What are the side effects of haldol?

Haldol

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

  • WARNINGS, Increased Mortality In Elderly Patients With Dementia-Related Psychosis
  • WARNINGS, Cardiovascular Effects
  • WARNINGS, Tardive Dyskinesia
  • WARNINGS, Neuroleptic Malignant Syndrome
  • WARNINGS, Treatment Withdrawal
  • WARNINGS, Falls
  • WARNINGS, Usage In Pregnancy
  • WARNINGS, Combined Use Of HALDOL And Lithium
  • WARNINGS, General
  • PRECAUTIONS, Leukopenia, Neutropenia, And Agranulocytosis
  • PRECAUTIONS, Other

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.

The data described below reflect exposure to haloperidol in the following:

  • 284 patients who participated in 3 double-blind, placebo-controlled clinical trials with haloperidol (oral formulation, 2 to 20 mg/day); two trials were in the treatment of schizophrenia and one in the treatment of bipolar disorder.
  • 1295 patients who participated in 16 double-blind, active comparator-controlled clinical trials with haloperidol (injection or oral formulation, 1 to 45 mg/day) in the treatment of schizophrenia.

Based on the pooled safety data, the most common adverse reactions in haloperidol-treated patients from these double-blind placebo-controlled clinical trials (≥5%) were: extrapyramidal disorder, hyperkinesia, tremor, hypertonia, dystonia, and somnolence.

Adverse Reactions Reported At ≥1% Incidence In Double-Blind Placebo-Controlled Clinical Trials With Oral Haloperidol

Adverse reactions occurring in ≥1% of haloperidol-treated patients and at higher rate than placebo in 3 double-blind, parallel, placebo-controlled, clinical trials with the oral formulation are shown in Table 1.

Table 1. Adverse Reactions Occurring in ≥1% of Haloperidol-Treated Patients in Double-Blind, Parallel Placebo-Controlled Clinical Trials (Oral Haloperidol)

System/Organ Class
Adverse Reaction
Haloperidol
(n=284)
%
Placebo
(n=282)
%
Gastrointestinal Disorders
Constipation 4.2 1.8
Dry mouth 1.8 0.4
Salivary hypersecretion 1.2 0.7
Nervous System Disorders
Extrapyramidal disordera 50.7 16.0
Hyperkinesia 10.2 2.5
Tremor 8.1 3.6
Hypertonia 7.4 0.7
Dystonia 6.7 0.4
Bradykinesia 4.2 0.4
Somnolence 5.3 1.1
a Represents the total reporting rate for extrapyramidal disorder (reported term) and individual symptoms of extrapyramidal disorder, including events that did not meet the threshold of ≥1% for inclusion in this table

Additional Adverse Reactions Reported In Double-Blind, Placebo-Or Active Comparator-Controlled Clinical Trials With Injectable Or Oral Haloperidol

Additional adverse reactions that are listed below were reported by haloperidol-treated patients in double-blind, active comparator-controlled clinical trials with the injectable or oral formulation, or at <1% incidence in double-blind, parallel, placebo-controlled, clinical trials with the oral formulation.

Cardiac Disorders: Tachycardia

Endocrine Disorders: Hyperprolactinemia

Eye Disorders: Vision blurred

Investigations: Weight increased

Musculoskeletal and Connective Tissue Disorders: Torticollis, Trismus, Muscle rigidity, Muscle twitching

Nervous System Disorders: Akathisia, Dizziness, Dyskinesia, Hypokinesia, Neuroleptic malignant syndrome, Nystagmus, Oculogyric crisis, Parkinsonism, Sedation, Tardive dyskinesia

Psychiatric Disorders: Loss of libido, Restlessness

Reproductive System and Breast Disorders: Amenorrhea, Galactorrhea, Dysmenorrhea, Erectile dysfunction, Menorrhagia, Breast discomfort Skin and Subcutaneous Tissue Disorders: Acneiform skin reactions Vascular Disorders: Hypotension, Orthostatic hypotension

Postmarketing Experience

The following adverse reactions relating to the active moiety haloperidol have been identified during postapproval use of haloperidol or haloperidol decanoate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders: Pancytopenia, Agranulocytosis,

Thrombocytopenia, Leukopenia, Neutropenia Cardiac Disorders: Ventricular fibrillation, Torsade de pointes, Ventricular tachycardia, Extrasystoles

