Off-Label Use of Atypical Antipsychotics Minimally Effective

Atypical antipsychotics are effective in only a few of the many off-label conditions for which they are currently used, according to a meta-analysis in the Sept. 28 issue of JAMA.

In particular, there is no good evidence to support the use of atypical antipsychotics for substance abuse disorder, eating disorders, or insomnia. And the evidence for using them for posttraumatic stress disorder and personality disorders is characterized as "mixed," said Dr. Alicia Ruelaz Maher of Rand Health, Southern California Evidence-Based Practice Center, Santa Monica, and her colleagues.

Atypical antipsychotics are approved for use in schizophrenia, bipolar disorder, and, for select agents, depression. But their use has rapidly increased in recent years, and it is estimated that their off-label use doubled between 1995 and 2008.

Dr. Maher and her colleagues reviewed 2,066 articles published through May 2011 on the off-label use of aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. For their meta-analysis, Dr. Maher and her colleagues included 162 efficacy trials and 231 trials or large observational studies that addressed adverse events (JAMA 2011;306:1359-69).

Among their findings were the following:

• "First, aripiprazole, olanzapine, and risperidone were associated with small but statistically significant benefits for the treatment of behavioral symptoms in dementia." These drugs improved psychosis, agitation, and symptoms such as hallucinations, suspiciousness, dysphoria, anxiety, aggression, disinhibition, and apathy, though they did so only to a degree "considered to be the minimum clinically observable change."

• In three large and very recent trials not included in previous meta-analyses, quetiapine showed significant benefits for generalized anxiety disorder. However, "we classified the strength of evidence for this outcome as ‘moderate,’ based on the inconsistency of results and because all [the trials] were funded by manufacturers."

• Risperidone was associated with significant improvement in OCD. But that finding was tempered by the fact there may have been publication bias affecting the pooled results.

• "The strength of evidence has decreased from moderate to low for [use of] quetiapine in patients with OCD."

• New evidence indicates that atypical antipsychotics are ineffective for eating disorders and substance abuse disorder.

• The level of evidence is mixed regarding personality disorders, and is moderate for an association of risperidone with improving PTSD."

Dr. Maher and her colleagues cautioned that most of the studies they reviewed – for example, 27 of the 38 trials of dementia and 12 of the 14 trials of anxiety – were sponsored by drug manufacturers. And they found no studies at all on the off-label use of three newer atypical antipsychotic drugs: asenapine, iloperidone, and paliperidone.

In addition, studies published after June 1, 2011, including a large randomized, control trial of risperidone for patients with military-related PTSD and symptoms resistant to selective serotonin reuptake inhibitors, were not included in the current review.

Still, evidence found in the meta-analysis should provide guidance to clinicians who are considering off-label prescribing of atypical antipsychotics, the investigators wrote.

This study was supported by the Agency for Healthcare Research and Quality, with some support from the Department of Veterans Affairs. One of Dr. Maher’s colleagues reported ties to Eli Lilly.

Atypical antipsychotics are effective in only a few of the many off-label conditions for which they are currently used, according to a meta-analysis in the Sept. 28 issue of JAMA.

In particular, there is no good evidence to support the use of atypical antipsychotics for substance abuse disorder, eating disorders, or insomnia. And the evidence for using them for posttraumatic stress disorder and personality disorders is characterized as "mixed," said Dr. Alicia Ruelaz Maher of Rand Health, Southern California Evidence-Based Practice Center, Santa Monica, and her colleagues.

Atypical antipsychotics are approved for use in schizophrenia, bipolar disorder, and, for select agents, depression. But their use has rapidly increased in recent years, and it is estimated that their off-label use doubled between 1995 and 2008.

Dr. Maher and her colleagues reviewed 2,066 articles published through May 2011 on the off-label use of aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. For their meta-analysis, Dr. Maher and her colleagues included 162 efficacy trials and 231 trials or large observational studies that addressed adverse events (JAMA 2011;306:1359-69).

Among their findings were the following:

• "First, aripiprazole, olanzapine, and risperidone were associated with small but statistically significant benefits for the treatment of behavioral symptoms in dementia." These drugs improved psychosis, agitation, and symptoms such as hallucinations, suspiciousness, dysphoria, anxiety, aggression, disinhibition, and apathy, though they did so only to a degree "considered to be the minimum clinically observable change."

