Pharmacological Recommendations for Delirium with COVID-19

TABLE 1. Pharmacologic Agents With Potential Utility in Treating Delirium in COVID-19

Medication Mechanism Advantages Disadvantages
Melatonin Circadian rhythm regulation; Minimal side effects PO formulation only; caution in the
anti-inflammatory immunosuppressed
Alpha-2 agonists
Dexmedetomidine Decreases NE release both Available in IV; can be rapidly Use restricted to ICU setting;
centrally and peripherally titrated; no respiratory sedation; expensive; occasional shortages;
analgesic properties hypotension, bradycardia
Clonidine Decreases NE release both PO and patch formulation; short Hypotension and bradycardia acutely,
centrally and peripherally time to peak concentration and rebound tachycardia and
short half-life hypertension if not tapered
Guanfacine Decreases NE release Less systemic effects than clonidine Only PO formulation; longer to peak
centrally . peripherally effect
Antipsychotic agents
Aripiprazole D2 partial agonist Shortens QTc; less likely to cause PO only; akathisia; long half-life
EPS requires extensive washout period
Chlorpromazine H1, a1, muscarinic antagonist. PO, IM, IV formulations, very Hypotension; anticholinergic side
5HT2A antagonism . D2 sedating, wide dose range, less effects; greater QT prolongation
antagonism EPS
Haloperidol D2 antagonist PO, IV, IM formulations; most High risk of EPS with PO, reports of
evidence in hospital delirium TdP with IV formulation
literature
Olanzapine D2, H1, a1, and muscarinic PO (tab and dissolvable) and IM IM formulation cannot be combined
antagonist formulations; sedating; fast- with benzodiazepines; anticholinergic
acting side effects
Quetiapine H1, a1, a2, 5HT2A, D1, and D2 Wide dose range; different PO only; onset of action up to 1 h;
antagonist. 5HT1A partial receptors targeted at different hypotension at doses . 100 mg
agonist. doses; minimal EPS
Risperidone D2 and 5HT2A antagonist Tab and dissolvable available; High risk of EPS
minimally anticholinergic
Ziprasidone D2, 5HT2A, H1 antagonist, 5HT1A IM formulation available Greater QT prolongation
partial agonist
Trazodone 5HT2A antagonist, a1antagonist Preferred hypnotic for geriatric PO formulation only; onset of action
patients; low EPS and QTc risk up to 1 h
Valproic acid Unclear; regulated GABA/ PO and IV formulations; weight- CYP450 inhibitor; contraindicated in
glutamate, D, NE, and 5HT. based loading possible; useful in patients with pancreatic or hepatic
sodium channel blocker comorbid seizure d/o, TBI, and failure
ETOH withdrawal
Dopamine agonists
Amantadine Indirect D agonist and NMDA- Useful for abulia, akinetic mutism, PO formulation only in United States;
receptor antagonist and catatonia when lorazepam/ contraindicated in end-stage renal
ECT contraindicated disease; lowers seizure threshold; can
worsen delirium and psychosis
Methylphenidate D and NE reuptake inhibition PO (IR and ER) and patch Increases heart rate and blood
formulations; short-half life for pressure; may worsen appetite; can
ease of titration; useful for abulia worsen delirium and psychosis
Lorazepam Enhances the activity of GABA at PO, IV and IM formulations; rapid Respiratory suppression, especially
the GABA-A receptor onset; very sedating; can decrease when combined with opioids; can
neuroleptic requirement worsen delirium

We review and summarize medications commonly used in the treatment of delirium. Attention is given to the advantages and disadvantages
of medications specific to their use in patients with COVID-19.
5HT = 5-hyrdoxytryptamine; D = dopamine; ECT = electroconvulsive therapy; EPS = extrapyramidal symptoms; ER = extended release; ETOH =
ethanol; GABA = gamma aminobutyric acid; H = histamine; ICU = intensive care unit; IM = intramuscular; IR = immediate release; IV = intravenous;
NE = norepinephrine; NMDA = N-methyl-D-aspartate; PO = per oral; QTc = corrected QT interval; TBI = traumatic brain injury; TdP = torsades de pointes.

Melatonin
More recent data also suggest specific utility in COVID-
There is significant interest in using melatonin and 19, perhaps due to its sleep-regulating, immunomodula-
melatonin-receptor agonists in delirium management.20,21 tory, and neuroprotective factors.20–22 In theory, the

588 www.psychosomaticsjournal.org Psychosomatics 61:6, November/December 2020