Endocrine Disorders: Inappropriate antidiuretic hormone secretion Gastrointestinal Disorders: Vomiting, Nausea General Disorders and Administration Site Conditions: Sudden death, Face edema, Edema, Hyperthermia, Hypothermia

Hepatobiliary Disorders: Acute hepatic failure, Hepatitis, Cholestasis, Jaundice, Liver function test abnormal Immune System Disorders: Anaphylactic reaction, Hypersensitivity Investigations: Electrocardiogram QT prolonged, Weight decreased Metabolic and Nutritional Disorders: Hypoglycemia Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis Nervous System Disorders: Convulsion, Headache, Opisthotonus, Tardive dystonia

Pregnancy, Puerperium and Perinatal Conditions: Drug withdrawal syndrome neonatal

Psychiatric Disorders: Agitation, Confusional state, Depression, Insomnia

Renal and Urinary Disorders: Urinary retention

Reproductive System and Breast Disorders: Priapism, Gynecomastia

Respiratory, Thoracic and Mediastinal Disorders: Laryngeal edema, Bronchospasm, Laryngospasm, Dyspnea

Skin and Subcutaneous Tissue Disorders: Dermatitis exfoliative, Hypersensitivity vasculitis, Photosensitivity reaction, Urticaria, Pruritis, Rash, Hyperhidrosis

Read the entire FDA prescribing information for Haldol (Haloperidol Injection)

When is Haldol the Right Choice?

Haldol has received the label of a “bad” drug, but the World Health Organization has deemed it one of 20 essential medications in end-of-life care. It is the drug of choice in hospice for the treatment of terminal agitation and delirium.

Haldol (also known as haloperidol) is an antipsychotic medication. In hospice, it is used to treat terminal delirium, severe agitation in end-stage dementia. Sometimes it’s also used in the treatment of nausea and vomiting and can even be used to treat intractable hiccups. It is a very effective medication in managing all these symptoms.

The hospice nurse always works with the hospice medical director to ensure there is an appropriate indication (reason) for the use of Haldol and will ensure there is a specific goal of therapy.

What is an Appropriate Reason and What is the Goal of Therapy with Haldol?

Haldol may be appropriate in management of terminal delirium in the hospice patient. Terminal delirium is frequently seen as rapid onset of confusion, restlessness, changes in perception and it can — but doesn’t always — include agitation.

Agitated terminal delirium may be an indication death is near and can be quite distressing to the patient and their families. Haldol is the drug of choice to treat terminal delirium, and the specific goal in its use is to minimize agitation and keep the patient as comfortable as possible.

There are reversible causes of delirium. Reversible causes of delirium include:

  • Pain
  • Urinary retention
  • Severe constipation

If the patient is not in the final hours of life and is experiencing delirium, the hospice nurse will assess to ensure any reversible causes for agitation and confusion are identified and addressed.

Haldol can also be effective in the management of severe agitation in end-stage dementia patients as well. Even so, if agitation and confusion have a sudden onset, the hospice nurse will assess the patient to rule out reversible causes.

So is Haldol a Bad Medication?

Haldol may have gotten a “bad” rap because it, along with many medications (and many other antipsychotic medications), has appeared on the “Beers Criteria for Potentially Inappropriate Medication Use in Older Adults” in the past. All the medications on the Beers List are potentially inappropriate.

For Haldol, the list recommended: “Avoid use for behavioral problems of dementia unless nonpharmacological options have failed and patient is a danger to self or others.”

The Centers for Medicare and Medicaid Services (CMS) began an initiative in 2006 to decrease the unnecessary use of antipsychotics in nursing homes and surveyors of skilled nursing facilities. Healthcare professionals in these environments have been mandated to ensure:

  • Antipsychotic medication has a specific reason to be used
  • If a patient is receiving antipsychotic medications (including Haldol) for behaviors, they have been appropriately evaluated and other reasons for behaviors have been assessed
  • Appropriate monitoring of patient response to antipsychotic medications
  • Gradual dose reductions are attempted
  • If antipsychotic medications cannot be stopped there is adequate documentation reflecting why it can’t be stopped

Some skilled nursing facilities may avoid use of Haldol, even in hospice patients, because they fear surveyors will give a tag or a deficiency for its use. However, if it is clearly documented on the patient’s medical record that Haldol, or any antipsychotic medication, is being used to manage end-of-life symptoms and the patient is on hospice care, a survey deficiency should not be a concern.

