Introduction

Nightmares are defined as highly dysphoric dreams involving intense negative emotions which primarily present during late-night rapid eye movement (REM) sleep.¹ About 5% of the general population experiences at least one nightmare every week, and 80% of the population experiences sporadic nightmares.² However, this prevalence is higher in patients with psychiatric conditions such as those with post-traumatic stress disorder (PTSD), borderline personality disorder and schizophrenia, and in the elderly.¹ The use of certain medications can also increase the risk of nightmares, which will be discussed below. 

In contrast, some medications can reduce or improve nightmares in patients who experience them. The presence of nightmares can have negative consequences, such as psychological distress, self-harm, and suicidal behaviour.¹ The term used for nightmares caused by medications that can alter dreaming and REM sleep is drug-induced nightmares.¹ 

The mechanism by which certain drugs cause nightmares is mostly unknown; however, REM suppression and effects on several neurotransmitters such as melatonin, serotonin and dopamine, and drug-induced psychosis are hypothesised pathways.² The treatment of nightmares with medication depends on the cause, which will also be discussed below.

Which medications alter the REM state, dreaming and how

As mentioned above, the key mechanism behind drug-induced nightmares is suppression of REM sleep, thereby causing rebound REM sleep and increased intensity of nightmares.² Sleep occurs in five stages: wake, N1, N2, N3 and REM. Stages N1-N3 are considered Non-Rapid Eye Movement stages (NREM), with each stage leading to deeper sleep. Approximately 75% of sleep is present in NREM stages.⁴

Beta blockers suppress central adrenergic receptors and melatonin production, which can induce nightmares during REM sleep.² Nightmares caused by risperidone (an antipsychotic used to treat Schizophrenia) may be associated with slow release and depletion of dopamine, which can also be associated with nightmares.² Dopamine receptor stimulation through the use of dopamine agonists, such as levodopa, used to treat Parkinson’s Disease, is also associated with nightmares. However, differentiating between the drug and Parkinson's disease itself being the root cause of the nightmares is a clinical challenge.²

Other drugs associated with nightmares include antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs), Monoamine Oxidase Inhibitors (MAOIs) and Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs).³ Sudden withdrawal of most antidepressants is associated with nightmares in patients.³ Fluoxetine, an SSRI, tends to increase the recall of nightmares, giving the impression of an increase in the incidence of nightmares. Venlafaxine, an SNRI, causes an increase in “abnormal dreams”, and particularly realistic nightmares are observed. Trazodone, which blocks the reuptake of serotonin, can also cause nightmares.³

Second-generation antipsychotic drugs, such as olanzapine, clozapine, quetiapine and risperidone, show an increase in reported nightmares by patients with schizophrenia.³ 

Anxiolytics (such as benzodiazepines) and hypnotic drugs can either improve (which will be discussed later) or worsen dreams. Eszopiclone, a hypnotic drug derived from benzodiazepines, seems to stimulate abnormal dreams upon withdrawal, especially in older patients.³

Mefloquine is used as malaria prophylaxis or treatment of chloroquine-resistant malaria.⁵ It is known to cause serious and potentially long-lasting neuropsychiatric effects.⁵ One of these side effects includes nightmares.⁵ This pathway is hypothesised to be through receptor interaction with hallucinogens.⁶

Corticosteroids such as prednisone are used as a systemic anti-inflammatory medication in conditions such as asthma, chronic obstructive pulmonary disease (COPD), allergic reactions, and rheumatoid arthritis. They are also associated with sleep disturbances and delirium.⁷ 

The mechanism of this is thought to be through the orexin neuropeptide pathway. Orexins are produced in the hypothalamus and stimulate daytime wake activity.⁷ Orexins also mitigate nighttime hyperarousal and sleep disruption. Orexin overexpression may be a causal factor in steroid-induced sleep disturbance and nightmares.⁷

Melatonin is a naturally occurring hormone, synthesised by the pineal gland and regulates the sleep-wake cycle.⁸ It can also be taken as a supplementary medication to promote sleep in insomnia. Despite this, at supra-pyshiological doses, it may result in nightmares and insomnia.⁸ 

