What documentation can be found concerning treatment of venlafaxine discontinuation (withdrawal) sy

Fråga: What documentation can be found concerning treatment of venlafaxine discontinuation (withdrawal) symptoms with flouxetine? A middle-aged woman with unipolar depression has been treated with Efexor (venlafaxine) for two years. She is now fully recovered. Despite several weeks of tapering, she experiences electric shock-like sensations all over her body when discontinuing venlafaxine (37.5 mg). The manufacturer advises giving the patient 10-20 mg of fluoxetine for 1-2 weeks after stopping venlafaxine, to reduce withdrawal symptoms.

Sammanfattning: There are three case reports describing successful treatment of venlafaxine withdrawal symptoms with fluoxetine. Primarily, a very slow tapering, reducing the dose by 1/4 every 4-6 weeks should be considered.

Svar: Discontinuation symptoms have been reported for antidepressants from all the major classes including tricyklic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI) as well as venlafaxine, nefazodone and mirtazapine. Sensory symptoms with electric-shock like sensations have been described specific for the SSRI group. Symptoms range from mild to severe reactions like difficulty in walking due to shock-like sensations or dizziness (1). The underlying mechanisms have not yet been established. It has been suggested that the symptoms are caused by the sudden decrease of serotonin at a time when the serotonin receptors have been down regulated. The effect of low doses of venlafaxine in vitro is mainly serotonergic. (2)

Two studies have compared the incidence of SSRI discontinuation symptoms under double blind conditions (paroxetine/sertraline/fluoxetine). The incidence was significantly lower in flouxetine treated subjects. The reason may be the long half-life of fluoxetine, and its active metabolite norflouxetine (84 hours and 4-16 days respectively). The shorter half-life in rapid metabolisers in cytochrome enzyme CYP2D6 could predispose these individuals to withdrawal symptoms (3). Determining the CYP2D6 genotype in this patient could therefore be of clinical interest.

There are three case reports describing the fluoxetine treatment of venlafaxine withdrawal symptoms. One describes a 37-year-old woman with depression. Due to worsening of depressive symptoms, she was to switch to reboxetin, a selective norepinephrine reuptake inhibitor. The venlafaxine was tapered during 8 weeks from 225 mg daily, to 75 mg. After 2 weeks on the lowest dosage, she stopped venlafaxine, and began 4 mg of reboxetin twice daily. 48 hours later she experienced a variety of symptoms including hot and cold feelings, irritability, unsteadiness and weakness of the legs. Reboxetin was discontinued, and venlafaxine reinstated (75 mg). Within 24 hours, the patient was fully recovered. Two more attempts to discontinue venlafaxine after 2 weeks on a lower dose (37,5 mg) failed, due to reoccurrence of the symptoms. She was then given 20 mg of fluoxetine daily, immediately after discontinuing venlafaxine. This suppressed her symptoms, and one week later she was able to stop the fluoxetine without any adverse symptoms (2).

In case two and three, the venlafaxine and fluouxetine were given concomitantly. In patient number two, the venlafaxine was gradually decreased from 18.75 three times a day, to 9.375 mg once a day over a period of three weeks. Despite tapering, the patient experienced recurrent withdrawal symptoms like hot flashes and dizziness when discontinuing venlafaxine. Ten mg of flouxetine was added, and the patient was able to stop venlafaxine after four weeks. Two weeks later, fluoxetine was discontinued successfully. The third patient had a combination treatment for four weeks, with a higher dosage of both venlafaxine (18.75 mg) and of fluouxetine (20 mg) for the last two weeks due to persistent depressive symptoms. Venlafaxine could be stopped with no withdrawal symptoms (4).

In the present case, where the patient no longer is in need of an antidepressant medication, an even slower rate of tapering may also be worth trying, ie reducing the dose by 1/4 every 4-6 weeks (1).