The time course of neuroleptic therapy for psychosis: role of learning processes and implications for concepts of psychotic illness.

In neuroleptic therapy for psychotic illness, clinical improvement is produced more slowly than is central dopamine blockade, and its time course is highly variable between patients. A theory of neuroleptic-responsive psychotic illness thus requires more than dopamine blockade, though that appears to be the first step in the therapeutic process. Some previous explanations given for the protracted time course of neuroleptic therapy are discussed, with emphasis on the hypothesis of delayed inactivation of midbrain dopamine neurones. For various reasons all explanations are unsatisfactory. An alternative hypothesis is proposed in which neuroleptic-responsive psychoses are seen as arising from a hyperactivity of the associations of thought. Such psychoses thus involve a disorder of a high-level learning process, namely the elaboration of memories of thoughts and beliefs. Neuroleptic drugs are envisaged to remedy this process, but not to eradicate the abnormal memories already formed. Psychotic symptoms may thus outlast the start of neuroleptic therapy by many weeks. It is suggested that the pharmacological characteristics of the hypothetical learning process involved in generating psychotic symptoms are analogous to those of a simpler learning process, defineable in animal experiments - namely, the reward component in instrumental conditioning. A preliminary case is made that the relative potency of different neuroleptic drugs in antipsychotic therapy can better be predicted by their relative potency in retarding such a variety of learning, than by other behavioural tests of these drugs.