If treatment of the neuroleptic malignant syndrome is started early, when consciousness is first altered and the temperature is rising, bromocriptine in oral doses of 5 mg tid (up to 20 mg tid) will terminate the condition in a few hours. If oral medication can no longer be taken because of the patient’s condition, dantrolene, 0.25 to 3.0 mg intravenously, may be lifesaving. Once coma has supervened, shock and anuria may prove fatal or leave the patient in a vegetative state. The rigors during high fever may cause muscle damage and myoglobinuria, and shock may lead to hypoxic-ischemic brain injury.
One pitfall is to mistake neuroleptic malignant syndrome for worsening of the psychosis and inadvisably administer more antipsychosis medication. Meningitis, heat stroke, lithium intoxication, catatonia, malignant hyperthermia, and acute dystonic reactions figure in the differential diagnosis. Of course, neuroleptic medication must be discontinued as soon as any of the severe extrapyramidal reactions are recognized. It has been common practice to avoid future administration of the offending neuroleptic but the risk of using another class of antipsychotic agents has not been fully addressed.
The neuroleptic malignant syndrome bears an uncertain relationship to malignant hyperthermia by way of its clinical aspects but also in its response to bromocriptine and dantrolene (see later). Malignant hyperthermia in susceptible individuals is triggered by inhalation anesthetics and skeletal muscle relaxants (see Chap. 45). This disorder was described before the introduction of neuroleptic drugs, and in a small proportion of cases, has been related to a mutation of the ryanodine receptor gene. A genetic factor may underlie a small number of cases of the neuroleptic malignant syndrome (a polymorphism in the D2 receptor gene; see Suzuki et al) possibly provoked by fatigue and dehydration. There is no evidence that the occurrence of one of these syndromes confers a susceptibility to the other.
Four classes of drugs—the MAO inhibitors, the tricyclic compounds, the serotonergic drugs, and lithium—are particularly useful in the treatment of depressive illnesses. The adjective antidepressant refers to their therapeutic effect and is employed here in deference to common clinical practice. Antidepressive or antidepression drugs would be preferable, as the term depressant still has a pharmacologic connotation that does not necessarily equate with the therapeutic effect.
The observation that iproniazid, an inhibitor of MAO, had a mood-elevating effect in tuberculous patients initiated a great deal of interest in compounds of this type and led quickly to their exploitation in the treatment of depression. Iproniazid proved exceedingly toxic to the liver, as were several subsequently developed MAO inhibitors; but other drugs in this class, much better tolerated, are still available. These include isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate), the latter two being the more frequently used. Tranylcypromine, which bears a close chemical resemblance to dextroamphetamine, may produce unwanted stimulation, but the most common adverse effect of all the MAO inhibitors is postural hypotension. Also, interactions with a wide array of other drugs and ingested substances may induce severe hypertension.