Psychosis is a mental state where there is a grossly impaired appreciation of reality as evidenced by the presence of delusions, hallucinations and bizarre behaviour. Many disorders cause psychosis, including organic states, schizophrenia, mania, psychotic depression and paranoid syndromes.
Evidence now demonstrates persuasively that antipsychotics reverse the symptoms of psychosis (and prevent their recurrence) in all psychotic states, although efficacy can vary considerably (e.g. chronic paranoid states are often refractory).
Antipsychotics include phenothiazines (chlorpromazine, thioridazine, trifluoperazine, fluphenazine decanoate), butyrophenones (haloperidol, droperidol), thioxanthenes (thiothixene) and phenylbutylpiperidines (pimozide). These drugs differ in adverse effect profiles, but have equivalent effects in diminishing the positive symptoms of psychosis. They are less beneficial for negative symptoms. About one third of patients fail to respond adequately to these drugs, and many patients experience serious adverse effects.
Among the extra pyramidal adverse effects characteristic of antipsychotics, patients find akathisia (an irresistible restlessness) troubling and may fail to comply as a result. Dystonic reactions (oculogyric crisis, torticollis, opisthotonus, laryngeal dystonia) and secondary Parkinsonism also occur frequently. In the long term, there is a risk of tardive dyskinesia (usually manifesting as choreiform movements in the oro-bucco-facial region) which can become irreversible. Other important adverse effects include sedation, anticholinergic effects (dry mouth, blurred vision, urinary retention, constipation, tachycardia), weight gain, photosensitivity, pigmentation, hyperprolactinaemia and neuroleptic malignant syndrome.
Antipsychotics were thought to act solely by blocking the dopamine D2 receptor subfamily in mesocorticolimbic pathways, while causing extra pyramidal adverse effects through nigrostriatal dopamine blockade. Recently, D3 and D4 receptor subtypes have been identified. As both receptor types have significant homology with the D2 receptor subtype, the issue of which receptors are involved in the antipsychotic effect is being re-evaluated.