Statins
Cholesterol-lowering medicines that also dampen inflammation. A Dutch trial in early schizophrenia found no overall benefit for symptoms.
At a glance
- Type
- Medicine: HMG-CoA reductase inhibitors
- Used for
- Tested as add-ons for symptoms of schizophrenia
- Status
- Experimental
- Evidence
- EarlyHow evidence is rated
- Administration
- Tablets, once a day, added to an antipsychotic. In the Dutch trial, for a year
- Common side effects
- Muscle pain, about as often as on placebo in the Dutch trial
- In Europe
- Tested in the Netherlands
Clinical summaryFor health professionals
- Sommer 2021 (Netherlands): 119 patients within 3 years of diagnosis; simvastatin 40 mg or placebo for 12 months. No effect on PANSS or cognition at 12 months; PANSS about 5 points lower at 6 and 24 months.
- Simvastatin had no effect in a four-arm trial of 232 patients with naproxen (Weiser 2023). Meta-analyses disagree: a small benefit across 9 trials with 533 patients (Peng 2024); none across 4 simvastatin trials with 425 patients (Chen 2024).
- Myalgia 21 in 100 on simvastatin and 22 in 100 on placebo; serious adverse events 7 in 100 and 19 in 100 (Sommer 2021).
What they are
Statins lower cholesterol by blocking HMG-CoA reductase, the enzyme that makes it. They also dampen inflammation and may protect nerve cells, and simvastatin passes from the blood into the brain.1 This entry is about statins as a treatment for symptoms of schizophrenia, not for cholesterol.
How well they work
The largest European trial was run from UMC Utrecht. It gave 119 people diagnosed with schizophrenia within the previous three years simvastatin or a placebo for a year, on top of their usual treatment. After a year, symptoms and thinking skills did not differ between the groups. Symptoms were about 5 points lower with simvastatin at 6 months and again at 24 months, a year after treatment had ended.1 A later analysis found that people with a particular inflammatory pattern in their blood cells improved most on simvastatin, but they did not differ clearly from the placebo group.2
In a trial of 232 people, simvastatin had no effect.3 In Pakistan, 303 people took simvastatin, ondansetron, both or neither for six months; simvastatin alone eased negative symptoms slightly, but the combination took the benefit away.4 Pooled analyses disagree. One, of 9 trials with 533 people, found a small benefit;5 another, of 4 simvastatin trials with 425 people, found none.6 In English health records, people who took simvastatin, which reaches the brain, were admitted to psychiatric hospital no less often than people who took other statins.7
Side effects
In the Dutch trial, muscle pain affected 21 in 100 people on simvastatin and 22 in 100 on placebo. Serious adverse events were less common on simvastatin: 7 in 100, against 19 in 100 on placebo.1
Alternatives
Other medicines tested against inflammation in schizophrenia include minocycline (opens in a new tab), celecoxib and aspirin (opens in a new tab) and N-acetylcysteine (opens in a new tab). None is an established treatment.
What we don’t know yet
- Whether statins help a subgroup with signs of inflammation.
- Why symptoms were lower at 6 and 24 months but not at 12.
