Public health efforts to reduce the
opioid overdose epidemic and treat
opioid use disorder (OUD) have met with challenges associated with current non-standardized approaches to managing
opioid withdrawal symptoms, such as
itching, jitteriness, anxiety, depression, craving,
vomiting,
diarrhea,
insomnia, and
anorexia. These symptoms pose substantial obstacles to the safe initiation of medications for OUD, maintenance of long-term sobriety, and prevention of relapse. In clinical practice, multiple medications (
polypharmacy) are prescribed to manage these
withdrawal symptoms, including
ondansetron and
promethazine for
vomiting and
nausea,
loperamide and
Lomotil for
diarrhea,
hydroxyzine and
doxepin for
pruritus,
benzodiazepines, the Z-drugs, and
melatonin for
insomnia, and benzos,
tricyclic antidepressants (TCAs), and various
serotonergic agents for anxiety. This
polypharmacy is associated with an increased risk of adverse
drug-drug interactions and
adverse drug events, increased medical costs, and increased odds of medication non-adherence and relapse. We propose an alternative single medication,
mirtazapine, a noradrenergic and specific serotonergic receptor antagonist, that can be used for myriad symptoms of
opioid withdrawal. Case series, clinical studies, and clinical trials have shown
mirtazapine to be effective for treating
nausea and
vomiting resulting from multiple etiologies, including
hyperemesis gravidarum and
chemotherapy-induced
emesis. Other evidence supports the salutary effects of
mirtazapine on
itching and craving. Research findings support
mirtazapine's beneficial effects on
diarrhea and anxiety, a consequence of its modulating effects on serotonergic receptors mediating mood and gastrointestinal symptoms. There is also evidence supporting its efficacy as a potent and non-addictive sleep aid, which presents itself as a
solution for
insomnia associated with
opioid withdrawal. The current review presents evidence from extant literature supporting
mirtazapine as a one-
drug strategy to treat the variety of symptoms of
opioid withdrawal. This one-
drug strategy has much potential to decrease
polypharmacy,
adverse drug events, relapse, and healthcare cost and increase the likelihood of prolonged sobriety and better quality of life for people living with OUD.