| Antidepressants fall into several classes. An overdose of almost any of them can result in development of serotonin syndrome (see below). |
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Selective Serotonin Reuptake Inhibitors: |
| This group of antidepressant agents include sertraline, fluoxetine, paroxetine, and fluvoxamine. They block the activity of serotonin receptors at presynaptic membranes and have little effect on other neurotransmitters. |
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Tricyclic Antidepressants: |
| These antidepressants (eg, amitriptyline, clomipramine, nortriptyline) are commonly used psychoactive agents. They are structurally similar to the phenothiazines, with a similar anticholinergic, adrenergic, and α-blocking properties. Following absorption, these agents are extensively bound to plasma proteins and also bind to tissue and cellular sites,
including the mitochondria. Cyclic antidepressants block the amine pump and stop neuronal reuptake of norepinephrine, serotonin, and dopamine. These agents also appear to have a slight a-adrenergic blocking effect. Tricyclics may exert their major toxicity via a nonspecific membrane-stabilizing effect, similar to chlorpromazine and the β-blockers. Tricyclics also have central and peripheral anticholinergic activity, along with antihistaminic effects. Clinical signs of toxicosis
include CNS stimulation (agitation, confusion, pyrexia), cardiac arrythmias, hypertension, myoclonus, nystagmus, seizures, metabolic acidosis, urinary retention, dry mouth, mydriasis, and constipation. This may be followed by CNS depression (lethargy), ataxia, hypothermia, respiratory depression, cyanosis, hypotension, and coma. |
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| Treatment: |
| Emesis should be induced in cases of recent exposure if the animal is asymptomatic. This can be followed by activated charcoal (even several hours after ingestion) plus a cathartic such as sorbital or sodium sulfate (magnesium sulfate is contraindicated, as it can add to CNS depression). Diazepam can be given to control seizures. Serotonin syndrome signs should be managed as needed. Heart rate and rhythm should be monitored and cardiac arrythmias treated. Atropine should not be
used to control bradycardia as it can aggravate anticholinergic effects of tricyclic antidepressants. |
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Serotonin Syndrome: |
| This group of clinical signs usually includes 3 of the following features: altered mental status, agitation, myoclonus, hyperreflexia, tremors, diarrhea, incoordination, and fever. It often occurs after overdose or ingestion of substances that result in elevated free levels of serotonin, such as antidepressants or profound stimulants (eg, amphetamines, cocaine, pseudoephedrine, and ephedra). Cyproheptadine is a serotonin antagonist often used for treatment. It is available only
as a tablet, but can be dissolved in a small amount of saline and administered per rectum at 1.1 mg/kg in dogs or 2 mg/dose in cats. If there is a good response to the initial dose, it can be repeated if signs recur. |
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