Delirium tricyclic antidepressants

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. 

Selegiline should not be coadministered with tricyclic antidepressants or selective serotonin uptake inhibitors because of the possibility of a severe adverse drug reaction (e.g., hyperpyrexia, agitation, delirium, coma). 

Because of the multiple receptor sites that TCAs bind to, there are a variety of possible side effects that can be seen in treatment. The blockade of muscarinic receptors leads to increased anticholinergic tone and subsequent anti-cholinergic side effects, especially in the gastrointestinal system. These include delirium, dry mouth, tachycardia, constipation, and urinary retention in adults. In children, anticholinergic side effects are often not seen with treatment (Geller et ah, 1992). Tricyclic antidepressant blockade of the presynaptic a 2 receptors leads to increased autonomic tone throughout the body, causing elevations in heart rate and blood pressure. 

The classic anticholinergic (technically, "antimuscarinic") syndrome is remembered as "red as a beet" (skin flushed), "hot as a hare" (hyperthermia), "dry as a bone" (dry mucous membranes, no sweating), "blind as a bat" (blurred vision, cycloplegia), and "mad as a hatter" (confusion, delirium). Patients usually have sinus tachycardia, and the pupils are usually dilated (see Chapter 8). Agitated delirium or coma may be present. Muscle twitching is common, but seizures are unusual unless the patient has ingested an antihistamine or a tricyclic antidepressant. Urinary retention is common, especially in older men. 

Delirium, which also occurs with tricyclic antidepressants, has been reported with trazodone (21). 

Early signs of tricyclic antidepressant toxicity are due to anticholinergic effects and include tachycardia, mydriasis, dry mouth, low-grade fever, diminished bowel sounds, CNS excitation, and delirium. More serious toxicity is manifested by coma, respiratory depression, seizures, and cardiovascular toxicity including conduction disturbances, hypotension, ventricular arrhythmias, and asystole. Seizures cause hyperthermia, rhabdomyolysis, and metabolic acidosis. Clinical deterioration can be rapid and catastrophic in patients with tricyclic antidepressant overdose. Death most often occurs due to dysrhythmia and circulatory collapse. The typical therapeutic dose of a tricyclic antidepressant is 2-4 mg kg day Doses of 15-20 mg kg are potentially lethal. Therapeutic drug levels for most tricyclic antidepressants range from 100 to... 

Livingston RL, Zucker D, Isenberg K, et al Tricyclic antidepressants and delirium. J Clin Psychiatry 44 173-176,1983 Marcos LR, Cancro R Pharmacotherapy of Hispanic depressed patients clinical observations. Am J Psychother 36 505-513,1982 Mendoza R, Smith MW, Poland RE, et al Ethnic psychopharmacology the Hispanic and the Native American perspective. Psychopharmacol Bull 27 449-461,1991... 

The CNS manifestations of tricyclic antidepressant overdose may vary from mild agitation or drowsiness to delirium, coma, respiratory depression, or seizures. These manifestations are thought to result in part from central anticholinergic and antfliistaminic actions of these drugs. 

GI distress, dizziness, somnolence slurred speech and delirium possible in elderly. Cimetidine is a major inhibitor of P450 isoforms drug interaction via T effects of quinidine, phenytoin, tricyclic antidepressants, and warfarin. Cimetidine —androgens -> gynecomastia and l libido. 

The antimuscarinic action of clozapine and thioridazine can cause tachycardia and enhance the peripheral and central effects (confusion, delirium) of other anticholinergic agents, such as the tricyclic antidepressants and antiparkinson agents. 

A small dose of physostigmine (see p 489), 0.5-1 mg IV in an adult, can be given to patients with severe toxicity (eg, hyperthermia, severe delirium, or tachycardia). Caution physostigmine can cause atrioventricular block, asystole, and seizures, especially in patients with tricyclic antidepressant overdose. 

B. Cyclobenzaprine and orphenadrine can produce anticholinergic findings, such as tachycardia, dilated pupils, and delirium. Despite its stmctural similarity to tricyclic antidepressants, cyclobenzaprine has not been reported to cause quinidine-like cardiotoxicity... 

A number of other reports and studies clearly confirm that marked increases occur in the levels of amitriptyline, " clomipramine, desipramine, " imipramine " and nortriptyline, " accompanied by toxicity, if fluoxetine is added without reducing the dosage of the tricyclic antidepressant. Delirium and seizures have also been described, and a death has been attributed to chronic amitriptyline toxicity caused by fluoxetine. The pharmacokinetics of fluoxetine appear not to be affected by amitriptyline. ... 

Cases cf Neurotoxicity Toxicity at therapeutic or subtherapeutic levels was reported in three cases. In two of these cases, the role of lithium is questionable. In one case of a rapidly fatal presentation of neuroleptic malignant syndrome (NMS) in a 72-year-old woman whose lithium level was 1.5 mM, the authors report a lithium-induced fatal NMS because she was not prescribed an antipsychotic [84 ]. However, her presentation is also consistent with fatal catatonia, sepsis, or unknown consumption of an antipsychotic, none of which were ruled out, and all of which are more likely than lithium-induced NMS. A second case in which a delirium with dyspraxia, but not ataxia in a 57-year-old man with a lithium level of 0.44 mM, that resolved after discontinuation of botii lithium and tricyclic antidepressant medication, was felt to be an interaction between the lithium and the antidepressant [85 ]. Lithium may have played a role, but he had been on lithium for years, and had developed anticholinergic problems with quetiapine previously, suggesting that the anticholinei c effects of the tricyclic antidepressant were more important in the delirium than the lithium. The third case of a 65-year-old man with multisystem atrophy becoming considerably worse with lithium at a level of 1.1 mM, is much more likely to represent lithium-related neurotoxicity at therapeutic levels [86 ]. 

Hayward D, Luff B. Lithium and tricyclic antidepressant-induced delirium presenting with prominent dyspraxia case report. Ther Adv Psychopharmacol 2012 2(4) 147-8. 

A 73-year-old man developed anticholinergic delirium on a combination of VPA and amitriptyline. The adverse effects included muscular rigidity, ataxia, dysarthria, somnolence, agitation, and disorientation. This prompted a retrospective review in which it was discovered that patients taking tricyclic antidepressant medications (amitriptyline or nortriptyline) in conjunction with VPA had higher mean serum levels of amitriptyline or nortriptyline compared to those taking tricyclic antidepressants without VPA [194 ]. 

Heiser, J. F. and Wilbert, D. E. (1974) Reversal of delirium induced by tricyclic antidepressant drugs with physostigmine. Amer. J. Psychiat., 131, 1275. 

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