How the SNRI’s interact with/affect the brain

The theory behind how SNRI’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.
It is a similar mechanism through which noradrenaline is released from a noradrenergic (noradrenaline releasing) pre-synaptic neuron, binds to noradrenaline receptors on the post-synaptic neuron and is then ‘re-absorbed’ into the neuron it was originally released from.
When a SNRI is introduced into the body, it attaches itself to the ‘re-absorbing’ receptors for serotonin and noradrenaline on the pre-synaptic neuron, therefore enabling serotonin and noradrenaline to stay in the synaptic cleft for longer and they will have a greater chance of re-attaching to a serotonin or noradrenaline receptors on the post synaptic neuron and generating further impulses/signals. Daily doses of Venlafaxine of 150 mg or less, do not exert any effect on noradrenaline re-uptake and so acts in a similar manner to an SSRI. Daily doses of Venlafaxine greater than 150 mg inhibits re-uptake of both serotonin and noradrenaline.

Potential abnormal synapse activity uon withdrawal of SNRI

Long term increased synaptic serotonin and noradrenaline, causes a down regulation of post synaptic serotonin and noradrenaline receptors. There is also an increase in serotonin and noradrenaline re-uptake transporters, due to long term blockage, resulting in an increased re-uptake of serotonin and noradrenaline from the synaptic cleft into the pre-synaptic neuron. This leads to an overall decrease in serotonin and noradrenaline transmission which may produce withdrawal effects. 

BNF Doses

The dose listed below is the maximum safe amount an individual theoretically could be prescribed daily. However, the usual ‘therapeutic’ doses will vary depending on the individual and the prescriber.

Venlafaxine: Adult max = 375 mg

Drug specific side-effects

Commoner side effects include; Constipation, nausea, dizziness, dry mouth, insomnia, nervousness, drowsiness, asthenia (weakness or loss of strength), headache, sexual dysfunction, sweating, anorexia (loss of appetite), weight changes, diarrhoea, dyspepsia (indigestion), vomiting, abdominal pain, high blood pressure, palpitations (sensations of heart beating fast), changes in blood cholesterol, chills, pyrexia (fever), shortness of breath, yawning, abnormal dreams, agitation, anxiety, confusion, hypertonia (increased muscle tone), paraesthesia (spontaneous tingling sensations), tremor, urinary frequency, menstrual disturbances, arthralgia (painful joints), myalgia (pain in the muscles), visual disturbances, ringing in the ears, rashes.  

Less commonly; taste disturbances, postural hypotension (low blood pressure upon standing, can lead individuals to faint), arrhythmias, hyponatraemia (low sodium in the blood), hallucinations, myoclonus (sudden spasm of muscles), urinary retention, bleeding disorders, hypersensitivity reactions

Rarely; ataxia (shaky movements and unsteady gait), inco-ordination, speech disorder, mania and hypomania, seizures, galactorrhoea (milk production and secretion from the breasts), thrombocytopenia (reduced levels of platelets), hepatitis (inflammation of the liver).

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