Discontinuation syndrome

Glutethimide (3-ethyl-3-phenyl-2,6-piperidinedione) is a sedative-hypnotic drug that is now rarely used therapeutically because of wide variation in gastrointestinal absorption, fast development of pharmacodynamic tolerance, a fairly severe discontinuation syndrome, and potential for abuse. Reports of... 

Miller LG, Greenblatt DJ, Roy RB, et al Chronic benzodiazepine administration, II discontinuation syndrome is associated with upregulation of gamma-aminobutyric acid receptor complex binding and function. J Pharmacol Exp Ther 246 177-182, 1988b... 

Warner, Christopher H., William Bobo, Carolynn Warner, Sara Reid and James Rachal, Antidepressant Discontinuation Syndrome , American Family Physician 74, no. 3 (2006) 449-56... 

In addition, whenever an antidepressant that blocks serotonin reuptake is discontinued, an unpleasant but harmless discontinuation syndrome manifested by abdominal discomfort, instability, anxiety, and occasionally painful shock-like sensations in the extremities can arise. The risk appears to be greatest with venlafaxine and paroxetine. Consequently, switching from one of these medications to another that does not block serotonin reuptake requires a gradual taper of the first medication over days to weeks. 

In general, the lowest effective dose of the drug should be used, particularly in elderly patients. Dose titration should be undertaken slowly. Similarly, on discontinuation of a drug, the dose should be reduced slowly, the rate of decrease being decided by the elimination half-life of the drug. Some psychotropic drugs produce a discontinuation syndrome that can usually be avoided by slow withdrawal. In particular, sedatives, anxiolytics and antidepressants can cause withdrawal effects. 

Administer a high therapeutic dose of a "dual action" antidepressant such as venlafaxine or possibly mirtazepine. A discontinuation syndrome may occur if venlafaxine is abruptly withdrawn. The... 

Antidepressant Efficacy Tolerability Safety Discontinuation syndrome... 

Discontinuation Problems Further controversy has surrounded misleading claims in the lay media that SSRls have addictive properties. These centre around reports of patients suffering symptoms when trying to discontinue medication. As with the benzodiazepines, these symptoms may be a recurrence of the premorbid anxiety, although rebound anxiety has not been clearly demonstrated. Self-limiting symptoms associated with SSRl withdrawal have been widely reported (Haddad 1998), and are generally described as the SSRl discontinuation syndrome (Table 4). The most frequently occurring symptoms are dizziness, nausea and headache. 

There is a large evidence base for the antidepressant efficacy of venlafaxine, but fewer studies have been carried out in anxiety disorders. The best evidence is for GAD (Allgulander et al. 2001) and anxiety symptoms associated with depression (Silverstone and Ravindran 1999). Side-effects on initiation of therapy are similar to those of SSRIs, with nausea being the most common. Higher doses can cause raised blood pressure. A discontinuation syndrome similar to that seen with SSRIs has been reported. Toxicity causes cardiac conduction problems, seizures and coma, and venlafax-... 

Buspirone is well-tolerated, with the main side-effects being dizziness, anxiety, nausea and headache. It is tolerated by the elderly (Bohm et al. 1990). It does not cause sexual dysfunction and does not appear to be associated with a discontinuation syndrome. Overdose causes drowsiness but there are no reports of serious toxic effects. A potential for interaction with drugs that inhibit the CYP450 3A4 isoenzyme is not a significant problem in cHnical practice. GAD is usually a chronic condition and buspirone is suitable for long-term treatment. Patients should be advised to expect a slow onset of benefits and be reviewed regularly in the early stages of treatment. 

Haddad P (1998) The SSRI discontinuation syndrome. J Psychopharmacol 12 305-313 Healy D (2003) Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. Psychother Psychosom 72 71-79... 

Rosenbaum, J.F., Fava, M., Hoog, S.L., Acroft, R.C., and Krebs, WB. (1998) Selective serotonin reuptake inhibitor discontinuation syndrome a randomized clinical trial. Biol Psychiatry 44 77-87. 

Until recently few guidelines were available to help physicians determine whether continued BZD use is appropriate and, if not, how to prevent BZD discontinuation syndromes (e.g., PBDS and the immediate withdrawal syndrome). Rickels (261) and his colleagues suggest tapering schedules, emphasizing the need to treat the patient s underlying psychopathology. 

Reassuring that the discontinuation syndrome Is the nature of the psychophysiological process and not the fault of the patient or the doctor... 

SNRIs have many of the serotonergic adverse effects associated with SSRIs. In addition, SNRIs may also have noradrenergic effects, including increased blood pressure and heart rate, and CNS activation, such as insomnia, anxiety, and agitation. The hemodynamic effects of SNRIs tend not to be problematic in most patients. A dose-related increase in blood pressure has been seen more commonly with the immediate-release form of venlafaxine than with other SNRIs. Likewise, there are more reports of cardiac toxicity with venlafaxine overdose than with either the other SNRIs or SSRIs. Duloxetine is rarely associated with hepatic toxicity in patients with a history of liver damage. All the SNRIs have been associated with a discontinuation syndrome resembling that seen with SSRI discontinuation. 

Haddad P. Newer antidepressants and the discontinuation syndrome. J Clin Psychiatry 1997 58(Suppl. 7) 17-21discus-sion 22. 

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