Hospice service providers can partner with skilled nursing facilities to ensure appropriate documentation reflecting the need for Haldol is in the patient medical record.

Haldol is not without side effects, some serious, some less serious, and it may not be right for every behavior or for every patient. But Haldol is not a bad medication. Remember: The World Health Organization has identified it as one of 20 essential medications in palliative care.

If you have questions about the use of Haldol or about the care of hospice patients, please visit our hospice care tips and guides section to learn more. You can also give us a call at 888-564-3405.

Sally Drummond
Crossroads Hospice & Palliative Care
Corporate Pharmacy Consultant, RN, CHPN

What is Haloperidol?

Your doctor should check your progress at regular visits, especially during the first few months of treatment with this medicine. The amount of haloperidol you take may be changed to meet the needs of your condition and to prevent side effects.

Do not stop taking this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping completely. This will allow your body time to adjust and help avoid a worsening of your medical condition.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicine, prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

This medicine may cause some people to become dizzy, drowsy, or may cause trouble with thinking or controlling body movements, which may lead to falls, fractures or other injuries. Even if you take haloperidol at bedtime, you may feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Dizziness, lightheadedness, or fainting may occur, especially when you get up from a lying or sitting position. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.

This medicine will often make you sweat less, causing your body temperature to increase. Use extra care not to become overheated during exercise or hot weather while you are taking this medicine, since overheating may result in heat stroke. Also, hot baths or saunas may make you feel dizzy or faint while you are using this medicine.

Haloperidol may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn. When you begin taking this medicine:

  • Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.
  • Wear protective clothing, including a hat or sunglasses.
  • Apply a sun block product that has a sun protection factor (SPF) of at least 15. Some patients may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your doctor.
  • Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.
  • Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

Haloperidol may cause dry mouth. For temporary relief, use sugarless candy or gum, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth continues to feel dry for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections.

Contact your doctor as soon as possible if you have chest pain or discomfort, a fast heartbeat, trouble breathing, or fever and chills. These can be symptoms of a very serious problem with your heart.

This medicine may cause tardive dyskinesia (a movement disorder). Check with your doctor right away if you have any of the following symptoms while taking this medicine: lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of the tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs.

Check with your doctor right away if you have any of the following symptoms while using this medicine: convulsions, difficulty with breathing, a fast heartbeat, a high fever, high or low blood pressure, increased sweating, loss of bladder control, severe muscle stiffness, unusually pale skin, or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter ) medicines and herbal or vitamin supplements.

Haloperidol as a means of calming people who are aggressive or agitated due to psychosis

Results

Forty-one studies are now included in the review but information in these is of low-quality. Main results show that when compared with placebo or no treatment, more people having haloperidol were asleep after two hours. However, evidence is not strong. Results are made more complex by large variety of available treatments (24 comparisons).

Conclusions

The review authors conclude there is weak evidence that haloperidol calms people down and helps manage difficult situations. However, this is not based on good-quality trails and therefore health professionals and people with mental health problems are left without clear evidence-based guidance. In some situations, haloperidol may be the only choice, but this is far from ideal because although haloperidol is effective at calming people down it has side effects (e.g. restlessness, shaking of the head, hands and body, heart problems). These side effects can be just as distressing as psychosis and may act as a barrier that stops people coming back for future treatment. More research is needed to help people consider and understand which medication is better at calming people down; has fewer side effects; works quickly and rapidly; and can be used at lower dosages (or less frequent injections).

This plain language summary is based on a summary written by a consumer Ben Gray from Rethink.

Risperidone Provides Better Improvement of Sleep Disturbances Than Haloperidol Therapy in Schizophrenia Patients With Cannabis-Positive Urinalysis

