Thioridazine Ziprasidone

Ziprasidone prolonged the QTc interval about one-half as much as thioridazine. Ziprasidone s effect on the ECG is probably without clinical sequelae except in patients with baseline risk factors. 

May enhance QTc effects with alfuzosin, ciprofloxacin, cisapride, dronedaron, lumefantrine, nilotinib, quinidine, tetrabenazine thioridazine, ziprasidone. 

Current antipsychotics used to treat patients are divided into two classes the first generation antipsychotics (FGA) or typicals (e.g., chlorproma-zine, haloperidol, thioridazine, and loxapine) and the second generation antipsychotics (SGA) or atypicals (i.e., clozapine, olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, and asenapine). 

Low-potency piperidine phenothiazines (e.g., thioridazine), clozapine, and ziprasidone are more likely to cause ECG changes. 

Ziprasidone is well tolerated. Its common side effects are drowsiness, nausea, and constipation. Though there were initial concerns about untoward cardiological side effects similar to those produced by thioridazine and the tricyclic antidepressants, ziprasidone appears to be safe though it should probably not be used in patients with preexisting heart disease. 

Drugs that may affect disopyramide include antiarrhythmics, beta blockers, cisapride, clarithromycin, erythromycin, fluoroquinolones, hydantoins, quinidine, thioridazine, rifampin, verapamil, and ziprasidone. Drugs that may be affected by disopyramide include quinidine, anticoagulants, and digoxin. 

Hypersensitivity to the drug or any other component of the product (cross-sensitivity between phenothiazines may occur) comatose or greatly depressed states caused by CNS depressants or from any other cause (phenothiazines, clozapine, loxapine, molindone, pimozide, haloperidol) coadministration with other drugs that prolong the QT interval and in patients with congenital long QT syndrome or history of cardiac arrhythmias (mesoridazine, thioridazine, pimozide, ziprasidone see Drug..Interactions). 

Ziprasidone, pimozide, mesoridazine, and thioridazine have been shown to prolong the QT interval, and drugs with this potential have been associated with torsade de pointes-type arrhythmias and sudden death. Perform a baseline ECG and measure serum potassium and magnesium before initiation of treatment and periodically during treatment, especially during a period of dose adjustment. Patients with QT interval over 450 msec should not receive mesoridazine or thioridazine. Avoid ziprasidone in patients with histories of significant cardiovascular illness (eg. 

Cardiovascular side effects. Ziprasidone produced a mean QTc prolongation of 21 ms at maximal blood levels achieved with typical therapeutic doses. However, in all clinical trials, the rate of QTc intervals greater than 500 ms (considered a threshold for arrhythmia risk) did not differ from the rate associated with placebo (<0.1%). The QTc effect of ziprasidone is larger than that of other atypical antipsychotics but smaller than that of thioridazine. Blood levels of ziprasidone increased about 40% when ketoconazole (a metabolic inhibitor) was coadministered, and no change in QTc duration was detected. 

Antipsychotics produce more important pharmacodynamic than pharmacokinetic interactions because of their multiple effects. Additive effects may occur when these drugs are combined with others that have sedative effects, a-adrenoceptor-blocking action, anticholinergic effects, and—for thioridazine and ziprasidone—quinidine-like action. 

Hyperlipidemia associated with antipsychotic drugs has been reviewed (SEDA-29, 64). Haloperidol and the atypical antipsychotic drugs ziprasidone, risperidone, and aripiprazole would be associated with lower risks of hyperlipidemia, whereas chlorpromazine, thioridazine, and the atypical drugs quetiapine, olanzapine, and clozapine would be associated with higher risks. However, severe clozapine-induced hypercholesterolemia and hypertriglyceridemia has been reported in a patient taking clozapine (55). 

There has been one comprehensive meta-analysis including over 80 studies and over 30 000 patients (814). A meta-analysis of trials of neuroleptic drugs showed the following mean weight gains in kg after 10 weeks of treatment clozapine, 4.5 olanzapine, 4.2 thioridazine, 3.2 sertindole, 2.9 chlorpromazine, 2.6 risperidone, 2.1 haloperidol, 1.1 fluphenazine, 0.43 ziprasidone 0.04 molindone, —0.39 placebo, —0.74... 

Moban) olanzapine (Zyprexa) perphenazine (Trilafon) pimozide (Orap) quetiapine (Seroquel) risperidone (Risperdal) thioridazine (Mellaril) thiothixene (Navane) trifluoperazine (Stelazine) trifuluopromazine (Vesprin) ziprasidone (Geodon). 

Antidepressants mirtazapine, nefazodone, sertraline Neuroleptics thioridazine, haloperidol, clozapine, quetiapine, risperidone, sertindole, ziprasidone Mood stabilizers carbamazepine, gabapentin, lamotrigine... 

Clinically important, potentially hazardous interactions with amphetamines, aprepitant, astemizole, atazanavir, azithromycin, azole antifungals, clarithromycin, darunavir, dirithromycin, erythromycin, fluoxetine, fosamprenavir, grapefruit juice, imatinib, indinavir, itraconazole, ketoconazole, methylphenidate, nefazodone, nelfinavir, nilotinib, pemoline, phenothiazines, protease inhibitors, quinidine, ritonavir, saquinavir, sertraline, sparfloxacin, sulpiride, telithromycin, thioridazine, tipranavir, tricyclic antidepressants, troleandomycin, voriconazole, zileuton, ziprasidone... 

Clinically important, potentially hazardous interactions with cyclosporine, diltiazem, dofetilide, erythromycin, grapefruit, ketoconazole, quinidine, ritonavir, simvastatin, sotalol, thioridazine, verapamil, ziprasidone... 

Fluvoxamine (Luvox) Nefazodone (Serzone) Paroxetine (Paxil) CLOZAPINE, THIORIDAZINE, HALOPERIDOL, OLANZAPINE, THIOTHIXENE PHENOTHIAZINES, Risperidone, Aripiprazole Clozapine, Quetiapine, Ziprasidone QUETIAPINE, Clozapine, Ziprasidone ... 

Adverse Neurological Effects Many neurological syndromes, particularly involving the extrapyramidal motor system, occur following the use of most antipsychotic drugs, especially with the high-potency D -receptor antagonists (tricyclic piperazines and butyrophenones). Acute adverse extrapyramidal effects are less likely with aripiprazole, clozapine, quetiapine, thioridazine, and ziprasidone, or low doses of olanzapine or risperidone. 

---