Antipsychotic drugs produce shifts in the pattern of electroencephalographic (EEG) frequencies, usually slowing them and increasing their synchronization. The slowing (hypersynchrony) is sometimes focal or unilateral, which may lead to erroneous diagnostic interpretations. Both the frequency and the amplitude changes induced by psychotropic drugs are readily apparent and can be quantitated by sophisticated electrophysiologic techniques. Some antipsychotic agents lower the seizure threshold and induce EEG patterns typical of seizure disorders; however, with careful dosage titration, most can be used safely in epileptic patients.
F. Endocrine Effects
Older typical antipsychotic drugs, as well as risperidone and paliperidone, produce elevations of prolactin (see Adverse Effects, below). Newer antipsychotics such as olanzapine, quetiapine, aripiprazole, and brexpiprazole cause no or minimal increases of prolactin and reduce the risks of extrapyramidal system dysfunction and tardive dyskinesia, reflecting their diminished D2 antagonism.
G. Cardiovascular Effects
The low-potency phenothiazines frequently cause orthostatic hypotension and tachycardia. Mean arterial pressure, peripheral resistance, and stroke volume are decreased. These effects are predictable from the autonomic actions of these agents (Table 29–2). Abnormal electrocardiograms have been recorded, especially with thioridazine. Changes include prolongation of QT interval and abnormal configurations of the ST segment and T waves. These changes are readily reversed by withdrawing the drug. Since thioridazine is associated with torsades de pointes and an increased risk of sudden death, the branded drug was removed from the market in 2005, and its use currently is as a second-line agent if other drugs have proven intolerable or ineffective.
Among the newest antipsychotics, prolongation of the QT or QTc interval has received much attention. Because this was believed to indicate an increased risk of dangerous arrhythmias, ziprasidone and quetiapine are accompanied by warnings. There is, however, no evidence that this has actually translated into increased incidence of arrhythmias.
The atypical antipsychotics are also associated with a metabolic syndrome that may increase the risk of coronary artery disease, stroke, and hypertension.
A. Psychiatric Indications
Schizophrenia is the primary indication for antipsychotic agents. However, in the last decade, the use of antipsychotics in the treatment of mood disorders such as bipolar disorder (BP1), psychotic depression, and treatment-resistant depression has eclipsed their use in the treatment of schizophrenia.
Catatonic forms of schizophrenia are best managed by intravenous benzodiazepines. Antipsychotic drugs may be needed to treat psychotic components of that form of the illness after catatonia has ended, and they remain the mainstay of treatment for this condition. Unfortunately, many patients show little response, and virtually none show a complete response.
Antipsychotic drugs are also indicated for schizoaffective disorders, which share characteristics of both schizophrenia and affective disorders. No fundamental difference between these two diagnoses has been reliably demonstrated. It is most likely that they are part of a continuum with bipolar psychotic disorder. The psychotic aspects of the illness require treatment with antipsychotic drugs, which may be used with other drugs such as antidepressants, lithium, or valproic acid.