Thioridazine lithium

Physical examination revealed tachycardia with irregular heart rate, shallow respiration, decreased bowel sounds, dilated pupils, and hypertheimia. An ECG revealed a widened QRS complex with diffuse T wave changes. If this patient had taken a drug overdose the most likely causative agent was (A) Clozapine Fluoxetine Lithium Thioridazine Zolpidem... 

Freeman TW, Clothier JL, Pazzaglia P, et al A double-blind comparison of valproate and lithium in the treatment of acute mania. Am J Psychiatry 149 108-111,1992 Frenchman IB, Prince T Clinical experience with risperidone, haloperidol, and thioridazine for dementia-associated behavioral disturbances. Int Psychogeriatr 9 431-435, 1997... 

H2-labelled thioridazine 56 (the phenothiazine-type antipsychotic agent) has been obtained recently39 for metabolic and pharmacokinetic studies by a new route (equation 16) from 2-(2-hydroxyethyl)piperidine 57. The key steps in this sequence of reactions involve ruthenium tetroxide oxidation of the 7V,0-diacetylated starting material 58 and subsequent lithium aluminium deuteride reduction of the 2-(2-acetoxyethyl)-6-piper-idinone (59, R = Ac). Treatment of 60 with thionyl chloride produced 2-(2-chloroethyl)-l-methyl[6,6-2H2]piperidine which, on N(10)-alkylation of 2-methylthio-10i/-phenothia-zine, yielded 56. For each of the seven steps in the conversion of 57 to 56 the yield has been at least 76%40. 

There was no association of lithium with QTC prolongation but it was associated with nonspecific T-wave abnormalities (odds ratio 1.9) and increased QT dispersion (odds ratio 2.9). Caution was suggested if lithium is used with drugs associated with QTC prolongation, such as tricyclic antidepressants, droperidol, and thioridazine. 

Several cases of neurotoxicity in patients taking lithium and thioridazine have been reported. The cause of this interaction has not been resolved, but lithium seems compatible with all neuroleptic drugs, although patients should be carefully monitored (726-728). 

Several cases of neurotoxicity have been reported when lithium was combined with thioridazine, and patients should be carefully monitored (642-644). 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, amphotericin B, cisapride, clonidine, digitalis, diltiazem, disopyramide, erythromycin, glucocorticoids, halofantrine, haloperidol, hypokalemic diruretics, imipramine antidepressants, levodopa, lithium, pentamidine, pimozide, quinidine, sotalol, stimulant laxatives, tetracosactides, thioridazine... 

There is an increased frequency of neurotoxic symptoms in patients treated with lithium and antipsychotics (mainly described with lithium and haloperidol) or high-dose thioridazine. Marked electroencephalogram changes and tonic-clonic seizures have been observed when lithium has been combined with clozapine. ° ... 

There are a few reports of rapid development of extrapyramidal side-effects (parkinsonism and tremor) or neurotoxicity (delirium and seizures) when iithium was co-ad ministered with fluphenthixoi, fiuphenazine, haloperidoi, thioridazine, or thiothixene. Some of these events were apparent while lithium serum levels were within the normal range. Chlorpromazine serum levels are reduced in the presence of lithium. 

Cantor CH. Encephalopathy witii lithium and thioridazine in combination. MetfJylus/(1986) 144, 164-5. 

Spring GK. Neurotoxicity with combined use of lithium and thioridazine. J Clin Psychiatry... 

A study, undertaken to confirm the involvement of the cytochrome P450 isoenzyme CYT2D6 in the metabolism of trazodone, found that when 11 depressed patients were given trazodone 150 to 300 mg at bedtime for 18 weeks, and then with thioridazine 20 mg twice daily for one week, the plasma levels of the trazodone and its active metabolite, /w-chlorophenyl-piperazine, rose by 36% and 54%, respectively. No adverse reactions were described. In contrast, a case of fatal hepatic necrosis with cholestasis has been attributed to the concurrent use of trazodone and phenothiazines. A 72-year-old woman taking trifluoperazine, trazodone and lithium carbonate developed an elevated alanine aminotransferase level. Trifluoperazine was replaced with thioridazine, but 9 weeks later she became jaundiced and developed hepatic encephalopathy, and died 6 weeks after the onset of jaundice. The authors consider that the combination of the phenothiazines and trazodone were the cause of her hepatic necrosis both phenothiazines and trazodone have been reported to individually cause hepatic adverse effects. ... 

Chloroquine, halofantrine, quinine Chlorpromazine, haloperidol, flufenazine, lithium, mesoridazine, pimozide, prochlorperazine, roperidol, sultopride, sertindole, risjreridone, thioridazine, trifluoperazine... 

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