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1st Peer response to LeeAnn Still

For this discussion I choose to discuss Haloperidol(Haldol). This is a widely used first generation antipsychotic.

The FDA indications for treatment   

Haldol can be used to treat schizophrenia for long term antipsychotic therapy. 

Schizophrenia can be described as a disturbance that last for at least six months which includes one month of delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, or negative symptoms (Stahl, 2013).

Haldol could be combined with Benadryl and Ativan to form a cocktail to treat violent or very agitated patients(Heldt, 2017). 

Antipsychotics are not FDA-approved for the treatment of dementia-related psychosis in geriatric patients due to increased occurence of cerebrovascular events like stroke or transient ischemic attack(Prescribers’ Digital Reference, 2021).

The mechanism of action   

Haldol blocks D2 receptors which leads to less anticholinergic, antihistamic, or antiadrenergic effects(Stahl, 2013).  

The side effects   

Haldol can cause extrapyramidal side effects such as acute dystonia, akathisia, parkinsonism, and tardive dyskinesia(Stahl, 2013)  

Also if D2 receptors in the mesolimbic system are blocked, it can also block the reward mechanisms. This can cause the patients to be apathetic, anhedonic, lacking motivation, interest, and joy from social interactions (Stahl, 2013). 

Dosage   

The dosing for Haldol varies depending on various factors such as  acute or chronic occurrences or if pregnant or elderly.

Psychotic disorders – 0.5 mg to 2 mg for moderate symptoms and 3 mg to 5 mg for severe symptoms, two to three times daily. 

Schizophrenia – 0.5 mg to 2 mg for moderate symptoms and 3 mg to 5 mg for severe symptoms, two to three times daily. (Mandal, 2019) 

Acute dosing 

Single doses of 1 mg to 5 mg can be given orally or intramuscularly every 4 to 8 hours if needed.

Max of 100 mg per day orally is the limit.

For intravenous administration, single doses of 5 mg to 10 mg can be given but must not exceed 50 mg per day (Mandal, 2019)

Intramuscular haloperidol lactate is used for prompt control of patients with acute agitation, where frequent doses are injected until symptoms are controlled before switching to oral therapy (Hanafi et al., 2017) 

Chronic 

For chronic conditions, the oral daily dose of haloperidol is usually between 0.5 mg and 20 mg (Mandal, 2019) 

A new non?invasive intranasal route was introduced for haloperidol, which provides a direct nose?to?central nervous system delivery with no first?pass metabolism, thus a rapid uptake in the brain, enabling its application in psychiatric emergencies when there is no intravenous access (Hanafi et al., 2017) 

Pearls for treatment   

Depot forms of haloperidol are also available, the drug is deeply injected into the tissue where it can be slowly released into the body over a period of weeks. (Mandal, 2019) 

Special considerations-   

Severe toxic central nervous system depression or comatose states from any cause. 

Can help reduce delirium  duration (Stahl, 2013). 

Haloperidol is not approved for use in children under 3 years of age. (Mandal, 2019) 

This medication is available in intravenous form but patients require cardiac monitoring. IV form is easier to cause the QTC to be prolonged which can lead to torades des pointes and possibly death (Heldt, 2017). 

Extrapyramidal symptoms, catatonia and neuroleptic malignant syndrome appears to be relatively rare with IVH. In most prospective studies, IVH did not cause greater QT prolongation than placebo (Beach et al., 2020)
Haloperidol is not approved for use in children under 3 years of age. 

Specifically, we recommend electrocardiogram monitoring only when using doses >5 mg of IVH and telemetry only for high-risk patients receiving cumulative doses of at least 100 mg or with accurately corrected QTc >500 m (Beach et al., 2020) 

Lab work to monitor   

Haldol can be easily monitored by taking blood levels. Therapeutic range is 2 to 15 ng/ml in serum. Blood levels should be monitored at 12-hour or 24-hour intervals or after the last dose of haloperidol use in a patient. (Rahman, 2021) 

Pregnancy/breastfeeding indication   

Haloperidol use during pregnancy has been linked to severe limb reduction defects. 

Effects of antipsychotic use in lactating mothers are mostly unknown. For chlorpromazine, which is in the same class as Haldol, has been reported to result in drowsiness and lethargy in breastfed infants. Use of antipsychotic drugs by pregnant and lactating mother may only be justified if the potential benefit (Iqbal et al., 2005) 

Elderly special considerations   

There is a risk of hyperprolactinemia which can interfere with fertility, sexual dysfunction, weight gain, especially in women. In the older postmenopausal women, it might lead to more rapid demineralization of bones if not on estrogen replacement therapy.(Stahl, 2013). 

Renal and hepatic considerations, etc.   

Hepatic Impairment 

Specific guidelines for dosage adjustments in hepatic impairment are not available; however, reduced dosages or avoidance is advisable in patients with significant liver dysfunction. Haloperidol is extensively metabolized in the liver(Prescribers’ Digital Reference, 2021).

Renal Impairment 

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However it is still good practice to start low dosage a increase slowly if needed(Prescribers’ Digital Reference, 2021).

References 

Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). Cambridge University Press. 