Introduction

The prognosis of schizophrenia is often worsened with Cannabis use (Foti et al., 2010; Manrique-Garcia et al., 2014), mainly through potentiation of the well-established dopamine dysregulations in schizophrenia (Bossong et al., 2009, 2015). High percentages of Cannabis users (CU) report that it promotes sleep (Cousens and DiMascio, 1973; Schofield et al., 2006; Schaub et al., 2008; Goonawardena et al., 2012; Walsh et al., 2013); however, polysomnographic sleep assessment show relatively inconsistent sleep-promoting properties of Cannabis (Gates et al., 2014, 2016). Pharmacological intervention in schizophrenia requires long-term administration of antipsychotic drugs (Mercolini et al., 2007; Fumagalli et al., 2009; Uchida et al., 2011), which block the dopaminergic system. In early polysomnographic studies, typical antipsychotic drugs, such as haloperidol (Clarenbach et al., 1978; Taylor et al., 1991; Maixner et al., 1998; Dursun et al., 1999), demonstrate sleep-promoting effects and improve sleep maintenance/continuity, mainly through the reduction of sleep latency (SL) and frequency of awakening, prolongation of sleep time and an increase in sleep efficiency in healthy subjects and schizophrenia patients (Taylor et al., 1991; Benson, 2006; Cohrs, 2008; Anderson and Bradley, 2013). In contrast to typical antipsychotics, the atypical agents, including risperidone, have demonstrated greater improvement of sleep efficiency, due to the higher affinity for serotonin 5-HT2A/2C receptors, which are involved in controlling sleep quality (Dursun et al., 1999; Ichikawa et al., 2001; Miller, 2004; Cohrs, 2008; Anderson and Bradley, 2013). Furthermore, schizophrenia patients treated with risperidone display better sleep quantity, sleep quality, and general functioning compared to patients treated with typical antipsychotic drugs (Dursun et al., 1999; Yamashita et al., 2002; Giménez et al., 2007; Apiquian et al., 2008; Wichniak et al., 2011).

It is possible for Cannabis use to alter the clinical benefits of antipsychotic drugs (Thomas et al., 2015; Patel et al., 2016; Foglia et al., 2017); however, there is a paucity of information evaluating the impact of Cannabis use on the sleep outcomes of schizophrenic patients being treated with antipsychotics. Through actigraphy, this study examined the differences in sleep parameters in schizophrenia patients treated with risperidone vs. haloperidol and the impact of Cannabis use. Sleep quality can be estimated through sleep efficiency percentage, which incorporates the ratio of total sleep time and total time in bed; both of which can be altered by the SL, wake after sleep onset (WASO) duration and number of awakening (Shrivastava et al., 2014; Reed and Sacco, 2016; Sathyanarayana et al., 2016).

Methods and Subjects

Ethical approval was obtained from the University of the West Indies Ethics Committee. Males of at least 18 years of age were recruited from the University Hospital of the West Indies’ psychiatric ward between October 2015 and October 2016, if they met the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria for schizophrenia, schizophreniform disorder or brief psychotic disorder, as assessed by trained psychiatrists managing each patient. Psychiatric assessments were conducted by three psychiatrists. Written informed consent was obtained from each subject’s relative/guardian on day 1. After consent, urine samples (5 mL) were collected in sterile containers and screened for the possible use of Cannabis, using the SD BIOLINE drug of abuse kit, based on the analysis for 11-nor-Δ9-tetrahydrocannabinol-9-Carboxylic acid; the main metabolite of Δ9-tetrahydrocannabinol, with a detection limit of 50 ng/mL. Subjects were classified as Cannabis users (CU) or non-users (non-CU), with a positive or negative kit result, respectively. Psychiatrists managing subjects were blinded from the Cannabis result.

Subjects were hospitalized for the 2-weeks study period, and recruited if administered either risperidone or haloperidol, orally at a dose prescribed by the assigned psychiatrists. Therapy could be flexibly adjusted within the therapeutic range as clinically warranted (risperidone, 6–8 mg/day; haloperidol, 10–20 mg/day). In addition, all enrolled subject received daily administrations of benztropine, 2 mg/day. Subjects were excluded from the study if they were receiving any other concomitant medications. Subjects who presented with diagnoses of other central nervous system disorders, mental retardation, somatic diseases, trauma or brain injury and primary sleep disorders were also excluded. Female subjects were excluded to control for the hormone-dependent confounding differences with Cannabis use (Craft et al., 2013; Castelli et al., 2014) and sleep disturbances (Sharkey et al., 2014). Demographic information collected from each subject’s docket included age, ethnicity, marital status, occupational status and educational level. History of psychosis (schizophrenia, schizophreniform disorder, or brief psychotic disorder) and previous substances abused (Cannabis, tobacco, alcohol, other), if any, were also recorded upon admission to the psychiatric ward.

