Venlafaxine drug overdose

Few data are available regarding venlafaxine in overdose, but the drug s pharmacological profile suggests that it is safer than TCAs. In most of the reported cases to date, symptoms were not present. 

Nefazodone, like the SSRIs and venlafaxine, has negligible effect on Na ion fast channels and therefore does not slow intracardiac conduction. As a result, during clinical trials development, patients survived drug overdoses exceeding 11,200 mg without the need for any intervention beyond observation and routine nursing care (146, 451). One nonstudy patient who took 2,000 to 3,000 mg of nefazodone with methocarbamol and alcohol experienced a seizure (type not documented) but otherwise recovered uneventfully. 

In 225 patients who had taken overdoses of antidepressant drugs in suicide attempts, venlafaxine and citalopram were more likely to be associated with seizures than mir-tazapine and nefazodone and 5HT toxicity was more common after overdose of venlafaxine (94). These findings confirm the potential toxicity of venlafaxine in overdose and also suggest a pro-convulsant effect of large doses of citalopram. 

Drug overdose Seizures are a recognized, albeit uncommon, complication of overdose with a number of SSRI antidepressants, but the susceptibility factors have not been elucidated. Qf 241 patients who presented with overdose of citalopram, 7.5% had generalized seizures [33 ]. Co-ingested venlafaxine or tricyclic antidepressants increased the risk substantially (QR = 15). In the absence of co-ingested drugs, the minimum citalopram dose associated with seizures was 400 mg, with an increase in the odds ratio for seizures of 1.1 for every 100 mg increment in citalopram dose. 

Drug overdose There has been growing awareness of the cardiac adverse effects of venlafaxine (SEDA-32, 35). A 51-year-old woman with no known risk factors for coronary artery disease had an episode of non-ST-elevation myocardial infarction in association with an overdose of venlafaxine [62 ]. 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

Highly suicidal patients should be given agents posing less risk of lethality with overdose and less risk of interacting with other drugs taken in an overdose attempt (i.e., sertraline, citalopram, or venlafaxine). 

Suicidal ideation of some kind almost invariably accompanies severe depression. Hence the relative toxicity of antidepressants in overdose can be important in determining treatment choice. It is accepted that SSRIs are less dangerous in overdose than tricyclic antidepressants, but there are fewer data on the toxicity of other antidepressants. The presentation and likely toxicity in overdose of several newer antidepressant drugs have been reviewed (9). Deaths in overdose have been most clearly associated with amfebutamone and venlafaxine. 

The selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of depression in the elderly. Compared with tricyciic antidepressants (TCAs), they are much safer in overdose and, for the most part, their side-effects are better tolerated. The antidepressants that have been shown, in controlled studies, to be effective in geriatric major depression are the SSRIs fluoxetine, paroxetine, and sertraline, the TCAs clomipramine and nortriptyline, and the serotonin and norepinephrine reuptake inhibitor (SNRi) venlafaxine. Given that most antidepressants are effective in the elderly, the choice of drug is based on its side-effect profile and its potential to interact with other medications. 

A 32-year-old man taking moclobemide 20 mg twice daily and diazepam developed the serotonin syndrome 40 minutes after taking a single 150-mg dose of venlafaxine. Serotonin toxicity (the serotonin syndrome) occurred in 4 patients who took an overdose of moclobemide with venlafaxine (just 150 mg in one case and 750 mg in another). In this analysis of moclobemide overdoses, the risk of developing serotonin toxicity was increased 35 times in patients who also took another serotonergic drug. Venlafaxine was taken in 4 of the 11 cases mentioned." Another man very rapidly developed the serotonin syndrome after taking considerable overdoses of moclobemide (3 g) and venlafaxine (2.625 g). ... 

Both venlafaxine and trimipramine can cause seizures, although usually after overdose. Either a pharmaeokinetic interaetion involving inhibition of drug metabolism by the isoenzyme CYP2D6, or a pharmacodynamic interaction may have resulted in seizures. ... 

Nervous system Serotonin syndrome with rhabdomyolysis occurred in a patient with Parkinson s disease after he had taken venlafaxine 75 mg/day for depression for 2 weeks [23" ]. Previous reports of serotonin syndrome with venlafaxine have been related to overdose [24 ]. Parkinsonism or drug-drug interactions with the antiparkinsonian medications may have predisposed this patient to serotonin syndrome at such low doses of venlafaxine. 

Indirect effects of drugs on catecholamines have ako resulted in takotsubo syndrome. In one case there was transient typical ballooning of the left ventricular apex during systole following the use of cocaine, thought to have been due to inhibition of catecholamine reuptake [22ft]. A 43-year-old woman who took an overdose of venlafaxine, an inhibitor of serotonin and noradrenaline reuptake, developed a takotsubo cardiomyopathy and there was an increase in urinary normetadrenaline (normetanephrine) concentration [23 ]. 

Pascale P, Oddo M, Pacher P, Augsburger M, liaudet L. Severe rhabdomyolysis following venlafaxine overdose. Ther Drug Monit 2005 27(5) 562-4. 

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