Loxapine adverse effects

A further reminder of the structural resemblance of amoxapine to the neuroleptic drugs has been provided by an adverse effect reported with both amoxapine and its close congener, loxapine (87). 

A 49-year-old man had major adverse effects 11 days after taking a combination of sertraline, buspirone, and loxapine (25). The adverse effects were characteristic of the serotonin syndrome, which is characterized by a constellation of symptoms, including hypomania, agitation, seizures, confusion, restlessness, hyper-reflexia, tremor, myoclonus, ataxia, incoordination, anxiety, double vision, fever, shivering, variable effects on blood pressure, nausea and vomiting, sweating, and diarrhea. 

After 6 and 12 weeks of treatment with loxapine, patients with schizophrenia (n = 24 aged 18-70 years) showed both lymphocyte D2 dopamine-like and 5HT2a platelet receptor binding down-regulation, which suggests that both receptors are involved in the mechanism of action of the drug, as well as its possible extrapyramidal adverse effects (1). 

The authors of the report suggest that this reaction was possibly caused by the additive dystonic effects of the loxapine and sumatriptan, despite the presence of the benzatropine. Dystonia is not an uncommon extrapyramidal reaction associated with antipsychotics, and neck stiffness and dystonia are recognised adverse effects of sumatriptan, but of low incidence. This seems to be the first and only report of this apparent interaction, and therefore its general significance is unclear. 

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. 

Galactorrhoea is a known adverse effect of loxapine, but just why fluvoxamine apparently increased this effect is not understood. ... 

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