Focus On Venlafaxine
by Dr Ivan Goldberg
13. What is the usual final dose of venlafaxine? 14. How long does it take venlafaxine to relieve depression?
Venlafaxine (venlafaxine) is a new antidepressant with a novel chemical structure. Venlafaxine has a structure that does not resemble those of any currently used antidepressants. venlafaxine is not a tricyclic anti- depressant or an MAO inhibitor.
Venlafaxine seems to have the relative freedom from side-effects associated with the SSRIs [fluoxetine , sertraline , paroxetine, fluvoxamine ] and the impact on both the serotonin and norepinephrine associated with the tricyclic antidepres- sants (amitriptyline , imipramine etc.). It is hypothesized that the action of the venlafaxine molecule upon both serotonin and norepinephrine will cause venlafaxine to be a successful antidepressant for some people who have not responded to treatment with SSRIs.
As venlafaxine and its active metabolite have relatively short half-lives; 4 hours and 11 hours respectively, venlafaxine should be administered in divided does, two or three times a day.
While the pre-marketing studies were restricted to patients with a DSM-III-R diagnosis of Major Depressive Disorder (with or without melancholia), it is to be expected that venlafaxine will be prescribed for patients with Dysthymia, Major Depression, and Bipolar Disorder.
While venlafaxine was only studied for periods of administration of up to 6-weeks, it is to expected that patients with long-standing depressions will take the drug for longer periods of time.
The most common side-effects and the percentage of people reporting them during clinical trials are:
Raised blood pressure *
Male sexual dysfunction
Female sexual dysfunction
* While the manufacturer says that hypertension only occurs in patients receiving over 300 mg/day, there been reports of moderately severe hypertension in patients taking smaller doses.
In the premarketing studies 19% (537 out of the 2897) of depressed patients taking venlafaxine discontinued the medication because of side- effects. The side effects and the percentages of total patients who dropped out for each are:
Male sexual dysfunction
* % of men
As with other antidepressants, people with bipolar disorder who are not being treated with a mood regulator such as lithium, valproate, or carbamazepine , may be pushed into a manic episode when treated with venlafaxine.
- Lithium - No interaction.
- Diazepam (Valium) - No interaction.
- Cimetidine (Tagamet) - Slight increase in blood level of venlafaxine's active metabolite. Not of clinical significance.
- Fluoxetine (Prozac) - Significant increase in the concentration of venlafaxine and its active metabolite. Potential for increased side-effects.
Although venlafaxine has not been found to increase the impairment of cognitive or motor skills caused by alcohol, the manufacturer warns against drinking while taking venlafaxine.
There is no data to establish the safety of venlafaxine for the fetus or nursing infant.
Although here have been no published studies on the use of venlafaxine for the treatment of children and adolescents with depression, it is expected that the drug will be prescribed for depressed children and adolescents.
No special problems were encountered when venlafaxine was prescribed for elderly people with depression.
I usually start adults on 25 mg of venlafaxine every 12-hours. Every five days, I usually add 25 mg to each dose until the patient either responds or reaches reaches 150/day. If there is no response within 2-weeks of reaching 150 mg/day the dose is again increased in steps of 25 mg/dose until a total daily dose of 300 mg/day is achieved. If this dose is not effective, and the patient is tolerating the venlafaxine without problems, I then increase the dose to between 500 and 600 mg/day.
When venlafaxine is given to elderly patients the starting doses are the same as for other adults. As older people may be more sensitive to increases in dose they should be made slowly.
While doses up to 375 mg per day are approved by the FDA, some severely depressed patients have been treated with higher doses. Most depressed people respond to doses under 300 mg per day.
While most people taking venlafaxine become aware of some lessening of depression within two to four weeks, there are some who experience relief within the first week and others who only experience relief after a couple of months of therapy.
Because of the very short half-life, venlafaxine should be discontinued gradually over at least 2-weeks. If venlafaxine is suddenly discontinued, a withdrawal syndrome involving fatigue, nausea, dizziness, headache, insomnia, and nervousness, may develop.
Fourteen overdoses of venlafaxine have been reported. In some cases venlafaxine was taken along with alcohol and/or other medications. All individuals who took an overdose recovered without sequelae.
When switching from an MAO inhibitor to venlafaxine, there should be a 14-day interval between the discontinuation of the MAOI and the initiation of venlafaxine therapy. When switching from venlafaxine to an MAOI a 7-day interval is adequate, because of venlafaxine's short half-life.
In patients who have not responded to three antidepressants from at least two of the major classes of antidepressants, venlafaxine was found to effective in nearly one-half of the people with depression who took it.
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