Neuroleptics

Neuroleptics, also known as antipsychotic medications, are medications that block dopamine receptors in the nervous system. They are mainly prescribed to manage mental illnesses, such as schizophrenia and bipolar disorder, as well as psychosis. Psychosis describes loss of touch with reality, with specific symptoms such as difficulty concentrating, hallucinating, and engaging in movements without a purpose (i.e., psychomotor activity). 

Neuroleptics typically work by affecting dopamine and, sometimes, serotonin levels in the brain to decrease psychosis symptoms. Dopamine and serotonin are both neurotransmitters, small molecules that transmit information across nerve cells and affect many major body systems, like the cardiovascular and nervous systems. Dopamine can affect four pathways in the brain: the mesolimbic, mesocortical, nigrostriatal, and tuberoinfundibular pathways. Due to its effect on these pathways, dopamine plays an important role in significant body functions, including motor control, motivation, arousal, reinforcement, and reward. Meanwhile, serotonin is known for its roles in the regulation of mood, body temperature, and appetite, among other body functions. Maintaining a balance of neurotransmitters is critical for proper execution and regulation of body functions. In cases of imbalance, neuroleptics work to regulate the associated functions.

Neuroleptics block dopamine receptors in the brain, so they are prescribed when symptoms are associated with an excess of dopamine in the body. Most neuroleptics affect dopamine D2 receptors in the mesolimbic pathway of the brain, decreasing the positive, or present, symptoms of psychosis, such as hallucination, delusion, and disorganized thought. However, first-generation neuroleptics also block the dopamine receptors on other pathways, such as the mesocortical pathway. These additional blocks have been associated with potentially worsening negative symptoms, or symptoms that take away typical functions. Examples of negative symptoms include lack of emotionality, social withdrawal, and lack of motivation. In contrast, second-generation neuroleptics block both D2 receptors and serotonin 5-HT2A receptors in the mesocortical pathway of the brain, which reduces negative symptoms. 

In general, neuroleptics are most commonly prescribed for reducing psychosis symptoms associated with schizophrenia. Schizophrenia is defined by the American Psychiatric Association as a serious mental disorder characterized by a variety of positive, negative, and disorganized symptoms, which can affect many aspects of daily functioning, including mood, thoughts, and feelings. Schizophrenia typically begins in early adulthood and often presents with incoherent or illogical thought, disordered speech, impaired emotional expression, and hallucinations. Since schizophrenia is commonly believed to result from increased dopamine levels, neuroleptics may effectively treat the disorder. 

Neuroleptics may produce a wide-range of side effects depending on the potency and class of neuroleptic medications prescribed.

High-potency, first-generation neuroleptics, such as haloperidol and fluphenazine, are likely to produce extrapyramidal symptoms, which are movement disorders caused by medications. Examples of extrapyramidal symptoms include muscle spasms (i.e., acute dystonia), motor restlessness (i.e., akathisia), and parkinsonism, which is characterized by instability, shuffling gait, and muscle rigidity. Tardive dyskinesia is another extrapyramidal effect, characterized by involuntary, repetitive movement, such as smacking lips or waving arms. Tardive dyskinesia may occur after long-term use of the medication and can be irreversible. Neuroleptic malignant syndrome is a rare, potentially fatal extrapyramidal side effect, presenting with symptoms such as confusion, muscle rigidity, seizures, coma, agitation, and hyperthermia and requiring immediate medical attention. Additional potential side effects of high-potency, first-generation neuroleptics include an increased time between heart beats and metabolic symptoms, such as weight gain and high cholesterol.

Low-potency, first-generation neuroleptics, such as chlorpromazine and thioridazine, will commonly result in side effects similar to those seen with anticholinergics, which are medications that block the neurotransmitter acetylcholine. These side effects may include dry mouth, sedation, constipation, and dizziness. In general, low-potency, first-generation neuroleptics are less likely to cause extrapyramidal symptoms. 

Second-generation neuroleptics are associated with fewer extrapyramidal and anticholinergic side effects. They can, however, lead to weight gain, drug-induced type 2 diabetes, and tiredness.