Methods of controlling insects include applying at least one spinosyn compound to a locus of a neonicotinoid-resistant insect, such as a strain of Drosophila melanogaster resistant to a neonicotinoid compound. The spinosyn compound may be a mixture of spinosyn A and spinosyn D. The spinosyn compound may cause up to approximately ten times increased mortality in the neonicotinoid-resistant insect compared to an insect susceptible to a neonicotinoid compound.