Neuroleptics

Neuroleptics, or antipsychotics, are a class of medicines used to treat psychotic disorders. Most traditional or first-generation neuroleptics act as antagonists of dopamine D2 receptors in the brain, particularly in the mesolimbic pathway, which helps reduce positive symptoms such as delusions and hallucinations. Many second-generation or atypical neuroleptics also block serotonin 5-HT2A receptors and may affect other neurotransmitter systems, contributing to their broader efficacy and side-effect profile.

Common typical neuroleptics include chlorpromazine, haloperidol, and fluphenazine. They are effective for positive symptoms but carry a higher risk of extrapyramidal symptoms and tardive dyskinesia. Atypical neuroleptics such as risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and clozapine tend to cause fewer EPS and may improve negative symptoms, but many are associated with weight gain, metabolic syndrome, hyperprolactinemia, and raised lipids. Clozapine is reserved for treatment-resistant cases due to risk of agranulocytosis and requires regular blood monitoring.

Indications include schizophrenia and schizoaffective disorders, bipolar disorder with manic or depressive episodes, other psychotic disorders, and Tourette syndrome. Some indications are off-label in mood disorders or agitation. Caution is advised in elderly patients with dementia-related psychosis due to increased mortality in trials.

Common adverse effects reflect dopamine blockade and other receptor interactions: EPS (dystonia, parkinsonism, akathisia), tardive dyskinesia with long-term use, hyperprolactinemia, sedation, anticholinergic symptoms, metabolic effects with many atypicals, QT prolongation, and rare but life-threatening neuroleptic malignant syndrome. Drug interactions and cumulative sedation should be considered.

Monitoring includes assessment of motor symptoms, metabolic parameters (weight, glucose, lipids), prolactin, and cardiovascular status. Clozapine requires routine hematologic monitoring. Dosing is individualized and may require slow titration.