Thioridazine SSRIs

Hypersensitivity to SSRIs in combination with a monoamine oxidase inhibitor (MAOl), or within 14 days of discontinuing an MAOl administration of thioridazine with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued coadministration of fluvoxamine with cisapride, thioridazine or pimozide concomitant use of thioridazine with paroxetine concomitant use of pimozide with sertraline coadministration of sertraline oral concentrate and disulfiram. 

There are several antipsychotics that are substrates to CYP2D6 (von Bahr et ah, 1991 Jerling et ah, 1996 Ring et ah, 1996 (Fang and Gorrod, 1999 Flockhart and Oesterheld, 2000) (Table 26.3). Moreover, several antipsychotics may act as inhibitors of CYP2D6-mediated biotransformation. These include thioridazine, chlorpromazine, haloperidol, fluphenazine, and pimozide (Desta et ah, 1998 Shin et ah, 1999). Of particular salience is the fact that the serotonin selective reuptake inhibitors (SSRIs) fluoxetine and paroxetine are metabolized to a significant extent by this isoenzyme. 

Several factors increase the risk of thioridazine toxicity pre-existing cardiac disease, hypokalemia, a glucose load, alcohol, exercise, and concomitant therapy with tricyclic antidepressants, erythromycin, co-trimoxazole, cisapride, risperidone, hydroxyzine, and drugs that inhibit CYP2D6 (some SSRIs, fluphenazine, and perphenazine) (11). 

On the whole no significant adverse interactions appear to occur between the antipsychotics and the SSRIs. However, a number of case reports describe extrapyramidal adverse effects following the use of fluoxetine or paroxetine with an antipsychotic, and ga-lactorrhoea and amenorrhoea developed in one patient given loxapine and fluvoxamine. Fluoxetine and fluvoxamine appear to raise haloperidol levels, which may increase adverse effects. Thioridazine levels are expected to be increased with fluoxetine, fluvoxamine, or paroxetine treatment with a risk of QT interval prolongation. 

On the whole significant interactions between the antipsychotics and SSRIs appear rare (although see thioridazine, below). The combination can be useful and so the isolated cases of extrapyramidal adverse effects should not prevent concurrent use. However, if extrapyramidal effects become troublesome bear this interaction in mind as a possible cause. The significance of the rise in haloperidol levels caused by fluoxetine and fluvoxamine is unclear, be aware that haloperidol adverse effects may be increased in some patients and consider reducing the haloperidol dose if problems occur. The rise in perphenazine levels caused by paroxetine seems to result in a greater number of more serious adverse effects and so consideration should be given to reducing the dose of perphenazine if paroxetine is started. Citalopram may be a suitable alternative as it does not appear to affect perphenazine levels. 

Note that, although the studies with thioridazine did not appear to show any clinically significant interaction the US manufacturers of fluoxetine, fluvoxamine, and paroxetine, contraindicate the concurrent use of thioridazine as they suggest that its metabolism (by CYP2E)6) may be inhibited by these SSRIs, leading to raised levels and the risk ofQT prolongation The use of thioridazine is also contraindicated for 5 weeks after fluoxetine has been stopped. Similarly, it has been suggested that the... 

Haloperidol (Haldol), risperidone (Risperdal), loxapine (Loxitane), ziprasidone (Geodon), quetiapine (Seroquel), clozapine (Clozaril), aripiprazole (Abilify), and thioridazine (Mellaril) are targeted in this solid phase extraction (SPE), liquid chromatography— tandem mass spectrometry (LC-MS/MS) method. Both 9-hydroxy-risperidone (Paliperiodone), an equipotent metabolite, and mesoridazine (Serentil) are also included in this method as they are pharmacologically active major metabolites of risperidone and thioridazine, respectively (4). Olanzapine (Zyprexa) can be quantified with this instrument method however, the extraction method is a liquid-liquid basic extraction (see Note 1). Due to the subsequent administration of antidepressants in conjunction with antipsychot-ics, this method can also be used for many of the common antidepressants, including the selective serotonin reuptake inhibitors (SSRIs) (see Note 2). 

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