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.
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./
Citalopram: Adult max = 60mg daily (Elderly max = 40mg daily)
Escitalopram: Adult max = 20mg daily
Fluoxetine: Adult max = 80 mg daily (Elderly max = 60mg 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.
Dizziness, vertigo (feeling like the room is spinning around you/), ataxia (/loss of muscle co- ordination/
Electric head ' strange brain sensations- 'brain is having a version of goose pimples' and electric shock like sensations
The half life of a drug is a rough measure of how long a drug is in someone's body before it gets excreted. Because individuals vary in how fast their bodies metabolise and excrete substances from the body, how long it takes for the quantity of a drug in the average persons blood to drop by half is measured, the half-life. Withdrawal reactions appear to be more severe in SSRI's with shorter half lives compared to those with longer half lives. Therefore, if you can gain the support of your doctor, asking them to prescribe you an SSRI with a longer half-life (fluoxetine) may aid in the coming off process (Table 1).
Minimum available dose
Equivalent dose of 20 mg Fluoxetine
Table 1. Plasma half-lives of the SSRI's and equivalent doses of Fluoxetine
Rates of withdrawal from your SSRI
Bearing in mind that withdrawal effects tend to last for approximately two weeks, this suggests that it takes at least two weeks for the brain to adapt to the decreased amount of SSRI. Therefore, it would be sensible to assume that at least two weeks should pass between each dose reduction.
As for how much to reduce the dose by, this is not a finite science. Some individuals are able to come off all at once without ay problems, whereas others develop severe withdrawal effects. Reducing in 10% steps would seem to be a sensible target, especially if the drug has been take consistently for over a year. A maximum of 25% reduction every 2 weeks is probably the fastest you could sensibly attempt to reduce, however, it should be bourn in mind that the more gradual the reductions the more time the brain has to adapt and based on the evidence, the fewer withdrawal effects are experienced. But ultimately the choice as to how fast and how much to reduce by is the individuals.
Example /So if an individual was taking 200mg Sertraline a day and wanted to reduce the drug by 10% every two weeks, the first 2 weeks they would take 180mg per day, the next 2 weeks 160mg per day etc. Approximately 5 months later they would have fully come off the drug. However, if after 4 weeks they found that they were developing withdrawal effects it would perhaps be sensible to avoid further reductions until they no longer felt the withdrawal effects and if they felt the need to increase the dose by 10% until the withdrawal effects subsided they did this. Also, they could decide to reduce in 10mg steps from that point on rather than the original 20mg steps to further avoid developing unpleasant withdrawal effects./
Even if you are not successful in coming off your medication at the first attempt you will probably learn from the experience, what was beneficial, what could you have done differently and ultimately had an opportunity to evaluate the role of the drug in your life.
Certain SSRI's are also available in liquid forms which can enable you to reduce at a very gradual pace. Citalopram, Paroxetine and Fluoxetine are all available in liquid form.
If you are taking any medications other than your psychiatric drugs it is worthwhile speaking to your GP about what potential interactions your psychiatric medications may have with your other medications. Listed below are interactions that occur between some psychiatric drugs. If you are taking an SSRI and other types of psychiatric drugs it is worthwhile reading through the interactions section to work out which drug you should reduce first.
Fluoxetine and Fluvoxamine increase plasma concentration of Carbamazepine therefore come off Carbamazepine first.
Fluoxetine increases plasma concentration of Clozapine, Haloperidol, Risperidone, Sertindole, Zotepine therefore come off the Clozapine, Haloperidol, Risperidone, Sertindole, Zotepine before beginning to reduce Fluoxetine.
Fluvoxamine increases plasma concentration of Olanzapine, therefore come off of Olanzapine first
Fluvoxamine increases plasma concentration of some benzodiazepines, therefore come off of benzodiazepines first
Plasma concentration of Paroxetine is reduced by Carbamazepine therefore come off Paroxetine first.
Paroxetine increases plasma concentration of Procyclidine therefore come off Procyclidine first. If you are taking a neuroleptic (anti-psychotic) also, come off the neuroleptic before starting to reduce Procyclidine.
Paroxetine increases plasma concentration of Thioridazine, therefore come off of Thioridazine first
Fluvoxamine, Sertraline and Paroxetine increase plasma concentration of Clozapine therefore come off of Clozapine first
Sertraline increases plasma concentration of Pimozide, therefore come off of Pimozide first
Paroxetine increases plasma concentration of Sertindole, therefore come off of Sertindole first