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Repurposing commonly-used drugs may benefit those with serious mental illness

Exposure to hydroxylmethyl glutaryl coenzyme A reductase inhibitors, L-type calcium channel antagonists and biguanides may lead to improved outcomes for people with serious mental illnesses, according to study data.

Prior research has found that certain drugs may have potential for repurposing to treat serious mental illnesses, Joseph F. Hayes, PhD, from the division of psychiatry, University College London, and colleagues wrote in JAMA Psychiatry.

Hayes and colleagues examined whether drugs commonly used to treat physical health problems — hydroxylmethyl glutaryl coenzyme A reductase inhibitors (HMG-CoA RIs; ie, statins); L-type calcium channel (LTCC) antagonists (eg, verapamil hydrochloride); and biguanides (eg, metformin hydrochloride) — could benefit people with serious mental illness.

Using data from national registries in Sweden, Hayes and colleagues compared rates of psychiatric hospitalization and self-harm admissions during periods of exposure/nonexposure to the study drugs in more than 140,000 people with serious mental illness treated with psychiatric medication. They also adjusted for time-varying covariates.

Of the patients included in the study, 76,759 had bipolar disorder, 30,954 had schizophrenia and 34,978 had nonaffective psychosis.

The study showed that exposure to HMG-CoA RIs was linked to reduced rates of psychiatric hospitalization in patients with bipolar disorder (adjusted HR = 0.86; 95% CI, 0.83-0.89), schizophrenia (aHR = 0.75; 95% CI, 0.71-0.79), and nonaffective psychosis (aHR = 0.8; 95% CI, 0.75-0.85). In addition, HMG-CoA RI use was associated with lower rates of self-harm among those with bipolar disorder (aHR = 0.76; 95% CI, 0.66-0.86) and schizophrenia (aHR = 0.58; 95% CI, 0.45-0.74).

When exposed to LTCC antagonists, participants with the three serious mental illnesses were more likely to have lower rates of psychiatric hospitalization and self-harm in subgroups:

• bipolar disorder (aHRs = 0.92 [95% CI, 0.88-0.96] and 0.81 [95% CI, 0.68-0.95]);
• schizophrenia (aHRs = 0.8 [95% CI, 0.74-0.85] and 0.3 [95% CI, 0.18-0.48]); and
• nonaffective psychosis (aHRs = 0.89 [95% CI, 0.83-0.96] and 0.56 [95% CI, 0.42-0.74]).

Psychiatric hospitalization rates were lower in subgroups with bipolar disorder (aHR = 0.8; 95% CI, 0.77-0.84), schizophrenia (aHR = 0.73; 95% CI, 0.69-0.77) and nonaffective psychosis (aHR = 0.85; 95% CI, 0.79-0.92) during exposure to biguanide. However, self-harm was lower in bipolar disorder (aHR = 0.73; 95% CI, 0.62-0.84) and schizophrenia (aHR = 0.64; 95% CI, 0.48-0.85) only, not nonaffective psychosis.

“If substantiated, this study has considerable implications for clinical practice and drug development,” Hayes and colleagues wrote. 

“The study drugs — HMG-CoA RIs, LTCC antagonists, and biguanides — are globally licensed, commonly-used, cheap, and relatively safe medications,” they continued. “They are therefore ideal candidates for repurposing. Understanding their mode of action on the central nervous system may facilitate better understanding of the pathophysiology of [serious mental illnesses] and offer opportunities for innovative pharmacotherapy development.” – by Savannah Demko

Disclosure: Hayes reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.