Thioridazine is a typical low-potency neuroleptic that is slighly less potent than chlorpromazine. It has a halflife of 7 to 13 hours. (Other sources have 16 to 24 hours.) It has the advantage of a low incidence of early and late extrapyramidal side-effects (tardive dyskinesia). In this regard it is very similar to the atypical neuroleptic clozapine (Clozaril®). Thioridazine has also intrinsic mild to moderate antidepressive properties. It has antiemetic properties. Sedation is said to be less pronounced compared with chlorpromazine.

Indications

Previous additional indications were agitated depression, tension and anxiety linked to alcohol withdrawal and dysphoria of epileptic patients. It had even (Melleretten® in Europe) an indication for the treatment of psychosis in children and adolescents (10mg to 60mg daily).

It was also given off-label for the treatment of insomnia and for alleviation of opiate withdrawal.

Thioridazine is known to kill multidrug-resistant mycobacterium tuberculosis and MRSA at clinical concentrations..

Metabolism

Thioridazine is a racemic compound with two enantiomers, both of which are metabolized, according to Eap et al, by CYP2D6 into (S)- and (R)-thioridazine 2-sulfoxide, better known as mesoridazine, and into (S)- and (R)-thioridazine-5-sulfoxide. Mesoridazine is in turn metabolized into sulforidazine. Thioridazine is an inhibitor of CYP1A2 and CYP3A2

Side Effects

Central nervous system side-effects occur. These are mainly drowsiness, dizziness, fatigue, and vertigo. Early and late extrapyramidal side-effects are seen only infrequently (less than 1% altogether). There is no clear dose-effect relationship, as with higher doses anticholinergic effects of thioridazine become more prominent.

Thioridazine causes also an unusual high incidence of impotence and anorgasmia due to a strong alpha-blocking activity. Painful ejaculation or no ejaculation at all is also sometimes seen.

Autonomous side-effects (dry mouth, urination-difficulties, obstipation, induction of glaucoma, postural hypotension, and sinus tachycardia) occur obviously less often than with most other mildly potent antisychotics.

Thioridazine is no longer recommended as first-line treatment due its side-effect of prolonging the QT interval on the EKG. Thioridazine-5-sulfoxide is responsible for the (ventricular tachycardia, torsades de pointes) according to Heath, Svensson and Martensson.

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3 days of Cipro better than amoxicillin-clavulanate for uncomplicated UTI
From Journal of Family Practice, 5/1/05 by T.M. Hooton

Hooton TM, Scholes D, Gupta K, Stapleton AE, Roberts PL, Stature WE. Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women. A randomized trial JAMA 2005; 293:949-955.

* Clinical Question

Are amoxicillin-clavulanate (Augmentin) and ciprofloxacin (Cipro) equivalent as a 3-day treatment for uncomplicated cystitis in women?

* Bottom Line

Three days of ciprofloxacin is superior to 3 days of amoxicillin-clavulanate in the treatment of uncomplicated cystitis in women. In areas where resistance is not yet a significant problem, clinicians should still use a less expensive option as a first-line agent. (LOE=lb-)

Study Design Randomized controlled trial (single-blinded)

Allocation Uncertain

Setting Outpatient (primary care)

Synopsis

The investigators identified 370 women, aged 18 to 45 years, with symptoms of acute uncomplicated cystitis and a positive urine culture for at least 100 colony-forming units of uropathogens per mL. Subjects were randomized (uncertain allocation concealment) to receive 3 days of amoxicillin-clavulanate 500 mg/125 mg twice daily, or ciprofloxacin 250 mg twice daily. Follow-up was available for 98% of the women at 4 months. The authors do not state whether individuals assessing outcomes were blinded to treatment group assignment.

Using intention-to-treat analysis, a clinical cure--defined as the absence of persistent or recurrent symptoms--occurred in 77% of women treated with ciprofloxacin vs 58% of women treated with amoxicillin-clavulanate (number needed to treat=5; 95% confidence interval, 4-12). Microbiological cure, defined as no uropathogens on a follow-up urine culture, was also more common in women treated with ciprofloxacin. Amoxicillin-clavulanate was still less effective than ciprofloxacin even when the cystitis was due to bacterial pathogens sensitive to both drugs.

DRUG BRAND NAMES

Amoxicillin-clavulanate * Augmentin Carbamazepine * Tegretol Chlorpromazine * Thorazine Ciprofloxacin * Cipro Citalopram * Celexa Donepezil * Aricept Galantamine * Reminyl Haloperidol * Haldol Levofloxacin * Levaquin Memantine * Namenda Olanzapine * Zyprexa Risperidone * Risperdal Rivastigmine * Exelon Thioridazine * Mellaril Thiothixene * Navane Valproate * Depakote

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