• The most common adverse effects seen in clinical trials were nausea, dry mouth, fatigue, and constipation, which usually occur in the first week of treatment.
• Duloxetine treatment is associated with small increases in blood pressure (BP).
• Monitor BP in people with known hypertension or other cardiac disease and those whose conditions could be affected by an increase in BP (see the section on Monitoring in the CKS topic on Neuropathic pain - drug treatment).
• Consider reducing the dose or gradual discontinuation in people who experience a sustained increase in BP while taking duloxetine.
• Hyponatraemia is associated with all types of antidepressants (duloxetine is a serotonin-noradrenaline reuptake inhibitor).
• Consider hyponatraemia if the person develops dizziness, drowsiness, confusion, nausea, muscle cramps, or seizures.
• If hyponatraemia is suspected, stop duloxetine and manage according to severity and duration of symptoms, and state of hydration.
• Bleeding abnormalities have been reported with serotonin-noradrenaline reuptake inhibitors.
• This risk is increased in people who are also taking low-dose aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) — consider gastroprotection for people who are prescribed duloxetine with an NSAID or aspirin.
• This increased risk may also apply to those who are very old or those with a history of gastrointestinal bleeding — consider using an alternative drug in these groups.
• Exercise caution in people taking warfarin.
• Suicidal thoughts and suicide attempts have rarely been reported during duloxetine treatment or early after stopping treatment.
• Advise people to seek medical advice immediately if they notice any changes in mood, increased anxiety and agitation, negativity and hopelessness, or suicidal ideation.
• Treatment with duloxetine has been associated with an increase in fasting plasma glucose.
• The clinical significance of this is not clear, but it may be prudent to monitor blood glucose in people who are taking duloxetine to treat painful diabetic neuropathy.

[ABPI Medicines Compendium, 2008a]

• Recent data has shown high discontinuation rates during the first 4 weeks of duloxetine treatment caused by adverse effects [Women's Health Specialist Library, 2009].

• Duloxetine has been associated with small increases in blood pressure and clinically significant hypertension in some people [ABPI Medicines Compendium, 2008a; Micromedex, 2009].
• In clinical trials, treatment with duloxetine led to a mean increase in blood pressure of up to 2.1 mmHg systolic and 2.3 mmHg diastolic, compared with placebo.
• Cases of hypertensive crisis have been reported with duloxetine, especially in people with pre-existing hypertension.
• The recommendation regarding antidepressants and hyponatraemia is in line with advice from the Committee on Safety of Medicines (now the Commission on Human Medicines) [MHRA, 1994].
• Most of the evidence for an increased risk of bleeding is from observational studies of selective serotonin reuptake inhibitors (SSRIs) [de Abajo et al, 1999; van Walraven et al, 2001; Dalton et al, 2003; Meijer et al, 2004]. However, there have also been reports of bleeding abnormalities with serotonin-noradrenaline reuptake inhibitors [Micromedex, 2009]. Recommendations for minimizing this adverse effect are expert opinion extrapolated from managing this adverse effect with SSRIs [Paton and Ferrier, 2005].
• Isolated cases of suicidal thoughts and suicide attempts have been reported during duloxetine therapy or early after treatment discontinuation. The Commission on Human Medicines recommends that people be monitored frequently for the emergence of suicidal thoughts or behaviour during treatment with duloxetine [CSM, 2006].