Safely Prescribing Antipsychotic Medications

Risks versus benefits of antipsychotic medications

Posted Feb 05, 2013

Antipsychotic medications are prescribed by physicians for a wide variety of psychiatric disorders. Older antipsychotics include drugs such as chlorpromazine and haloperidol. There are an increasing number of new-generation antipsychotic medications including risperidone, olanzapine, quetiapine, and aripiprazole. Recent studies suggest that there has been a substantial increase in use of antipsychotic medications and highlight concerns about the side effects and risks associated with these drugs.

Antipsychotic medications have been prescribed since the 1950s. Their effects can be dramatic in helping to control psychotic symptoms such as hallucinations (hearing voices, seeing visions) and delusions (holding fixed beliefs that are not true).  Psychotic symptoms can be associated with illnesses such as schizophrenia, bipolar disorder, and a subtype of depression known as psychotic depression.  Psychotic symptoms can also occur in patients with other illnesses including dementias such as Alzheimer’s disease.  Although antipsychotic medications can help ameliorate psychotic symptoms associated with dementias, they work less well than in schizophrenia, bipolar disorder, or psychotic depression.  Importantly, older patients with dementia are at increased risk of serious side effects from such medications, including death.  Short term use of antipsychotics can often help calm psychotic symptoms in patients with Alzheimer’s disease, but the side effects of using them for longer periods of time may result in more harm than benefit.

Doctors are now prescribing antipsychotic medications for various types of anxiety disorders, eating disorders, and personality disorders. Although individual patients may show improvement, there is limited evidence to support the use of these drugs for these conditions.  Hence, the decision to recommend these medicines for such conditions should be considered carefully in light of the significant side effects associated with antipsychotic medications.

Based on their antidepressant effects, some antipsychotics are approved by the FDA for use in depressed patients already taking more typical antidepressant medications. This is an example of an “augmentation” strategy in which a drug (in this case an antipsychotic) is used to enhance the effects of other drugs (in this case an antidepressant medication). A variety of augmentation strategies already exist that utilize non-antipsychotic medications to augment the effectiveness of antidepressants. When a doctor recommends an antipsychotic medication for a patient with a non-psychotic depression, the risks and benefits should be carefully evaluated and compared to the risks and benefits of other augmentation strategies.

As already mentioned, antipsychotic medications can have substantial side effects. Some of these medications are associated with involuntary movement disorders (e.g., parkinsonism, tardive dyskinesia, and dystonias). Some can cause substantial weight gain and can negatively influence blood sugar levels and blood lipid levels. In the elderly, these medications are associated with increased chances of death and stroke. These are powerful drugs that have potentially serious risks. They should not be prescribed casually. In the face of these concerns, it is interesting to see how the use of these medications has changed over time.

A recent paper in the Archives of General Psychiatry by Mark Olfson and colleagues reported a marked increase in the number of visits to a doctor’s office during which an antipsychotic medication was prescribed. In children, the rate increased an astounding 7-fold between the mid 1990s and 2005. In adolescents, the increase was over 4-fold. In adults, the number of visits during which an antipsychotic medication was prescribed almost doubled. Associated with this increase has been the increasing use of these medications for illnesses for which there are limited data about their effectiveness.

Another important paper was recently published in the Journal of Clinical Psychiatry by Dilip Jeste, the current president of the American Psychiatric Association, and colleagues. These authors noted that 62% of all antipsychotic prescriptions involve people over 40. These researchers enrolled patients in this age group who were either already taking an antipsychotic medication or who were about to be prescribed such a medicine. The patients were being treated for a variety of illnesses, including schizophrenia, schizoaffective disorder, psychotic depression, post-traumatic stress disorder, and dementia. The patients (with their doctors’ consent) agreed to being assigned to one of the new generation medications (risperidone, olanzapine, aripiprazole, and quetiapine). The researchers found no improvement in psychotic symptoms over two years of follow-up. (Of course, it is possible that deterioration might have occurred without the medication.) About 80% of the patients discontinued their assigned medication, 50% within the first 6 months. Half dropped the original medication due to side effects and another 27% due to lack of effect. Many patients were then switched to another antipsychotic. 

Disturbingly, over a third of patients who didn’t have a metabolic syndrome when they entered the study developed such a syndrome over the first year of taking the antipsychotic. This is in addition to the 50% who entered the study with an existing metabolic syndrome. What is a metabolic syndrome? It is combination of risk factors that predispose a person to developing heart disease, diabetes, and stroke. These risk factors include high blood pressure, large waist circumference, increased fasting blood sugars, and abnormal cholesterol levels. In addition, about 24% of the patients in this study developed other serious side effects. Some had strokes or died. Although it is not known whether these adverse outcomes directly resulted from the antipsychotic medication, other studies in elderly patients with dementia have found that rates of stroke and death increased substantially in persons taking these medications.

Jeste and colleagues indicated that antipsychotics may be useful in treating middle-aged and older people, but, whenever possible, low doses should be used for as short a period of time as is clinically indicated and the patients should be monitored carefully for side effects.

In conclusion, data suggest that the use of antipsychotic medications has increased dramatically. In addition to being used for illnesses that have been shown to respond to these drugs, they are increasingly being prescribed for illnesses for which there is limited evidence supporting their use. The risks of antipsychotics are substantial, especially in older patients with compromised brain function. In this population, serious side effects can occur, including the possibility of strokes and increased rates of death.

We want to emphasize that antipsychotics are powerful medications that can be lifesaving when used for appropriate reasons. All medications have risks and benefits. Doctors should help patients and their families determine if the potential benefits of a particular drug outweigh the potential risks.

This column was co-written by Eugene Rubin MD, PhD and Charles Zorumski MD