Discontinuation syndrome, SSRIs

It should be noted that the abrupt discontinuation of an SSRI can cause a withdrawal syndrome. This syndrome is often referred to as discontinuation syndrome . SSRI discontinuation syndrome is often manifested by symptoms of fatigue, gastrointestinal complaints (nausea, vomiting, diarrhea, cramping), shortness of breath, memory impairment, dizziness, insomnia, chills, headache, eye discomfort, tinnitus, ataxia, and abnormal sensations (e.g., electric shocks , skin tingling sensations, and involuntary movements). 

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-... 

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... 

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. 

When ceasing use of an antidepressant, the dose should be reduced over at least 6 weeks to avoid a discontinuation syndrome (symptoms include anxiety, agitation, nausea and mood swings). Discontinuation of SSRIs and venlafaxine are associated additionally with dizziness, electric shocklike sensations and paraesthesia. Short-acting drugs that do not produce active metabolites are most likely to cause such problems. Paroxetine in particular is associated with severe withdrawal symptoms including bad dreams, paraesthesia and dizziness (which can be misdiagnosed as labyrinthitis). 

Discontinuation of SSRIs can cause adverse events including dizziness, insomnia, nervousness, nausea, and agitation. See Discontinuation Syndrome under the section Human Toxicology (Acute) for more information. 

SSRIs are the drugs of choice for PD. All SSRIs have demonstrated effectiveness in controlled trials, with 60% to 80% of patients achieving a panic-free state.28,48,49 With similar efficacy reported and no trials comparing SSRIs with other SSRIs, selection generally is based on pharmacokinetics, drug interactions, side effects, and cost differences (see Chap. 35 for more discussion). The most common side effects of SSRIs include headaches, irritability, nausea and other gastrointestinal complaints, insomnia, sexual dysfunction, increased anxiety, drowsiness, and tremor.49 SSRIs should not be discontinued abruptly to avoid a withdrawal syndrome characterized by dysphoric mood, irritability, and agitation. 

Case reports have indicated an association between SSRIs and the syndrome of inappropriate secretion of antidiuretic hormone. Symptoms include lethargy, headache, hyponatremia, increased urinary sodium excretion, and hyperosmotic urine. Acute treatment of this syndrome should consist of discontinuation of the drug as well as restriction of fluid intake. Patients experiencing severe confusion, convulsions, or coma should receive intravenous sodium chloride. Elderly persons may he at a higher risk for developing this syndrome. 

The prototype SSRI, fluoxetine, differs from other SSRIs in some important respects (Table 30-1). Fluoxetine is metabolized to an active product, norfluoxetine, which may have plasma concentrations greater than those of fluoxetine. The elimination half-life of norfluoxetine is about three times longer than fluoxetine and contributes to the longest half-life of all the SSRIs. As a result, fluoxetine has to be discontinued 4 weeks or longer before an MAOI can be administered to mitigate the risk of serotonin syndrome. 

But later, in Phase II, after two years of continuous use, the SSRIs may contribute to a more ominous motor syndrome, the REM sleep behavior disorder described in chapter 8 as the enactment of dreamed movement. Eor reasons still not well understood, the drugs interfere with our normal ability to inhibit motor outputs. As with tardive dyskinesia victims, patients who develop SSRI-induced RBD may find that their sleep disorder does not abate when they discontinue the drug. The RBD can itself be treated with benzodiazepines—Clonazepam, for example. But that may be throwing good drug money after bad. And a more disturbing possibility, not yet observed, is that the SSRI-induced RBD will evolve in the same way that spontaneous RBD does to full-blown Parkinson s disease. 

In their review of 12 reported cases, Barnhart et al. (2004) found three cases associated with fluvoxamine, seven with fluoxetine, and two with paroxetine. The apathy states improved or resolved with dose reduction or discontinuation. The authors believed that the syndrome frequently goes undetected despite its significant clinical impact. Opbroek et al. (2002) reported that 80% of patients with SSRI-induced sexual dysfunction reported suffering from treatment-emergent emotional blunting. This is consistent with my clinical observations that so-called sexual dysfunction in patients receiving antidepressants often involves a more generalized loss of interest in both sex and loved ones. 

Discontinuing selective serotonin reuptake inhibitors (SSRIs) may induce a syndrome wherein the main neuropsychiatric symptoms are dizziness, shock-like sensations, anxiety, irritability, agitation, and insomnia. These symptoms usually develop 1 to 7 days after abrupt or gradual discontinuation. Antidepressant discontinuation may also induce mania, mainly reported with tricyclics and monoamine oxidase inhibitors but also observed with SSRIs. 

SSRIs PROCARBAZINE T risk of serotonin syndrome and CNS toxicity Additive toxicity Monitor BP closely and also CNS side-effects. Because of the long half-life of fluoxetine and its active metabolites, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of therapy with an MAOI... 

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