A patient with depression is treated with paroxetine (Seroxat) 20 mg 2.5 x1. Because of absent effe

Fråga: A patient with depression is treated with paroxetine (Seroxat) 20 mg 2.5 x1. Because of absent effect the patient increased the dosage to 20 mg x3 without consulting his psychiatrist. Recommended maximum dose is 50 mg/day.

The questioner wants to know if the patient can continue with this dosage.

Sammanfattning: Paroxetine is reported to be well tolerated and have been used in dosage regimens over recommended maximum dose. In the present case, if the patient has no adverse effects we recommend a clinical and possibly laboratory follow-up.

Svar: Paroxetine is a novel phenylpiperidine antidepressant which is selective for serotonin reuptake mechanisms and has little affinity for other neurotransmitter receptors, including cholinergic, histaminergic, dopaminergic and serotonergic receptors. It is well tolerated and has been used in dosage regimens which involved escalation to the maximum dose permitted (50 mg daily) (1). In the present case, it may be difficult to determine whether response to the treatment is attributable to the low dose given initially or to the higher dose taken later. This is a particular problem in a disease such as depression where response to treatment is often delayed. There is a interindividual variability due to genetic polymorphism of one of the cytochrome P450 isozymes, CYP2D6, or "debrisoquine hydroxylase" leading to differences in the achieved plasma concentrations of the drug. This explains why the dosage requirement and therapeutic response may vary widely between patients.

Nausea, headache and somnolence are the dose related adverse effects most frequently reported. The potential to induce seizures, particularly in overdosage, is one of the most serious safety considerations for paroxetine therapy. In a population base of more than 4000, the incidence of seizures during paroxetine therapy was 0.1 per cent (1). Laboratory monitoring is possible for paroxetine. 1 Montgomery SA: A review of the safety of paroxetine. Eur Psychiatry 1993; 8(suppl 1): 25S-30S