Amitriptyline Valproate

TCAs VALPROATE t amitriptyline and nortriptyline levels Uncertain Be aware watch for clinical features of t levels of these TCAs (e.g. sedation, dry mouth)... 

Carbamazepine induces hepatic catabolic enzymes, with a consequent reduction in serum levels of antidepressants (mainly described with amitriptyline, desipramine, doxepin, imipramine, mianserin, and nortriptyline). A decrease in bupropion serum levels was also reported with carbamazepine. These effects were not observed with clomipramine. Fluoxetine and fluvoxamine inhibit the metabolism of carbamazepine and valproate (up to 30% and 50% increases in serum levels, respectively). No significant interaction has yet been found between paroxetine and carbamazepine or valproate. 

A man with severe pain, well controlled with amitriptyline, sodium valproate and intrathecal boluses of diamorphine, experienced severe pain within 5 minutes of an intrathecal test dose of clonidine 75 mierograms. ... 

A 37-year-old woman who had been taking amitriptyline 75 mg daily, valproate and olanzapine for 3 years, developed extreme dryness of the mouth, nausea and dizziness shortly after starting to take terbinafine 250 mg daily. Serum levels of amitriptyline and its metabolite nortriptyline rose from just under 400 nanomol/L to over 1800 nanomol/L. Terbinafine was stopped, and the amitriptyline dose reduced to 25 mg daily, but the amitriptyline and nortriptyline levels did not return to baseline for several months. The patient had normal CYP2D6 metaboliser status. ... 

Amitriptyline and nortriptyline plasma levels can be increased by sodium valproate and valpromide, but in contrast, an isolated report attributes a paradoxical rise in serum desipramine levels to the withdrawal of valproic acid. Valproate pharmacokinetics may be moderately affected by amitriptyline. Status epilepticus has been attributed to elevated clomipramine levels in a patient taking valproic acid. 

In one study, 15 healthy subjects were given a single 50-mg dose of amitriptyline 2 hours after taking the ninth dose of semisodium valproate 500 mg every 12 hours. The maximum plasma levels and AUC of amitriptyline were raised by 19% and 30%, respectively. The corresponding values for the nortriptyline metabolite were 28% and 55%, respectively. A study in 6 patients with depression found that amitriptyline 100 mg daily for 3 weeks produced a 43% increase in the volume of distribution and a 16% increase in the plasma half-life of a single 400-mg intravenous dose of sodium valproate. The AUC and total body clearance of valproate were not significantly changed. ... 

Information seems to be limited to these reports. It would seem prudent to monitor for trieyolie adverse effeets (sueh as dry mouth, blurred vision and urinary retention) in patients given valproate and amitriptyline, clomipramine, or nortriptyline and to reduee the dosage of the tricyclic if necessary. Where possible eonsider monitoring tricyclic levels. Information about other trieyelie antidepressants seems to be lacking. The occurrence of status epileptieus in another patient reinforces the fact that the tricyclics can lower the eonvulsive threshold and should therefore be used with caution in patients with epilepsy. 

Paroxysmal Disorders. Migraines are paroxystic, intense hemicranial pain episodes, accompanied by vomiting and light sensitivity. The cause of these episodes is still unclear. Acute treatment of migraine employs drugs such as sumatriptan and ei otamine, while prophylactic therapy uses various agents such as propranolol, verapamil, amitriptyline, and valproate. 

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