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Psychopharmacological options for psychotic disorders in elderly people on treatment for SARS-COv 2 infection

Submitted by Jorge Cuevas-Esteban, MD, PhD
Universitat Autonoma Barcelona.Hospital Germans Trias I Pujol, Badalona

Key Highlights:


  • Psychopharmacological treatment of  psychotic syndromes in elderly people suffering from COVID-19 is a challenge.
  • Experimental treatments for COVID-19 such as lopinavir / ritonavir and hydroxychloroquine / chloroquine may prolong the QT interval.
  • Haloperidol, risperidone, and quetiapine are at high risk of adverse reactions mediated by increased QTc interval in addition to cytochrome interactions, therefore may be contraindicated in the context of experimental treatments for COVID-19.
  • Aripiprazole, olanzapine or paliperidone may be useful alternatives.

We are experiencing a worldwide health emergency with the COVID-19 pandemic, which is far from over. Elderly people with underlying diseases like diabetes, hypertension, cardiovascular disease, and cerebro-vascular disease are more susceptible to infection. Furthermore, the elderly are more susceptible to severe illness requiring admission to intensive care units (ICU), and have a higher rate of mortality.

On the other hand, advanced age is associated with more psychotic symptoms such as delusions, hallucinations, paranoia, irritability or psychomotor agitation. Antipsychotic drugs have been a cornerstone for treating psychotic symptoms. Various guidelines and routine clinical practice often recommend haloperidol, risperidone, or quetiapine for the acute treatment of psychosis, agitation, or severe aggressiveness in the context of dementia. Specific treatments recommended by the COVID-19 protocols include: lopinavir / ritonavir, chloroquine / hydroxychloroquine, and in selected cases interferon and tocilizumab and remdesivir. Both Lopinavir / Ritonavir and Hydroxychloroquine / Chloroquine may prolong the QT interval when taken alone and when interacting with other medications.  The addition of yet another medication like haloperidol, risperidone or quetiapine may compound this risk leading to acute arrhythmias.

In order to summarize the main interactions that may occur between commonly prescribed antipsychotic medications and medications also used to treat patients with COVID-19, eight Spanish societies presented the document “Psychopharmacological options for psychotic disorders in elderly people on treatment for SARS-COv 2 infection” with the main recommendations specified below.

Haloperidol, risperidone and quetiapine which are commonly used for psychotic symptoms in the elderly are contraindicated in the context of experimental treatments for COVID-19. There is a high risk of adverse reactions mediated by increased QTc interval in addition to cytochrome interactions.  USE IS NOT RECOMMENDED.

