Antipsychotics, previously known as neuroleptics, are a class of psychotropic medications used to manage severe mental health conditions. While “neuroleptic” is historically based on the drugs’ neurological effects, “antipsychotic” is the preferred, modern name. These drugs are generally not curative, but they are effective in reducing the intensity of symptoms. This discussion will cover how these medications are classified, their mechanism of action, adverse reactions, and safety protocols for long-term use.
Understanding Antipsychotic Generations
The earliest medications in this class, developed in the 1950s, are categorized as first-generation or typical antipsychotics. These agents primarily manage symptoms associated with psychosis, such as hallucinations, delusions, and disorganized thought. Typical antipsychotics are still prescribed today, particularly for managing severe agitation and acute psychosis.
Second-generation or atypical antipsychotics were introduced later in the 1970s and 1980s. This newer class was developed to maintain efficacy while potentially reducing certain neurological side effects. Atypical antipsychotics are now widely used and are often the initial choice for many patients.
Both generations are prescribed for conditions like schizophrenia and the treatment of manic and mixed episodes in bipolar disorder. The distinction between the two groups is based on their chemical structure, specific targets within the brain, and their associated adverse reaction profile.
How These Medications Affect Brain Chemistry
The core understanding of how these drugs work is rooted in the Dopamine Hypothesis of psychosis. This model suggests that psychotic symptoms are linked to overactive dopaminergic signaling, specifically in the brain’s mesolimbic system. Antipsychotics reduce this excessive signaling to alleviate symptoms like delusions and hallucinations.
First-generation antipsychotics primarily function as antagonists, blocking the D2 receptor for the neurotransmitter dopamine. By occupying these D2 receptor sites, the drugs prevent dopamine from binding and over-stimulating nerve cells. This D2 receptor blockade is considered the main mechanism responsible for the anti-psychotic effect.
Second-generation antipsychotics also block D2 receptors, but they additionally influence serotonin pathways. These atypical agents have a high affinity for blocking the 5-HT2A serotonin receptor, which modulates dopamine release in certain brain regions. This dual action contributes to a broader efficacy profile and a lower risk of movement-related side effects compared to older drugs.
Managing Adverse Reactions
Adverse reactions are a significant concern, and their type often depends on the drug generation. First-generation antipsychotics are strongly associated with Extrapyramidal Symptoms (EPS), which are movement disorders resulting from dopamine blockade. These can manifest as acute dystonia (painful muscle contractions), parkinsonism (tremor, rigidity, and slowed movement), and akathisia (a feeling of inner restlessness).
A concerning long-term effect, more common with older agents, is tardive dyskinesia (TD), involving involuntary, repetitive movements of the face, tongue, and limbs. Second-generation antipsychotics carry a higher risk of metabolic side effects. These reactions include weight gain, increased risk of type 2 diabetes, and dyslipidemia (abnormal cholesterol and fat levels).
A rare but fatal reaction for any antipsychotic is Neuroleptic Malignant Syndrome (NMS). NMS is a medical emergency characterized by extremely high fever, severe muscle rigidity, changes in mental status, and autonomic instability. Immediate discontinuation of the medication and aggressive supportive care are required to manage this condition.
Safety Measures and Long-Term Treatment
Effective management requires regular, proactive monitoring to detect adverse effects early. Due to the risk of metabolic changes, especially with second-generation agents, patients should have their weight and waist circumference measured frequently. Blood tests are also required to check fasting glucose levels or HbA1c to screen for diabetes.
Monitoring includes regular checks of lipid panels to assess cholesterol and triglyceride levels. For some individuals, prolactin levels are measured to check for sexual side effects and menstrual irregularities, as this hormone can increase due to dopamine blockade. An electrocardiogram (ECG) may also be performed periodically to monitor for cardiac rhythm changes.
Adherence to the prescribed regimen is important for treatment success and to prevent relapse. If the medication is stopped, it must be done gradually under a physician’s supervision. Abrupt cessation can lead to discontinuation symptoms, such as nausea and insomnia, and significantly increase the risk of relapse.