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Mirtazapine

From Pharmacopedia
Mirtazapine
Remeron (US brand discontinued; generic widely available), Remeron SolTab (ODT)

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Titration strategies

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Summary
Common uses
Major depressive disorder (FDA)0, Insomnia adjunct (off-label; particularly with concurrent depression)0, Anxiety disorder adjunct (off-label)0, Chemotherapy-induced nausea (off-label)0, Appetite stimulation in cancer or HIV cachexia (off-label, leveraging weight-gain side effect)0, PTSD-related sleep disturbance (off-label)0
Pharmacy
Starting dose
15 mg PO at bedtime, titrate to 30-45 mg/day after 1-2 weeks. Counterintuitive dose paradox: lower doses (7.5-15 mg) are more sedating than higher doses because H1 antihistamine effect dominates at low dose
Preparations
Tablets 7.5, 15, 30, 45 mg; orally disintegrating tablets (SolTab) 15, 30, 45 mg
US FDA Max
45 mg/day
Pharmacology
Routes
Oral
Onset
Sleep effect from first dose; antidepressant effect over 1-4 weeks
Duration
24 hours (HS dosing)
Half-life
20-40 hours[1]
Bioavailability
~50% (oral; substantial first-pass)[1]
Pregnancy
Limited human data; some observational signals reassuring relative to other antidepressants.[citation needed]
Legal status
Rx-only in US. Carries the antidepressant Boxed Warning for suicidality in children, adolescents, and young adults[1]
Purported mechanism
Atypical antidepressant with a multi-receptor mechanism: central α2-adrenergic autoreceptor antagonism (disinhibiting noradrenergic and serotonergic neuron firing), 5-HT2A and 5-HT2C antagonism (the antidepressant rationale and the side-effect-favorable profile), 5-HT3 antagonism (antiemetic and pro-appetite), and strong H1 antihistamine activity (the sedation and weight-gain mediators). Net effect raises synaptic serotonin and norepinephrine indirectly without reuptake inhibition.0 Lacks the sexual dysfunction, discontinuation syndrome, and nausea associated with SSRIs and SNRIs, the principal selling points. Weight gain and sedation are the dose-limiting features. Rare but recognized agranulocytosis warrants monitoring for sore throat, fever, and infection during the first months of therapy[1].

References

  1. 1.0 1.1 1.2 1.3 FDA Prescribing Information, Remeron (mirtazapine), Organon/Merck, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020415s029,021208s019lbl.pdf