On the whole no significant adverse interactions appear to occur between most antipsychotics and the SSRIs. However, a number of case reports describe extrapyr- amidal adverse effects and serotonin syndrome following the use of fluoxetine or paroxetine with an antipsychotic. The levels of some antipsychotics are raised by SSRIs:
  • Aripiprazole levels are predicted to be raised by fluoxetine and paroxetine.
  • Clozapine and olanzapine levels are raised by fluoxetine, paroxetine, sertraline and
    possibly citalopram: particularly large increases can occur with fluvoxamine. Toxicity has been seen in some patients.
  • Haloperidol levels raised by 20 to 30% by fluoxetine and by 20 to 60% by
  • Perphenazine levels possibly raised by fluoxetine and paroxetine, which increased
    extrapyramidal adverse effects in a few cases.
  • Risperidone levels raised by fluvoxamine, fluoxetine and paroxetine.
  • Sertindole levels are raised 2- to 3-fold by fluoxetine and paroxetine.
  • Zotepine levels are raised by fluoxetine (amount unstated).
    Where antipsychotic levels are raised monitor the outcome of concurrent use and adjust the doses as necessary. Some have suggested that the antipsychotic dose should be re-evaluated before the SSRI is started. The manufacturers of sertindole suggest that low maintenance doses of sertindole are used and that ECG monitoring is necessary as sertindole can prolong the QT interval. The manufac- turers recommend halving the dose of aripiprazole. Note that both groups of drugs lower the seizure threshold.
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