Drug-Induced Psychiatric Disorders and their Management

Summary

Psychiatric disorders induced by drugs are of most concern when they occur in the context of therapeutic use of a drug. Such iatrogenic psychiatric disturbances may interfere considerably with the treatment of the primary illness and may cause concern to patients, their relatives and the medical staff. Because many drugs are often used simultaneously in seriously ill patients, it may be difficult to be sure which drug may have been responsible. The best procedure is to remove those drugs which are most probable causes of the psychiatric disturbances as well as any drugs that are not truly essential for the treatment of the patient.

Problems involved in evaluating the relationship between use of drugs and psychiatric disorders are considerable. Many reports are isolated cases and the denominators which might provide some idea of the potential risk are unknown. Many relationships are still controversial, such as the association of depression with sedatives, antihypertensives and oral contraceptives. Areas of uncertainty are great.

Psychomotor impairment may be caused by a drug that can alter consciousness, or any drugs that can produce more delineated psychiatric syndromes. Sedative drugs are those most commonly associated with psychomotor impairment, and may include psychotherapeutic drugs, sedative antihistamines, narcotic analgesics and, of course, the widely used social drug, alcohol.

Delirious states are most often associated with drugs that possess central anticholinergic actions. These include not only drugs clearly identified as anticholinergics, but also tricyclic antidepressants and anti-Parkinson drugs. Cimetidine, which is often used parenterally in seriously ill patients, is also a prominent cause. Delirium is most often seen in elderly patients and in those who have received rather large doses of drugs.

The association of schizophrenic-like psychoses with dopaminomimetic drugs tends to support the prevailing dopamine hypothesis of schizophrenia. Levodopa, the dopamine precursor, and bromocriptine, a direct dopamine agonist, are examples of such relationships. Abuse of social drugs has also been thought to provide a useful model of schizophrenia. Hallucinogens are probably a rather poor model, abuse of amphetamines may provide a better model, and possibly the best is the psychotic state elicited by phencyclidine.

Manic reactions are clinically difficult to differentiate from schizophrenic-like psychoses and are often produced by similar drugs. Corticosteroids may produce either manic or schizophrenic-like disorders, as well as occasionally confusion and depression. Mania evoked by tricyclic antidepressants and monoamine oxidase inhibitors has been variously construed as unmasking a latent manic-depressive disorder or producing an isolated secondary mania. Sympathomimetics have also been associated with manic reactions.

The best drug model of depression has been reserpine, which provided the basis for the current amine hypothesis of depression. Whether depression is associated with other anti-hypertensive drugs that affect amines or their receptors in the central nervous system is more questionable. In fact, the frequent association of depression with hypertension has suggested to some that it is independent of drugs. Whether oral contraceptives are associated with increased depression is also difficult to prove, but the situation may become moot with increasing use of ‘mini-pills’.

Anxiety may be provoked by many drugs that are sympathomimetic. Some of these, such as isoprenaline (isoproterenol), adrenaline (epinephrine), caffeine and yohimbine, have actually been used to provide an experimental model of anxiety. Whether or not this is a valid model remains questionable.

Each clinical case must be judged on its own merits. When in doubt, it is best to consider the possibility that a new mental state or mood may be related to the drugs the patient is taking and to eliminate those most likely to cause mischief.