Antipsychotic Drug Therapy

Antipsychotics are medications mainly used to treat symptoms of psychotic disorders, like schizophrenia and bipolar disorder. There are two main categories of antipsychotic medications, known as first generation, or typical antipsychotics, and second generation, or atypical antipsychotics.

Typical antipsychotics, like haloperidol, are highly effective, but have an increased risk of adverse effects, so they’re prescribed less often. On the other hand, atypical antipsychotics, like aripiprazole, generally cause less side effects so they’re considered first-line therapy.

Okay, so psychotic disorders can be broadly defined as mental disorders characterized by fragmented and abnormal patterns of thinking. These disorders cause patients to have a variety of symptoms that impair normal functioning, such as delusions, hallucinations, and disorganized speech and behavior. Two of the most common psychotic disorders are schizophrenia and bipolar disorder.

Now, the mechanism of action of an antipsychotic medication depends on whether it’s a typical or an atypical antipsychotic. Typical antipsychotics work by antagonizing dopamine, or D2 receptors, as well as histamine, or H1, acetylcholine, or Ach, and alpha-1 receptors. Atypical antipsychotics also antagonize H1, Ach, and alpha-1 receptors, but they are weaker D2 antagonists, and they are also serotonin, or 5-HT2 antagonists. It’s important to note that all atypical antipsychotics antagonize these receptors to varying degrees, except for aripiprazole, which is a partial agonist of D2 and 5-HT1 receptors, and a pure antagonist at 5-HT2 receptors.

Alright, so common side effects of antipsychotics are called extrapyramidal symptoms, or EPS, which are associated with D2 blockade. These symptoms include acute dystonia, which refers to muscle spasms of the eyes, face, neck, and back; akathisia, which is categorized by restlessness and a constant urge to move the limbs; Parkinsonian symptoms, including muscle rigidity, usually in the facial muscles, as well as symptoms, such as bradykinesia or slow movements, and tremors in the hands and fingers; and tardive dyskinesia, characterized by constant, involuntary, rhythmic movements. Tardive dyskinesia usually affects the perioral muscles causing the patient to repeatedly smack or purse their lips. Unlike the other extrapyramidal symptoms, which usually resolve once the medication is stopped, tardive dyskinesia can be irreversible, so it’s important to discontinue the medication at the first sign of this side effect.

Other side effects associated with typical antipsychotics include central nervous system depression and sedation, due to H1 blockade, as well as hypotension and orthostatic hypotension, due to alpha-adrenergic blockade. More serious cardiovascular effects include QT prolongation that can lead to torsades de pointe, which is a life-threatening cardiac arrhythmia.

There are also anticholinergic effects like dry mouth, urinary retention, and blurred vision, due to Ach blockade. Typical antipsychotics can also cause agranulocytosis, though the cause is unknown. Lastly, a rare but potentially fatal side effect called neuroleptic malignant syndrome, is related to D2 blockade. It’s characterized by high fever, confusion, muscle rigidity, and blood pressure fluctuations.

Atypical antipsychotics, like aripiprazole, can also cause weight gain, which is related to H1 blockade, and can lead to metabolic syndrome, diabetes, and dyslipidemia, which can increase the risk of cardiovascular disease. Other side effects can include headache, dizziness, insomnia, nausea, and vomiting.