Tolerance And Physical Dependence

As defined in Chapter 23, the antipsychotic drugs are not addicting, but some degree of physical dependence may occur, with malaise and difficulty in sleeping developing several days after abrupt drug discontinuation after prolonged use.

Loss of efficacy with prolonged treatment is not known to occur with antipsychotic agents, but some tolerance to sedative effects of antipsychotics usually develops over days or weeks. One correlate of tolerance in forebrain dopaminergic systems is the development of supersen-sitivity, probably mediated by upregulation and sensitization of DA D2 receptors. These changes may underlie the clinical phenomenon of withdrawal-emergent dyskinesias (e.g., choreoathetosis on abrupt discontinuation of antipsychotic agents, especially following prolonged use of high doses of potent agents) and may contribute to the pathophysiology of tardive dyskinesias.

Elimination Half-Lives of Antipsychotic Drugs


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