Haldol: antipsychotic medication

Question:

What is your opinion/experience on using Haldol IM in large doses (100mg. x 3 and 300mg/month for maintenance) for rapid tranquillization? I have been doing this in a prison population with good results, but wonder what risks may be.

Answer:

If I understand your question correctly, there are really two distinct issues being raised:

1. The use of injectable haloperidol (non-decanoate) intramuscular (IM) for “rapid tranquilization;”
2. The use of haloperidol decanoate for “maintenance” treatment of psychosis.

With respect to “rapid tranquilization” (or “rapid neuroleptization”) there is little evidence that “large doses” of haloperidol or the equivalent are superior to smaller ones, and some concern that large doses may lead to more adverse reactions.

Specifically, several recent studies have shown that 10-20 mg/day of haloperidol, or the equivalent, is sufficient for exacerbations of schizophrenia. Doses of greater than 40 mg of haloperidol (or equivalent) appear no more effective than lower dosages [see, e.g., McEvoy et al, Arch Gen Psychiatry 48:739-45, 1991]. (There is laboratory evidence that dopamine-2 receptors are “saturated” at doses greater than about 15 mg/day of haloperidol, or with plasma levels greater than about 14 ng/ml. Thus, higher doses generally do not provide additional D2 blockade).

Some (but not all) data suggest that very high doses of neuroleptics over brief periods of time increase extrapyramidal symptoms and/or the risk of neuroleptic malignant syndrome (see Janicak et al, Principles & Practice of Psychopharmacotherapy, 1993, p. 113). To my knowledge, there is no convincing evidence that megadoses of antipsychotics (IM or p.o.) during the first few days of acute psychosis actually speed up the recovery process; indeed, core psychotic symptoms are rarely affected, and sedation is the main effect achieved.

Better results are probably obtained (in acute situations) using a combination of haloperidol and lorazepam IM (e.g., 4 mg of haloperidol plus 2 mg lorazepam); this can be given in the same syringe, though this “cocktail” makes it difficult to know “what’s doing what” if the patient has an adverse or allergic reaction. This combination may be repeated 3 or more times during a 12 hour period, usually with good effect.

Having said this, it is true that some practitioners (notably at Mass. General Hospital) have had good results in ICU settings, using high doses of intravenous haloperidol – sometimes over 100 mg/day – for extremely agitated delirious patients. But even in the ICU, lower doses are often effective. With respect to your second question, maintenance haloperidol decanoate is generally most effective when provided in monthly doses of 10-15 times the previously effective daily oral dose. For a typical patient–taking, say, 15 mg of oral haloperidol per day–the monthly decanoate dose would be around 180-200 mg per month.

Some data suggest that haloperidol plasma levels of between 4-15 ng/ml are optimal; there is little evidence that levels above this range are superior for most patients. Of course, there are always “outliers” on the bell curve; in my experience, a few patients may require 300 mg or more of haloperidol decanoate per month, perhaps reflecting rapid hepatic metabolism, or difficulty getting the drug across the blood-brain barrier.

Similarly, there are always patients who seem to require very high oral doses of antipsychotics; in my experience, most of these patients will run rather low plasma levels, owing to poor gut absorption. The bottom line: use the lowest amount that “works” for the particular patient, vis-a-vis acute symptoms, avoiding relapse, etc.