Use of Statins, Other Nonpsychotropic Drugs Tied to Better Mental-Illness Outcomes

January 17, 2019

By Will Boggs MD

NEW YORK—Use of statins, L-type-calcium-channel antagonists and biguanides are associated with lower rates of psychiatric hospitalization and self-harm in people with serious mental illness, researchers report.

"We believe randomized controlled trials of these medications for severe mental illness should be the next step, and a number are underway," Dr. Joseph F. Hayes from University College London, UK, told Reuters Health by email. "Alongside this work, we believe it will be useful to clarify the central nervous system (CNS) effects of these classes of drugs, as there may be potential for optimization of effectiveness or new drug development."

Numerous medications have been identified as having the potential for repurposing in such serious mental illnesses as bipolar disorder (BPD), schizophrenia and nonaffective psychoses (NAP).

Dr. Hayes's team used data from Swedish national registers to investigate whether individuals with serious mental illnesses had lower rates of psychiatric hospitalization and self-harm during periods when they were prescribed statins, L-type-calcium-channel antagonists (like verapamil) and biguanides (like metformin) than during periods when they were not exposed to those medications.

While taking statins, patients with schizophrenia were 25% less likely, those with BPD were 14% less likely and those with NAP were 20% less likely to require psychiatric hospitalization than when they were not taking statins - all statistically significant findings.

Patients with BPD were 24% less likely and those with schizophrenia were 42% less likely to harm themselves during statin exposure compared with non-exposure periods, also significant reductions.

The use of L-type-calcium-channel antagonists or biguanides was also associated with reduced psychiatric admissions and self-harm events, although the magnitude of the effects was lower with these medications, the researchers report in JAMA Psychiatry, online January 9.

In contrast, the use of thiazide diuretics (which have not been suggested to benefit serious mental illnesses) was not associated with the rates of psychiatric hospitalization or self-harm, but was associated with an 8% reduced rate of nonpsychiatric admissions.

"At this stage, we are not suggesting people with these mental illnesses change their treatment," Dr. Hayes said. "However, there is evidence that people with schizophrenia, bipolar disorder, and other psychotic illnesses tend to have their physical health undertreated. Particularly, they are at increased risk of cardiovascular disease, hypertension, and diabetes - illnesses these medications are designed to treat. It is, therefore, worth working with your doctor to optimize prescribing for these physical conditions, which may then have additional beneficial effects on mental health."

"All the patients in our cohort were prescribed psychiatric medications at some time during the follow-up period, but the effects we see with statins, L-type-calcium-channel antagonists, and biguanides are independent of whether a patient is on or off psychiatric medication at that time," he said.

"In this type of observational study, it is impossible to totally rule out that these associations reflect something other than a benefit of the drugs themselves," Dr. Hayes cautioned. "In particular, times when people were taking the drugs studied may be periods when they were receiving more support or were more well generally."

Dr. Ole Koehler-Forsberg from Aarhus University Hospital, in Aarhus, Denmark, who has studied the association between statin treatment and depression risk, told Reuters Health by email, "These findings support previous studies indicating that several drugs with primary somatic indications (e.g., statins, RAS drugs, NSAIDs) may have some protective neuropsychiatric effects. It is known that many somatic drugs also have receptors and important functions in the CNS. Hence, these findings are promising in the light of personalized medicine, potentially yielding the possibility to improve treatment of patients with mental disorders. Nevertheless, although intriguing, large randomized controlled trials need to investigate which patients may benefit from which add-on treatment to their psychotropic medications."

"The limitation of the applied within-individual design (used in this study) is that it compares the same individual during different stages of life (and hence during different stages of their mental and somatic diseases)," he said. "The authors have tried to adjust for this, but this issue will always remain in observational studies."

"Therefore, the (use) of a somatic drug may indeed be interpreted as a period where the individual was well - hence the lower admission rate, which is not per se due to the drugs," Dr. Koehler-Forsberg said. "Furthermore, it is known that better treatment of the somatic diseases improves outcomes of the mental disorders. Hence, although interesting, these findings should be interpreted with caution."


JAMA Psychiatry 2019.

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