Withdrawal
Index
2. Avoiding Withdrawal Symptoms during Venlafaxine Withdrawal (and
other anti-depressant medications)
Rapid elimination of some antidepressant medication, e.g. venlafaxine,
can introduce feelings of being unwell some of which can be quite
severe and lead to the reintroduction of the medication, not necessarily
because of the need for the drug to treat the illness but because
of a crisis precipitated by its dependency.
For venlafaxine these are flu like symptoms which pass after a week
or two in a severe case. Both this and the rate of recovery will be
dependent on:
- the size of the reduction in terms of both the actual amount (mg)
and in percentage terms,
- the usage/decay rate of the drug in the body,
- how long the drug has been taken.
The rate of reduction must be slow to avoid any withdrawal symptoms
or relapse.
To do this effectively it is necessary to understand how long the
drug remains in the body after being taken. The important factor is
not the amount being taken but the level in the body at any one time.
This is particularly important if different forms of the same drug
are available.
Anti-depressant half-life
The length of time it takes a drug to be consumed or dissipated in
the body is characterised by the half-life. If we assume that the
drug is rapidly absorbed into the blood, the level will then start
to fall over a period of time. When the amount has fallen to half
the initial level achieved, this is referred to as the half-life usually
measured in hours or days. Some drugs have a short half-life because
the body rapidly assimilates them. This is like a sugar lump effect
when it is dissolved in the mouth relatively quickly.
Taking a short half life tablet twice per day will lead to little
accumulation in the body. Some drugs have a longer half-life and may
remain in the body at significant concentrations for several days.
This results in an accumulation of the drug in the body. Understanding
this is particularly important where a medication like venlafaxine
has more than one form. Changing from one form to another at the same
dosage level can lead to major changes in body concentration and withdrawal
problems.
Drug levels in the body
There is a standard tablet form of venlafaxine which has half-life
of 8 to 10 hours. These figures are taken from the manufacturer’s
web site. In practice the actual rate will depend on whether it is
taken with food and the individual’s own metabolic rate but
this is not critical to the process. Taken twice per day, a drug with
a half-life of 9 hours will build to a level of 1.64 times the dosage
assuming an exponential decay rate. Therefore a dosage of 75 mg twice
per day roughly gives 123 mg in the body. This is made up of:
- the dose of the new tablet 1.00
- the remaining dose from 12 hours before 0.39
- the remaining dose from 1 day before 0.16
- the remaining dose from 1.5 days before 0.06
- the remaining dose from 2.0 days before 0.02
- the remaining dose from 2.5 days before 0.01
Total 1.64 x 75 mg = 123 mg.
The elimination of a tablet with a short half-life will have a more
rapid reduction in the amount of the drug in the body than when a
same sized (mg) longer half-life capsule is eliminated as described
below.
There is also a venlafaxine XL capsule whose half-life is given as
22 to 24 hours. Assuming the same decay mechanism for the capsule
as for the tablet, a half-life of 23 hours would build to a level
of 3.27 times the dosage. Therefore a dosage of 75 mg twice per day
roughly gives 246 mg in the body. This is made up of:
- the dose of the new capsule 1.00
- the remaining dose from 12 hours before 0.71
- the remaining dose from 1 day before 0.49
- the remaining dose from 1.5 days before 0.35
- the remaining dose from 2.0 days before 0.24
- the remaining dose from 2.5 days before 0.16
- the remaining dose from 3.0 days before 0.11
- the remaining dose from 3.5 days before 0.08
- the remaining dose from 4.0 days before 0.06
- the remaining dose from 4.5 days before 0.04
- the remaining dose from 5.0 days before 0.02
- the remaining dose from 5.5 days before 0.01
Total 3.27 x 75 mg = 245 mg.
The above numbers are not exact because of different metabolisation
characteristics of the differing drug forms and the fact that the
initial dose is not absorbed instantly. However, if they had the same
release mechanism in principle the XL capsule variety would give roughly
double the body concentration of the tablet for the same dose taken.
In practice the modified release mechanism for the XL capsule results
in the ratio being lower at more like 1.7 instead of 2.0. This means
that the maximum dose for the drug is different depending on whether
the patient is taking the capsule or the tablet form. In fact, in
the drug handbook in the UK, MIMS (Monthly Index Of Medical Specialities)
this difference in maximum levels is stipulated clearly showing the
tablet maximum to be 375 mg and the capsule maximum to be 225 mg.
This confirms the mechanism for the modified release capsule is not
exponential. However the principle remains valid: the amount of drug
in the body when taking the capsule is very significantly greater
than when taking tablet form.
This was discovered by us after a consultant psychiatrist had arbitrarily
changed the dose from 150 mg twice per day of XL capsule (way over
the maximum) to 150 mg twice per day of tablet giving horrendous withdrawal
problems over 2 weeks followed 3 months later by extreme nausea when
he arbitrarily switched back to the XL variety at the same dose.
Using Prozac for withdrawal due to its longer half-life
There are web sites claiming that substituting Prozac for venlafaxine
in the final stages provides a rate of reduction of antidepressant
which gives the patient no withdrawal problems. This is because of
the long half-life on Prozac (4 days and 8 days for its intermediary
– see the note in Section 5). Therefore the level of the drug
in the body falls slowly at a rate to which the body can adjust when
a capsule is eliminated from the dose taken. Therefore this Prozac
decay rate was used initially as a model to calculate how quickly
to reduce the venlafaxine medication levels. The option of changing
over to Prozac was considered but this would have introduced a new
drug and a new learning curve. The Prozac web site states 7% of patients
cannot metabolise the drug in which case the body concentration quickly
grows. This was seen as potentially being exposed to an unnecessary
risk if the reduction could be done safely in another way.
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