Cholesterol, Diabetes, BP Meds May Help Serious Mental Illness

UPDATED January 17, 2019 // Statins, calcium channel blockers, and metformin may have a role in treating serious mental illness, new research suggests.

Joseph Hayes, PhD

In a large observational study, investigators found individuals with schizophrenia, bipolar disorder (BPD), or nonaffective psychosis (NAP) were less likely to experience psychiatric hospitalization during periods of exposure to any of these agents compared with unexposed periods. In addition, people with schizophrenia or BPD were less likely to self-harm during exposure periods.

"There has been a lack of new drug development for these devastating disorders, but there is some research suggesting that a number of drugs already licensed for other indications may have positive effects on psychiatric symptoms," first author Joseph Hayes, PhD, from the Division of Psychiatry, University College London, UK, told Medscape Medical News.

The study was published online January 9 in JAMA Psychiatry.

New Life for Old Drugs?

The researchers analyzed data on 142,691 patients, including 76,759 with BPD, 30,954 with schizophrenia, and 34,978 with NAP. They focused on patients prescribed statins to reduce cholesterol/heart disease, L-type calcium channel (LTCC) antagonists (such as verapamil) to treat hypertension, or biguanides (such as metformin) to treat diabetes.

Periods of exposure to statins, LTCC antagonists, and biguanides were significantly associated with reduced rates of psychiatric hospitalization in BPD, schizophrenia, and NAP.

Adjusted Hazard Ratios for Psychiatric Hospitalization During
Exposure (95% CI)

Disorder	Statins	LTCC Antagonists	Biguanides
BPD	0.86 (0.83 - 0.89)	0.92 (0.88 - 0.96)	0.80 (0.77 - 0.84)
Schizophrenia	0.75 (0.71 - 0.79)	0.80 (0.74 - 0.85)	0.73 (0.69 - 0.77)
NAP	0.80 (0.75 - 0.85)	0.89 (0.83 - 0.96)	0.85 (0.79 - 0.92)

In addition, self-harm was reduced in patients with BPD and schizophrenia during exposure to all study drugs and in patients with NAP during exposure to LTCC antagonists.

"At this stage, we are not suggesting people with these mental illnesses change their treatment and we wouldn’t recommend using these medications instead of conventional medication for severe mental illness," said Hayes.

"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 patients working with their doctors to optimize prescribing for these physical conditions, which may then have additional beneficial effects on mental health," he added.

Hayes noted that a number of randomized controlled trials of these medications for severe mental illness are underway globally and his team hopes to "reproduce their findings in other large datasets available around the world."

It will also be important 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," Hayes said.

Although none of these drugs have been comprehensively investigated as repurposed agents to improve mental disorders, each has a theoretical basis for effectiveness. Potential mechanisms for statins in psychiatric illness include anti-inflammatory effects or potentially increased absorption and CNS uptake of antipsychotics.

As for calcium channel blockers, calcium dysregulation in BPD is well known and calcium signaling is implicated in the etiology of schizophrenia. Metformin is also hypothesized to improve cognitive and mood dysfunction symptoms by mitigating metabolic disturbances.

Encouraging Findings

Commenting on the findings for Medscape Medical News, Hon-Cheong So, MBBS, PhD, assistant professor, School of Biomedical Sciences, The Chinese University of Hong Kong, said "drug repositioning may serve as a cost-effective way to uncover new therapies for severe mental illnesses such as schizophrenia, as there has not been much progress in developing new agents for these disorders."

"This article," said So, "is very interesting and employs a large database to look for relationships between several classes of quite widely used drugs and serious mental illness. The results are encouraging and help to prioritize drugs for further randomized trials."

Timothy Sullivan, MD, chair of psychiatry and behavioral sciences, Staten Island University Hospital, New York City, also welcomed the study.

"Drug development takes time and is expensive, so clinical researchers are always alert to unexpected signals, from other lines of research, that may recommend the utility of compounds developed for another purpose but shown to have some effect on mental illnesses or symptoms," he told Medscape Medical News.

"There is a long tradition of this type of research: indeed, lithium, antipsychotic medications, and some antidepressants all came into use following the serendipitous but thoughtful observations of clinicians noting clinical responses to medications used, for example, in surgical anesthesia (lithium, and also chlorpromazine, the 'grandfather' antipsychotic) that might provide insights into the management of mental illnesses," said Sullivan.

The authors of this study, he added, "rightly point out that if these findings are verified, repurposing the drugs mentioned above for use as adjuncts in the treatment of serious mental illness could rapidly improve outcomes and avoid the risks and delays associated with standard drug studies. As such, clinicians and researchers alike will welcome these findings while awaiting confirmation from other centers before instituting de novo adjunctive therapy with agents not yet approved for this type of use."

The study was supported by the Wellcome Trust, University College London Hospitals, National Institute for Health Research Biomedical Research Centre, and Swedish Research Council. Hayes and So have reported no relevant financial relationships.

JAMA Psychiatry. Published online January 9, 2019. Full text

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