Antipsychotic Drugs : Introduction

ANTIPSYCHOTIC DRUGS : INTRODUCTION

The psychopharmacological agents or psychotropic drugs are those having primary effects on psyche (mental processes) and are used for treatment of psychiatric disorders.

During the past 50 years psychiatric treatment has witnessed major changes due to advent of drugs which can have specific salutary effect in mental illnesses. The trend has turned from custodial care towards restoring the individual patient to his place in the community. All that could be done before 1952 was to dope and quieten agitated and violent patients. The introduction of chlorpromazine (CPZ) in that year has transformed the lives of schizophrenics; most can now be rehabilitated to productive life. Reserpine was discovered soon after. Though it is a powerful pharmacological tool to study monoaminergic systems in brain and periphery, its clinical use in psychiatry lasted only few years. Next came the tricyclic and MAO inhibitor antidepressants in 1957–58 and covered another group of psychiatric patients. Many novel and atypical antipsychotics and antidepressants have been introduced since the 1980s. Meprobamate (1954) aroused the hope that anxiety could be tackled without producing marked sedation. This goal has been realised more completely by the development of Chlordiazepoxide (1957) and other benzodiazepines in the 1960s. Buspirone is a significant recent addition.

Little attention was paid to Cade’s report in 1949 that Lithium could be used for excitement and mania: its effective use started in the 1960s and now it has a unique place in psychiatry. Interestingly some antiepileptics like carbamazepine, valproate and lamotrigine, etc. have shown promise in mania and bipolar disorders.

Psychiatric diagnostic categories are often imprecise. The criteria adopted overlap in individual patients. Nevertheless, broad divisions have to be made, primarily on the basis of predominant manifestations, to guide the use of drugs. It is important to make an attempt to characterise the primary abnormality, because specific drugs are now available for most categories. Principal types are:

Psychoses

These are severe psychiatric illness with serious distortion of thought, behaviour, capacity to recognise reality and of perception (delusions and hallucinations) . There is inexplicable misperception and misevaluation; the patient is unable to meet the ordinary demands of life.

a) Acute And Chronic Organic Brain Syndromes (Cognitive Disorders)

Such as delirium and dementia; some toxic or pathological basis can often be defined; prominent features are confusion, disorientation, defective memory and disorganized behaviour.

b)  Functional Disorders

No underlying cause can be defined; memory and orientation are mostly retained but emotion, thought, reasoning and behaviour are seriously altered.

i) Schizophrenia (split mind), i.e. splitting of perception and interpretation from reality—hallucinations, inability to think coherently.

ii) Paranoid states with marked persecutory or other kinds of fixed delusions (false beliefs) and loss of insight into the abnormality.

Affective Disorders

The primary symptom is change in mood state; may manifest as:

Mania—elation or irritable mood, reduced sleep, hyperactivity, uncontrollable thought and speech, may be associated with reckless or violent behavior.

Depression—sadness, loss of interest and pleasure, worthlessness, guilt, physical and mental slowing, melancholia, selfdestructive ideation.

It may be bipolar (manicdepressive) with cyclically alternating manic and depressive phases or unipolar (mania or depression) with waxing and waning course.

Neuroses

These are less serious; ability to comprehend reality is not lost, though the patient may undergo extreme suffering. Depending on the predominant feature, it may be labelled as:

a)  Anxiety An unpleasant emotional state associated with uneasiness, worry, tension and concern for the future.

b)  Phobic States Fear of the unknown or of some specific objects, person or situations.

c)   Obsessive-compulsive Limited abnormality of thought or behaviour; recurrent intrusive thoughts or rituallike behaviours which the patient realizes are abnormal or stupid, but is not able to overcome even on voluntary effort.

d)  Reactive Depression due to physical illness, loss, blow to selfesteem or bereavement, but is excessive or disproportionate.

e)   Posttraumatic Stress Disorder Varied symptoms following distressing experiences like war, riots, earthquakes, etc.

f)     Hysterical Dramatic symptoms resembling serious physical illness, but situational, and always in the presence of others; the patient does not feign but actually undergoes the symptoms, though the basis is only psychic and not physical.

Pathophysiology of mental illness is not clear, though some ideas have been formed, e.g. dopaminergic overactivity in the limbic system may be involved in schizophrenia and mania, while monoaminergic (NA, 5HT) deficit may underlie depression. Treatment is empirical, symptom oriented and not disease specific. However, it is highly effective in many situations. Depending on the primary use, the psychotropic drugs may be grouped into:

1. Antipsychotic (neuroleptic, ataractic, major tranquillizer) useful in all types of functional psychosis, especially schizophrenia.

(The term ‘Neuroleptic’ is applied to chlorpromazine/ haloperidollike conventional antipsychotic drugs which have potent D2 receptor blocking activity and produce psychic indifference, emotional quietening with extrapyramidal symptoms, but without causing ataxia or cognitive impairment.)

2. Antimanic (mood stabiliser) used to control mania and to break into cyclic affective disorders.

3. Antidepressants used for minor as well as major depressive illness, phobic states, obsessivecompulsive behaviour, and certain anxiety disorders.

4. Antianxiety (anxiolyticsedative, minor tranquillizer) used for anxiety and phobic states.

Antidepressants and antimanic drugs are sometimes collectively referred as ’Drugs for Affective Disorders’.

5. Psychotomimetic (psychedelic, psychodysleptic, hallucinogen). These are seldom used therapeutically, but produce psychosislike states; majority are drugs of abuse, e.g. cannabis, LSD.

Tranquillizer It is an old term meaning “a drug which reduces mental tension and produces calmness without inducing sleep or depressing mental faculties.” It was used to describe the effects of reserpine or chlorpromazine. However, it has been interpreted differently by different people; some extend it to cover both chlorpromazine-like and antianxiety drugs, others feel that it should be restricted to the antianxiety drugs only. Their division into major and minor tranquillizers is not justified, because the ‘minor tranquillizers’ are not less important drugs: they are more frequently prescribed and carry higher abuse liability than the ‘major tranquillizers’. The term tranquillizer is, therefore, best avoided.