After 7 days of antipsychotic therapy, only subjects remaining on monotherapy and confirmed by psychiatrist as displaying mild to moderate symptoms (scores < 53), using the Brief Psychiatric Rating Scale (BPRS) were then given the Actiwatch-2 device (Respironics, Inc., Murrysville, PA, United States) to wear on the non-dominant wrist. This device recorded sleep data in each subject for seven consecutive nights, 8 h each night, from 10:00 P.M. to 6:00 A.M. Computer scoring of actigraphy-recorded sleep parameters were performed using Respironics Actiware software, version 5.70.0. The software default setting of immobile minutes was used as the sleep interval detection algorithm. Immobility was determined if the activity counts (AC) was <4 in a 1 min epoch. The data were analyzed using medium wake thresholds (40 AC), with 10 min of immobility set for sleep onset and sleep end. Sleep parameters were calculated during the sleep/rest period (when AC was <40 AC threshold), which was set three different ways: (1) automatic scoring of major rest intervals by the software; (2) pre-determined bedtimes and wake-up times for each subject; (3) manual setting based on surrounding activity level. With the manual setting, the start and end of the sleep period were set close to the pre-determined times on the ward, providing that the AC were not >500 for 2 min, or >1,000 for 5 min, at the start. End of sleep was set when the AC increased to >0 for 5 min, without an epoch scored as sleep. A subject was likely scored as sleep when immobile for 3 h or more. While each of these parameters may have been manipulated by the user, sleep/wake analysis was performed automatically by the software. The scorer was blinded to Cannabis status when manually setting the rest intervals. Sleep parameters measured include SL, frequency of awakening, duration of WASO and total sleep time (TST).

Data and Statistical Analysis

Sleep efficiency percentage (SE%) is a good overall descriptor of a night’s sleep, as it reflects the percentage of time in bed actually spent sleeping (Shrivastava et al., 2014; Reed and Sacco, 2016; Sathyanarayana et al., 2016). SE% was calculated as the percentage of the ratio TST/Time spent in bed (TIB); with TIB calculated as the sum of SL, TST, and WASO. Additionally, sleep efficiency scores were classified as good-quality sleep (SE% ≥ 85%) or poor-quality sleep (SE% < 85%) (Reed and Sacco, 2016; Sathyanarayana et al., 2016). The power of the study was calculated using SE% for CU and non-users, prescribed either haloperidol or risperidone. The power for SE% was >80%, which was adequate. Daily drug dosages were converted to chlorpromazine equivalent (CPZE) doses (Danivas and Venkatasubramanian, 2013) to facilitate drug dosage comparisons.

Statistical analysis was conducted using the Statistical Package for the Social Sciences (SPSS v.20) for Windows (SPSS, Inc., Chicago, IL, United States), with the level of significance set at p < 0.05. Demographic data and continuous variables were evaluated using descriptive statistics and expressed as medians and IQR, frequencies (n) and percentages, as appropriate. Subjects were divided into four groups: CU vs. non-CU receiving haloperidol therapy and CU vs. non-CU receiving risperidone therapy. Inferential statistics involved use of Spearman Rho to determine correlations between Cannabis grouping and the actigraphy-measured sleep parameters, Kruskal-Wallis test for comparisons across all four groups, with post hoc analysis between groups using Bonferroni corrections, and Friedman test for the change in SE% over the seven nights.

Results

Table 1 gives demographic information of the 50 male subjects of Afro-Caribbean descent who completed the study. The sample population consisted of 30 subjects (60%) presenting with first-time psychotic episodes (acute psychosis/drug-naive). The remaining 20 subjects (40%) had undergone outpatient therapy or had previously been treated in an inpatient setting. Duration of illness was the only variable significantly different between the acute vs. relapse subjects . Based on self-declaration, initiation of Cannabis use was from a median (IQR) age of 14 (2) years. Majority of subjects (n = 30, 60%) used Cannabis within one week of admission to the psychiatric ward and were classified as CU, with urinalysis. Eighteen CU subjects received risperidone and 12 received haloperidol. The remaining 20 subjects were grouped as non-CU, with 14 receiving risperidone and 6 receiving haloperidol. CU subjects received significantly higher doses of haloperidol compared to non-CU subjects (p = 0.001) and CU subjects receiving risperidone (p = 0.001). There was no significant difference in dose between CU and non-CU receiving risperidone. By day seven of therapy, there was no significant difference in the BPRS score of schizophrenia symptoms between CU and non-CU receiving haloperidol or risperidone .

