Sertraline toxicity

Use of die MAOIs must be discontinued 2 weeks before the administration of die SSRIs. When the SSRIs are administered witii die tricyclic antidepressants, tiiere is an increased risk of toxic effects and an increased tiierapeutic effect. When sertraline is administered witii a MAOI, a potentially fatal reaction can occur. Sjymptoms of a serious reaction include hyper-tiiermia, rigidity, autonomic instability witii fluctuating vital signs and agitation, delirium, and coma Sertraline blood levels are increased when administered witii cimetidine. 

Other Antidepressants. Antidepressant refinements for the next 30 years primarily consisted of the development of new TCAs. However, in 1988, a novel antidepressant class, the selective serotonin reuptake inhibitors (SSRIs), was introduced in the United States. The chief innovation of the SSRIs was that they afforded the comparable effectiveness of the TCAs with fewer side effects and minimal toxicity. The debut of the SSRIs coincided with the reworking of the nosology of the anxiety disorders in DSM-III and DSM-IV. As a result, the SSRIs have been studied extensively in each of the respective anxiety disorders and in many cases have obtained FDA approval for the treatment of one or more of these anxiety syndromes. The SSRIs currently available in the United States include citalopram (Celexa), escitalo-pram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). 

SSRIs—fluvoxamine, fluoxetine, and paroxetine, more than sertraline and citalopram Inhibition of metabolism at CYP2D6 isoenzyme TCA toxicity due to up to 10-fold increase in TCA levels with coadministration Lower TCA dose Baumann, 1996... 

All SSRIs have an antipanic effect. Their advantages are limited adverse effects and lack of toxicity. Because of more acceptable adverse effect profiles, the SSRIs are usually the drugs of choice. Several studies consistently indicate that SSRIs such as fluoxetine, sertraline, paroxetine, fluvoxamine, as well as agents such as clomipramine and trazodone, all possess antipanic efficacy, although the last may be less effective than imipramine ( 24, 105, 106, 107, 108 and 109). 

Fluoxetine was the first SSRI to reach general clinical use. Paroxetine and sertraline differ mainly in having shorter half-lives and different potencies as inhibitors of specific P450 isoenzymes. While the SSRIs have not been shown to be more effective overall than prior drugs, they lack many of the toxicities of the tricyclic and heterocyclic antidepressants. Thus, patient acceptance has been high despite adverse effects such as nausea, decreased libido, and even decreased sexual function. 

Kaufman KR, Gerner R. Lamotrigine toxicity secondary to sertraline. Seizure 1998 7 163-165. 

A 45-year-old man had definite symptoms of serotonin toxicity (hypomania, myoclonus, sweating, and shivering), first when taking a low therapeutic dose of citalopram (20 mg/day) and then with low-dose sertraline (25 mg/day) he was also taking zolpidem (17). 

Of 93 cases of neonatal symptoms associated with the use of SSRIs in mothers around the time of delivery 64 were associated with paroxetine but reactions were also reported in infants whose mothers had taken citalopram, fluoxetine, and sertraline (87). It is unclear from these data whether paroxetine is actually most likely to provoke the neonatal syndrome, but in adults its use is associated with more severe withdrawal reactions than other SSRIs. It should also be noted that it is not clear whether the syndrome described in neonates is due to SSRI withdrawal or a form of serotonin toxicity. 

The authors proposed that in this case erythromycin had inhibited sertraline metabolism by inhibiting CYP3A. This could have led to increased concentrations of sertraline and signs of serotonin toxicity. Unfortunately sertraline concentrations were not measured to confirm this suggestion. 

AMIODARONE SSRIs-SERTRALINE Sertraline may t amiodarone levels Sertraline may inhibit CYP3A4-mediated metabolism of amiodarone Watch for amiodarone toxicity for those taking high doses of amiodarone, consider using an alternative SSRI with a lower affinity for CYP3A4... 

METOPROLOL SSRIs T plasma concentrations of metoprolol SSRIs inhibit metabolism of metoprolol (paroxetine, fluoxetine, sertraline, fluvoxamine via CYP2D6, and (es)citalopram via mechanism uncertain at present) Monitor PR and BP at least weekly watch for metoprolol toxicity, in particular loss of its cardioselectivity... 

MAOIs SSRIs t risk of serotonin syndrome >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome Additive inhibitory on serotonin reuptake Avoid co-administration. MAOIs should not be started for at least 1 week after stopping SSRIs (2 weeks after sertraline, S weeks after fluoxetine). Conversely, SSRIs should not be started for at least 2 weeks after stopping MAOIs... 

ESCITALOPRAM, FLUOXETINE, FLUVOXAMINE, PAROXETINE, SERTRALINE BUPROPION T plasma concentrations of these SSRIs, with risk of toxic effects Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 Initiate therapy of these drugs at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. paroxetine)... 

FLUVOXAMINE FOOD-CHARGRILLED MEAT, BROCCOLI, CABBAGE, SPROUTS 1 plasma concentrations of fluvoxamine with loss of therapeutic efficacy Fluvoxamine and fluoxetine are metabolized mainly by CYP1A2 isoenzymes, while the role of CYP1A2 in the metabolism of sertraline is probably not clinically significant Monitor for lack of therapeutic effect. When inducers are withdrawn, monitor for fluvoxamine toxicity... 

CANNABIS SERTRALINE, VENLAFAXINE Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes... 

Sertraline Carbamazepine Diazepam Lamotrigine Phenytoin Risk of toxicity of the object drugs Inhibition of metabolism of the object drugs... 

Because this group as a whole engages in frequent suicidal acting out, it is advisable to treat borderline patients with medications that have been found to have a low degree of toxicity when taken in overdose. These include antipsychotics and the following antidepressants fluoxetine, paroxetine, bupropion (note above caution), trazodone, and sertraline. Most other antidepressants are quite toxic when taken in overdose. 

High suicide risk Less toxic antidepressants (fluoxetine, trazodone, paroxetine, sertraline, bupropion, venlafaxine, nefazodone)... 

Sertraline has a relatively low risk of toxicity. It is less sedating and has fewer cardiovascular effects than the tricyclic antidepressants. It has a high therapeutic index, which is consistent with other serotonin uptake inhibitors. 

Therapeutic chronic use of sertraline has reportedly caused visual defects, cardiac toxicity, gastrointestinal irritation, renal pathology, and loss of appetite. 

Carbamazepine Some, but not all, reports indicate that carbamazepine serum levels can be increased by fluoxetine and fluvoxamine. Toxicity may develop. Sertraline normally appears not to affect carbamazepine, but sertraline levels may be reduced by carbamazepine. Isolated cases of Par-kinson-like and serotonin syndrome have occurred with fluoxetine and carbamazepine, while an isolated case of pancytopenia has been reported with sertraline and carbamazepine. The metabolism of citalopram may be increased. 

Clozapine Fluoxetine, paroxetine, sertraline, and possibly citalopram can raise serum clozapine levels. Particularly large increases can occur with fluvoxamine. Toxicity has been seen in some patients. 

Lamotrigine Toxicity has been reported following the addition of sertraline. 

Phenytoin Phenytoin serum levels can be increased in some patients by fluoxetine. Toxicity may occur. There are also isolated reports of phenytoin toxicity with the concurrent use of fluvoxamine and paroxetine. Phenyltoin and sertraline do not normally interact nevertheless, two patients have shown increased serum phenytoin levels. 

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