Venlafaxine is prescribed for individuals diagnosed with depression or
generalised anxiety disorder. Duloxetine is an SNRI but is not commonly
prescribed for psychiatric diagnoses in the UK.
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.
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
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,
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.
When discussing coming off psychiatric drugs the terms withdrawal and
discontinuation will be used interchangeably. Although the term
withdrawal is usually associated with coming off drugs to which an
individual is addicted to, when an individual comes off SNRI's they are
not addicted to the drug, they do not consciously crave the drug. The
effects an individual may experience when
withdrawing/discontinuing/reducing a SNRI are not related to addiction
but rather to the body struggling to adapt to the absence of a chemical
it has become used to being present.
Reported adverse effects upon venlafaxine withdrawal include;
(the most commonly reported effects are highlighted in italics)
' Feelings of abdominal distension
' Tinnitus (ringing in the ears)
' Congested sinuses
' Dysphoria (state of dissatisfaction or unease)
' Dizzyness or lightheadedness/
' Excessive sweating
' Vertigo (feels like you or the environment are rotating constantly)
' Paraesthesia (spontaneous abnormal tingling sensations)
' Auditory Hallucinations
' Urinary frequency (passing urine more frequently)
' 'Bizarre' dreams
' Shock like sensation in the head and neck when turning head suddenly
' Ataxia (shaky movements and unsteady gait)
' Arthralgia (painful joints)
If a symptom is due to withdrawal of a drug, it will typically occur
soon after a reduction (or discontinuation) of the drug and disappear
within about 2 weeks (and generally not persist beyond 3 weeks).
Symptoms usually occur with 36-48 hours following discontinuation (or
reduction); however delayed withdrawal reactions have been reported to
occur upon 1 week after discontinuation.
Although there is not a recognised Venlafaxine withdrawal syndrome, many
of the withdrawal effects experienced mirror those seen in SSRI
discontinuation. This has lead authors to speculate that a similar
mechanism may be responsible for SSRI and SNRI withdrawal symptoms.
Venlafaxine at low doses works in a similar way to SSRI's, only at
higher doses does Venlafaxine have a dramatic effect on inhibition of
noradrenaline re-uptake. Therefore a similar approach could be taken
when attempting Venlafaxine withdrawal as one could when attempting SSRI
The three primary risk factors for developing withdrawal symptoms when
discontinuing a SSRI are;
- long duration of anti-depressant treatment
- abrupt withdrawal from the SSRI
- withdrawing from SSRI's with short half-lives
Withdrawal effects have been reported to occur with both abrupt and more
gradual withdrawal but seem to be reduced by a truly gradual withdrawal
that lasts at least two to three months.
Rates of withdrawal
We would recommend that at least two weeks should pass between each
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 fewer
withdrawal effects experienced. But ultimately the choice as to how fast
and how much to reduce by is the individuals.
So if an individual was taking 150mg Venlafaxine a day and wanted to
reduce the drug by 10% every two weeks, the first 2 weeks they would
take 135mg a day, the next 2 weeks 120mg a dayetc. 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 smaller steps from that point on rather
than the original 15mg steps to further avoid developing unpleasant
Venlafaxine is available in 37.5mg tablets (minimum tablet dose) which
could make things tricky, trying to cut the tablets to reduce in 15mg
Alternative way to withdraw from Venlafaxine
Venlafaxine has a half-life of 5 hours which is relatively short and
studies looking at selective serotonin re-uptake inhibitor (SSRI)
withdrawal demonstrate that individuals who withdraw from an SSRI with a
longer half-life are less likely to experience any withdrawal effects.
It is be possible to switch to an SSRI with a long half-life
(Fluoxetine) and withdraw from that. The equivalent dose of 75mg
Venlafaxine is 20mg Fluoxetine. Fluoxetine is also available in liquid
form which makes it easier to reduce the dose by 10%, so you could speak
to your doctor about prescribing Fluoxetine liquid. It is advised that
you then 'stabilise' on the liquid Fluoxetine for 2-4 weeks before
beginning the dose reductions/withdrawal.
So if an individual was taking 150mg Venlafaxine a day, they would
convert to 40mg Fluoxetine per day (preferably liquid). To reduce the
drug by 10% every two weeks, the first 2 weeks they would take 36mg per
day, the next 2 weeks 32mg per day etc. Approximately 5 months later
they would have fully come off the drug.
As with the previous example, if the individual was developing
withdrawal effects they could 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 smaller steps from that point on
(e.g. reduce by 2 mg every 2 weeks).
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.
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 Venlafaxine and other types of psychiatric drugs it is
worthwhile reading through the interactions section to work out which
drug you should reduce first.
Venlafaxine increases plasma concentrations of Clozapine and
Haloperidol therefore come off of Clozapine or Haloperidol before