What are antidepressants used to treat?
Antidepressants are drugs used for the treatment of moderate to severe depressive episodes and dysthymia.
They are also used for a range of other conditions including severe anxiety and panic attacks, obsessive– compulsive disorder (OCD), chronic pain, eating disorders and posttraumatic stress disorder (PTSD) .
Briefly describe how antidepressants work
All antidepressants work on the basis of the monoamine hypothesis by enhancing the activity of the monoamine neurotransmitters, noradrenaline (NA) and serotonin (5-HT).
Give examples of classes of antidepressants
SSRI: selective serotonin reuptake inhibitor
SNRI: serotonin and noradrenaline reuptake inhibitor
TCA: tricyclic antidepressant
MAOI: monoamine oxidase inhibitor
Which class of antidepressant are the first line? Why?
SSRIs are better tolerated, work more quickly and have lower risk of inducing mania with other antidepressants. Therefore, they are generally considered first-line for depression.
How long does it take for antidepressants to start working?
Research suggests that antidepressants begin to take effect by one week and at 4-6 weeks the benefit is clinically detectable.
Give examples of SSRIs
Citalopram, escitalopram, fluoxetine, paroxetine, sertraline, fluvoxamine.
What are the indications of SSRIs?
Depression (all SSRIs), panic disorder (citalopram, escitalopram, paroxetine), social phobia (escitalopram, paroxetine), bulimia nervosa (fluoxetine), OCD (most SSRIs), PTSD (paroxetine, sertraline), GAD (paroxetine).
Note: fluvoxamine is not regularly prescribed as it is a cytochrome P450 enzyme inhibitor and therefore commonly interacts with other medications, potentiating their effects.
What is the mechanism of action of SSRIs?
They work by inhibiting the reuptake of serotonin from the synaptic cleft into pre-synaptic neurones and therefore SSRIs increase the concentration of serotonin in the synaptic cleft.
What are the side effects of SSRIs?
- Gastrointestinal: nausea, dyspepsia, bloating, flatulence, diarrhoea and constipation
- Sweating
- Tremor
- Rashes
- Extrapyramidal side effects (uncommon)
- Sexual dysfunction
- Somnolence
- ‘Stopping SSRI’ symptoms (discontinuation syndrome)- GI symptoms, ‘chills’, insomnia, hypomania, anxiety and restlessness
Whar are the contraindications and cautions of SSRIs?
Cautions: history of mania, epilepsy, cardiac disease (sertraline is the safest), acute angle-closure glaucoma, diabetes mellitus (monitor glycaemic control after initiation), concomitant use with drugs that cause bleeding, GI bleeding (or history of GI bleeding), hepatic/renal impairment, pregnancy and breast-feeding, young adults (possible ↑ suicide risk) and suicidal ideation.
Contraindications: mania.
What are the doses of the following SSRIs?
- Sertraline
- Fluoxetine
- Citalopram
- Escitalopram
- Paroxetine
Sertraline: 50-200 mg/day.
Fluoxetine: 20-60 mg/day.
Citalopram: 20-40 mg/day.
Escitalopram: 10-20 mg/day.
Paroxetine: 20-50 mg/day.
What is the route for SSRIs?
Oral.
What factors need to be taken into consideration before choosing the right antidepressant?
There are a number of factors which influence the type of antidepressant prescribed to a patient:
- Overall safety profile: most national and local guidelines suggest SSRIs as first choice because of their safety profile in overdose as well as their effectiveness.
- Patient preference: after discussing side effects of each antidepressant, it is appropriate and important to involve the patient in the decision making.
- Prior treatment: if a patient has had benefit from a previously used antidepressant, that same one should be used, provided no contraindications have developed; equally if an antidepressant has already been tried and not benefited, another one should be trialled.
- Type and severity of depression: SSRIs are usually indicated for all severities of depression and when there is mixed anxiety and depression. In SSRI-resistant cases, SNRIs should be tried. When insomnia is present or weight gain is desired, mirtazapine can be given.
- Suicidal ideation: avoid drugs that are toxic in overdose such as TCAs and MAOIs. SSRIs should still be used with caution and appropriate review.
- Age and co-morbidities: SSRIs are usually the safest in elderly. Sertraline is the safest drug post-MI.
- Drug– drug interactions: avoid SSRIs in those on blood-thinning agents such as warfarin, heparin and the newer anticoagulant agents (e.g. rivaroxaban, apixaban and dabigatran), as well as NSAIDs.
- Pregnancy and breast feeding: all antidepressants should be used with caution and if required, the lowest effective dose should be used. Sertraline and fluoxetine are the safest during pregnancy along with some TCAs such as amitriptyline. The SSRIs paroxetine and sertraline are most likely suitable first-line agents during breast feeding.
- History of mania: all antidepressants have the potential to trigger a manic episode but SSRIs are usually the safest (avoid TCAs).
What is serotonin syndrome? What can cause serotonin syndrome?
The serotonin syndrome is a rare but life-threatening complication of increased serotonin activity, usually rapidly occurring within minutes of taking the medication.
It is most commonly caused by SSRIs but can be caused by other drugs such as TCAs and lithium.
What are the clinical features of serotonin syndrome?
Clinical features include:
- Cognitive effects→ headache, agitation, hypomania, confusion, hallucinations and coma.
- Autonomic effects→ shivering, sweating, hyperthermia, hypertension and tachycardia.
- Somatic effects→ myoclonus (muscle twitching), hyperreflexia and tremor.
How is serotonin syndrome treated?
Management involves stopping the offending drug and supportive measures.
What are the DO’S when prescribing SSRIs?
Prescribe SSRIs first-line for moderate to severe depression unless contraindicated.
Be cautious when prescribing to children and adolescents- fluoxetine is the drug of choice in this age group.
Prescribe sertraline post myocardial infarction as there is more evidence for its safe use in this situation over other antidepressants.
Review patients after 2 weeks of prescribing SSRIs- patients <30 years of age or at ↑ risk of suicide should be reviewed after 1 week.
Warn patients about side effects- GI being the most common.
Counsel patients to be vigilant for ↑ anxiety and agitation after starting an SSRI.
What are the DON’T when prescribing SSRIs?
Co-prescribe NSAIDs and SSRIs, but if you have to, prescribe a proton pump inhibitor too.
Co-prescribe SSRIs and heparin/ warfarin.
Stop SSRIs suddenly – if stopping an SSRI, the dose should be gradually reduced over a 4 week period (this is not necessary with fluoxetine).
Prescribe citalopram or escitalopram in congenital long QT syndrome, known pre-existing QT interval prolongation, or in conjunction with other medicines that prolong the QT interval, as they are associated with dose-dependent QT interval prolongation.
