Availability of parenteral newer antipsychotics: Are we near to changing the preference drug in the treatment of delirium in acute settings?



 

Illustrative case:

A 71 year old male is admitted with Acute Heart Failure. He subsequently develops sepsis and AKI. Drought over protracted recovery he develops alternating constipation periods and poor oral intake. His physiology is maintained utmost possible with adequate sleep and daylight exposure. Family notices change in behavior and periods of violence was relentless.

 

Neuropsychiatrist considered drug therapy as inevitable.

 

 

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Delirium is acute onset disturbed consciousness, attention perception and memory. Older age is one of the predispositions which is compounded by disturbed physiology, lack of sleep, inadequate sensory inputs such as specks and the acute illness etc.

 

There is no pharmacological agent yet approved for the use in this condition. The use of antipsychotics is off label.

 

Antipsychotic medicine for treatment of delirium is common.

▪Typical agents- Haloperidol, Chlorpromazine

▪Atypical agents- Risperidone, Olanzapine Quetiapine, Ziprasidone, Aripiprazole

 

The main reason for Haloperidol’s preference as first choice drug in this condition is its availability in variety of routes such as Oral, IV, IM or SC. When a patient is violent an oral route may pose difficulty with delayed onset of action. Sedatives can be counterproductive.

 

The extra pyramidal side effects (EPS) of the typical antipsychotics are one of the feared complication for which the newer antipsychotics may be preferred. In larger doses the EPS may be significant. 

 

There is general fear among practitioners in using antipsychotic drugs in this condition thinking that it is risky to use these medicines.

 

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Q. Which one is better Typical or Atypical?

Ans. The fear of extra pyramidal and cardiac side effects in Typical Antipsychotics cannot be overturned. At least in low doses Haloperidol cannot be rated inferior to atypical agents in short term in terms of efficacy. Most of the studies show equivalence. Haloperidol enjoys the top position amongst antipsychotic medication in delirium.

However in terms of safety, typical antipsychotics are inferior and have more life threatening events in the following 30 day period (3.8 versus 3.2 life threatening events).

In terms of cost the atypical agents are costlier.

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Olanzapine and Risperidone are now available in parenteral formulation in India. 

Other atypical antipsychotics which are available in parenteral formulations are Aripiprazole and Paliperidone elsewhere.

 

Extra pyramidal symptoms and QT prolongation is also least in atypical agents.

 

Safety profile is also high in atypical agents.

 

Once started even the oral drugs require at least one week of therapy. In this situation the depot preparations may be considered strongly.    

 

 

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Cost and availability: 

Injection Oliza 10 mg (₹59.2); 

Inj. Tolaz LA 300 mg (Depot) ₹1061.8 For IM

Risperdal Consta 25 (Depot) for IM (₹4080)

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Ref.

1.       https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005594.pub2/full

 

2.       Breitbart W. Why off -label antipsychotics remain first-choice drugs for delirium. Current Psychiatry Vol. 6, No. 10.

 

3.     MARKOWITZ JD. Delirium and Antipsychotics: A Systematic Review of Epidemiology and Somatic Treatment Options. Psychiatry (Edgemont) 2008; 5(10):29–36.

 

4.     Rochon PA, Normand S, Gomes T, et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Int Med. 2008; 168(10):1090–1096.

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Which one will you go for, typical or atypical?

 

--

Dr. Prashant Kumar

MD, IDCCM, FNB (Critical Care), EDIC, ADHCA, DOA

Editor 'Critical Care WAarticles'

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Location: Delhi, India

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