reported very rarely:
alanine aminotransferase increased,
alkaline phosphatase increased,
anaphylactic reaction,
angioneurotic edema,
aspartate aminotransferase increased,
bilirubin increased,
glaucoma,
hepatitis,
hyponatremia,
jaundice,
orthostatic hypotension (especially at the initiation of treatment),
Stevens–Johnson syndrome,
syncope (especially at initiation of treatment), and
urticaria.
[39]
Discontinuation syndrome[
edit]
Further information:
SSRI discontinuation syndrome
During marketing of other SSRIs and SNRIs, there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following:
dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g.,
paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy,
emotional lability,
insomnia,
hypomania,
tinnitus, and seizures. The
withdrawalsyndrome from duloxetine resembles the
SSRI discontinuation syndrome.
When discontinuing treatment with duloxetine, the manufacturer recommends a gradual reduction in the dose, rather than abrupt cessation, whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate. The use of a liquid form of the drug may facilitate more gradual tapering."
[40]
In placebo-controlled clinical trials of up to nine weeks' duration of patients with MDD, a systematic evaluation of discontinuation symptoms in patients taking duloxetine following abrupt discontinuation found the following symptoms occurring at a rate greater than or equal to 2% and at a significantly higher rate in duloxetine-treated patients compared to those discontinuing from placebo: dizziness, nausea, headache, paresthesia, vomiting, irritability, and nightmare.
[41]
Suicidality[
edit]
The FDA requires all antidepressants, including duloxetine, to carry a
black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25. This warning is based on statistical analyses conducted by two independent groups of the FDA experts that found a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18–24 age group.
[42][43][44]
To obtain
statistically significant results the FDA had to combine the results of 295 trials of 11 antidepressants for psychiatric indications. As
suicidal ideation and behavior in clinical trials are rare, the results for any drug taken separately usually do not reach statistical significance.
In 2005 the United States FDA released a public health advisory noting that there had been 11 reports of suicide attempts and 3 reports of suicidialty within the mostly middle-aged women participating in the open label extension trials of duloxetine for the treatment of stress urinary incontinence. The FDA described the potential role of confounding social stressors "unclear". The suicide attempt rate in the SUI study population (based on 9,400 patients) was calculated to be 400 per 100,000 person years. This rate is greater than the suicide attempt rate among middle-aged U.S. women that has been reported in published studies, i.e., 150 to 160 per 100,000 person years. In addition, one death from suicide was reported in a Cymbalta clinical pharmacology study in a healthy female volunteer without SUI. No increase in suicidality was reported in controlled trials of Cymbalta for depression or diabetic neuropathic pain.
[45]