Monoamine oxidase inhibitors overdose

Linden CH, Rumack BH, and Strehlke C (1984) Monoamine oxidase inhibitor overdose. Annals of Emergency Medicine 13 1137-1144. 

Monoamine oxidase inhibitors can induce hyperpyrexia anchor seizures or opioid overdose symptoms Used in severe pain Do not use transdermal in acute pain... 

Monoamine oxidase inhibitors have a low therapeutic index. Adverse effects include orthostatic hypotension, impotence and insomnia. Overdoses become manifest by symptoms of agitation, hyper-reflexia followed by convulsions. Rare but serious cases of hepatotoxicity have been associated with the use of isocarboxazid and of phenelzine. 

Because of neurotoxicity and overdose concerns, 2C-B may have potentially dangerous interactions with users taking monoamine oxidase inhibitors (MAOIs). MAOIs are most commonly found in the prescription antidepressants Nardil (phenelzine), Parnate (tranylcypromine), Marplan (isocarboxazid), Eldepryl (1-deprenyl), and Aurorex or Manerix (moclobemide). Ayahuasca also contains MAOIs (harmine and harmaline). 

Overdose of moclobemide by itself rarely appears to give rise to serious problems. This is in contrast to overdose with conventional monoamine oxidase inhibitors, which can cause fatal 5HT toxicity. However, if patients take moclobemide together with serotonergic antidepressants, such as SSRIs or clomipramine, 5HT toxicity is common. 5HT toxicity occurred in 11 of 21 patients who took overdoses of moclobemide and serotonergic agents but in only one of 33 patients who took moclobemide alone (13). Consistent with this, four patients died, presumably of 5HT toxicity, after co-ingesting 3,4-methyle-nedioxymethamphetamine (MDMA, ecstasy) and moclobemide (14). 

Antidepressant drugs of various classes (tricyclics, monoamine oxidase inhibitors, SSRIs) have broad efficacy in generalized anxiety and in panic disorder, for which they are the treatments of choice (6,7). While not likely to cause benzodiazepine-like dependence or abuse, they do have a significant therapeutic latency, and the older drugs are very toxic in overdose. 

Action on receptors provides numerous examples. Beneficial interactions are sought in overdose, as with the use of naloxone for morphine overdose (opioid receptor), of atropine for anticholinesterase, i.e. insecticide poisoning (acetylcholine receptor), of isoproterelol (isoprenaline) for overdose with a P-adrenoceptor blocker (p-adrenoceptor), of phentolamine for the monoamine oxidase inhibitor-sympathomimetic interaction (a-adrenoceptor). 

Meperidine IM 50-1 50 mg q 3 h IV 5-10 mg q 5 min prn Use in severe pain Oral not recommended Do not use in renal failure May precipitate tremors, myoclonus, and seizures Monoamine oxidase inhibitors can induce hyperpyrexia and/or seizures or opioid overdose symptoms... 

Atomoxetine, bupropion, and TCAs are second-line alternatives to the stimulants for treatment of ADHD in children, teens, and adults. The potential benefits of these agents in comparison with stimulants include reduced risk of abuse and somewhat lower potential for sleep disturbance. TCAs are the most dangerous in overdose and pose the greatest risk for cardiovascular side effects. The monoamine oxidase inhibitor tranylcypromine is effective but used infrequently due to the potential for dangerous drug and dietary interactions. Selective serotonin reuptake inhibitors (SSRIs) are not effective for ADHD. ... 

Methylphenidate should not be used with monoamine oxidase inhibitors such as tranylcypromine. Symptoms of overdose may include euphoria, confusion, delirium, coma, toxic psychosis, agitation, headache, vomiting, dry mouth, mydriasis, self-injury, fever, diaphoresis, tremors, hyper-reflexia, muscle twitching, seizures, flushing, hypertension, tachycardia, palpitations, and arrhythmias. 

Selective serotonin reuptake inhibitors (SSRIs) are the first-line therapy for PTSD. Efficacy for fluoxetine, paroxetine, and sertraline has been demonstrated in well-designed double-blind placebo-controlled studies to reduce all symptom domains (intrusive recollection, avoidance/numbness, and hyperarousal). - Other treatment options include the tricyclic antidepressants (TCAs) amitriptyline and imipramine and the irreversible monoamine oxidase inhibitor (MAOl) phenelzine, which have been shown to reduce re-experiencing. However, in comparison with SSRIs, TCAs and phenelzine are associated with a higher incidence of side-effects, risk of overdose, and poor compliance. Alprazolam has demonstrated anecdotal efficacy however, regular use of benzodiazepines is not recommended. Benzodiazepines can be used on an as-needed basis for specific symptoms (e.g. sleep disturbances). CBT has shown beneficial effects in relatively well-controlled studies, while the results with exposure therapy are... 

Tricyclic antidepressants are commoniy taken in overdose by suicidal patients and represent a major cause of poisoning hospitaiizations and deaths. Currently available tricyclic antidepressants are described in Table 11-7. Amitriptyline is also marketed in combination with chlordiazepoxide (Limbitrol ) or perphenazine (Etrafon or Tria-viF ). Cyclobenzaprine (FlexerilTW), a centrally acting muscle relaxant (see p 339), is structurally related to the tricyclic antidepressants but exhibits minimal cardiotoxic and variable CNS effects. Newer, noncyclic antidepressants are discussed on p 88. Monoamine oxidase inhibitors are discussed on page 269. 

Drug overdoses involving stimulants (eg, amphetamines, cocaine, phencyclidine, monoamine oxidase inhibitors) or strychnine. 

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

In a controlled comparison between clomipramine and amitriptyline, the former caused adverse effects more often, especially drowsiness (3). Overdose toxicity is the same as with other tricyclic antidepressants (4) fatal interactions with monoamine oxidase (MAO) inhibitors have been reported (SEDA-18, 16 5). Altogether, toxic effects are not substantially different. 

Tranylcypromine is a non-hydrazine monoamine oxidase (MAO) inhibitor with actions and uses similar to those of phenelzine, but with less prolonged inhibition. Its half-life is 90-190 minutes. It is structurally related to amfetamine, to which it is metabolized in overdose (1). 

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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