Fluoxetine drug overdose

Revicki DA, Palmer CS, Phillips SD, et al (1997). Acute medical costs of fluoxetine versus tricyclic antidepressants a prospective multicentre study of antidepressant drug overdoses. Pharmacoeconomics 11, 48—55. 

Physical examination revealed tachycardia with irregular heart rate, shallow respiration, decreased bowel sounds, dilated pupils, and hypertheimia. An ECG revealed a widened QRS complex with diffuse T wave changes. If this patient had taken a drug overdose the most likely causative agent was (A) Clozapine Fluoxetine Lithium Thioridazine Zolpidem... 

Fluoxetine is a potential drug of abuse.136 Overdose with sertraline causes suicidal tendencies, whereas citalopram causes fatal reactions such as cardiac dysfunction.137 The adverse effects could be treated with stomach wash, administration of activated charcoal, dialysis, and hemoperfusion. 

Muijen et al. (1988) conducted a 6-week double-blind study comparing fluoxetine, mianserin, and placebo with 26, 27, and 28 starters, respectively, and 14, 14, and 16 finishers, respectively. Two of the fluoxetine patients took an overdose within two weeks of starting the study, and in both cases this was related to a deteriorating clinical state that necessitated hospitalization (p. 386). None of the patients in the other drug group or the placebo group suffered from this decline and suicidality. 

Later, in his safety update of the NDA on October 17, 1986, Kapit spoke of several cases of a syndrome of fluoxetine-induced hyper-arousal and excessive stimulation... [that] resemble episodes of stimulant drug intoxication. It was especially likely to occur at higher doses, but it could occur at the standard 20 mgs. The state of overstimulation included anxiety, agitation, insomnia, headache, confusion, dizziness, obnubilation [mental clouding], memory dysfunction, tremor, impaired motor coordination. Hyperactivity, hypomania, and mania may sometimes occur. In overdose, the drug produces an even more flagrant stimulant syndrome culminating in seizures. Thus there is a continuum of stimulation effects. 

A meta-analysis of 20 short-term studies of five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) has been published (8). There were no overall differences in efficacy, but fluoxetine had a slower onset of action. Citalopram and sertraline were least likely to cause drug interactions, but citalopram was implicated more often in fatal overdoses. 

Nine patients took overdoses of fluoxetine in amounts up to 3000 mg (37 times the recommended dose) (3). One, who also took several other drugs, including amitriptyline, died, but the other eight all recovered with relatively minor symptoms in most cases. Four patients had suspected seizures during studies (3) and one who took a 3000 mg overdose had unequivocal convulsions but recovered. 

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. 

Serotonin syndrome occurs primarily in patients taking monoamine oxidase (MAO) inhibitors (see p 269) who also take serotonin-enhancing drugs, such as meperidine (Demerol ), fluoxetine (Prozac ), or other serotonin reuptake inhibitors (SSRIs see Antidepressants, p 88), and is characterized by irritability, rigidity, myoclonus, diaphoresis, autonomic instability, and hyperthermia. It may also occur in people taking an overdose of or combinations of SSRIs even without concurrent use of MAO inhibitors. 

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