TABLE 1

TABLE 1. Demographic characteristics of study participants.

FIGURE 1

FIGURE 1. Average Sleep for Seven Consecutive Nights of Actigraphy Recording for CU and Non-CU Receiving either Haloperidol or Risperidone. Box-plots represent median (thick, dark horizontal lines), IQR (boxes), minimum and maximum (whiskers) of each sleep parameter recorded using actigraphy. Circles represents outliers in sleep data. bSignificant differences between CU and non-CU groups. cSignificant difference between CU treatment groups. (A) TST was significantly less for CU than non-CU when receiving either haloperidol (p = 0.015) or risperidone (p = 0.035); there was significantly less TST between CU receiving haloperidol and CU receiving risperidone (p = 0.045). (B) SL was significantly longer for CU than non-CU when receiving haloperidol (p = 0.009), but not when receiving risperidone. (C) Frequency of awakening after sleep onset was significantly more for CU than non-CU when receiving either haloperidol (p = 0.017) or risperidone (p = 0.004). (D) WASO duration was significantly longer for CU than non-CU when receiving either haloperidol (p = 0.005) or risperidone (p = 0.020); there was significantly longer WASO between CU receiving haloperidol and CU receiving risperidone (p = 0.022). CU, Cannabis user; non-CU, non-user of Cannabis; SL, sleep latency; TST, total sleep time; WASO, wake after sleep onset.

Sleep parameters were not significantly different between the antipsychotic groups for non-CU subjects. Comparisons between CU groups showed no difference in SL and frequency of awakening; however, CU subjects receiving risperidone had longer TST (p = 0.045) and shorter WASO duration (p = 0.022) than CU subjects receiving haloperidol.

FIGURE 2

Discussions

Risperidone and haloperidol can improve sleep outcomes in schizophrenia patients (Taylor et al., 1991; Wetter et al., 1996; Maixner et al., 1998; Dursun et al., 1999; Haffmans et al., 2001, 2004; Yamashita et al., 2002; Miller, 2004; Monti and Monti, 2004). Similarly, in this study, both risperidone and haloperidol showed improvement in sleep outcomes over the 7 days among schizophrenic subjects not exposed to Cannabis. Contrastingly, subjects exposed to Cannabis use within 1 week of admission, displayed less total sleep time, with more frequent awakening and longer WASO duration, whether being treated with haloperidol or risperidone; thus, suggesting that the presence of Cannabis may be impacting the therapeutic benefits of both drugs on sleep. Converting the antipsychotic doses to CPZEs, our study found haloperidol therapy involved larger doses than risperidone therapy. For subjects exposed to Cannabis, the haloperidol dose requirements were much larger when compared with the dose given to non-users. This was not so for risperidone, as the dose was similar between non-users and subjects exposed to Cannabis.

Since last use of Cannabis by subjects in this study was more than 7 days before actigraphy measurements, the findings may be consistent with signs of Cannabis withdrawal on sleep (Bolla et al., 2008, 2010; Babson and Bonn-Miller, 2014; Gates et al., 2014, 2016; Babson et al., 2017). Sleep disturbance is a prominent Cannabis withdrawal symptom, usually noted after two nights (Bolla et al., 2008), and progresses over the first 2 weeks (Bolla et al., 2010) of abstinence. Budney et al. (2003) examined the impact of Cannabis withdrawal in 18 current users with 12 previous users of Cannabis as controls. Users abstained from smoking (confirmed through urine assay for Cannabis metabolites) and were assessed using Sleep Inventory questionnaires, administered by telephone daily for 50 days. The study reported sleep difficulty with Cannabis use, which peaked 2–6 days after abstinence and remained elevated over a course of 45 days.

Our findings are the first to use actigraphy readings to show that the benefits of haloperidol and risperidone can be significantly impacted by the use of Cannabis. Interestingly, risperidone therapy showed better sleep outcomes with recent use of Cannabis, as SL was equivalent to non-users. Also, CU awoke for longer durations after sleep onset and thus, slept less, with poor sleep quality when treated with haloperidol. Furthermore, only risperidone was successful at increasing the sleep efficiency among these subjects for the 7 days of observation.

