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Simvastatin has no effect on schizophrenia symptoms, cognition

Journal
Schizophrenia Bulletin
Reuters Health - 17/03/2021 - A year of simvastatin treatment had no effect on schizophrenia symptoms or cognition in a double-blind, placebo-controlled trial.

"Although negative findings fail to spark hope like positive studies do, this manuscript does provide important evidence," Dr. Iris Sommer of the University of Groningen, the Netherlands told Reuters Health by email.

"Our rather sobering conclusion, that lowering the increased pro-inflammatory status in schizophrenia spectrum disorders (SSD) is not an effective treatment for total symptom severity or cognition, is in line with recent large-scale studies that could not replicate previous smaller RCTs showing positive effects of anti-inflammatory augmentation," she said. "This is true for minocycline, celecoxib, and very recently aspirin."

The study's second author, Dr. Shiral Gangadin, "has done extensive research into inflammation in the sample from this trial and found no evidence for increased inflammation," she noted. "However, there have been many reports about this. Also, many null findings, but taken together in meta-analysis, there is a net increase in inflammation."

"We hypothesize that metabolic syndrome may be an important factor, as we found increased inflammation only in participants with high BMI," she noted. "Perhaps simvastatin could be a very useful augmentation for the group of obese SSD patients, but this is something we need to test first."

As reported in Schizophrenia Bulletin, trial included 119 SSD patients across the Netherlands, <3 years after their diagnosis. Participants were randomly assigned to simvastatin 40 mg or placebo, stratified for sex and study site. The primary outcomes were symptom severity and cognition at 12 months.

No treatment effect was found for simvastatin versus placebo on total symptom severity at 12 months. Group differences varied over time, with significantly lower symptom severity in the simvastatin group at six months (mean difference, −4.8) and at 24 months follow-up (mean difference, −4.7).

Adherence did not influence the findings. When comparing adherent participants (i.e., those who showed >20% reduction of LDL-cholesterol at all measurements) to non-adherent participants, no significant main or time interaction effects for simvastatin.

Similarly, no effect was found for cognition or secondary outcomes, including depression, symptom subscores, general functioning, metabolic syndrome, and movement disorders.

From a safety standpoint, myalgia was reported by 13 (21%) participants in the simvastatin group and 13 (22%) in the placebo group. Dark-colored urine was reported by four (7%) participants taking simvastatin and seven (12%) on placebo.

Serious adverse events occurred more frequently with placebo (19%) than with simvastatin (6.6%).

The authors conclude, "This study, together with other recent large studies with negative findings, imply that anti-inflammatory augmentation may not be beneficial for symptom severity and cognition in schizophrenia."

Dr. Kirk Harris, a psychiatrist at Rush University Medical Center in Chicago commented in an email to Reuters Health that the findings "aren't surprising, given frequency of negative results in this line of research. The importance of inflammatory markers in SSD remains very poorly understood. The same is true of about neuroprotective effects of medications generally, and for a variety of other disorders."

"We can expect to see more studies for medications with putative anti-inflammatory effects, but so far there are few established benefits," he said.

Dr. Alex Dimitriu founder of Menlo Park Psychiatry and Sleep Medicine in California also commented by email. "There appears to be improvement at six months, which is then lost at 12 months. Also, and perhaps suggestive of a placebo effect, for both adherent and non-adherent."

"While there may still be a relationship between SSD and inflammation, at least per this study it appears that simvastatin, via an ant-inflammatory or cholesterol lowering effect, does not change the course of the illness," he said. "It is worth noting that while there was no benefit to illness severity, the metabolic benefits of statins including lowering cardiovascular morbidity are still impressive."

SOURCE: https://bit.ly/3bVEIzO Schizophrenia Bulletin, online February 20, 2021

By Marilynn Larkin



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