Management of Nightmare Disorder in Adults

Erin D. Callen, PharmD, BCPS; Tiffany L. Kessler, PharmD, BCPS; Krista G. Brooks, PharmD; Tom W. Davis, MD

US Pharmacist. 2018;43(11):21-26.

Nonpharmacologic Treatment

The only treatment strategy with enough evidence to be recommended in the AASM's position paper is behavioral intervention with imagery-rehearsal therapy (IRT).^[3] IRT is based on the theory that nightmares are a learned behavior and can be replaced by a less disruptive behavior that will not ultimately affect sleep or daytime functioning. Patients are asked to recall the nightmare, write it down, alter its content to a positive outcome, and rehearse the rescripted dream for 10 to 20 minutes each day. Additional treatments that may be used for both PTSD-associated nightmares and nightmare disorder include cognitive behavioral therapy and exposure, relaxation, and rescripting therapies. Other behavioral strategies include hypnosis, lucid-dreaming therapy, eye-movement desensitization and reprocessing, and progressive deep-muscle relaxation techniques.^[3]

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Table 1. Medications Associated With Nightmares
Drug Class	Medications
Acetylcholinesterase inhibitors	Donepezil, rivastigmine
Antidepressants	Bupropion, MAOIs, SNRIs, SSRIs, TCAs
Antihistamines	Chlorpheniramine
Antimicrobials	Efavirenz, ganciclovir
Atypical antipsychotics	Clozapine, risperidone
Beta-blockers	Atenolol, labetalol, nadolol, propranolol, sotalol
Calcium channel blockers	Verapamil
Dopaminergics	Amantadine, levodopa, ropinirole, selegiline
Sedative/hypnotics	Alcohol, barbiturates, temazepam, triazolam
Statins	Atorvastatin, simvastatin

MAOI: monoamine oxidase inhibitor; SNRI: serotonin-norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant.
Source: Reference 4.