• In three large and very recent trials not included in previous meta-analyses, quetiapine showed significant benefits for generalized anxiety disorder. However, "we classified the strength of evidence for this outcome as ‘moderate,’ based on the inconsistency of results and because all [the trials] were funded by manufacturers."

• Risperidone was associated with significant improvement in OCD. But that finding was tempered by the fact there may have been publication bias affecting the pooled results.

• "The strength of evidence has decreased from moderate to low for [use of] quetiapine in patients with OCD."

• New evidence indicates that atypical antipsychotics are ineffective for eating disorders and substance abuse disorder.

• The level of evidence is mixed regarding personality disorders, and is moderate for an association of risperidone with improving PTSD."

Dr. Maher and her colleagues cautioned that most of the studies they reviewed – for example, 27 of the 38 trials of dementia and 12 of the 14 trials of anxiety – were sponsored by drug manufacturers. And they found no studies at all on the off-label use of three newer atypical antipsychotic drugs: asenapine, iloperidone, and paliperidone.

In addition, studies published after June 1, 2011, including a large randomized, control trial of risperidone for patients with military-related PTSD and symptoms resistant to selective serotonin reuptake inhibitors, were not included in the current review.

Still, evidence found in the meta-analysis should provide guidance to clinicians who are considering off-label prescribing of atypical antipsychotics, the investigators wrote.

This study was supported by the Agency for Healthcare Research and Quality, with some support from the Department of Veterans Affairs. One of Dr. Maher’s colleagues reported ties to Eli Lilly.

Atypical antipsychotics are effective in only a few of the many off-label conditions for which they are currently used, according to a meta-analysis in the Sept. 28 issue of JAMA.

In particular, there is no good evidence to support the use of atypical antipsychotics for substance abuse disorder, eating disorders, or insomnia. And the evidence for using them for posttraumatic stress disorder and personality disorders is characterized as "mixed," said Dr. Alicia Ruelaz Maher of Rand Health, Southern California Evidence-Based Practice Center, Santa Monica, and her colleagues.

Atypical antipsychotics are approved for use in schizophrenia, bipolar disorder, and, for select agents, depression. But their use has rapidly increased in recent years, and it is estimated that their off-label use doubled between 1995 and 2008.

Dr. Maher and her colleagues reviewed 2,066 articles published through May 2011 on the off-label use of aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. For their meta-analysis, Dr. Maher and her colleagues included 162 efficacy trials and 231 trials or large observational studies that addressed adverse events (JAMA 2011;306:1359-69).

Among their findings were the following:

• "First, aripiprazole, olanzapine, and risperidone were associated with small but statistically significant benefits for the treatment of behavioral symptoms in dementia." These drugs improved psychosis, agitation, and symptoms such as hallucinations, suspiciousness, dysphoria, anxiety, aggression, disinhibition, and apathy, though they did so only to a degree "considered to be the minimum clinically observable change."

• In three large and very recent trials not included in previous meta-analyses, quetiapine showed significant benefits for generalized anxiety disorder. However, "we classified the strength of evidence for this outcome as ‘moderate,’ based on the inconsistency of results and because all [the trials] were funded by manufacturers."

• Risperidone was associated with significant improvement in OCD. But that finding was tempered by the fact there may have been publication bias affecting the pooled results.

• "The strength of evidence has decreased from moderate to low for [use of] quetiapine in patients with OCD."

• New evidence indicates that atypical antipsychotics are ineffective for eating disorders and substance abuse disorder.

• The level of evidence is mixed regarding personality disorders, and is moderate for an association of risperidone with improving PTSD."

Dr. Maher and her colleagues cautioned that most of the studies they reviewed – for example, 27 of the 38 trials of dementia and 12 of the 14 trials of anxiety – were sponsored by drug manufacturers. And they found no studies at all on the off-label use of three newer atypical antipsychotic drugs: asenapine, iloperidone, and paliperidone.

In addition, studies published after June 1, 2011, including a large randomized, control trial of risperidone for patients with military-related PTSD and symptoms resistant to selective serotonin reuptake inhibitors, were not included in the current review.

Still, evidence found in the meta-analysis should provide guidance to clinicians who are considering off-label prescribing of atypical antipsychotics, the investigators wrote.

This study was supported by the Agency for Healthcare Research and Quality, with some support from the Department of Veterans Affairs. One of Dr. Maher’s colleagues reported ties to Eli Lilly.