mefloquine + mirtazapine

Mefloquine + mirtazapine is a combination therapy consisting of two small molecule drugs, mefloquine and mirtazapine. Mefloquine is an antimalarial agent that has demonstrated in vitro activity against the JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), by inhibiting viral replication after entry into cells. Mirtazapine is an antidepressant that acts as a serotonin receptor antagonist, particularly at the 5-HT2A receptor, which may block JCV infection of oligodendrocytes and prevent further demyelination. This combination has been used off-label in case reports for treating PML in both HIV-positive and non-HIV patients, with some cases showing clinical improvement or stabilization. The regimen typically involves oral administration of both agents; however, large-scale clinical trials have not established efficacy[1][2][3][4][5].