Anticonvulsants TCAs

Temazepam (Restoril) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia, anxiety, depression, panic attacks Action Benzodiaz ine Dose 15-30 mg PO hs PRN X in elderly Caution [X, /-] Potentiates CNS dqjressive effects of opioids, barbs, EtOH, antihistamines, MAOIs, TCAs Contra NAG Disp Caps SE Confusion, dizziness, drowsiness, hangover Interactions T Effects W/ cimetidine, disulfiram, kava kava, valerian T CNS depression W/ anticonvulsants, CNS depressants, EtOH t effects OF haloperidol, phenytoin X effects W/ aminophylline, dyphylline, OCPs, oxtriphylline, rifampin, theophylline, tobacco X effects OF levodopa EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH can T CNS depression abruptly D/C after >10 d use may cause withdrawal OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote, activated charcoal may be effective... 

Seizures Unknown, occurs in 0.1% to 4% of patients on TCA Seizures Use with care in patients with known seizure disorder Increase anticonvulsant levels for continued control Rosenstein et al., 1993... 

The results of 40 panic treatment trials conducted between 1975 and 1995 were reviewed. This included studies evaluating TCAs, SRIs, benzodiazepines, anticonvulsants, and propranolol. Three studies report efficacy rates by... 

In contrast to anticonvulsants and alcohol, drugs such as bupropion, fluoxetine, fluvoxamine, nefazodone, quinidine, paroxetine, and some antipsychotics can inhibit specific CYP enzymes (7, 11, 36, 37, 41, 42, 43 and 44). Thus, TCAs, certain BZDs, bupropion, some steroids, and antipsychotics can all have their metabolism inhibited by drugs such as fluoxetine. For example, fluoxetine at 20 mg/day produces on average a 500% increase in the levels of coprescribed drugs which are principally dependent on CYP 2D6 for their clearance. That can lead to serious or even life-threatening toxicity if the drug has a narrow therapeutic index and the dose is not adjusted for the change in clearance caused by the coadministration of fluoxetine. 

Because most antidepressants require oxidative metabolism as a necessary step in their elimination, they can be the target of a pharmacokinetic drug-drug interaction, as well as the cause. The CYP enzymes mediating the biotransformation of the various antidepressants are also shown in Table 7-30. CYP 1A2 and 3A3/4 are induced by anticonvulsants such as barbiturates and carbamazepine. As expected, coadministration of these anticonvulsants has been shown to lower plasma levels of TCAs and would be predicted to have the same effect on nefazodone, sertraline, and venlafaxine. 

Because anticonvulsants calm the activity of the brain, they often produce unwanted side effects such as drowsiness, sedation, dizziness, confusion, loss of coordination, and slurred speech. Some anticonvulsants can produce other side effects, such as nausea, vomiting, constipation, double vision, and even abnormal hair growth. As with TCAs, people suffering from chronic pain often have to try several different anticonvulsants before they find the one that is most effective in relieving their pain while having the least amount of unwanted side effects. 

Patients prescribed concomitant phenytoin or carbamazepine with fluoxetine may have increased anticonvulsant plasma concentrations and symptoms of toxicity. Markedly increased plasma concentrations of TCAs with resulting symptoms of toxicity have been reported in patients taking fluoxetine. 

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