Pauline Anderson

February 19, 2016

PALM SPRINGS, California — Adding the atypical antipsychotic drug olanzapine to a patient's therapeutic regimen might help ease their refractory pain, a new systematic review suggests.

Although not US Food and Drug Administration (FDA)–approved for pain, and not traditionally considered an analgesic, olanzapine has the strongest evidence for pain control of all the atypical antipsychotics, according to the review.

"The results further strengthened my sense — and the sense of my colleagues in the consultation psychiatry world — that anecdotally, clinically, this medication can be very helpful," said Xavier Jimenez, MD, staff psychiatrist and soon-to-be section head of chronic pain, Center for Neurological Restoration, Cleveland Clinic, Ohio, who carried out the review.

Dr Jimenez presented these results at the American Academy of Pain Medicine (AAPM) 2016 Annual Meeting.

Using PubMed, he searched for all studies examining antipsychotic use for pain. The final analysis included 18 studies, 10 of which included olanzapine. Of the rest, 4 were of quetiapine, 2 of aripiprazole, and 1 each of risperidone and ziprasidone.

Olanzapine's antinociceptive activity might involve an opioid mechanism. "That's been corroborated in rat models and animal studies, and this has been reversed with naloxone, so it's been proven in two kinds of directions," said Dr Jimenez.

Another mechanism by which olanzapine might work to curb pain is by decreasing sympathetic tone, "which we know exacerbates pain," said Dr Jimenez.

One of the advantages of olanzapine compared with a drug such as risperidone is that it has fewer adverse effects, "Olanzapine has some side effects, for example sedation, but they're easily reversed whereas with risperidone, you have some motor problems, even tremors" with escalating doses, said Dr Jimenez.

The analysis showed that olanzapine has efficacy in fibromyalgia and headache/migraine, although only one study was a randomized controlled trial with level I evidence of efficacy. All the other antipsychotics, including quetiapine, failed to demonstrate efficacy in various pain syndromes and/or lacked robust study designs.

Many clinicians already know that olanzapine works in some pain patients. Like Dr Jimenez, they might have observed patients who had pain that was unresponsive to opiates or other traditional analgesics and who responded well once olanzapine was added.

Pain Perception

Patients taking an antipsychotic probably have a lessened perception of pain, he said. "I think anecdotally that we can say confidently, at least in the field of psychiatry, that people's somatic sensations, including pain, are lessened or ameliorated if they're taking an antipsychotic."

While he has seen cancer patients respond "very nicely" to an olanzapine addition, "and these patients had zero history of depression or psychosis," Dr Jimenez said those with psychopathology likely respond best.

"I suspect that if we were to test this, there would be a subgroup of patients with central pain syndromes that are likely related to psychopathology — depression, anxiety, et cetera — that are more responsive to this medication."

The ideal future direction would be to do a randomized study that takes a group of patients with the same type of pain who are taking analgesics and give some of them a placebo and others, olanzapine.

"You could also do subgroup analysis to see if those with comorbid depression, anxiety, or psychosis do much better or the same."

Asked to comment on these findings, pain management specialist Lynn Webster, MD, vice president, scientific affairs, PRA Health Sciences, Raleigh, North Carolina, said "it makes sense" that antipsychotics can be therapeutic.

"They can be beneficial in relieving chronic pain because chronic pain has a significant cognitive contribution towards the experience of pain," explained Dr Webster. "If we minimize the contribution to the pain perception by improving the cognition, the anxiety component, then we're going to reduce the amount of pain experienced."

Although he doesn't now treat pain patients, when he did, he often prescribed an antipsychotic — in many cases for sleep — and found it "very effective."

Dr Webster noted that other psychiatric drugs are useful when it comes to treating pain. For example, he said, "amitriptyline is not meant for pain but is the most effective drug for neuropathic pain."

American Academy of Pain Medicine (AAPM) 2016 Annual Meeting. Poster 202. Presented February 19, 2016.

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