Serotonin discontinuation syndrome

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. 

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. 

Abrupt discontinuation or noncompliance with serotonin reuptake inhibitor (SRI) treatment regimens may result in a recently described SRI Discontinuation Syndrome, characterized by disequilibrium, dizziness, vertigo, and ataxia. Although no randomized, placebo-controlled studies have been published regarding this entity, case reports of successful alleviation of its symptoms by ginger root have been emerging (25). The dose of ginger root most frequently utilized to treat this syndrome is 500 to 1000 mg three times daily. 

Affective symptoms Use serotonin reuptake inhibitors only during the luteal phase (e.g., 7-14 days premenstrual) for a 2-month trial. Switch to continuous daily administration if response is inadequate and increase dose 7-14 days premenstrually if needed. A discontinuation syndrome may occur if using higher doses without tapering dose down gradually over several days. 

In a similar study, however, reduced Glx levels were observed in the anterior cingulum of depressed patients. The level of Glx was found to increase upon effective ECT." The effects of selective serotonin reuptake inhibitor discontinuation syndrome have been investigated in patients with unipolar major depression who had been stabilised on paroxetine or fluoxetine. H NMR spectroscopic imaging of the rostral anterior cingulate was carried out 3 days after substitution of medication with a selective serotonin reuptake inhibitor or a placebo. The ratio of Cho/tCr was deceased in patients who met the criteria of selective serotonin reuptake inhibitor discontinuation syndrome compared to asymptomatic subjects." ... 

Neuroleptic malignant syndrome is an acute iatrogenic condition caused by neuroleptics, characterized by tremor, catatonia, fluctuating consciousness, hyperthermia, and cardiovascular instability. It is relatively uncommon, occuring in 1-1.5% of patients but is fatal in 11-38%, most often due to cardiovascular collapse (Jahan et al. 1992). The pathogenesis of neuroleptic malignant syndrome is poorly understood, but it is believed to result from altered dopamine and serotonin transmission in the hypothalamus, spinal cord, and striatum. Treatment includes discontinuation of neuroleptics and administration of drugs that increase dopamine transmission bromocriptine or L-dopa (Jahan etal. 1992 Baldessarini 1996). 

When switching between a MAOl and other antidepressants that affects serotonin activity, the first medication must be allowed to wash out of the patient s system before the new antidepressant is started. The duration of this washout period is determined by the half-life of the antidepressant that is being discontinued. If a washout is neglected, then a potentially dangerous serotonin syndrome may result. 

Coplan JD, Gorman JM. Detectable levels of fluoxetine metabolites after discontinuation an unexpected serotonin syndrome. Am J Psychiatry 1993 150 837. 

There were two cases of hypertension from the United States, or possible serotonin syndrome reported with fluvoxamine while on St. John s wort concomitantly. A 44-year-old male with obsessive-compulsive disorder received fluvoxamine and experienced severe hypertensive crisis (160-170/ 120mmHg) after two tablets of St. John s wort. The physician stated that the reaction was probably due to the combination of fluvoxamine and St. John s wort, which has MAOI activity. A 38-year-old male was on fluvoxamine for approximately two months and hypericum 600 mg daily for approximately two weeks before reporting possible serotonin syndrome with severe bitemporal headache. He was hospitalized to rule out myocardial infarction. There were no electrocardiogram (EKG) changes or apparent causative pathology. Symptoms resolved on discontinuation of both drugs. 

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. 

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. 

MAOIs DULOXETINE, VENLAFAXINE Risk of severe hypertensive reactions and of serotonin syndrome > For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome. Duloxetine inhibits the reuptake of both serotonin and norepinephrine. Due to impaired metabolism of these amines, there is an accumulation of serotonin and norepinephrine in the brain and at peripheral sites Do not co-administer duloxetine and venlafaxine prior to 14 days after discontinuing an MAOI, and do not co-administer MAOI for 5 days after discontinuing duloxetine, 1 week after venlafaxine... 

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... 

Treatment of an overdose of the atypical antidepressants and SSRIs is directed primarily toward decontamination of the gastrointestinal tract with activated charcoal, symptomatic treatment, and general supportive care. Management of the serotonin syndrome involves discontinuation of the serotinergic agent and supportive therapy. Beu-zodiazepines, propranolol, and cyproheptadine, a serotonin antagonist, have been used successfully. ... 

---