Lastly, methylphenidate, more commonly known as Ritalin, and amphetamine-dextroamphetamine, more commonly known as Adderall, are both medications used in the treatment of attention deficit hyperactivity disorder (ADHD).⁹ Withdrawal from this class of medications (called stimulants) can sometimes cause vivid nightmares, amongst other symptoms such as depressed mood, insomnia or hypersomnia.⁹

Drugs that can reduce nightmares

Conversely, several drugs are associated with reducing nightmares.¹² Nightmares are a common feature of PTSD, and cause sleep-wake cycle disruptions in those affected.¹² The increase in sympathetic arousal following trauma is responsible for many of the PTSD spectrum symptoms.¹² Therefore, a range of drugs can be used to combat nightmares, particularly in those with PTSD.¹²

Drugs such as clonidine (a centrally acting alpha 2 adrenergic receptor agonist) and prazosin (an alpha 1 adrenergic antagonist), used for the treatment of nighttime PTSD symptoms, have been reported to be associated with decreased frequency of nightmares and improved nighttime PTSD symptoms.¹⁰ Literature shows that clonidine reduces nightmares by altering time spent in REM sleep, increasing it at low doses and decreasing it at high doses.¹⁰ In turn, prazosin can decrease levels of norepinephrine in the central nervous system, thereby reducing nightmares.¹¹

As mentioned above, benzodiazepines can worsen but also improve nightmares.³ A reduction of unpleasant dreams is seen with diazepam and clorazepate dipotassium. While patients under oxazepam and midazolam have a reduction in dream recall, patients may still be having nightmares but not remembering them.3 In the same vein, improvement of unpleasant dreams is observed with triazolam and nitrazepam, and is associated with improvement of sleep quality. Escitalopram, an SSRI antidepressant, and trimipramine and Imipramine, both TCAs, can also improve dream positivity.³

Differential diagnosis of nightmares

Whether nightmares are caused by medication use or PTSD, a differential diagnosis should always be considered. Dysphoric dreams, other parasomnias such as rapid eye movement sleep behaviour disorder, sleep terrors and psychiatric disorders such as nocturnal panic attacks need to be differentiated from drug-induced psychosis.¹⁴ The key clinical feature of drug-induced nightmares is full alertness and dream recall upon awakening, and with occurrence later in the night when REM is more frequent. It is also associated with an absence of motor behaviour while sleeping.¹⁴

Practical advice for patients 

If the cause of nightmares in adults is established to be caused by medications, a healthcare provider should be consulted.¹³ Sometimes, drug-induced nightmares can be resolved with a dose or type of medication adjustment.¹³ Cognitive behavioural therapy can also alleviate symptoms, but advice from a professional should be taken first.¹³

Summary

Several classes of prescription medications can cause nightmares, as well as some being able to alleviate nightmares, particularly in patients with post-traumatic stress disorder.¹ The mechanism behind drug-induced nightmares is hypothesised to be the alliteration of serotonin, dopamine and melatonin at neural synapses, thereby altering REM sleep and inducing nightmares.² The classes of drugs that most commonly cause drug-induced nightmares are divided into: beta blockers, antipsychotics such as risperidone, Parkinson’s treatments, such as levodopa, pergolide and cabergoline and other dopamine agonists,² 

Sudden withdrawal of most antidepressants and stimulants used to treat attention deficit hyperactivity disorder can also lead to nightmares or increased recall of nightmares.³ Benzodiazepines, hypnotics, some anti-malarials, corticosteroids and melatonin can also lead to drug-induced nightmares.⁹ 

If experiencing drug-induced nightmares, one should consult their healthcare provider to discuss medication adjustment and the use of cognitive behavioural therapy.¹³ Conversely, in patients with PTSD, certain drugs can ameliorate nightmares. These include clonidine, prazosin, certain benzodiazepines such as diazepam, clorazepate and dipotassium.¹³ These, too, have to be prescribed by a healthcare professional after consultation.