These drugs often included picrotoxin, amiphenazole (Daptazile), bemegride (Megimide), and methamphetamine sulfate (Methedrine) in dosages sometimes exceeding 250 mg over the first 24-hour period of being admitted into an intensive care unit (ICU).

While a quantitative relationship between the blood levels of barbiturate derivatives and the depression of the central nervous system (CNS) had become established by researchers in 1955, they also emphasized that the accurate correlation of these factors is complicated by the presence of tolerance to the drug, intercurrent disease and senility, as well as the concurrent administration of other noxious substances.

Some psychiatrists will attempt to duplicate this effect, albeit only partially, using stimulants in conjunction with benzodiazepines such as clonazepam in patients with certain forms of refractory depression where monoamine oxidase inhibitors such as nardil or parnate would be indicated, but lacking the dangers associated with that class of medication, as maois are extremely toxic in cases of overdose or deliberate or accidental ingestion of tyramine.

This combination is regarded as extremely effective by patients and practitioners alike, and retains efficacy over time when used as directed, but both drugs do carry risks of abuse and dependency.

Typically the CNS stimulant within these older combination drugs was racemic amphetamine, dextroamphetamine, or methamphetamine as various single or mixed salts, and phenmetrazine hydrochloride (Preludin) was also marketed albeit less frequently.