Cyclic antidepressants, and

Ray WA, Meredith S.Thapa PB, et al. Cyclic antidepressants and the risk of sudden cardiac death. Clin Pharmacol Ther 2004,75 234-241. 

Two major classes of antidepressant medications now are prescribed cyclic antidepressants and monoamine oxidase inhibitors (MAOIs). In the United States, cyclics are prescribed more frequently than MAOIs. 

A. Benztropine has additive effects with other drugs exhibiting antimuscarinic properties (eg, antihistamines, phenothiazines, cyclic antidepressants, and disopyramide). 

A. Contraindications include hypotension, bradycardia, or congestive heart failure secondary to intrinsic cardiac disease or cardiac-depressant effects of dmgs and toxins (eg, cyclic antidepressants and barbiturates). 

Fluniazenil is not indicated in all cases of suspected BZ overdose, and it is contraindicated when cyclic antidepressant involvement is known or suspected because of the risk of seizures. It should be used with caution when BZ physical dependence is suspected, as it may precipitate BZ withdrawal. 

Seizures The use of flumazenil has been associated with the occurrence of seizures. These are most frequent in patients who have been on benzodiazepines for long-term sedation or in overdose cases where patients are showing signs of serious cyclic antidepressant overdose. Individualize the dosage of flumazenil and be prepared to manage seizures. 

Contraindications Anticholinergic signs (such as mydriasis, dry mucosa, and hypo-peristalsis), arrhythmias, cardiovascular collapse, history of hypersensitivity to benzodiazepines, patients with signs of serious cyclic antidepressant overdose (such as motor abnormalities), patients who have been given a benzodiazepine for control of a potentially life-threatening condition (such as control of status epilepticus or increased intracranial pressure ICP )... 

Autonomic symptoms are most common and include gastrointestinal disturbance (nausea, diarrhea), general somatic distress (myalgias, malaise, headache, rhinorrhea), sleep disturbances (insomnia, nightmares), and cardiovascular symptoms (arrhythmias, ventricular ectopy). Psychotic decompensation, withdrawal mania, and general anxietylike symptoms have been attributed to abrupt withdrawal of cyclic antidepressants. 

Gill HS, DeVane CL, Risch SC. Extrapyramidal symptoms associated with cyclic antidepressant treatment a review of the literature and consolidating hypotheses. J Clin Psychopharmacol 1997 17(5) 377-89. 

Antidepressant medications have been shown to often be helpful in chronic pain syndromes. These medications are effective only for chronic pain and not for acute pain. They help reduce pain and, when combined with narcotic analgesics, potentiate the effects of the narcotic. The cyclic antidepressants are the best studied and have the most supporting evidence. When there is not an accompanying depression, lower than the usual antidepressant doses may be effective. Venlafaxine, because of its similarities to the cyclic antidepressants, is probably effective also. There are a few studies showing the effectiveness of the SSRIs, but some studies that do not. 

We now have at least three major groups of antidepressants cyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and MAO inhibitors. Additionally, stimulants (such as Dexedrine, Ritalin), atypical antidepressants (bupropion and venlafaxine) and buspirone have been used to treat depression. 

Carbamazepine is both an important anticonvulsant in therapeutic doses and a powerful proconvulsant in overdose. The therapeutic anticonvulsant mechanism is primarily related to blockade of presynaptic voltage-gated sodium channels. Blockade of the sodium channels is believed to inhibit the release of synaptic glutamate and possibly other neurotransmitters. Carbamazepine is also a powerful inhibitor of the muscurinic and nicotinic acetylcholine receptors, N-methyl-D-aspartate (NMDA) receptors and the central nervous system (CNS) adenosine receptors. In addition, carbamazepine is structurally related to the cyclic antidepressant impramine and in massive overdose may affect cardiac sodium channels. 

James LP, Kearns GL. Cyclic antidepressant toxicity in children and adolescents. J CUn Pharmacol 1995 35 343-350. 

Smilkstein MJ. Reviewing cyclic antidepressant cardiotoxicity Wheat and chaff. J Emerg Med 1990 8 645-648. 

A. Enhanced pressor response may occur in the presence of cocaine and cyclic antidepressants owing to inhibition of neuronal reuptake. 

C. Cocaine and cyclic antidepressants may enhance stimulant effects owing to inhibition of neuronal epinephrine reuptake. 

A. Physostigmine should not be used as an antidote for cyclic antidepressant overdose because it may worsen candiac conduction disturbances, cause bradyarrhythmias or asystole, and aggravate or precipitate seizures. 

C. They may have additive depressant effects on cardiac conduction in patients with cyclic antidepressant, beta-adrenergic antagonist, and calcium antagonist overdoses. 

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