Heldt, J. P., MD. (2017). Memorable psychopharmacology. Create Space Independent Publishing Platform 

Mandal, D. A. (2019, February 27). Haloperidol Dosage. News. https://www.news-medical.net/health/Haloperidol-Dosage.aspx (Links to an external site.). 

Hanafi, I., Arafat, S., Al Zayed, L., Sukkar, M., Albeirakdar, A., Krayem, D., & Essali, A. (2017, October 19). Haloperidol (route of administration) for people with schizophrenia. The Cochrane Database of Systematic Reviews. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485536/ (Links to an external site.).  

Beach, S. R., Gross, A. F., Hartney, K. E., Taylor, J. B., & Rundell, J. R. (2020, August 22). Intravenous haloperidol: A systematic review of side effects and recommendations for clinical use. General Hospital Psychiatry. https://www.sciencedirect.com/science/article/abs/pii/S0163834320301213 (Links to an external site.).  

Rahman, S. (2021, February 19). Haloperidol. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK560892/ (Links to an external site.). 

Iqbal, M. M., Aneja, A., Rahman, A., Megna, J., Freemont, W., Shiplo, M., Nihilani, N., & Lee, K. (2005, August). The potential risks of commonly prescribed antipsychotics: during pregnancy and lactation. Psychiatry (Edgmont (Pa. : Township)). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000213/ (Links to an external site.). 

Prescribers’ Digital Reference. (2021). PDR Search. Haldol (haloperidol) dose, indications, adverse effects, interactions… from PDR.net. https://www.pdr.net/drug-summary/Haldol-haloperidol-942 (Links to an external site.). 

2nd response to Martha Ruiz

Invega, Invega Sustenna   (Paliperidone)

No Generic Brand available at this time

FDA approved for  *Schizophrenia ( ages 12 and older) * Maintaining response in Schizophrenia * Schizoaffective disorder

MOA: Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms.  Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and reducing motor side effects and improving cognitive and affective symptoms. 

SE: May cause dizziness, hypotension, syncope, weight gain, increased incidence diabetes, and dyslipidemia.  Notable side effects: Drug induced dose dependent Parkinsonism, Hyperprolactinemia, rare tardive dyskinesia.  Life threatening side effects: Hyperglycemia, in some cases ketoacidosis or hyperosmolar coma or death, rare neuroleptic malignant syndrome, hyperpyrexia, muscle rigidity, delirium and acute renal failure.  

Dosage: 6mg/day  (oral)  initial dose taken in the morning, can increase by 3mg/day every 5 days; maximum dose generally 12mg/day. 

              1-month injection starts @ 39mg, 78mg, 117 mg, 156mg, 234mg.   3-month injection starts @ 273mg, 410mg, 546mg, and 819mg

Pearls for treatment: *Some patients tolerate Paliperidone better than Risperidone.  *Hyperprolactinemia in woman with low estrogen may accelerate osteoporosis *May cause more side effects especially if administered to a patient with Parkinson’s disease or Lewy body Dementia. * LAI may not require simultaneous oral medication. * 6 month injection-able formulation is in development. 

Special Considerations: May increase effects of anti hypertensive agents, May antagonize Levodopa, Dopamine agonists, and May enhance QTc prolongation of other drugs capable of prolonging QTc interval.   Before starting any atypical antipsychotic, weight the pt and track BMI during treatment.  Get baseline information on family history for diabetes, obesity, HTN, CV disease, dyslipidemia.  Get waist circumference, blood pressure, fasting glucose, and fasting lipid profile.  Consider monitoring fasting triglycerides monthly for several months in patients high risk of metabolic complications and when switching anti psychotics. 

Special Populations:  Renal Impairment: Mild impairment- Max dose is recommended @ 6mg/day, Moderate impairment is recommended @ 3mg/day and Severe impairment initial dose is @ 1.5mg/day and max dose is 3mg/day. 

                                   Hepatic Impairment: No dose adjustment needed @ mild or moderate.  Studies for severe impairment has not been studied. 

                                   Elderly:  Some patients may tolerate lower doses better.  Elderly patients with dementia-related psychosis treated with atypical anti psychotics are at high risk of death as compared to placebo and risk of CV events. 

                                   Pregnant and Breast Feeding: Controlled studies have not been conducted on pregnant woman.  There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mother took an anti psychotic during the third trimester.  Some of the drug was found in mother’s breast milk, recommended to discontinue med or bottle feed (Stahl, 2021).

Articles:

       Patel, C., Emond, B., Lafeuille, MH. et al. Real-World Analysis of Switching Patients with Schizophrenia from Oral Risperidone or Oral Paliperidone to Once-Monthly Paliperidone Palmitate. Drugs – Real World Outcomes 7, 19–29 (2020). https://doi.org/10.1007/s40801-019-00172-9 (Links to an external site.)

      Zachary O., & Barnett, B., “Tachycardia during Treatment with Risperidone and Paliperidone Palmitate in a Patient without Previous Cardiovascular Disease”, Case Reports in Psychiatry, vol. 2021, Article ID 9954991, 5 pages, 2021. https://doi.org/10.1155/2021/9954991 (Links to an external site.)

Reference: 

      Stahl, S.M., Grady, M.M., & Muntner, N., (2021). Stahl’s essential psychopharmacology prescriber’s guide (7th). Cambridge University Press.