Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline

• SSRIs are generally prescribed to individuals deemed to be moderately to severely depressed. They may also be prescribed for individuals deemed to have anxiety, panic, obsessive-compulsive or post-traumatic stress disorders.

How the SSRI’s interact with/affect the brain

The theory behind how SSRI’s and other antidepressants elevate individuals mood is based around the assumption that individuals who are feeling depressed have reduced levels of neurotransmitters, particularly serotonin and noradrenaline in the brain. Neurotransmitters are released from neurons (cells found in the brain and other parts of the nervous system) and act as messengers, passing signals between neurons. For example, when a nerve impulse arrives at a serotonergic neuron (also known as a pre-synaptic neuron), serotonin is released from the cell and diffuses through a space between two neurons, called the synaptic cleft. Serotonin then binds to specific serotonin receptors on a different neuron (post-synaptic neuron) producing a specific signal, impulse or effect. Serotonin is then released from its receptors and ‘re-absorbed’ into the pre-synaptic neuron, or degraded by enzymes in the synaptic cleft.               

When an SSRI is introduced into the body, it attaches itself to the ‘re-absorbing’ receptors on the pre-synaptic neuron, therefore enabling the serotonin to stay in the synaptic cleft for longer and has a greater chance of re-attaching to a serotonin receptor on the post synaptic neuron and generating further impulses/signals.

Potential abnormal synapse activity upon withdrawal of SSRI

Although the exact biological mechanisms underlying withdrawal associated symptoms is unknown, researchers have postulated that discontinuation events result from a sudden decrease in the availability of synaptic serotonin in the face of down-regulated serotonin receptors. Excessive long term synaptic serotonin, causes a down regulation of post synaptic serotonin receptors. There is also an increase in serotonin re-uptake transporters, due to long term blockage, resulting in an increased re-uptake of serotonin from the synaptic cleft into the pre-synaptic neuron. This leads to an overall decrease in serotonin transmission which may produce withdrawal effects.

For further information the following articles may be of interest;

Link to full paper (Blier and Tremblay, 2006). Physiological mechanisms underlying the anti-depressant discontinuation syndrome. J Clin Psychiatry 67(suppl4): 8-13.

 Link to full paper (Schatzberg et al, 1997). Possible biological mechanisms of the serotonin reuptake inhibitor discontinuation syndrome. Discontinuation Consensus Panel. J Clin Psychiatry 58(suppl 7):23-7

BNF Doses

The doses listed below are the maximum safe amounts an individual theoretically could be prescribed daily. However, the usual ‘therapeutic’ doses will vary depending on the individual and the prescriber. The dose an individual is prescribed may also reflect the diagnosis, for example the maintenance dose of Fluvoxamine for individuals diagnosed with depression is 100mg daily, whereas for individuals with a diagnosis of obsessive compulsive disorder maintenance doses of Fluvoxamine can be between 50-300mg daily.

Fluvoxamine: Adult max = 300 mg daily

Paroxetine: Adult max = 60 mg daily (Elderly max = 40mg daily)

Sertraline: Adult max = 200mg daily

Side effects of SSRI's

Nausea, vomiting, indigestion like symptoms, abdominal pain, diarrhoea, constipation, loss of appetite and weight loss. Joint and muscle aches and developing a sensitivity to light have also been reported. Other side effects include dry mouth, nervousness, anxiety, headache, insomnia, tremor, dizziness, asthenia (weakness or loss of strength), hallucinations, drowsiness, convulsions, galactorrhoea (secretion of milk from the breasts), sexual dysfunction, urinary retention, sweating, hypomania and mania, movement disorders, visual disturbances, low body sodium concentration and cutaneous bleeding disorders. Suicidal ideation has been linked with SSRI’s.

Other drug specific side-effects have been noted:

Citalopram/Escitalopram - Palpitations (abnormal awareness of the heart beating), tachycardia (increased heart rate, greater than 100 beats per minute), postural hypotension (the blood pressure drops upon standing, can lead to dizziness or fainting), coughing, yawning, confusion, impaired concentration, fatigue, memory loss, migraine, paraesthesia (spontaneous abnormal tingling sensations), abnormal dreams, taste disturbance, increased salivation, ringing in the ears, excessive urination, disorders of urination and euphoria.

Fluoxetine - fever, abnormal bleeding, aplastic anaemia (reduced production of red blood cells due to bone marrow damage), stroke, bruising, stomach-bowel haemorrhage, haemolytic anaemia (destruction of red blood cells), pancreatitis (inflammation of the pancreas), pancytopenia (reduced red and white blood cells and platelets), thrombocytopenia (reduced numbers of platelets in the blood), vaginal bleeding on withdrawal, violent behaviour and hair loss.

Fluvoxamine - Palpitations (abnormal awareness of the heart beating), tachycardia (increased heart rate, greater than 100 beats per minute), postural hypotension (the blood pressure drops upon standing, can lead to dizziness or fainting), confusion, ataxia (impaired co-ordination of limbs and torso), elevated liver enzymes.

Paroxetine - Postural hypotension (the blood pressure drops upon standing, can lead to dizziness or fainting), rarely liver disorders.

Sertraline - Tachycardia (increased heart rate, greater than 100 beats per minute), confusion, memory loss, aggressive behaviour, psychosis, pancreatitis (inflammation of the pancreas), hepatitis (inflammation of the liver), jaundice (yellowing of the skin and eyes), liver failure, menstrual irregularities, paraesthesia (spontaneous abnormal tingling sensations), thrombocytopenia (reduced numbers of platelets in the blood).

There may be other side effects of taking SSRI's which are not listed above, those listed are just the more commonly seen side effects or the acknowledged ones.