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Antipsychotic medications (APMs) are a mainstay for managing major psychiatric illnesses such as schizophrenia and bipolar disorder, and can do enormous good for patients with these problems.
However, in recent years newer agents, the atypical APMs, have been promoted widely for use in very different conditions, for which their efficacy is often not well established. These include the management of patients with Alzheimer’s disease, and as a core treatment for depression. Besides their limited efficacy, these drugs can cause weight gain, raise blood sugar, prolong the Q-T interval, and increase cholesterol levels. They also significantly increase the risk of death in older patients.
Antipsychotic medications and depression
Given their risks, these drugs should not be used for most patients to manage depression resistant to conventional antidepressant therapy.
First, make sure the patient actually has depression, based on DSM-IV criteria:
• Aripiprazole, quetiapine, and olanzapine (in combination with fluoxetine) are FDA approved for depression therapy augmentation, but should be used when other augmentation strategies have failed.
——There is robust evidence for mild efficacy for these SGAs (number needed to treat for improvement of 9) but the side effects, especially weight gain, are much more significant than with the other recommended augmentation strategies.
• APMs are not FDA approved for monotherapy in depression.
In patients with psychotic depression (that is, with disruptive or dangerous delusions or hallucinations), an antipsychotic can be combined with an antidepressant.
The risks of APMs often outweigh their benefits, especially when used for non-severe problems. In a randomized trial, only 20-30% of patients had improvement in symptoms when treated with an antipsychotic drug for dementia symptoms.
All APMs carry a black box warning about the risk of death.
It has been estimated that for every 100 patients with dementia treated with an antipsychotic medication, only 9 to 25 patients will benefit and 1 will die.
Despite their risks, antipsychotic medications are often used loosely in patients with dementia to manage a wide variety of behaviors, including wandering, socially inappropriate interactions, and difficulty sleeping. Many nursing home patients with dementia are prescribed APMs without a clear indication.
If these drugs must be used to manage agitation or aggressive behavior:
• identify the target behaviors being treated
• start at a low dose
• reassess regularly
—— to gauge the response of the targeted symptoms
—— to monitor for side effects
• use for the shortest time possible.
Antipsychotic drugs in other conditions
These drugs may be of use in some patients with post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), but usually after other therapies (including psychotherapy) have been tried.
Post-traumatic stress disorder:
• For PTSD, first treat any sleep disturbance, then prescribe an SSRI.
• Sertraline and Paroxetine are the only FDA-approved medications for PTSD. Of the two, paroxetine has the better evidence-base, but also more side effects such as weight gain and sexual dysfunction.
• Resort to antipsychotic medications for PTSD patients with psychotic symptoms that persist on SSRIs
Obsessive-compulsive disorder:
• First treat with an SSRI (most OCD patients will need maximum or higher doses); if poor response, try another SSRI.
• Continued symptoms may require an antipsychotic medication (risperidone is the most effective in OCD). Patients whose symptoms are severe enough to require consideration of an APM are likely to need the care of a psychiatrist.
Screening and monitoring are necessary
Whatever the indication, all patients prescribed an APM will require a number of screening tests both at baseline and at regular intervals, to monitor adverse effects.
Cost
All second generation antipsychotics are expensive. Antipsychotics are the 5th most costly medication class in the U.S., with annual spending of >$16 billion. Even with low doses or generics, the monthly cost of all these agents may be unaffordable for many patients.