Discontinuation symptoms

Patients requiring detoxification from high or supratherapeutic dosages of benzodiazepines constitute a smaller number of patients, but they are at greater risk for life-threatening discontinuation symptoms, such as seizures, delirium, and psychoses. There has been more experience with inpatient detoxification in this group, but outpatient detoxification is possible if conducted slowly (5% reduction in dose per week), with frequent contact, and in the context of a therapeutic alliance with the patient. Often, such an alliance proves unworkable because the patient s impoverished control results in supplementation from outside sources or early exhaustion of prescribed supplies meant to be tapered. In these cases, as in the cases of patients with a history of seizures, delirium, or psychoses during previous detoxification attempts, inpatient detoxification is indicated. 

Venlafaxine (Effexor, Effexor XR). Venlafaxine works by blocking the reuptake of both serotonin and norepinephrine. Because of this dual action, some believe that venlafaxine may be more effective than the SSRIs when treating severe depression. Its side effects and toxicity are similar to the SSRIs with abdominal discomfort, sexual dysfunction, and anxiety being commonly reported. At higher doses, it may mildly elevate blood pressure therefore, blood pressure should be checked periodically. When stopping venlafaxine, serotonin discontinuation symptoms may be especially problematic. Therefore, gradually tapering of the dose every 2-4 weeks is recommended. 

Discontinuation - When discontinuing venlafaxine after more than 1 week of therapy, it is generally recommended that the dose be tapered to minimize the risk of discontinuation symptoms. Patients should have their dose tapered gradually over a 2-week period. 

A second issue relating to long-term medication is the effect of withdrawing medication at the end of a period of treatment. Benzodiazepines are associated with discontinuation symptoms, and their repeated use may foster the development of true physiological dependence. In a study of discontinuation of treatment for panic disorder [Rickels et al. 1993) with either alprazolam [n = 27), imipramine [n = 11) or placebo [n = 10), a withdrawal syndrome was observed in almost all patients treated with alprazolam but in few pa-... 

Several reports have described a series of symptoms after discontinuation or dose reduction of serotonergic antidepressant medications. The most common symptoms include dizziness, headache, paresthesia, nausea, diarrhea, insomnia, and irritability. Of note, these symptoms may also be seen when a patient misses doses. A prospective, double-blind, placebo-substitution study confirmed that discontinuation symptoms are most common with short half-life antidepressants, such as paroxetine (Rosenbaum et al. 1998). 

The side-effect profile of venlafaxine is similar to that of SSRIs and includes gastrointestinal symptoms, sexual dysfunction, and transient discontinuation symptoms. Like the SSRIs, venlafaxine does not affect cardiac conduction or lower the seizure threshold. In most patients, venlafaxine is not associated with sedation or weight gain. Side effects that differ from those of SSRIs are hypothesized to be related to the increased noradrenergic activity of this drug at higher doses these side effects are dose-dependent anxiety (in some patients) and dose-dependent hypertension. 

Discontinuation of antidepressant medication should be concordant with the guidelines for treatment duration (see Acute Major Depression subsection in the preceding section). It is advisable to taper the dose while monitoring for signs and symptoms of relapse. Abrupt discontinuation is also more likely to lead to antidepressant discontinuation symptoms, often referred to as withdrawal symptoms. The occurrence of these symptoms after medication discontinuation does not imply that antidepressants are addictive. 

Discontinuation symptoms appear to occur most commonly after discontinuation of short-half-life serotonergic drugs (Coupland et al. 1996), such as fluvoxamine, paroxetine, and venlafaxine. 

Rebound symptoms usually are followed by recurrence symptoms, which may persist until effective treatment is prescribed. In contrast to rebound and recurrence symptoms, withdrawal symptoms are subjective and objective events that did not exist prior to the use of the BZD. These tend to appear after rebound and recurrence symptoms, but not necessarily. Common discontinuance symptoms include insomnia, restlessness, irritability, unsteadiness, flu-like symptoms, hyperacusis, anxiety, and depression. Uncommon symptoms are tinnitus, seizures, and psychosis, which rarely may be life-threatening (238). 

Discontinuation during and after slow tapering has been shown to be well tolerated ( 79). A slow discontinuation of clonazepam usually results in a benign withdrawal course. Withdrawal from higher doses, particularly rapid withdrawal, however, can be associated with more severe discontinuation symptoms ( 80). 

Zajecka J, Tracy KA, Mitchell S Discontinuation symptoms after treatment with serotonin reuptake inhibitors A literature review. J Clin Psychiatry 1997 58(7) 291. [PMID 9269249]... 

REBOUND Also known as discontinuation symptoms, these occur when the benzodiazepines are withdrawn. These symptoms are an aspect of withdrawal in which the patient develops anxiety, insomnia, or other serious emotional reactions that are more intense than before treatment with the drug was begun. 

If mild discontinuation symptoms can be mistaken for relapse, it would be predicted that studies that used hospitalisation as the relapse criterion would find smaller differences between drug treatment and placebo than other studies. The only study included in the Gilbert et al. (1995) meta-analysis to define relapse exclusively as hospitalisation found a difference of only 17% in relapse rates between people who continued to receive drugs and those withdrawn to placebo after two years (Carpenter, Jr. et al. 1990). This compares with an average difference in relapse rates of 37% at 10 months for all studies included in the analysis. 

Markowitz JS, DeVane CL, Liston HL, Montgomery SA. An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram. Int Clin Psychopharmacol 2000 15(6) 329-33. 

Rajagopalan M, Little J. Discontinuation symptoms with nefazodone. Aust NZ J Psychiatry 1999 33(4) 594-7. 

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