Antipsychotic drugs are divided into conventional antipsychotics and 2nd-generation antipsychotics (SGAs) based on their specific neurotransmitter receptor affinity and activity. SGAs may offer some advantages, both in terms of modestly greater efficacy (although recent evidence casts doubt on SGAs' advantage as a class) and reduced likelihood of an involuntary movement disorder and related adverse effects.
Recent results suggest that new antipsychotic drugs with novel actions—namely, trace amines and muscarinic agonists—may become available. Currently, SGAs comprise about 95% of antipsychotics prescribed in the US. However, risk of metabolic syndromelong QT syndrome
Conventional antipsychotics
Conventional antipsychotics (see table Conventional Antipsychotics
Different drugs are available in tablet, liquid, and short- and long-acting IM preparations. A specific drug is selected primarily based on the following:
Adverse effect profile
Required route of administration
The patient’s previous response to the drug
Conventional antipsychotics may cause significant adverse effects, particularly some related to cognition and extrapyramidal movement disorders (eg, dystonia, tremor, tardive dyskinesia).
Second-generation antipsychotics
About 95% of all antipsychotics prescribed in the US are SGAs.
positive symptoms and the adverse effect benefits of SGAs.
SGAs also do the following:
Tend to alleviate positive symptoms
May lessen negative symptoms to a greater extent than do conventional antipsychotics (although such differences have been questioned)
May cause less cognitive blunting
Are less likely to have extrapyramidal adverse effects (including a much lower risk of tardive dyskinesia)
Can generate a metabolic syndrome
SGAs may appear to lessen negative symptoms because they are less likely to have parkinsonian adverse effects than conventional antipsychotics.
Newer SGAs (see table Second-Generation Antipsychotics
long-acting injectable formulation.
Weight gain, hyperlipidemia, and elevated risk of type 2 diabetes are the major adverse effects of SGAs. Thus, before treatment with SGAs is begun, all patients should be screened for risk factors, including personal or family history of diabetes, weight, waist circumference, blood pressure, and fasting plasma glucose and lipid profile. Those found to have or be at significant risk of metabolic syndromesymptoms and signs of diabetes, including polyuria, polydipsia, weight loss, and diabetic ketoacidosis (nausea, vomiting, dehydration, rapid respiration, clouding of sensorium), should be provided. In addition, nutritional and physical activity counseling should be provided to all patients when they start taking an SGA. All patients taking an SGA require periodic monitoring of weight, body mass index, and fasting plasma glucose and referral for specialty evaluation if they develop hyperlipidemia or type 2 diabetes.
Sometimes, combining an antipsychotic with another drug is beneficial (1). These drugs include
Antidepressants/selective serotonin-norepinephrine reuptake inhibitors
Another antipsychotic
Benzodiazepines
2).
Long-acting antipsychotic drugs
Some conventional and second-generation antipsychotics (SGAs) are available as long-acting depot preparations (see table Depot Antipsychotic Drugs). These preparations are useful for eliminating drug nonadherence. They may also help patients who, because of disorganization, indifference, or denial of illness, cannot reliably take daily oral drugs.
Adverse effects of antipsychotic drugs
Conventional antipsychotics have several adverse effects, such as sedation, cognitive blunting, dystonia and muscle stiffness, tremors, elevated prolactin levels (causing galactorrhea), weight gain, and lowered seizure threshold in patients with seizures or at risk of seizures (for treatment of adverse effects, see table Treatment of Acute Adverse Effects of Antipsychotics
Second-generation antipsychotics are less likely to cause extrapyramidal (motor) adverse effects, including tardive dyskinesia, but these may occur. Metabolic syndrome
Tardive dyskinesia is an involuntary movement disorder most often characterized by puckering of the lips and tongue, finger movements, writhing of the arms or legs, or more. For patients taking conventional antipsychotics, the incidence of tardive dyskinesia is about 5% each year of drug exposure and incidence is considerably lower with SGAs. In about 2%, tardive dyskinesia is severely disfiguring. In some patients, tardive dyskinesia persists indefinitely, even after the drug is stopped. Because of this risk, patients receiving long-term maintenance therapy should be evaluated at least every 6 months. Rating instruments, such as the Abnormal Involuntary Movement ScaleQT prolongation, and parkinsonism.
Neuroleptic malignant syndrome, a rare but potentially fatal adverse condition, is characterized by rigidity, fever, autonomic instability, and elevated creatine kinase.
Antipsychotic drug references
1. Correll CU, Rubio JM, Inczedy-Farkas G, et al: Efficacy of 42 pharmacologic cotreatment strategies added to antipsychotic monotherapy in schizophrenia: Systematic overview and quality appraisal of the meta-analytic evidence. JAMA Psychiatry 74(7):675-684, 2017. doi: 10.1001/jamapsychiatry.2017.0624
2. Wang SM, Han C, Lee SJExpert Opin Investig Drugs 26(6):687-698, 2017. doi: 10.1080/13543784.2017.1323870
