A controlled trial found that oral ivermectin was more likely to cure infestation with treatment-resistance head-lice than professionally-applied malathion lotion.

Topical insecticides, mainly pyrethroids as first-line and malathion as an alternative, are the standard therapy for head-lice, however there is increasing evidence of resistance to both these options and it is not clear what alternative therapies are likely to be most effective. Oral ivermectin is widely used to treat a wide range of invertebrate infestations, however a small study at the standard dose of 200 microg/kg body-weight did not show efficacy against head-lice. This cluster-randomised trial examined whether a higher dose of 400 microg/kg would be effective, compared with topical malathion 0.5%, professionally applied, in patients who had not responded to previous insecticidal therapy.

A double-dummy technique was used with a cluster defined as a household (max. 6 individuals). Eligible patients were aged 2 and over, had proven head-lice infestation at baseline that was present despite treatment with topical pyrethroid or malathion between 2 and 6 weeks previously. All household members were randomised to receive malathion lotion 0.5% plus placebo tablets, or oral ivermectin plus dummy lotion; the lotion was applied and tablets administered at the study centre, and the treatment was repeated on day 8 from randomisation. The primary endpoint was absence of head-lice on day 15, according to a standardised combing procedure. Those who failed this were continued on to a blinded extension stage during which they received the alternate treatment. An initial non-inferiority analysis was carried out, followed by a superiority analysis.

In total, 376 households comprising 812 patients were enrolled in the study; most (93.5% of patients) completed the study. In both the intention-to-treat (ITT) and per-protocol populations, more patients were head-lice free at day 15 in the ivermectin group compared to the malathion group (95.2% vs. 85% ITT, 97.1% vs. 89.8% per-protocol). In both analyses the difference was statistically significant: ITT, difference 10.2 percentage points (95% CI, 4.6 to 15.7; P<0.001), per-protocol, difference 7.3 percentage points (95% CI, 2.8 to 11.8; P=0.002).

There were 39 patients with persisting infestation at day 15, 8 patients from the ivermectin group and 31 from the malathion group. At day 29, after extension stage treatment, only 1 patient (originally treated with malathion) had persisting head-lice.

Both treatments were generally well tolerated: only two severe adverse events were recorded, one in each group, 12 patients discontinued due to an adverse event (1.8% ivermectin, 1.2% malathion), and 75 had adverse events considered to be treatment-related (7.5%, 10.9% respectively).

The authors conclude that ivermectin 400 microg/kg, in two divided doses given with a seven-day interval, was more effective than topical malathion 0.5% for difficult-to-treat head-lice infestation. As a result, they suggest that this might be an effective option in such patients, although its use should be specifically restricted to this target population to limit the development of resistance.