TeacherOfMedicine: Antidepressants, selective serotonin reuptake inhibitors

As first-line treatment for moderate-to-severe depression, and in mild depression if psychological treatments fail.
Panic disorder.
Obsessive compulsive disorder.

Selective serotonin reuptake inhibitors (SSRIs) preferentially inhibit neuronal reuptake of serotonin (5-HT) from the synaptic cleft, thereby increasing its availability for neurotransmission. This appears to be the mechanism by which SSRIs improve mood and physical symptoms in depression and relieve symptoms of panic and obsessive disorders.
SSRIs differ from tricyclic antidepressants in that they do not inhibit noradrenaline uptake and cause less blockade of other receptors. The efficacy of the two drug classes in the treatment of depression is similar. However, SSRIs are generally preferred as they have fewer adverse effects and are less dangerous in overdose.

Common adverse effects include gastrointestinal upset, appetite and weight disturbance (loss or gain) and hypersensitivity reactions, including skin rash. Hyponatraemia is an important adverse effect, particularly in the elderly, and may present with confusion and reduced consciousness. Suicidal thoughts and behaviour may be increased in patients on SSRIs. SSRIs lower the seizure threshold and some (e.g. citalopram) prolong the QT interval and can predispose to arrhythmias. SSRIs also increase the risk of bleeding. At high doses, in overdose, or in combination with other antidepressant classes, SSRIs can cause serotonin syndrome. This is a triad of autonomic hyperactivity, altered mental state and neuromuscular excitation, which usually responds to treatment withdrawal and supportive therapy.
Sudden withdrawal of SSRIs can cause gastrointestinal upset, neurological and influenza-like symptoms and sleep disturbance.

SSRIs should be prescribed with caution where there is a particular risk of adverse effects, including in epilepsy and peptic ulcer disease.
In young people, SSRIs have poor efficacy and are associated with an increased risk of self-harm and suicidal thoughts, so should only be prescribed by specialists.
As SSRIs are metabolised by the liver, dose reduction may be required in people with hepatic impairment.

SSRIs should not be given with monoamine oxidase inhibitors as they both increase synaptic serotonin levels and together may precipitate serotonin syndrome.
Gastroprotection should be prescribed for patients taking SSRIs with aspirin or NSAIDs due to an increased risk of gastrointestinal bleeding.
Bleeding risk is also increased where SSRIs are co-prescribed with anticoagulants.
They should not be combined with other drugs that prolong the QT interval, such as antipsychotics.

TeacherOfMedicine