Schizophrenia

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Treatment

Schizophrenia is seldom curable; it requires chronic treatment to reduce suffering and to restore daily function. Because schizophrenia is a biological disease, it does not respond to changes in environment or to support therapy alone. Medication that influences brain activity is the cornerstone of treatment, and behavioral management therapy is used to support medication in most cases.

Research has shown a 90% chance for recurrence in untreated schizophrenia within a year of the first episode. The chance for relapse drops to about 30% with treatment.

Hospitalization is used primarily to achieve the following goals, often at the onset of schizophrenia:

• To evaluate and diagnose a person
• To stabilize dangerous behavior
• To begin medication
• To monitor and ensure self-care and safety
• To familiarize a person with treatment

Generally, hospitalization is brief and used clinically to assess a person's situation or management skills, as the maintenance of normal routine and function is the long-term goal of treatment. Of course, a severe episode, especially where the person's safety is jeopardized, may require extended hospitalization.

Medications
Medications used to treat schizophrenia include the following:

• Traditional antipsychotics (neuroleptic drugs)
• Atypical antipsychotics

Antipsychotic medications are the main drugs used to treat schizophrenia. Their introduction in the 1950s marked a breakthrough in the treatment of psychosis, the results of which were apparent in the reduction of hospitalized patients. It is estimated that 300,000,000 people worldwide have been treated with them, more than the current population of the United States.

Antipsychotics reduce delusions, hallucinations, and improve overall functioning. Generally, they are divided into two subgroups, traditional and atypical, which are used according to a person's response to treatment and tolerance of side effects.

What Do They Do?
Traditional antipsychotics include chlorpromazine (Thorazine®) and haloperidol (Haldol®). These drugs primarily block the effects of the dopamine 2 (D2) receptor, which are thought to be hyperactive in the brains of people with schizophrenia. This is supported by the fact that dopamine suppression seems to improve schizophrenic symptoms. Excessive numbers of dopamine receptors have been found in the brains of some people with untreated schizophrenia.

Dopamine is a neurotransmitter important to the combined function of the limbic system and frontal regions of the brain. Among other functions, it assists in motor behavior, pleasure, and thought and memory processes.

Thorazine® is considered a low-potency drug. It frequently causes the following side effects associated with suppression of the neurotransmitter acetylcholine:

• Constipation
• Dizziness
• Dry mouth
• Sedation
• Urinary retention

Acetylcholine is important in the brain in counterbalancing dopamine levels. Neuromuscular and neurological side effects are less common with low-potency antipsychotics, but may occur in some people. These include the following:

• Acute dystonia (brief involuntary muscle spasm and twisting)
• Akathisia (severe restlessness that leads to agitation and anxiety)
• Mask-like expression
• Pseudo-Parkinson's disease (muscle tremor)
• Shuffling, unstable gait

Haldol® and Prolixin® are high-potency drugs used in treating schizophrenia. High-potency drugs are more likely than low-potency drugs to cause neuromuscular side effects. Their other versions, Haldol Deconoate® and Prolixin Deconoate®, are used to ensure dosage compliance in people who may not consistently take oral medication. They are given as a deep intramuscular injection—Haldol Deconoate® once a month and Prolixin Deconoate® every two weeks.

Other Side Effects and Limitations
In addition to other general side effects, there are limitations to all antipsychotic medications. For example, while they are useful in reducing the positive symptoms of schizophrenia, like delusions, hallucinations, and disorganized speech, they are typically not as effective in controlling negative symptoms, like lack of emotion and loss of will.

Generally, people who take traditional anitpsychotics always feel like they are on medication. They can seem confused or lost, which can adversely affect their judgment and physical performance. For these reasons, they frequently do not take their medication, so compliance is a concern.

Tardive dyskinesia (TD) is an involuntary movement disorder that causes slow, nonrhythmic muscle movements, intense aching, and painful spasms. It may appear late in the treatment of schizophrenia as a result of long-term use of antipsychotic medication, and can affect specific muscles or general muscle groups, from the tongue to the muscles of the arms and legs. Every year, another 4% of people taking traditional antipsychotic drugs develop TD. There is no known effective treatment for TD, and it may be irreversible.

Perhaps as many as 30% of people are not affected by traditional antipsychotics and may find benefit from treatment with atypical antipsychotics.

Atypical antipsychotics, like clozapine (Clozaril®), are the most recent class of drugs used in schizophrenia treatment. Clozapine's method of action only slightly affects the D2 receptor. It primarily blocks other dopamine receptors and other neurotransmitters, like norepinephrine, histamine, and, especially, serotonin. Atypical antipsychotics have helped more than 50% of people who could not improve with traditional antipsychotics.

There are two main advantages to clozapine. First, it significantly improves negative symptoms as well as positive symptoms; traditional anitpsychotics typically only control positive symptoms. Secondly, it is not associated with TD, probably because TD results when the D2 receptor is affected. For these reasons, clozapine is the benchmark for schizophrenia treatment.

In addition to the side effects common with traditional anitpsychotics, like sedation, dry mouth, and dizziness, clozapine is associated with agranulocytosis, an acute disease characterized by significant loss of white blood cells. It may be especially common in the first two years of treatment. A little more than 1% of people treated with clozapine develop it every year. Therefore, weekly or biweekly blood-level checks are necessary during treatment with clozapine to ensure proper white blood cell levels. This makes it an unpopular drug among patients.

New Atypical Antipsychotics
The search for other drugs that work like clozapine without the harmful side effects has resulted in a new group, also considered atypical antipsychotics. They typically cause fewer side effects than traditional antipsychotics, including a lower risk of TD and agranulocytosis. Like clozapine, they help control negative symptoms, and patients tend to comply with their use.

This new group of drugs includes the following:

• Aripiprazole (Abilify®)
• Risperidone (Risperdal®)
• Olanzapine (Zyprexa®)
• Quetiapine (Seroquel®)
• Ziprasadone (Zeldox®, Geodon®)

These drugs control psychosis by blocking dopamine D2 receptors and the serotonin 5HT2 receptors in the brain. The addition of a serotonin blocker may be what boosts their efficacy.

The following are common side effects for these medications:

• Aripiprazole
  • Headache
  • Nausea
  • Restlessness accompanied with anxiety and agitation (called acathisia or akathisia)
• Risperidone
  • Agitation
  • Anxiety
  • Headache
  • Insomnia
  • Muscle tremor
• Olanzapine
  • Drowsiness
  • Headache
  • Insomnia
  • Nasal congestion
  • Weight gain
• Quetiapine
  • Dizziness and vertigo
  • Drowsiness
  • Headache

Studies have indicated that ziprasadone produces less weight gain and fewer metabolic side effects (e.g., insulin resistance) than other medications. Side effects include excessive sleepiness (somnolence), nausea, dizziness, and upper respiratory infection.

At this time, there are no established risks associated with the use of antipsychotic drugs during pregnancy. Clinical research involving pregnant women is lacking. Women are advised to discuss the benefits and risks with their physician, especially during and after pregnancy, since these drugs are excreted in breast milk.

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