  1. During the acute COVID-19 infection when a treatment with lopinavir / ritonavir, hydroxychloroquine, or tocilizumab is required for older adults with a stable psychotic disorder consider the following alternatives when their current antipsychotic is  contraindicated:
       1.A. If there is anxiety, insomnia, or even agitation present with psychosis, gabapentin or pregabalin may be recommended as a first choice.
       1 B. If a benzodiazepine is required, lorazepam can be used as long as there is no severe acute respiratory failure.
       1 C. If an antipsychotic with a sedative effect is necessary, olanzapine 2.5-7.5mg / day could be used.
       1.D. If an incisive profile antipsychotic is required, aripiprazole at lower doses, may be recommended.
       1.E. As a last option, paliperidone could be recommended, considering that the starting dose of 3mg may be high for persons with frailty or dementia
  2. Recommendations for elderly people without previous psychotic disorder, who develop psychotic symptoms during the acute COVID 19 infection with or without hospital admission:
       2.A. If anxiety, insomnia, or psychomotor restlessness are present, consider gabapentin or pregabalin as the first choice.  Recommended starting doses are: gabapentin 100-300 mg or pregabalin 25 mg.
       2.B. If a benzodiazepine is necessary, lorazepam (0.5-1mg) or lormetazepam (0.5-2mg), can be considered with ongoing monitoring of respiratory function.
       2 C. If insomnia is present, lorazepam (0.5-1mg) or trazodone (25mg) can be used with caution due to the respiratory effects.
       2.D. If psychotic symptoms are clear, consider using aripiprazole (more incisive profile, starting dose 1-5mg), olanzapine (more sedating profile, administration at night, starting dose 2.5mg) or paliperidone (although the lower dose of 3 mg may be high in certain vulnerable patients). If there is a need for parenteral administration, consider olanzapine or aripiprazole with dose adjustment based on response.
  3. Recommendations for the treatment of depression with psychotic symptoms in elderly patients with COVID infection.
       3.A. For antidepressants a sudden interruption may cause a discontinuation syndrome, so it is advisable to change to an alternative antidepressant with a lower risk of interaction: duloxetine, vortioxetine, or sertraline temporarily until the discontinuation of antiretroviral treatment.
    If the patient is being treated with venlafaxine / desvenlafaxine, it is recommended to reduce the dose by at least 50% and to monitor noradrenergic, serotonergic, and cardiovascular complications: hypertension or tachyarrhythmia (atrial fibrillation).
       3.B. If a mood stabilizer is required, it is important to assess the arrhythmogenic effect of lithium or valproate, and consider reducing the lithium dose to at least 50% and / or maintain the valproate dose.
  4. Dementia and Psychotic Symptoms.
    Patients with mild-to-moderate dementia or undiagnosed dementia could be candidates for being treated with specific antiretroviral treatments with the potential for exacerbation of behavioral symptoms or delirium.
       4.A. For insomnia or anxiety, gabapentin (starting 100-300mg), pregabalin (starting 25mg), lorazepam (starting 0.5mg) or trazodone (starting 25mg) could be used with caution due to the possible respiratory effects.
       4.B. For psychotic disorders, consider using aripiprazole (first choice incisive profile, starting dose 1-5mg) or olanzapine (first choice sedative profile, starting dose 2.5-5mg).  Paliperidone can be used if severe behavioral symptoms are present (third choice, the lower 3mg dose may be excessive in vulnerable or underweight patients). If parenteral treatment is required, reduced doses of quick-release intramuscular aripiprazole (starting dose 2.5mg, which is one third of the 7.5mg dose quick-release intramuscular) or olanzapine intramuscular (starting dose 1.25mg) could be used.

 

Authors of the original Spanish recommendation document:
Esteve Arríen, Ainhoa. Geriatrician. Geriatrics Section. Hospital Infanta Leonor University. Madrid.
Luis Agüera Ortiz. Psychiatrist. Doce de Octubre University Hospital. Madrid.
Sagrario Manzano Palomo. Neurologist. Neurology Service. Hospital Infanta Leonor University. Madrid.

For further information, please visit SEPG site: http://www.sepg.es/assets/img/web/farmacologia-trastornos-psicoticos-mayores-covid-19.pdf

 

For further reading:

Li J.-.Y., You Z. The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future. Microbes Infect. 2020 In press, journal pre-proof Available online 20 February 2020

Guan W.J., Ni Z.Y., Zhong N.S., et al. Clinical characteristics of 2019 novel coronavirus infection in China. Med Rxiv, 2020, [Epub ahead ofprint]. 10.1101/2020.02.06.20020974

Gautret P, Lagier JC, Parola P, et al. Hydroxychoroquine and azithromycin as a treatment of COVID 19: results of an open-label non-randomized trial. INt Journal of antimicrobial agents- In press March 2020. DOI:10.1016/j.ijantimicag.2020.105949

Agüera-Ortiz L, Moriñigo-Dominguez A, Olivera-Pueyo J, Pla-Vidal J, Azanza JR. Documento de la Sociedad Española de Psicogeriatría sobre el uso de antipsicóticos en personas de edad avanzada. Psicogeriatría 2017; 7 (Supl 1): S1-S37

Agüera-Ortiz LF. Consenso de la Sociedad Española de Psicogeriatría sobre la depresión en el anciano. 2ª Edición. Barcelona, 2020. ISBN 978-84-09-13470-0

Angora-Cañego R, Esquinas-Requena JL, Agüera-Ortiz L. Guía de selección de psicofármacos en el anciano con patología médica concomitante. Psicogeriatría 2012; 4(1): 1-19

 

Dr. Jorge Cuevas, MD, PhD, is a Psychiatry Associate Professor at the Department of Psychiatry and Forensic Medicine of Universidad Autonoma de Barcelona, Spain. He is also a senior consultant of Psychiatry and coordinates the hospitalisation and emergency psychiatry department in Germans Trias i Pujol Universitary Hospital (Badalona, Barcelona, Spain). Regarding scientific activity, his focus is on motor, cognitive and psychopathological symptoms in mental disorders across the lifespan, especially in old age. He is a current board advisor of the Spanish Psychogeriatric Association (SEPG).

Acknowledgements

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