Chapter 10. Medical Complications of Psychotropic Drugs
OVERVIEW
Idiosyncratic Drug Reactions – Not Predictable
1. Common allergic reactions: Leukopenia or agranulocytosis may occur with any drug. Allergic skin rashes may occur with any drug. Cholestatic jaundice occasionally occurs with chlorpromazine.
Adverse Reactions – Related to Known Pharmacology
1. Central nervous system depression: Sedatives, including barbiturates, benzodiazepines and others. Excessive drowsiness may occur with virtually any psychotropic drug alone or in combination with nonpsychotropic agents. Management: Discontinue drug and reinstitute at lower dosage.
2. Anticholinergic effects: Central nervous system – confusion, toxic delirium. Peripheral-blurred vision. dry mouth, tachycardia, constipation, urinary retention, decreased sweating. Anticholinergic effects reversed by physostigmine. May occur with any psychotropic drug except lithium carbonate.
Management: Discontinue drug, treat with similar therapeutic agent possessing less anticholinergic activity, or reinstitute the same drug at a lower dose. High-potency neuroleptics are least anticholinergic (eg, haloperidol); thioridazine and chlorpromazine are the most anticholinergic. Amitriptyline and imipramine are the most anticholinergic antidepressants. Desipramine. trazodone, fluoxetine, maprotiline, and amexapine are the least anticholinergic antidepressant drugs; the MAOIs lack anticilolinergic effects.
3. Adrenergic blockade of alpha-receptors by low-potency neuroleptics such as chlorpromazine, mesoridazine. and thioridazine accounts for their prominent hypotensive action. High-potency antipsychotic agents, particularly haloperidol, produce little effect on alpha-adrenergic receptors, and likewise have little hypotensive action.
4. Adrenergic stimulation produced by antidepressants is partially responsible for their arrhythmogenic potential.
5. Myocardial depression and decreased membrane excitability may occur with some tricyclic drugs and phenothiazines such as thioridazine and chlorpromazine. These effects may he manifested as an antiarrhythmic action of tricyclic antidepressant drugs and by a potential additive interaction of these drugs with conventional antiarrhythmic agents. Decreascd myocardial contractility may lead to or worsen already existing congestive heart failure. Cardiac rhythm and conduction abnormalities may also occur.
6. Electrocardiographic changes produced, particularly by thioridazine and to a lesser extent by chlorpromazine and some tricyclic antidepressants, may resemble the changes seen in ischemic coronary heart disease, specifically ST segment depression, decreased T wave amplitude, or inverted or biphasic T waves.
7. Postural hypotension is among the more common adverse effects of tricyclic antidepressants, MAOI antidepressants, and low-potency antipsychotic drugs.
8. Hypertensive reactions, which may be mild or severe enough to produce a cerebrovascular accident, may occur in patients being treated with MAOI -type antidepressants who eat large quantities of tyramine-rich foods or take stimulant or vasoconstrictor-containing pharmaceutical products.
9. Seizure threshold is lowered by chlorpromazine and, to a somewhat lesser extent, by other neuroleptic drugs and by tricyclic and heterocyclic antidepressants particularly maprotiline potentially increasing the risk of seizures in patients with and without a prior history of convulsive disorders. Seizures may occur as a result of lithium intoxication.
10. Appetite is increased and there is often associated weight gain during treatment with phenothiazines, virtually all antidepressants, and lithium carbonate.
11. Sexual dysfunction with decreased ability to maintain erection in males and slowed or impaired orgasmic function in both men and women may occur with neuroleptics, cyclic antidepressants, and MAOI -type antidepressants.
12. Skin pigmentation may occur with phenothiaizines. especially chlorpromazine. This also produces increased sensitivity to sunlight with risk of sunhurn even with limited sun exposure.
13. Retinal pigmentation may ocur with phenothiazines, especially thioridazine and chlorpromazine. The risk of retinal damage with thioridazine is so great that long-term administration at doses exceeding 400 mg/day should generally be avoided. and doses exceeding 800 mg/day should never be prescribed.
14. Neuroleptic malignant syndrorne (NMS): Patients with NMS show muscular rigidity with akinesia, often with catatonic appearance. There is hyperthermia (temperature may he from 101f to 106 f), and consciousness is altered – the patient may be alert and show ”dazed mutism.” stupor. or may be comatose. There is profound autonomic dysfunction with labile blood pressure, profuse diaphoresis, sialorrhea, incontinence. dysphagia, and dyskinesia. Treatment requires discontinuation of all neuroleptic drugs, maintenance of adequate hydration by the oral or IV route. correction of electrolyte abnormalities, symptomatic management of fever and specific management of complications including pneumonia and pulmonary emboli. If medication is required to control behavior. use small doses of a short-acting benzadiazepine such as lorazepam. Antiparkinsonian drugs are not specific to reverse NMS: however, cautious use of benztropine may he helpful. Bromocriptine or dantrolene may be beneficial in severe cases of NMS. Males are affected twice as often as females. and 80%, of reported cases have occurred in patients under age 40 years.