Tricyclic antidepressants with opioid analgesics

Neuropathic Pain Burning, shooting, and tingling pain resulting from injury to a peripheral nerve treated with anticonvulsants, tricyclic antidepressants, and opioid analgesics... 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Sedation and sleep promotion can be achieved with drugs that are not classed as sedatives or hypnotics, including antihistamines (e.g., hydroxyzine) and opioid analgesics. Tricyclic antidepressants (TCAs) have been used in anxiety characterized by panic and/or phobias, and more recently the selective serotonin reuptake inhibitors (SSRIs) have been used. Propranolol has efficacy in performance anxiety and social phobias. 

Additive CNS depression This occurs when sedative-hypnotics are used with other drugs in the class as well as with alcoholic beverages, antihistamines, antipsychotic drugs, opioid analgesics, and tricyclic antidepressants. This is the most common type of drug interaction involving sedative-hypnotics. Additive CNS depression with buspirone is uncommon. 

While drug interactions based on pharmacokinetics do occur with sedative-hypnotics, the most common drug interaction is additive CNS depression. Additive effects can be predicted with concomitant use of alcoholic beverages, anticonvulsants, opioid analgesics and phenothiazines. Less obvious but equally important is enhanced CNS depression with many antihistamines, antihypertensives, and antidepressants of the tricyclic class. The answer is (A). 

Drug interactions The most important drug interactions involving opioid analgesics are additive CNS depression with ethanol, sedative-hypnotics, anesthetics, antipsychotic drugs, tricyclic antidepressants, and antihistamines. Concomitant use of certain opioids (eg, meperidine) with MAO inhibitors increases the incidence of hyperpyrexic coma. Meperidine has also been implicated in the serotonin syndrome when used together with selective serotonin rcuptake inhibitors. 

The CNS depressant effects of opioids and the tricyclic antidepressants are expected to be additive. The reasons for the increased morphine levels and analgesic effects that occur with some tricyclics are not understood. The increased analgesia may be due not only to the increased serum levels of morphine, but possibly also to some alteration in the way the morphine affects its receptors. Dextropropoxyphene probably inhibits liver metabolism of some tricyclic antidepressants by inhibiting the activity of the cytochrome P450 isoenzyme CYP2D6, and as a result the serum levels of the tricyclic antidepressants rise. It is suggested that the methadone may possibly inhibit the hydroxylation of the desipramine, thereby raising its levels. ... 

Cancer pain tricyclic antidepressants may be a helpful adjuvant in treating visceral and neuropathic pain of malignancy. Consider using them alone or as adjuncts to opioid analgesics for neuropathic symptoms in cancer pain such as burning, tingling, electric shock and sharp sensations. If minimal medical comorbidities are present, consider a rapid titration to maximum effective dose with tolerable side effects (150 mg/day for amitriptyline or nortriptyline). 

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