Antipsychotic Drugs

Types and differences of antipsychotics

Antipsychotics have been in use since the 1950s. The earlier (conventional) types of antipsychotics were effective in treating positive symptoms (abnormal thoughts and perceptions, such as delusions, hallucinations or disordered thinking). However, they had the potential to produce many unpleasant side effects, such as muscle stiffness, tremors and tardive dyskinesia (involuntary movements that may include tongue thrusting, repetitive chewing, jaw swinging and/or facial grimacing).

In the 1990s a new type of antipsychotics, atypical antipsychotics, was introduced. These antipsychotics are effective at treating both positive and negative symptoms (absence of thoughts and behaviors that would otherwise be expected). Examples of negative symptoms include lack of emotion, speech, social interaction and movement.

The first type of atypical antipsychotic introduced in the United States in 1990 was clozapine, which proved to be effective in treating disorders that did not respond to conventional antipsychotics. The risk of tardive dyskinesia was lower with clozapine than with earlier types of antipsychotic medications.

However, the use of clozapine results in the risk of a side effect called agranulocytosis (blood disorder that causes loss of white blood cells that fight infection). Therefore, patients taking clozapine must have a blood test performed every one to two weeks, which may be costly and inconvenient.

Several other atypical antipsychotics were introduced after clozapine, including risperidone, olanzapine, quetiapine and ziprasidone. There are side effects associated with each of these, but they are generally better tolerated than the conventional types of antipsychotics.

The following is a list of the different types of antipsychotic medications:

Pimozide (whose brand name is Orap) is an antipsychotic used to treat Tourette’s syndrome (an abnormal condition characterized by verbal outbursts, tics and other movements, such as eye blinks or facial twitches, which cannot be controlled).

In December of 2006, the U.S. Food & Drug Administration approved the use of paliperidone (Inviga) extended-release tablets to treat patients with schizophrenia. The drug is a new molecular entity, which contains a substance that has never been marketed before in the United States.

Conditions treated with antipsychotic medications

Antipsychotics are prescribed to treat a variety of mental health conditions, including:

• Schizophrenia. Thought disorder that makes it difficult for patients to distinguish between real and unreal experiences.
• Schizoaffective disorder. A condition in which a person exhibits signs of both schizophrenia and a mood disorder.
• Mood disorders. Antipsychotics may be used to treat psychotic symptoms experienced by patients with mood disorders, such as bipolar disorder.
• Delusional disorders. A condition characterized by at least one false belief that lasts for one month or longer.
• Schizotypal personality disorder. A condition marked by a pattern of problems in interpersonal relationships and disturbances in thought patterns, appearance and behavior. Patients exhibit odd beliefs and behaviors, but are not disconnected from reality.
• Borderline personality disorder. A condition characterized by impulsivity and instability in mood, self-image and personal relationships. This disorder is diagnosed more often in females than in males, and may be caused by both psychological and biological factors.
• Obsessive-compulsive disorder (OCD). Anxiety disorder marked by obsessions (recurrent and intrusive thoughts, feelings, ideas or sensations) and/or compulsions (conscious, recurrent patterns of behavior(s) a person feels driven to perform). Antipsychotics may be prescribed in severe cases of OCD.
• Tourette’s syndrome. An abnormal condition characterized by verbal outbursts, tics and other movements, such as eye blinks or facial twitches, that cannot be controlled. Certain types of antipsychotic drugs are used to treat this condition.
• Autism-related irritability. One antipsychotic drug (risperidone) was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of irritability associated with autism in children and adolescents.

Antipsychotics may also be prescribed to treat psychosis that results from some medications (e.g., stimulants), recreational drugs or conditions.

In addition, antipsychotic medications are increasingly being prescribed in an “off-label” manner by physicians for the psychosis associated with conditions such as dementia and depression. Off-label prescription means that a drug can be used for a purpose other than which it was originally intended, and that was not approved by the FDA.

Potential side effects of antipsychotics

There are many possible side effects with antipsychotics, which vary according to the specific drug. Some of the most common include:

• Extrapyramidal (disruption in the nerves and muscles controlling movement and coordination) side effects, including:
  • Parkinsonian side effects. Symptoms that resemble Parkinson’s disease (progressive disorder of the nervous system) such as slowed movements, decreased facial expression, resting tremor and a shuffling gait.
  • Dystonic symptoms. These involve sustained muscle spasms, usually of the neck or shoulders, which can be painful and frightening.
  • Akathisia. Intense feeling of restlessness. This can sometimes be confused with psychotic agitation.
• Anticholinergic (affecting the autonomic nervous system, which controls involuntary body functions such as circulation and intestinal functions) side effects. These symptoms may be very mild or severe, depending on the medication, and may include:
  • Dry mucous membranes (especially mouth and eyes).
  • Blurred vision (especially when viewing items at close range).
  • Intestinal slowing (constipation).
  • Difficulty urinating.
  • Sedation.
  • Sexual dysfunction.
  • Rapid heart rate (tachycardia).
• Antiadrenergic (blocking or reducing the effects of adrenaline in the body) side effects. These may include orthostatic hypotension. When a person stands, blood pressure drops dramatically. This can lead to transient lightheadedness and a potential fall and injury.
• Tardive dyskinesia. Involuntary movements that may include tongue thrusting, repetitive chewing, jaw swinging and/or facial grimacing. This is more common with conventional antipsychotics and usually occurs only if the medication is taken for extended periods of time on an ongoing basis.

