Selective serotonin reuptake inhibitors





Introduction

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used antidepressant. They are generally well-tolerated and indicated in a number of other psychiatric conditions such as anxiety.

Indications

Selective serotonin reuptake inhibitors (SSRIs) are considered first-line treatment for the majority of patients with depression.
  • Citalopram (although see below re: QT interval) and fluoxetine are currently the preferred SSRIs
  • Sertraline is useful post myocardial infarction as there is more evidence for its safe use in this situation than other antidepressants
  • SSRIs should be used with caution in children and adolescents. Fluoxetine is the drug of choice when an antidepressant is indicated

Adverse effects

  • Gastrointestinal symptoms are the most common side-effect
  • There is an increased risk of gastrointestinal bleeding in patients taking SSRIs. A proton pump inhibitor should be prescribed if a patient is also taking a NSAID
  • Hyponatraemia: thought to be secondary to SIADH
  • Patients should be counselled to be vigilant for increased anxiety and agitation after starting a SSRI
  • Fluoxetine and paroxetine have a higher propensity for drug interactions

Citalopram and the QT interval
  • The Medicines and Healthcare products Regulatory Agency (MHRA) released a warning on the use of citalopram in 2011
  • It advised that citalopram and escitalopram are associated with dose-dependent QT interval prolongation and should not be used in those with: congenital long QT syndrome; known pre-existing QT interval prolongation; or in combination with other medicines that prolong the QT interval
  • The maximum daily dose is now 40 mg for adults; 20 mg for patients older than 65 years; and 20 mg for those with hepatic impairment

Contraindications

Citalopram and the QT interval
  • The Medicines and Healthcare products Regulatory Agency (MHRA) released a warning on the use of citalopram in 2011
  • It advised that citalopram and escitalopram are associated with dose-dependent QT interval prolongation and should not be used in those with: congenital long QT syndrome; known pre-existing QT interval prolongation; or in combination with other medicines that prolong the QT interval
  • The maximum daily dose is now 40 mg for adults; 20 mg for patients older than 65 years; and 20 mg for those with hepatic impairment

Interactions
  • NSAIDs: NICE guidelines advise 'do not normally offer SSRIs', but if given co-prescribe a proton pump inhibitor
  • Warfarin / heparin: NICE guidelines recommend avoiding SSRIs and considering mirtazapine
  • Aspirin: see above
  • Triptans: avoid SSRIs
  • Monoamine oxidase inhibitors (MAOIs) - risk of serotonin syndrome

Monitoring

Following the initiation of antidepressant therapy patients should normally be reviewed by a doctor after 2 weeks. For patients under the age of 30 years or at increased risk of suicide they should be reviewed after 1 week. If a patient makes a good response to antidepressant therapy they should continue on treatment for at least 6 months after remission as this reduces the risk of relapse.

When stopping a SSRI the dose should be gradually reduced over a 4 week period (this is not necessary with fluoxetine). Paroxetine has a higher incidence of discontinuation symptoms.

Discontinuation symptoms
  • Increased mood change
  • Restlessness
  • Difficulty sleeping
  • Unsteadiness
  • Sweating
  • Gastrointestinal symptoms: pain, cramping, diarrhoea, vomiting
  • Paraesthesia