SSRIs
Selective serotonin re-uptake inhibitors (SSRIs) are considered first-line treatment for the majority of patients with depression.
Adverse effects
Interactions
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
The following table illustrates the side effects, interactions, and respective half life of the different SSRIs (summerised from the Maudsley Guidelines 11th Edition)
- citalopram and fluoxetine are currently the preferred SSRIs
- citalopram is useful for elderly patients as it is associated with lower risks of drug interactions
- 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
- patients should be counseled to be vigilant for increased anxiety and agitation after starting a SSRI
- fluoxetine and paroxetine have a higher propensity for drug interactions
- citalopram and sertraline and more suitable for patients with chronic physical health problems as they have a lower propensity for drug interactions.
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
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
The following table illustrates the side effects, interactions, and respective half life of the different SSRIs (summerised from the Maudsley Guidelines 11th Edition)
| SSRI | Half life | Main side effects | Major interactions |
|---|---|---|---|
| Citalopram | 33 hours | Nausea, vomiting, dyspepsia, abdo pain, diarrhoea, rash, sweating, agitation, anxiety, headache, insomnia, tremor, sexual dysfunction, hyponatremia, cutaneous bleeding disorders | Not a potent inhibitor of most cytochrome enzymes |
| Escitalopram | 30 hours | As for citalopram | As for citalopram |
| Fluoxetine | 4-6 days | As for citalopram but insomnia and agitation possibly more common Rash may occur more frequently May alter insulin requirements | Inhibits CYP2D6, CYP3A4. Increases levels of some antipsychotics, some benzodiazepines, carbamazepine, ciclosporin, phenytoin, tricyclics Never use with MAOIs Avoid selegiline and St John's Wort |
| Fluvoxamine | 17-22 hours | As for citalopram but nausea more common | Inhibits CYP1A2/2C9/3A4. Increases levels of some benzodiazepines, carbamazepine, ciclosporin, phyenytoin, some tricyclics, methadone, olanzapine, clozapine, propanolol, theophylline, warfarin |
| Paroxetine | 24 hours | As per citalopram but antimuscarinic effects and sedation more common EPSEs more common but rare | Potent inhibitor of CYP2D6/3A4. Increases levels of some antipsychotics and tricyclics Never use with MAOIs Avoid St John's Wort |
| Sertraline | 26 hours | As for citalopram | Inhibits CYP2D6. Increases levels of some antipsychotics and tricyclics Avoid St John's Wort |
