Discontinuation symptoms with nefazodone

Abstract

Nefazodone discontinuation can result in withdrawal symptoms and therefore needs to be tapered gradually. Those who have experienced discontinuation symptoms with other antidepressants in the past may be at increased risk.

Discontinuation Symptoms Associated with Nefazodone

“…The symptoms experienced by this patient (i.e. nausea, vomiting, sleep disturbances, headache, fatique) were in line with symptoms of previously reported cases of nefazodone discontinuation (Benazzi, 1998b;Kotylar et al, 1999;Lauber, 1999;Rajagopalan and Little, 1999) (Table 1). These symptoms were also quite similar to the symptoms reported during SSRI discontinuation syndromes (Price et al, 1996;Bogetto et al, 2002).…”

“…Of the 42 patients in one study (Black et al, 2000), 82% had onset of withdrawal symptoms within 1-3 days and 94% within 1 week; all patients were symptomatic within 2 weeks. The discontinuation symptoms in most cases of SSRIs and in all cases of nefazodone are mild and short-lived, even if untreated (Coupland et al, 1996;Rajagopalan and Little, 1999). Discontinuation symptoms usually resolve within 72 h after reinitiation of the same antidepressant or an antidepressant with an identical pharmacological profile (Tamam and Ozpoyraz, 2002).…”

“…For nefazodone, its relatively short elimination half life (i.e. 2-184 h) and the presence of three different active metabolites (a-hydroxyl-nefazodone, desethyl-hydroxynefazodone and m-chlorophenylpiperazine), which extends its half life from 2-4 h up to 18 h was shown to cause a greater risk for producing early and severe withdrawal symptoms (Rajagopalan and Little, 1999). Another factor emphasized in nefazodone discontinuation symptoms is the consequent down regulation of 5-HT 2 receptor binding sites after long-term use of nefazodone.…”

“…Discontinuation of the drug might cause acute enhancement of serotonin reuptake leading to a deficiency of serotonin in the synapse. The readaptation of these neurotransmitter systems should theoretically occur over several weeks, which correlates with total improvement of discontinuation symptoms in some cases (Rajagopalan and Little, 1999).…”

“…Discontinuation symptoms could also emerge after cessation of several new antidepressants affecting the serotonergic system such as venlafaxine (Boyd, 1998), mirtazapine (Benazzi, 1998a) and nefazodone (Lauber, 1999;Rajagopalan and Little, 1999). One of these new antidepressants, nefazodone, is a potent serotonin type 2 (5-HT 2 ) receptor antagonist with limited inhibition of presynaptic serotonin and norepinephrine reuptake (Kent, 2000).…”