Neuroleptic drugs drug-induced

Figure 7.8 Dopamine and motor function. When nigrostriatal dopamine activity is normal so is motor function. Any reduction in this DA activity, as in Parkinson s disease, results in reduced motor activity, i.e. akinesia. By contrast, too much DA activity, as in Huntington s Chorea, produces abnormal motor function, i.e. dyskinesia. The latter may be controlled by neuroleptic drugs (DA antagonists) but they can swing the balance in DA activity sufficiently to produce akinesia (Parkinsonism). DA agonists (and levodopa) may overcome akinesia but can induce DA overactivity and dyskinesia (peak dose effect) (see Chapter 15)...

The main indications for atypical antipsychotics are the acute and maintenance treatment of schizophrenic disorders, with an emphasis on the treatment of refractory and chronic disorders. However, because of the lower risk of EPS and in particular of tardive dyskinesia, there is a tendency toward a wider range of indications for some of the atypical neuroleptics. Favorable effects in drug-induced psychoses have been demonstrated for olanzapine. Clozapine seems effective in the treatment and relapse prevention of manic episodes and bipolar disorders, and risperidone has been shown to have good efficacy in conduct disorders and in the pervasive developmental disorders. 

The hypothetical link between dopamine and schizophrenia was forged by two reciprocally related findings. The first was that potent dopamine agonist stimulants like d-amphetamine and cocaine could cause a psychosis that was schizophrenia-like, in that it had auditory hallucinations and paranoia. The second was that the neuroleptic drugs that were effective in reversing both schizophrenia and stimulant-induced psychosis were dopamine blockers. Moreover, the antipsychotic potency of the neuroleptics was proportional to their binding affinity to the D2 receptor. 

A case report has suggested that risperidone, an atypical neuroleptic drug, can be useful in treating adolescents with glucocorticoid-induced psychosis and may hasten its resolution (105). 

Sex differences in hormone concentrations have been investigated in 47 patients (21 men and 26 women) with schizophrenia or related psychoses who were using different neuroleptic drugs (757). The median daily dose and the median body weight-adjusted daily dose were twice as high in men as in women. However, neuroleptic drug-induced hyperprolactinemia was more frequent and occurred at a lower daily dose in women. The growth hormone concentration was normal in all patients. 

Two women with neuroleptic-drug induced hyperprolactinemia, menstrual dysfunction, and galactorrhea had improvement in these adverse effects during treatment with olanzapine (855). 

The authors suggested that men with primary hypothyroidism may be particularly sensitive to neuroleptic drug-induced increases in prolactin concentrations. 

Drug-induced Parkinsonism may arise following the long-term administration of neuroleptics that block central dopamine receptors or reserpine-like drugs that deplete dopamine stores. Because of their mode of action, neuroleptics should never be coadministered to patients being treated with L-dopa or vice versa. 

Putten, rediscovered drug-induced dysphoria, which was noted to be associated with neurological effects, especially akathisia2 (Van Putten 1974, 1975). This was later labelled as akinetic depression (Van Putten May 1978). In the 1990s the term neuroleptic-induced deficit syndrome was coined to describe affective and cognitive impairment (Lader 1994) and drug-induced dysphoria was revisited (Hollister 1992 King, Burke, Lucas 1995). 

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