Compositions, and methods of use thereof, are provided for the prevention or treatment of side effects associated with the use of drugs that act as 5HT2 / 5HT3 
serotonin receptor antagonists and alpha-2 
adrenergic receptor antagonists (5HT2 / 5HT3 
antagonist / alpha-2 
antagonist). The method involves using 
dopamine-releasing compounds, such as 
amantadine, anticonvulsants, such as 
zonisamide, or 
dopamine / 
norepinephrine reuptake inhibitors, such as 
bupropion, in combination with 5HT2 / 5HT3 
antagonist / alpha-2 antagonists, such as 
mirtazapine, to reduce the excessive 
daytime drowsiness and / or 
weight gain associated with 5HT2 / 5HT3 antagonist / alpha-2 antagonist use for the treatment of disorders, such as, depression, 
schizophrenia, 
anxiety disorders, sleep-related 
breathing disorders, 
insomnia, 
migraine headache, chronic tension-type headache, hot flashes, lower 
back pain, 
neuropathic pain and functional somatic syndromes. Formulations of 
dopamine-releasing compounds or anticonvulsants with 5HT2 / 5HT3 antagonist / alpha-2 antagonists are provided. In particular embodiments, 
combination therapy with 
mirtazapine and 
zonisamide provides relief from chronic 
low back pain, while reducing or avoiding side effects associated with monotherapy with 
mirtazapine or 
zonisamide.