The most influential biological theories assume schizophrenic symptoms are caused by an imbalance in brain chemistry. The dominance of this theory is not a result of laboratory work directly linking schizophrenic symptoms with a chemical imbalance. Rather, it is derived from observations that drug treatment appears to blunt some of the outward displays of the symptoms. As a result it is crudely deduced that the cause of the symptoms is a shortage of the chemicals contained in the medication.
This reasoning is not very sound, and it could just as easily be argued that a person who counters shyness by drinking alcohol apparently has a shortage of alcohol in the brain. But the weakness in reasoning has not inhibited research based on this type of deduction. The ‘dopamine theory’ is the most prominent of the biochemical hypotheses, and a great deal of research has been undertaken to explore the relationship between the positive symptoms of schizophrenia and the supposed hyperactivity of the dopamine system in the brains of schizophrenics.
The dopamine hypothesis is principally derived from two kinds of observation. The first is that drugs which increase the supply of dopamine, such as amphetamines and L-dopa (which is used for the treatment of Parkinson’s disease), can sometimes cause a person to enter a psychotic-like state. The second is that neuroleptic drugs have been observed to block dopamine receptors in laboratory animals and thereby inhibit the supply of dopamine. The hypothesis derived from these observations argues that untreated schizophrenics have hyperactive dopamine systems and require neuroleptic medication to inhibit the supply of dopamine in their brains.
An often-cited weakness with this theory is that, whereas the dopamine receptors in the central nervous system are blocked within twenty minutes of neuroleptic medication, the drugs usually take days, sometimes many weeks, or even months, before they show any clinical effect.[1] A second weakness is that ‘these drugs reduce psychotic symptoms regardless of the diagnosis’.[2]
In other words, just as alcohol affects garrulous people in much the same way as it affects shy people—and therefore makes improbable a ‘lack of alcohol’ theory to explain the cause of shyness—so neuroleptics have much the same effect on people whether they have a prior diagnosis of schizophrenia or not. Everyone who is treated experiences ‘some degree of (often total) indifference and apathy’.[3] This means that although neuroleptic medication might temporarily ameliorate some of the florid features of schizophrenia, it is not a cure, and therefore the dopamine hypothesis is doubtful.
There are many variables involved in the prescription of neuroleptic medication for schizophrenia. A match has to be found for a particular patient, through trial and error, with a particular type and brand of neuroleptic according to the individual tolerance of the patient; an appropriate dosage has to be determined for each individual patient, with the right combination of drugs to suppress any side effects; and the treatment has to be continued for an indefinite period to suppress psychotic symptoms, which tend to fluctuate over time.
The mainstream of the psychiatric profession was in a state of semi-denial until recent years regarding the seriousness of the side effects caused by neuroleptic medication. This situation has now changed, and DSM-IV even has an appendix with a detailed survey of medication-induced movement disorders caused by the use of neuroleptics. The list includes Neuroleptic-Induced Parkinsonism which features a variety of tremors and muscle rigidity mimicking Parkinson’s disease. It afflicts some 50 per cent of patients on long-term neuroleptic treatment. Neuroleptic Malignant Syndrome is an acute toxic reaction to the drugs and occurs in 0.07–1.4 per cent of patients treated with neuroleptics. Of these 10–20 per cent die from it.[4]
Neuroleptic-Induced Acute Dystonia features abnormal positioning of the head and neck in relation to the body, spasms of the jaw muscles, impaired swallowing, thickened or slurred speech, tongue protrusion, eyes deviated up, down or sideways, and abnormal positioning of the limbs or trunk. Fear and anxiety are also often a symptom, and it occurs most commonly in young males.[5] If a person looked sane before treatment they certainly would not after developing this side effect.
Neuroleptic-Induced Acute Akathisia features symptoms of compulsive restlessness such as fidgety movements, walking on the spot and inability to sit still. The reported prevalence of this side effect in people receiving neuroleptics varies widely from 20 per cent to 75 per cent.[6] Once again a set of physical symptoms induced by the treatment contributes dramatically to the person’s appearance of being mad. Agitation, aggression and suicidal tendencies are a major problem for people suffering from akathisia, and most of the dangerous behaviour associated with schizophrenia is actually caused by the drug treatment, rather than the supposed underlying mental disorder.
But the most debilitating side effect of schizophrenia treatment is Neuroleptic-Induced Tardive Dyskinesia. The indications of tardive dyskinesia are involuntary movements which can be rapid and jerky, slow and sinuous or rhythmic. They might involve the tongue, jaw, trunk or extremities. 20–30 per cent of people receiving neuroleptics develop tardive dyskinesia, and up to 50 per cent amongst elderly people.[7] This side effect is serious because there is no supplementary drug treatment to mask its symptoms, and it appears to be an indication of permanent brain damage in many victims. If the neuroleptic treatment is discontinued, the tardive dyskinesia symptoms remain permanently in 50 per cent of cases. This permanency is much higher in elderly people, in whom it remains unremitted in up to 95 per cent of cases.[8]
These neuroleptic-induced movement disorders are collectively known as the central nervous system extrapyramidal side effects (EPSEs). It is perhaps incorrect to call these disorders side effects, because they occur as a direct result of blocking the dopamine receptors, and most of the patients receiving neuroleptics develop EPSEs. In fact it is partly through the existence of EPSEs that scientists have been able to work out how neuroleptics affect brain chemistry.
Next: Atypical Neuroleptics
[1] Norman L. Keltner, ‘Schizophrenia and Other Psychoses’, in Norman L. Keltner et al., (eds.), Psychiatric Nursing, p. 367.
[2] Harold I. Kaplan and Benjamin J. Sadock, Synopsis of Psychiatry, p. 639.
[3] David Richman, ‘Pursuing Psychiatric Pill Pushers’, p. 113. (For a more extensive description of the effects of neuroleptics see Chapter 6.)
[4] American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition, pp. 735–51.
[5] Ibid., p. 743.
[6] Ibid., p. 745.
[7] Ibid., pp. 747–9.
[8] Ibid., p. 748.