Other side effects of antipsychotic medications may include weight gain, a rise in blood sugar levels (occurs primarily with olanzapine use), seizures, hyperthermia (excessive body heat) and agranulocytosis (a blood disorder that causes a drop in white blood cells, which help fight infection; associated with clozapine use).

Research also suggests that certain antipsychotic medications (e.g., risperidone) may ibe associated with an ncreased risk of developing benign (noncancerous) pituitary tumors. In very rare instances, patients may develop neuroleptic malignant syndrome (NMS). NMS is characterized by fever, confusion and rigidity. If not treated promptly, it can lead to coma and death.

Patients who experience certain side effects should contact their physician immediately because medication changes may be necessary. These side effects include:

• Confusion
• Falls
• Inability to urinate
• Prolonged or severe constipation
• Rash
• High fever (this may be due to agranulocytosis or NMS)
• Involuntary movements
• Jaundice (yellowing of the skin, including eyes)
• Severe sedation
• Severe restlessness
• Muscle spasms

Patients sometimes use an antipsychotic side effects checklist (ASC) to monitor side effects. ASC is a screening tool developed by mental health professionals to help patients document common side effects associated with antipsychotic medications. Symptoms commonly tracked include:

• Loss of energy and drive
• Muscles that tremble or shake
• Weight change
• Dry mouth
• Insomnia

Many side effects can be managed so they are less troublesome to patients. Some side effects can be managed by altering the dosage or switching to a different type of antipsychotic medication. Others can be managed by taking an additional medication to counteract the side effect.

Drug or other interactions with antipsychotics

Patients should consult their physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications. Of particular concern to individuals taking antipsychotics are:

• Antihypertensive medications. Medications used to treat high blood pressure.
• Anticonvulsants. Medications used primarily to treat seizures. They may also be prescribed as mood stabilizers to treat depression.
• Medications that affect the central nervous system. Antipsychotics can alter the effect of medications and the effects of the antipsychotic drugs can, in turn, be altered by the use of other medications. Antipsychotics and these other medications can also have similar side-effects, most notably sedation. Examples of these medications include :
  • Antihistamines. Medications used to treat allergic reactions or allergies.
  • Antidepressants. Medications used primarily to prevent or treat depression and some cases of anxiety.
  • Barbiturates. Depressant drugs that produce relaxation and sleep.
  • Narcotic pain relievers. Drugs that relieve severe pain.
  • Benzodiazepines. Medications used to produce sedation, induce sleep, relieve anxiety and muscle spasms and prevent seizures.

In addition, substances such as alcohol and nicotine can reduce the effectiveness of antipsychotics.

Pregnancy use issues with Antipsychotic medications

If possible, antipsychotic medications should be avoided during pregnancy and while breastfeeding. Use of antipsychotics during pregnancy has been linked to birth defects.

Child use issues

Antipsychotic drugs are sometimes prescribed to treat psychiatric disorders in children and adolescents. They can be helpful in controlling psychotic symptoms and may also be prescribed to treat the symptoms of Tourette’s syndrome, such as muscle twitches. They are occasionally prescribed to treat severe anxiety and may help reduce very aggressive behavior in youngsters.

The U.S. Food and Drug Administration (FDA) has only approved the use of three antipsychotic medications in children under 18 years of age. To date, none of the newer atypical antipsychotics have been approved by the FDA for use in this population. However, they are increasingly being prescribed in an “off-label” manner by physicians. Off-label prescription means that a drug can be used for a purpose other than which it was originally intended, and that was not approved by the FDA.

Because these medications are known to cause a host of mild to severe side effects, physicians typically prescribe them for children only when the potential benefits of the drugs outweigh the risks.

Parents and guardians should obtain complete information about antipsychotic medications when prescribed. Children and adolescents should be included in discussions about medications. Side effects, which may range from mild to severe, should be closely monitored.

Elderly use issues

The U.S. Food and Drug Administration (FDA) has determined that treatment of behavioral disorders in elderly patients with dementia with newer (atypical) antipsychotic medications is associated with increased mortality. Several studies show numerical increases in mortality in seniors treated with atypical antipsychotics compared to those treated with placebos. However, it is important to note that a causal relationship between the medications and mortality has not been definitively established.

Currently, none of the atypical antipsychotic medications are FDA-approved for the treatment of behavioral disorders in patients with dementia. However, they are being prescribed in an “off-label” manner by physicians. Off-label prescription means that a drug can be used for a purpose other than which it was originally intended, and that was not approved by the FDA. Physicians typically prescribe atypical antipsychotics for elderly patients with dementia only when the potential benefits of the drugs outweigh the risks.