Antipsychotic Drugs

clozapine

Antipsychotics are psychiatric medications primarily used to treat schizophrenia and similar disorders.

As the name suggests, they help alleviate psychotic symptoms (e.g. hallucinations, delusions). First developed in the 1950s, these powerful drugs revolutionized the treatment of schizophrenia, a lifelong disorder that is considered one of the most serious and potentially debilitating mental illnesses. Many antipsychotics are also frequently used in the treatment of bipolar I disorder, as well as many other psychiatric disorders.

Antipsychotics are also often referred to as “neuroleptics” or “major tranquilizers”. They are typically divided into two groups: first generation and second generation antipsychotics. One of the newest antipsychotic drugs, aripiprazole (Abilify), is sometimes referred to as the first “third generation” antipsychotic.

First Generation Antipsychotics

Also known as “conventional” or “typical” antipsychotics, medications in this group were the first drugs used to treat schizophrenia. Although they can be very effective, they are often accompanied by very challenging side effects, particularly with long term use. However, for many patients, the benefits outweighed the risks.

Conventional antipsychotics, unfortunately, have very limited effectiveness in treating the negative symptoms of schizophrenia, such as emotional flatness and lack of initiative. They also provide little, if any, benefit for mood symptoms or cognitive impairment.

Despite the fact that many newer antipsychotics have been developed, many of the first generation antipsychotics are still frequently prescribed today. Others, such as trifluoperazine and molindone, have been discontinued.

First Generation Antipsychotics include:

Second Generation Antipsychotics

The early 1990s brought the development of a new group of antipsychotics, known as “second generation” or “atypical” antipsychotics. Because they were believed to have fewer side effects, they quickly began to replace conventional antipsychotics for the treatment of schizophrenia and related conditions.

Second Generation Antipsychotics include:

As for whether or not these newer antipsychotics are really better than the first generation antipsychotics, the debate continues. However, some recent studies have shown that some of the conventional antipsychotics are just as effective as newer ones.1, 2, 3 The CATIE study (Clinical Antipsychotic Trials of Intervention Effectiveness), funded by the NIMH, was a prominent research endeavor looking at this very issue.1

Since many of the newer antipsychotic drugs are significantly more expensive than conventional ones, the findings of these studies have positive treatment implications for patients who are uninsured or unable to afford high co-payments.

As with all medications, the degree of effectiveness can vary from one individual to the next. Because of this, there is often trial and error involved in determining the best antipsychotic medication for any given patient.

What They’re Used to Treat

As mentioned above, the primary use of antipsychotic medications is the treatment of schizophrenia and related psychotic disorders, such as schizoaffective disorder. However, in recent years, many antipsychotic medications have been approved by the FDA to treat several other disorders and conditions as well, either alone or combined with other medications.

These include bipolar disorder (particularly acute mania and bipolar depression), Tourette’s Syndrome, depression with psychotic symptoms, irritability associated with autism in children, and extreme nausea and vomiting. Antipsychotic medications are often used for agitation. For example, Haldol is often given to highly agitated patients in hospital settings.

It should be noted that only a small number of antipsychotics are FDA-approved for treating minors. For the ones that are, the indicators are very specific regarding the age group (e.g., 13 to 17 years only) and the particular disorder (e.g. schizophrenia or acute mania).

Sometimes doctors prescribe antipsychotics for “off-label” use. Off-label refers to the use of a drug that is not approved by the FDA for that particular disorder, symptom, or age group. While using antipsychotics off-label can be beneficial at times, it can also be very risky. A recent large-scale study revealed that 65% of children who were prescribed antipsychotic drugs in 2007 were using them “off-label”, most frequently for conduct disorder or ADHD.4 Some of these children were as young as age 3.

How They Work

Antipsychotic medications are believed to alleviate symptoms by impacting certain chemicals, called neurotransmitters, in the brain. The primary neurotransmitter affected by most antipsychotics is dopamine, although some of the second generation antipsychotics also impact serotonin. Specifically, they work by blocking (or partially blocking) the receptor sites of these chemicals. Both dopamine and serotonin are believed to play important roles in the development of psychotic symptoms and mood disorders. Each drug works a little differently, depending on its particular properties.

How They’re Administered

Antipsychotics are typically taken orally as a tablet, capsule, or liquid. Antipsychotics are often given via injection to treat acute symptoms. Some antipsychotics are also available in the form of a long-acting injection (LAI). These include risperidone, haloperidol, olanzapine, fluphenazine, and paliperidone. Long-acting injections are often used for patients with schizophrenia who don’t take their medications as prescribed and have frequent relapses as a result.

Side Effects

One of the greatest concerns with all antipsychotic medications is the potential side effects associated with these powerful drugs. The potential side effects vary depending on the particular medication.

Some of the more troubling or serious side effects, like tardive dyskinesia and neuroleptic malignant syndrome (discussed below), are more likely to occur with the older, conventional antipsychotics. However, they may occur with atypical antipsychotics as well. Metabolic side effects, such as diabetes, significant weight gain, and high cholesterol are more frequently associated with the newer antipsychotics, but may also occur with the first generation drugs.

Tardive Dyskinesia is a movement disorder that most often occurs in patients who have taken older antipsychotic medications for many years. Symptoms include involuntary, uncontrollable, and random movements like lip smacking, grimacing, blinking, and other unusual movement in the limbs, toes, fingers, hips, or upper body. In many cases, TD is irreversible, which makes it especially troubling.

Neuroleptic malignant syndrome (NMS) is a rare but very serious and potentially deadly side effect of some antipsychotic drugs. Symptoms include muscle stiffness, altered mental status, severe fluctuations in blood pressure, tremors, breathing difficulties, sudden renal failure, dehydration, rapid heartbeat, and high fever.

A very serious potential side effect of clozapine is agranulocytosis, in which white blood cells significantly decrease. As a result, those who take this medication have to have their blood monitored weekly or bi-weekly, depending on how long they’ve been taking the medication.

Other potential side effects of antipsychotic medications may include, but are not limited to:

  • Sedation
  • Restless leg syndrome
  • Muscle spasms
  • Sexual problems
  • Seizures
  • Constipation
  • Nausea and vomiting
  • Changes in appetite
  • Blurred vision
  • Fatigue
  • Dry mouth
  • Light-headedness
  • Behavioral changes
  • Headaches
  • Insomnia

Precautions

As with all medications, it is crucial to talk to your doctor about any current or past medical conditions, drug allergies, medication use (including herbal and other supplements and over-the-counter medications) before taking an antipsychotic medication. Your family medical history is also very important, and will help your doctor determine which medications are best suited for you. Be sure to tell your doctor if you are pregnant or nursing, or thinking about becoming pregnant, before taking antipsychotics. It’s also very important to let your doctor know if you use alcohol or drugs of any kind, or have a history of substance abuse or addiction. Once you start taking an antipsychotic medication, be sure to take it exactly as prescribed.

Antipsychotics are very powerful drugs that have helped thousands of people function well in spite of serious mental illness. That being said, they don’t work for everyone and they are not a cure for schizophrenia or any other psychiatric disorder. The potential benefits and risks must always be considered before starting an antipsychotic, as the potential side effects can be challenging.

Sources:

  1. http://www.nimh.nih.gov/trials/practical/catie/phase1results.shtml
  2. http://ajp.psychiatryonline.org/article.aspx?articleid=176853
  3. http://www.ncbi.nlm.nih.gov/pubmed/18794207
  4. http://www.sciencedaily.com/releases/2012/09/120910111700.htm

 
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