NPS. Antipsychotics’ efficacy in controlling dementia-related agitation, aggression, and psychosis has consistently shown a modest but statistically significant benefit. A Cochrane review found evidence that the use of risperidone and olanzapine resulted in improvements in agitation scale scores; risperidone was linked to improved scores on a psychosis scale, as well.10 A second meta-analysis showed small but statistically significant improvements in NPS with risperidone, olanzapine, and aripiprazole.8 Another study showed that nearly half (48%) of patients who had a positive response to risperidone relapsed when they stopped taking the drug.11
A rapidly aging population is expected to further increase the need for pharmacologic interventions to control NPS. Yet safety concerns about the use of antipsychotics in the elderly (more on this in a bit) call this practice into question.
Chronic pain. A 2008 Cochrane review analyzed the efficacy of antipsychotics for acute and chronic pain, pooling results of 11 studies of the treatment of conditions such as postherpetic neuralgia, tension headache, acute myocardial infarction (MI), and terminal cancer. Results from the pooled trials were described as mixed, although an overall statistically significant decrease in pain intensity was found.12
Polypharmacy. The simultaneous use of 2 or more antipsychotic agents is also increasingly prevalent,13 with levels exceeding 50% in one study of patients with schizophrenia.14 Because there is little data on the safety and efficacy of antipsychotic polypharmacy, this off-label approach should be considered only as a last resort.15
Off-label treatment of psychiatric conditions
GAD. In comparative effectiveness trials, quetiapine was found to be equal to both paroxetine and escitalopram for the treatment of GAD, with a favorable effect on symptoms 8 weeks after its initiation.8 Trials of other antipsychotics for the treatment of GAD have not demonstrated clear efficacy. Trifluoperazine is approved for GAD, as a short-term treatment.
MDD. Antipsychotics have been shown to be beneficial in the treatment of MDD, although only quetiapine and aripiprazole are approved (and only as adjunctive treatment). Evidence supports the use of both agents, as well as risperidone, as augmentation to selective serotonin reuptake inhibitors (SSRIs), and in pooled results from 5 placebo-controlled trials, quetiapine was found to be effective as monotherapy for MDD.9
Obsessive-compulsive disorder (OCD). Compared with placebo, risperidone showed a 4-fold increase in the likelihood of a favorable response (number needed to treat [NNT]=4) in patients with OCD,8 but the drug remains off-label for this purpose.
Posttraumatic stress disorder (PTSD). A meta-analysis of 7 studies demonstrated risperidone’s efficacy in the treatment of combat-related PTSD.9 In a large Veterans Administration study of patients with combat-related PTSD resistant to treatment with SSRIs, however, risperidone showed no benefit after 6 months of therapy.16 Antipsychotics have not been found beneficial for substance abuse, eating disorders, or insomnia.9
Identifying risk factos, monitoring for adverse effects
While FGAs carry an increased risk of EPS, SGAs increase the risk of obesity, hyperlipidemia, hypertension, and diabetes mellitus. The average life expectancy of patients with schizophrenia is 2 to 3 decades lower than that of age-matched controls,17 a finding largely attributed to the increased rate of cardiovascular disease. While this can be partly explained by differences in lifestyle and access to care, the metabolic effects of SGAs are a likely contributing factor.
Because of the adverse effects of FGAs and SGAs, the American Diabetes Association and American Psychiatric Association jointly issued guidelines addressing both the type and optimal frequency of monitoring for patients on antipsychotics (TABLE 2).18,19 Following them is critical, as both the initiation of an antipsychotic agent and any change in regimen can lead to the development—or exacerbation—of a number of diseases.
Before initiating antipsychotic therapy—or the first time you see a patient like Mr. B, whose care you will be monitoring—a thorough assessment of risk factors is needed. Foremost among them are overweight or obesity, insulin resistance or diabetes, a history of heart disease, and EPS.
In some cases, preexisting conditions and the potential harm of a specific drug must be weighed in determining which antipsychotic to prescribe. When adverse effects develop after drug therapy has been initiated, decisions about further actions should be based on both the degree of the unfavorable response and the availability of other treatments—and made, as appropriate, in consultation with the specialist who prescribed the drug.
CASE 1 › You tell Mr. B that metabolic side effects like weight gain, impaired glucose tolerance, and increased low-density lipoprotein cholesterol are common with SGAs like the one he is taking, and that you will monitor his fasting glucose levels to evaluate his risk for developing diabetes—starting with this visit. (Olanzapine, the drug he is taking, is 4 times more likely than an FGA to lead to diabetes.18)