Conventional antipsychotic drugs represent the first class of medications developed to specifically address the symptoms of psychosis. These compounds, often referred to as first-generation or typical antipsychotics, were introduced in the 1950s and dramatically changed the treatment landscape for severe mental illnesses. The discovery of chlorpromazine offered the first effective pharmacological option beyond sedation or institutionalization. While they remain in use today, their efficacy must be balanced against a distinct profile of potential side effects, which differs substantially from newer medications. They continue to serve as important tools in treating acute psychiatric episodes, especially when rapid stabilization is required.
Defining Conventional Antipsychotics and Their Mechanism
Conventional antipsychotics are chemically diverse compounds grouped as first-generation or “typical” agents based on their shared primary action in the brain. Key examples include haloperidol, chlorpromazine, and fluphenazine. These medications are categorized by their relative potency: low-potency drugs, such as chlorpromazine, tend to cause more sedative and anticholinergic effects, while high-potency drugs like haloperidol are more likely to cause movement-related side effects.
The therapeutic action of all conventional antipsychotics is linked to their potent blockade of dopamine D2 receptors within the central nervous system. Dopamine is a neurotransmitter involved in regulating mood, motivation, and motor control. The theory suggests that psychosis, particularly the positive symptoms of schizophrenia, involves overactivity in the brain’s mesolimbic dopamine pathway.
By blocking D2 receptors, these drugs effectively dampen the excessive dopaminergic signaling. For a therapeutic effect, approximately 72% of the D2 receptors must be occupied by the medication. However, this potent, widespread blockade affects other dopamine pathways, which accounts for the most significant drawback of this drug class. When D2 receptor occupancy exceeds about 78%, the risk of severe movement-related side effects dramatically increases, defining the narrow therapeutic window of these drugs.
Primary Therapeutic Applications
The primary clinical application for conventional antipsychotics is the management of symptoms associated with schizophrenia and other psychotic disorders. These medications are particularly effective at resolving the “positive” symptoms of psychosis, such as hallucinations and delusions.
They are frequently used for the acute treatment of a psychotic episode to achieve rapid control of agitation and disorganized thinking. For long-term management, they help prevent the recurrence of positive symptoms in patients with chronic schizophrenia. They are also prescribed for the management of acute manic episodes in bipolar disorder, often used alongside a mood stabilizer.
The sedating properties of some conventional agents make them useful for rapidly calming severe agitation. A short course of the medication can help stabilize a patient who poses a risk to themselves or others.
Common Non-Neurological Adverse Effects
Conventional antipsychotics affect multiple body systems due to their interaction with various non-dopamine receptors. Sedation is common, especially with lower-potency agents like chlorpromazine, causing significant drowsiness and impacting daily functioning. This effect is largely due to the medication’s strong blocking action on histamine (H1) receptors.
The drugs also block muscarinic acetylcholine receptors, leading to anticholinergic effects. These include dry mouth, blurred vision, constipation, and difficulty with urination. These effects can be clinically significant, particularly for elderly patients.
Orthostatic hypotension, a sudden drop in blood pressure when a person stands up, is another frequent side effect, causing dizziness or lightheadedness. This occurs because the drugs block alpha-1 adrenergic receptors, interfering with the body’s ability to regulate blood pressure upon changing posture.
Some conventional antipsychotics also cause endocrine changes by elevating prolactin levels. This can lead to sexual dysfunction, breast enlargement (gynecomastia) in men, and menstrual irregularities (amenorrhea) in women. Weight gain and changes in metabolism are also possible, contributing to long-term health risks.
Serious Movement-Related Complications
The most serious drawback of conventional antipsychotics is their tendency to cause drug-induced movement disorders, collectively known as extrapyramidal symptoms (EPS). These neurological effects arise from potent D2 receptor blockade in the nigrostriatal pathway, the part of the brain that controls motor function. EPS can manifest acutely, often early in the course of treatment, and includes three main syndromes.
Acute dystonia involves painful, sustained muscle spasms, which typically affect the face, neck, and torso, sometimes causing the eyes to roll up (oculogyric crisis). Drug-induced parkinsonism presents with symptoms indistinguishable from Parkinson’s disease, including resting tremors, muscle rigidity, and bradykinesia (slowness of movement). Akathisia is characterized by an intense feeling of inner restlessness that compels the patient to move constantly, such as pacing or fidgeting.
A far more concerning long-term complication is tardive dyskinesia (TD), the most severe movement disorder associated with this drug class. TD is characterized by involuntary, repetitive movements, most commonly affecting the mouth, tongue, and facial muscles, leading to lip-smacking or grimacing. The “tardive” designation signifies that this disorder develops late in treatment, typically after months or years of exposure.
TD is problematic because it has the potential to be irreversible even after the drug is discontinued, making prevention a major focus of care. A rare and potentially life-threatening complication is Neuroleptic Malignant Syndrome (NMS), which constitutes a medical emergency. NMS is characterized by a rapid onset of high fever, severe “lead-pipe” muscle rigidity, altered mental status, and autonomic instability (such as fluctuating blood pressure and heart rate).
NMS requires immediate discontinuation of the antipsychotic and intensive supportive medical care. The risk of NMS, combined with the high liability for TD and other EPS, is the primary reason that conventional antipsychotics are often reserved for specific clinical situations or used when newer agents have proven ineffective.