November 22, 2004

Mirtazapine to help with akathisia?

The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study.

Zoccali, Rocco; Muscatello, Maria Rosaria; Cedro, Clemente; Neri, Pietro; Torre, Diletta La; Spina, Edoardo; Rosa, Antonio Enrico Di; Meduri, Mario.

International Clinical Psychopharmacology. 19(2):71-76, March 2004.

Negative symptoms of schizophrenia (blunted affect, poverty of thought content and speech, avolition or apathy and social withdrawal) continue to be a substantial problem that currently have no consistent treatments. While there is some data for various behavioral treatments as well as some limited success with various medication interventions. This is another small study that uses an antidepressant to help treat negative symptoms. Antidepressants are compelling drugs for this purpose because the features that are most prominent in negative symptoms of schizophrenia also resemble prominent symptoms of depression. However, the use of older antidepressants such as the class called “tricyclics” had too many side effects and interactions with antipsychotic medications to be safe or effective. Other classes of antidepressants such as MAO-I (monoamine oxidase inhibitors) also had severe interactions with medications and foods and are rarely used in general but are never used with schizophrenia. Lastly, other trials have been done with stimulants but those medications are worrisome because they can induce psychosis in people who have never had it and therefore are especially dangerous in those that are prone for psychotic experiences. Some trials have been done with the SSRI (selective serotonin reuptake inhibitors) which are the most common antidepressants, but the data has not been convincing. This study looks at mirtazapine (Remeron® in the US) which is unique in its action and targets several very specific receptors in the brain and different neurotransmitters (the chemicals that signal brain cells to do different activities.)

This study utilized a well designed protocol to evaluate the effect of mirtazapine on negative symptoms. It was a double blind (neither the patient nor the raters knew the treatments the patients were on), randomized (anybody could have gotten placebo or active drug), and was controlled with placebo (so that it could be compared for possible placebo effect). At the beginning of the study, all the patients were evaluated and found to have the same average amount of symptoms between the groups. Both groups were generally free of positive symptoms (delusions, hallucinations, paranoia, etc.) All the patients were being treated with clozapine for their schizophrenia indicating that these were chronic patients as clozapine is generally reserved for people who have failed other treatments.

The authors found that overall patients with the mirtazapine did somewhat better than those who received the placebo. The results were statistically significant and borderline clinically significant (meaning that the groups were different, but the difference was minor in the overall treatment of the patients.) The authors postulated that maybe because mirtazapine and clozapine work in similar ways that they may be beneficial when used together but that was just a theory.

Overall, more research will need to be conducted on negative symptoms. Perhaps this might be another medication you might ask your doctor about if negative symptoms are a prominent problem. However, mirtazapine is not without its side effects. It can be very sedating at times and also is associated with weight gain. The sedation effects often go away with a higher dose, but the weight gain can be a persistent problem which can be especially troublesome given the weight gain issues of antipsychotics, particularly clozapine, quetiapine and olanzapine.

Click here to access the article on PubMed

Author: Jacob Ballon


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