Our findings among the subjects involved in this study may have significant implications, as they suggest risperidone may provide better clinical outcomes on sleep in schizophrenic patients who use Cannabis; more so in the Jamaican setting where Cannabis use among schizophrenic patients has been established to be high (Knight, 1976; Thomas et al., 2015). However, the positive confirmatory test for Cannabis is only able to detect acute Cannabis exposure; providing no measure of the history of Cannabis use, as documented by self-report of most subjects in this study. Subjects also provided self-report of using alcohol, tobacco and cocaine, which are possible confounders. Despite the presence of these substances and the time of admission not being assessed, the inpatient setting for the study period prevented access. Additionally, some of the subjects in this study previously received therapy with antipsychotics, which could also be a confounder. An antipsychotic-free control group would provide greater comparisons. However, in this setting, this would be unethical since all subjects were experiencing psychosis when admitted to the ward.

Conclusion

Cannabis use can attenuate the benefits of haloperidol and risperidone therapy on sleep in patients being treated for schizophrenia. The better sleep outcomes of risperidone support further examination of its possible superiority over haloperidol. However, the sample size was small, and a larger sample is recommended to confirm findings.

Ethics Statement

This study was carried out in accordance with the recommendations of the University of the West Indies/University Hospital of the West Indies/Faculty of Medical Sciences Ethics committee guidelines for conducting research. The protocol was approved by the University of the West Indies Ethics Committee. Relatives/Guardians of all subjects gave written informed consent in accordance with the Declaration of Helsinki.

Author Contributions

The study was designed by MG-W, JM, and WA. P-GT-B reviewed the literature and wrote the protocol for the study. JM, CS, and WA aided in the recruitment of the study participants and performed the psychiatric assessments. Patient recruitment and assessments, sample preparations and assays and the data analyses were conducted by P-GT-B, who also made initial interpretations and wrote the first draft of the manuscript. All authors further interpreted and discussed the findings and contributed to the final version of the manuscript.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer BC and handling Editor declared their shared affiliations.

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Haloperidol

Before taking haloperidol,

  • tell your doctor and pharmacist if you are allergic to haloperidol or any other medications.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: amiodarone (Cordarone); anticoagulants (blood thinners); antihistamines; disopyramide (Norpace); dofetilide (Tikosyn); epinephrine (Epipen); erythromycin (E.E.S., E-Mycin, Erythrocin); ipratropium (Atrovent); lithium (Eskalith, Lithobid); medications for anxiety, depression, irritable bowel disease, mental illness, motion sickness, Parkinson’s disease,seizures, ulcers, or urinary problems; methyldopa; moxifloxacin (Avelox); narcotic medications for pain; pimozide (Orap); procainamide ; quinidine ; rifampin (Rifater, Rifadin); sedatives; sotalol (Betapace, Betapace AF); sparfloxacin (Zagam) (not available in the US); sleeping pills; thioridazine; and tranquilizers. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had Parkinson’s disease (PD; a disorder of the nervous system that causes difficulties with movement, muscle control, and balance). Your doctor will probably tell you not to take haloperidol.
  • tell your doctor if you or anyone in your family has or has ever had prolonged QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause loss of consciousness, or sudden death). Also tell your doctor if you have or have ever had breast cancer; bipolar disorder (condition that causes episodes of depression, episodes of mania, and other abnormal moods); citrullinemia (condition that causes build-up of ammonia in the blood); an abnormal electroencephalogram (EEG; a test that records electrical activity in the brain); seizures; an irregular heartbeat; low levels of calcium or magnesium in your blood; trouble keeping your balance; chest pain; or heart or thyroid disease. Also tell your doctor if you have ever had to stop taking a medication for mental illness due to severe side effects.
  • tell your doctor if you are pregnant, especially if you are in the last few months of your pregnancy, or if you plan to become pregnant or are breast-feeding. If you become pregnant while taking haloperidol, call your doctor. Haloperidol may cause problems in newborns following delivery if it is taken during the last months of pregnancy.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking haloperidol.
  • you should know that this medication may make you drowsy and may affect your thinking and movements. Do not drive a car or operate machinery until you know how this medication affects you.
  • ask your doctor about the safe use of alcohol during your treatment with haloperidol. Alcohol can make the side effects of haloperidol worse.
  • you should know that haloperidol may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.

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