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Chlorpromazine is authorised in the world under the following brand names: Chlorpromanyl (discontinued), Intensol, Largactil Liquid, Largactil Oral Drops, Novo-Chlorpromazine, Thorazine Spansule.

(Country: Canada)

A healthy controversy continues to be manifested in the field of psychiatry concerning the use of drug therapy. This controversy is related to the following factors:
(a) The complexity of new drugs and the multiplicity of drugs offered from month to month to the physician.
(b) The difficulty in determining the effect of the drug as distinct from the psychological influence of placebo administration.
(c) The pressure on the physician for medication trials due to the distress of the patient and his need for a dramatic therapeutic procedure.

The drugs which will be considered in this paper are the tranquillizers and the antidepressants. A tranquillizer may be thought of as a drug effecting reduction of anxiety with minimal disturbance of concentration and memory. The drug acts primarily on the reticular structure of the brain stem and midbrain area, as compared with the sedative that has mainly a cortical site of action. The advantage of the tranquillizer is that it relieves anxiety and tension without disturbing high-level thought processes. Consequently it is useful for the ambulant patient who remains at work, and is of value in his psychotherapeutic treatment.

The antidepressants are specific drugs designed to counteract depression and have little effect on anxiety. They constitute a considerable advance in psychiatry, have reduced the use of electroshock treatment, and have facilitated the treatment of some depressive states on an office-patient basis. They have also prevented the recurrence of depression after successful treatment in hospital.

Principles Involved in Drug Management

It is necessary to have an adequate knowledge of the patient’s psychiatric background and physical health before determining the use of medication. It is to be remembered that a drug does not substitute for the doctor-patient relationship. Familiarity with the action, side effects and toxicity of any new drug in this field should be firmly established before it is prescribed, and the physician should change only with caution to a new drug offered in this area. The cost of drugs remains an important factor in their choice, as therapy may involve several months of medication. The author’s impression of the usefulness of these drugs is based on experience in the field of private practice in psychiatry and will differ somewhat from the indications applicable in a mental hospital setting.

The tranquillizers are mainly differentiated in three groups:
(1) the rauwolfia alkaloids,
(2) the phenothiazine derivatives, and
(3) a miscellaneous group such as meprobamate and hydroxyzine hydrochloride.

Rauwolfia Alkaloids

The rauwolfia alkaloids have been advocated for their tranquillizing effects and were the subject of research studies initiated in 1947. The alkaloid utilized for this purpose is reserpine. In 1950 clinical trials showed that this drug possessed a tranquillizing effect. It was also found to produce lowering of blood pressure and slowing of heart rate. It was consequently used in a wide range of psychiatric conditions, but in some cases precipitated acute depression and reactivation of psychotic symptoms. The unpredictability of its effects has made it a difficult drug to use in psychiatric practice outside the mental hospital.

Phenothiazine Derivatives

The phenothiazine derivatives include a considerable number of drugs, some of which are promethazine (Phenergan), chlorpromazine (Largactil), promazine (Sparine), thioridazine hydrochloride (Mellaril), trifluoperazine (Stelazine), perphenazine (Trilafon), and levomepromazine (Nozinan).

Promethazine was initially used as an antihistaminic and was found to have tranquillizing effects. This led to the study of related compounds, principally chlorpromazine. This drug rapidly found a wide range of usefulness in the medical fields of anesthesia, surgery, obstetrics, gynecology and psychiatry. Chlorpromazine was first synthesized in France in 1950 and introduced clinically in this country in 1954. In addition to its effects as a tranquillizer, it has an antiemetic action, as well as a potentiating influence on the effects of barbiturates and alcohol. Cardiovascular changes, particularly hypotension and tachycardia, were observed in association with this drug. It was soon recognized that chlorpromazine produced marked reduction of anxiety and was especially useful in states of excitement as found in the manic psychoses and acute delirium. In addition, chlorpromazine was found to be of value in schizophrenia, rendering the patient better able to manage the stresses of everyday living. It improved the treatment situation in mental hospitals, rendering patients more accessible to psychotherapy and other methods of treatment. The indications for the other phenothiazine derivatives are much the same as those outlined for the use of chlorpromazine. There is, however, a considerable difference in dosage range for patients in the ambulant group. The following doses are recommended for the various drugs in this group:

Chlorpromazine 25-50 mg. four times daily
Promazine 50-100 mg. four times daily
Thioridazine 10-25 mg. thrice daily
Trifluoperazine 2-4 mg. thrice daily

Perphenazine 4-8 mg. thrice daily Their side effects include tachycardia, accommodation disturbances, hypotension and drowsiness. The more serious side effects, such as parkinsonism, occur at high dosage levels, particularly in association with the drugs trifluoperazine and perphenazine. These, however, can be controlled by reduction of dosage or by the use of Cogentin. The serious toxic effects, agranulocytosis, jaundice and skin rashes, are related to sensitivity of the patient to the drug. The jaundice apparently occurs on the basis of obstruction of the bile canaliculi, with no effect on the liver parenchyma. The condition is reversible, usually in two or three weeks after cessation of drug therapy. It does not preclude the use of chlorpromazine, although this complication may be a source of worry to some physicians. The total experience is that this group of drugs is essentially safe under clinical supervision.