Table 2. AASM-Recommended Medications for Treatment of Nightmare Disorder
Medication	Indication	MOA	Trial and Number of Participants	Trial Dosagea	Common AEs
Prazosin	NDPTSD,^b ND	α₁- adrenergic antagonist	Raskind (2018), RCT; N = 304	14.8 (6.1) mg/day	Dizziness, drowsiness, weakness
			Ahmadpanah (2014), RCT; N = 100	15 mg/day
			Raskind (2013), RCT; N = 67	Men—AM: 4 mg (1.2), PM: 15.6 mg (6)Women—AM: 1.7 mg (0.5), PM: 7 mg (0.5)
			Germain (2012), RCT; N = 50	8.9 mg, range 1–15 mg/day
			Boynton (2009), retrospective chart review; N = 23	2.3 mg/day (1.4)
			Taylor (2008), crossover RCT; N = 13	3.1 mg/day (1.3)
			Raskind (2007), RCT; N = 34	13 mg/day (3)
			Daly (2005), case series; N = 28	1–6 mg/day
			Peskind (2003), open-label case series; N=9	2–4 mg/day
			Raskind (2003), double-blind crossover; N=10	9.5 mg/day (0.5)
Atypical antipsychotic: aripiprazole	PTSD	Serotonin, dopamine, histamine, and α-adrenergic antagonist	Lambert (2006), case series; N = 5	15–30 mg/day	Headache, extrapyramidal reaction, drowsiness
Atypical antipsychotic: olanzapine			Jakovljevic (2003), case series; N = 5	10–20 mg/day
Atypical antipsychotic: risperidone			David (2006), open-label; N = 20	2.3 mg/day (0.6)
Atypical antipsychotic: risperidone			Stanovic (2001), retrospective chart review; N = 10	0.5–2.0 mg/day
Benzodiazepines: ND nitrazepam, triazolam	ND	Enhances effect of neurotransmitter γ-aminobutyric acid (GAB_A) at the GABAA receptor	Ellingsen (1983), crossover RCT; N=40	One dose: 0.5 mg triazolam or 5 mg nitrazepam	Drowsiness, headache, nervousness
Clonidine	PTSD	α₂-adrenergic receptor agonist	Kinzie (1994), 2-wk pilot; N = 4	0.2 mg/day	Rash, Rash, drowsiness
Clonidine	PTSD	α₂-adrenergic receptor agonist	Kinzie (1989), prospective pilot; N = 9	Clonidine 0.2 mg/day + imipramine up to 150 mg/day	Rash, Rash, drowsiness
Cyproheptadine	PTSD	Serotonin antagonist, additional antihistaminicand anticholinergic effects	Clark (1999), case series; N = 16	4–8 mg/day	Drowsiness, incoordination, restlessness
			Gupta (1998), retrospective review; N = 9	4 days, 12 mg/day
			Brophy (1991), case series; N = 4	2–28 mg/day
Gabapentin	PTSD	Unknown, but activity may be due to binding at α₂δ subunit	Hamner (2001), retrospective case series; N=30	1,377 mg/day (701)	Dizziness, drowsiness, ataxia
Nabilone	PTSD	Synthetic CB₁ receptor agonist	Jetly (2015), RCT; N = 10	1.95 mg/day (0.9)	Drowsiness, dizziness, vertigo
Nabilone	PTSD	Synthetic CB₁ receptor agonist	Fraser (2009), open-label; N = 47	0.2–4 mg/day	Drowsiness, dizziness, vertigo
Phenelzine	PTSD	MAO glutamate receptor inhibitor	Lerer (1987), open-label, prospective trial; N = 25	30–90 mg/day	Dizziness, constipation, orthostatic hypotension
Phenelzine	PTSD	MAO glutamate receptor inhibitor	Hogben (1981), case series; N = 5	45–75 mg/day	Dizziness, constipation, orthostatic hypotension
SSRI: fluvoxamine	PTSD	Enhances serotonergic activity	Neylan (2001), open-label; N = 21	50 mg/day, then titrated to 100–250 mg/day	Headache, insomnia, nausea
SSRI: fluvoxamine	PTSD	Enhances serotonergic activity	De Boer (1992), prospective cohort trial; N = 24	Up to 300 mg/day	Headache, insomnia, nausea
Topiramate	PTSD	Unknown, but may be due to blockage of neuronal voltage dependent sodium channels; enhances GABA_A activity, antagonizes glutamatereceptors, andinhibits carbonicanhydrase enzymes	Alderman (2009), open-label pilot study; N = 29	200 mg/day	Paresthesias, decreased serum bicarbonate, upper respiratory tract infection
			Tucker (2007), RCT; N = 40	150 mg/day
			Berlant (2004), case series; N = 33	12.5–25 mg/day, then titrated to clinical response
			Berlant (2002), case series; N = 35	12.5–500 mg/day
Trazodone	PTSD	Serotonin, histamine, and alpha₁- adrenergicantagonist	Warner (2001), retrospective cohortstudy; N = 74	212 mg/day	Drowsiness, hypertension, dizziness
TCAs:amitriptyline, doxepin, imipramine	PTSD	Anticholinergic, antihistamine, inhibits serotonin-norepinephrinereceptors	Boehnlein (1985), case series; N = 10	Imipramine 75–125 mg/day (n = 3); imipramine150 mg/day + phenelzine30 mg bid (n = 1); phenelzine 30 mg bid+ doxepin 50–100 mg/day + amitriptyline100 mg/day (n = 1); amitriptyline 100 mg/day+ doxepin 50–100 mg/day(n = 1); doxepin 50–100mg/day (n = 4)	Anticholinergiceffects, orthostatichypotension, sedation

^a Trial doses are reported as either a mean (standard deviation) or a range.
^b PTSD-associated nightmares.
AASM: American Academy of Sleep Medicine; AE: adverse effect; CB1: cannabinoid type 1; GABA: gamma-aminobutyric acid; GABA_A: gamma-aminobutyric acid type A; MAO: monoamine oxidase; MOA: mechanism of action; ND: nightmare disorder; PTSD: posttraumatic stress disorder; RCT: randomized, controlled trial; SSRI: selective serotonin reuptake inhibitor. Source: References 5–21, 23–40.

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Management of Nightmare Disorder in Adults

Nonpharmacologic Treatment

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