Recovery From Schizophrenia: Psychiatry And Political Economy

ANTIPSYCHOTIC DRUGS: USE, ABUSE AND NON-USE 223an immediate problem, as the receptors are blocked by the neuroleptic drugs andthe increase in neurotransmitter can have little effect. There is a potential,however, for serious long-term effects.Chronic dopamine receptor blockade by the administration of the standardneuroleptic drugs, and the consequent elevation in dopamine turnover, have beenfound to produce a substantial increase in the number of binding sites fordopamine in the brains of rats and humans. 15 That is, the drugs create an artificialdopamine supersensitivity. Tardive dyskinesia—the delayed neurological sideeffect of chronic neuroleptic drug use that occurs in a proportion of patients—is adopamine supersensitivity phenomenon. Dopamine receptors in the nigrostriataltract overcompensate for the chronic blockade by becoming hypersensitive. Thesymptoms of tardive dyskinesia (involuntary muscle movements) usually appearafter a reduction in the dose of the neuroleptic drug, as this change exposes someof the previously blocked receptors to the action of the neurotransmitter. Anincrease in drug dosage, on the other hand, will block the receptors and mask thesymptoms of the disorder.In the mesolimbic system, chronic dopamine blockade by antipsychotic drugsleads to an increase in the number of dopamine-2 receptors and a worsening ofthe dopamine dysregulation that is one of the underlying problems inschizophrenia. 16 As in tardive dyskinesia the supersensitivity effect may betemporary, gradually disappearing over the course of weeks or months after drugwithdrawal, or—if drug treatment continues long enough - it may becomepermanent. Herein may lie one reason for the failure of the standard antipsychoticdrugs to produce improvements in the long-term outlook in schizophrenia.We may predict that certain consequences will flow from the tendency of thestandard antipsychotic drugs to produce dopamine supersensitivity. These include:• Psychotic symptoms will rebound, after the withdrawal of standardantipsychotic drug treatment, to a higher level than would have been the casewithout treatment. Drug-withdrawal studies that evaluate the efficacy ofantipsychotic drugs by substituting a placebo for the active drug will thereforegive an over-optimistic impression of the value of the drugs.• The adverse long-term effects of the standard antipsychotic drugs will be mostevident in the case of people with schizophrenia who would otherwise havehad a good prognosis. As illustrated in Figure 10.1, the outcome for peoplewith poor-prognosis schizophrenia is likely to be so serious that a worsening dueto drug withdrawal would be difficult to detect and the continuous use ofdrugs will still offer distinct advantages for these patients. In the case of peoplewith good-prognosis schizophrenia, on the other hand, drug withdrawal mayworsen the course of an otherwise benign condition and drug maintenancetherapy may increase the risk of psychosis, cause side effects or, at best, proveworthless.We may examine the evidence relating to these predictions in turn.